104年會論文摘要集 by Endo 電子書上傳區

Contents Floor Plan of Conference Rooms........................................................................... 3 Daily Program Schedule.......................................................................................... 4 Opening Remarks..................................................................................................... 6 Board of Directors..................................................................................................... 8 Sponsors.................................................................................................................... 9 Overseas Speakers................................................................................................. 10 Agenda...................................................................................................................... 42 Abstract: Plenary Lecture-Endo: Recent Advances in Pituitary Medicine................................................................. 89 Plenary Lecture-DM: Physiology and Pathophysiology of Incretins: From Bench to Bedside and Vice Versa................................................................ 90 DAROC-TADE Joint Symposium: Better Management of Injection Therapy in Diabetes........................................... 91 Symposium-Endo-1: Current Status of Endocrinology in the Region..................................................... 95 Symposium-DM-1: Diabetes Study and National Health Insurance Database in Taiwan.................. 103

Symposium-Endo-2: Recent Advances in Osteoporosis...................................................................... 105 Symposium-DM-2: New Treatments for Type 2 Diabetes: Roles of Incretin Therapy........................ 108 Symposium-Endo-3: Primary Aldosteronism.........................................................................................110 Symposium-DM-3: Protection of Cardiovascular System and Kidney Beyond Glucose Control in Diabetes...............................................................................................113 Symposium-Endo-4: Pituitary Disease-Update......................................................................................115 Symposium-DM-4: DAROC-TSOC Joint Symposium Guideline: an Update......................................119 Symposium-Endo-5: ESROC- KES Joint Symposium.......................................................................... 122 Symposium-DM-5: Comprehensive Eye Care in Diabetes................................................................ 126 Special Lecture: Current Guideline of Thyroid Cancer Management............................................. 129 2013 DM Research Grant Report........................................................................ 130 Oral Presentation.................................................................................................. 132 Poster Presentation.............................................................................................. 162 2015 Award............................................................................................................. 224

Floor Plan of Conference Rooms

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

The 36th Annual Meeting of The Endocrine Society and The Diabetes Association of the R.O.C.(Taiwan) Program March 21, 2015 (Sat) Time 08:55~09:00

Longevity Hall

1st

Conference Room

2nd

Conference Room

3rd

Conference Room

4th

Conference Room

DT-Joint Sym DR

09:00~09:30

2013 DM Better Sym-Endo-1 Research Grant Management of 09:30~10:00 Report Injection Therapy Current Status of in Diabetes 10:00~11:30 Endocrinology in the Region 11:30~12:00 LS-1

12:00~13:00

MSD

13:00~13:20

LS-2

LS-3

LS-4

Pfizer

Tanabe

Break Sym-Endo-2

Sym-DM-1

Diabetes Study Recent Advances and National in Osteoporosis Health Insurance Database in Taiwan

13:20~14:50

14:50~15:00

Oral Presentation DM

Group Picture

15:00~15:30

Coffee Break & Poster Presentation PL-Endo

15:30~16:10

Recent Advances in Pituitarsy Medicine Sym-Endo-3

16:10~17:40

18:20~20:30

Primary Aldosteronism

Sym-DM-2

New Treatments for Type 2 Diabetes: Roles of Incretin Therapy

O(E&D)

Oral Presentation English Section

The 35th Anniversary Congress Banquet International Reception (Tun-Mu) Hall, The Grand Hotel Taipei

Daily Program Schedule

March 22, 2015 (Sun) Time 08:00~09:00 09:00~10:00

10:00~10:30

1st

Conference Room SS-1

Novo Nordisk Sym-DM-3

Protection of Cardiovascular System and Kidney Beyond Glucose Control in Diabetes

2nd

Conference Room

3rd

SS-2

Conference Room SS-3

Tshbiopharm

ApexBio

4th

Conference Room SS-4

Otsuka

Sym-Endo-4

Pituitary DiseaseUpdate

Current Guideline of Thyroid Cancer Management

Coffee Break

10:30~10:40 PL-DM

10:40~11:20

11:20~12:00

Physiology and Pathophysiology of Incretins：From Bench to Bedside and Vice Versa Annual Meeting LS-5

Lilly / Boehringer Ingelheim

12:00~13:00

Sym-DM-4

DAROC-TSOC Joint Symposium Guideline：an Update

Novartis

Sym-Endo-5

ESROC-KES Joint Symposium Coffee Break & Poster Presentation

14:50~15:30 Sym-DM-5

15:30~17:00

Takeda

LS-7

Break

13:00~13:20

13:20~14:50

LS-6

Comprehensive Eye Care in Diabetes

Oral Presentation Endo

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Opening Remarks Dear members, Distinguished Guests, Ladies and Gentlemen! On behalf of the organizing committee, we would like to express our heartfelt appreciation on your active participating in the 2015 annual meeting in conjunction with the celebration of 35th anniversary, marking incorporation of the society. There are a broad spectrum of programs covering two plenary lectures, ten symposiums, one special lecture, eight satellite symposiums, four oral presentation sessions and a numerous posters presentation in this meeting. The symposium is arranged into two categories from five endocrinology-related to another five metabolism- related topics in the parallel fashion. The previous one includes the current status of endocrinology in the region, osteoporosis, primary aldosteronism, pituitary disease and Korean-Taiwan endocrine joint symposium, respectively. In the two-day program, the secretariat put a relentless effort to invite seventeen international speakers from our sister societies to set up the platform allowing the flow of knowledge and ideas among the endocrinologists in the region become possible. In the evening of the meeting, there is a multi-cultural exchange program in which each national representative will come forward to the stage to display his/her talent in art. We wish this activity will provide a great deal of opportunity for both the local and the overseas endocrinologists to review the overall progress in the field of Endocrinology and Metabolism. Let’s go through with this unforgettable endocrinology-related journey and enjoy the most avant-garde program to date. Take the lessons you learn and the teaching materials you collect at this meeting for perusal to achieve your goals and dreams to be the best endocrinologist you can be. Build up the new friendship and beef up the old camaraderie.

Best Regards

Tjin-Shing Jap, M.D. President, The Endocrine Society of ROC (Taiwan)

Opening Remarks

Opening Remarks Dear Colleagues and friends, On behalf of the Diabetes Association of the R.O.C.(Taiwan), it is my great pleasure to welcome you to attend the 36th Annual Meeting of the Endocrine Society and the Diabetes Association of the R.O.C.(Taiwan) in Taipei, Taiwan, March 21-22, 2015. As usual, we have planed scientific programs: one plenary lecture, six symposium and DM research grant report. Specially thanks to Taiwanese Association of Diabetes Educators (TADE) and Taiwan Society of Cardiology (TSOC) for their generous supports of the TADE/ TSOC joint symposium. It is our honor to successfully invited five distinguished international speakers and 12 local speakers, covering all related topics from diabetes to various complications, new therapeutic medications and techniques .In total, there will be 15 oral presentations (some by English) and 38 poster presentations through the two days of the meeting. Furthermore, I would like to take this opportunity to invite all of you to attend the 11th IDFWPR Congress and 8th AASD Scientific Meeting on October 27-30, 2016 in TICC, Taipei, Taiwan. The congress will be held by Chinese Taipei Diabetes Association (CTDA) and Taiwanese Association of Diabetes Educators (TADE). We cordially encourage you to mark the meeting schedule in your calendar and submit your papers. I am also looking forward to bringing you new insight and sharp inspiration at the venue. Finally, I wish all of you enjoy this excellent meeting with scientific exchanges and networking and have a nice weekend!

Sincerely yours,

Wayne H-H Sheu, MD, PhD President, Diabetes Association of the R.O.C.(Chinese Taipei Diabetes Association) Chair Elect 2013-2015 and Chair 2016-2017, IDF WPR Superintendent and Professor of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Board of Directors

（依照姓氏筆劃排序）

The Endocrine Society of the Republic of China(Taiwan) President

葉振聲 Tjin-Shing Jap

Standing Executive Board

翁錦興 Ging-Shing Won

黃天祥 Tien-Shang Huang

Executive Board

王佩文 Pei-Wen Wang 王治元 Chih-Yuan Wang 李亭儀 Annie Lee 張慶忠 Ching-Chung Chang

曾芬郁 Fen-Yu Tseng 蔡克嵩 Keh-Sung Tsai 鄧錦泉 Kam-Tsun Tang 簡銘男 Ming-Nan Chien

Standing Control Board

林仁德 Jen-Der Lin

Control Board

林宏達 Hong-Da Lin

Secretary General

陳涵栩 Harn-Shen Chen

Deputy Secretary General

林亮羽 Liang-Yu Lin 林慶齡 Cheering Lin 林興中 Hing- Chung Lam

張天鈞 Tien-Chun Chang

郭錦松 Chin-Sung Kuo 陳雁玲 Yan-Ling Chen 黃建寧 Chien-Ning Huang

The Diabetes Association of the Republic of China(Taiwan) President

許惠恒 Wayne Huey-Herng Sheu

Standing Executive Board

蔡世澤 Shih-Tzer Tsai

陳榮福 Jung-Fu Chen

Executive Board

江怡德 Yi-Der Jiang 杜思德 Shih-Te Tu 胡啟民 Chii-Min Hwu 莊峻鍠 Jyuhn-Huarng Juang

郭清輝 Ching-Fai Kwok 黃禹堯 Yu-Yao Huang 裴馰 Dee Pei 謝明家 Ming-Chia Hsieh

Standing Control Board

莊立民 Lee-Ming Chuang

Control Board

何橈通 Low-Tone Ho

Secretary General

林時逸 Shih-Yi Lin

Deputy Secretary General

王俊興 Jun-Sing Wang 朱志勳 Chih-Hsun Chu 李弘元 Hung-Yuan Li

戴東原 Tong-Yuan Tai

李奕德 I-Te Lee 林昆德 Kun-Der Lin 洪乙仁 Yi-Jen Hung

Sponsors

The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan) Would Like to Recognize the Following for Their Support of the 36th Annual Meeting 安克生醫股份有限公司

AmCad BioMed Corporation

五鼎生物技術股份有限公司

Apex Biotechnology Corp.

臺灣阿斯特捷利康股份有限公司

AstraZeneca Taiwan Limited

台灣拜耳股份有限公司

Bayer Taiwan Co., Ltd.

台灣拜耳股份有限公司

Bayer Taiwan Co., Ltd.

嘉德藥品企業股份有限公司

Char Deh Drugs Enterprise Co.,Ltd.

中化裕民健康事業股份有限公司

Chunghwa Yuming Healthcare Co., Ltd.

科林儀器股份有限公司

Clinico Inc.

台灣禮來股份有限公司

Eli Lilly and Company(Taiwan), Inc.

美商默沙東藥廠股份有限公司

Merck Sharp & Dohme (I.A.) Corp. Taiwan Branch

台灣諾華股份有限公司

Novartis (Taiwan) Co., Ltd.

台灣諾和諾德藥品股份有限公司

Novo Nordisk Pharma (Taiwan) Ltd.

輝瑞大藥廠股份有限公司

Pfizer Limited

台灣羅氏醫療診斷設備股份有限公司 Roche diagnostics Ltd.,Taiwan In-Vitiro Diagnostics Professional 賽諾菲股份有限公司

Sanofi Co., Ltd.

財團法人藥害救濟基金會

Taiwan Drug Relief Foundation

台灣大塚製藥股分有限公司

Taiwan Otsuka Pharmaceutical Co., Ltd.

台灣田邊製藥股份有限公司

Taiwan Tanabe Seiyaku Co.,Ltd

台灣武田藥品工業股份有限公司

Takeda Pharmaceuticals Taiwan, Ltd.

東生華製藥股份有限公司

TSH Biopharm Co., Ltd. 9

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Ken K.Y. Ho MBBS, FRACP, FRCP (UK), MD Professor Ho is Chair, Centres of Health Research, senior staff specialist Princess Alexandra Hospital, Professor of Medicine University of Queensland and Adjust Professor Queensland University of Technology, Brisbane. He was previously Chair, Department of Endocrinology St. Vincent’s Hospital, Head Pituitary Research Unit and Professor of Medicine University of New South Wales, Australia. He graduated in medicine at the University of Sydney, obtained a doctorate degree from the University of New South Wales and undertook postdoctoral studies at the University of Virginia. His research interests are on pituitary disease, hormones and metabolism, investigating the causation of and treatments for obesity, muscle loss and physical frailty. The work is strongly translational closely integrating laboratory and clinical studies, directed at understanding how hormones act on cells and on the whole body. He has published over 200 scientific papers and written editorial commentaries for the Lancet. He is a sub-Editor for the European Journal of Endocrinology and Growth Hormone and IGF Research. He serves or has served on the Editorial Boards of leading endocrinology journals including Journal of Clinical Endocrinology and Metabolism, Endocrinology, Pituitary, Endocrine and Best Practice in Endocrinology and Metabolism and as Section Editor of the Oxford Textbook of Endocrinology. He received the inaugural 2011 Senior Plenary Award of the Endocrines Society of Australia, the 2000 Visiting Trust Professor and the 2008 Asia Oceania Medal of the British Endocrine Society. He is a past-president of the Endocrine Society of Australia and of the international Growth Hormone Research Society and the Pituitary Society.

Overseas Speakers

Nobuya Inagaki, M.D., Ph.D. Professor and Chairman Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University Vice-Director Kyoto University Hospital, Kyoto University Pace of Birth: Osaka, Japan Educational Background & Professional Experience: 2011-present: Vice-director, Kyoto University Hospital 2005-present: Professor and Chairman, Department of Diabetes and Clinical Nutrition, (from 2013, Department of Diabetes, Endocrinology and Nutrition) Graduate School of Medicine, Kyoto University, Kyoto 1997-2005: Professor and Chairman, Department of Physiology, Akita University School of Medicine, Akita, Japan 1996- 1997: Associate Professor, Chiba University School of Medicine, Chiba, Japan 1995- 1996: Lecturer, Chiba University School of Medicine, Chiba, Japan 1992- 1995: Instructor, Chiba University School of Medicine, Chiba, Japan (Prof. Susumu Seino) 1987 - 1992: Graduate School of Medicine, Kyoto University, Kyoto, Japan. (Prof. Yutaka Seino and Prof. Hiroo Imura) 1985 - 1987: Clinical Resident and Fellow, Department of Internal Medicine, Kitano Hospital, Osaka, Japan 1984 - 1985: Clinical Resident, Department of Internal Medicine, Kyoto University Hospital, Kyoto, Japan Membership in Scientific Societies: Japan Diabetes Society (executive director) Japan Society of Metabolism and Clinical Nutrition (director) Japan Association for Diabetes, Education, and Care (director) Japan Society of Experimental Diabetes and Obesity (director) Asian Association for the Study of Diabetes（Executive board member） Japan Society of Diabetic Complications (director) The Japanese Society of Internal Medicine (councilor) The Japan Society for Regenerative Medicine (councilor) The Japan Endocrine Society (councilor) The Japanese Society of Internal Medicine (councilor) Physiological Society of Japan (councilor) The Japanese Biochemical Society (councilor) The Molecular Biology Society of Japan (councilor) American Diabetes Association European Association for the Study of Diabetes

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

The Endocrinology Society Award: The Lilly Award of Japan Diabetes Society (May 1995) “Molecular Biology of the ATP-sensitive Potassium Channels” Grant Award of Japan Medical Association (Nov. 1995) “Clarification of Action Mechanism of the Anti-diabetic Agent Sulfonylureas” 50th Erwin von Berz Prize (Oct. 2013) Aglaia Award of Japan Society of Metabolism and Clinical Nutrition (Jan. 2014) Editor: Endocrinology, Editorial Board Member (Jan. 2013-present) Journal of Diabetes Investigation, Associate Editor (Jul. 2009-present) Diabetology International, Editorial Board Member (Nov. 2010-present） Diabetes and Metabolism Journal, International Editorial Board Member (Apr. 2011-present) Journal of Japan Diabetes Society, Editorial Board Member (May 2001-May 2005; May 2007-present) Research Interest: I have an interest in the molecular mechanism of insulin secretion and the pathophysiology of diabetes. We previously determined structure of ATP-sensitive K+ channel in pancreatic β-cells which is the target of the major anti-diabetes drug sulfonylureas, and identified mutations of the channel in patients with familial persistent hyperinsulinemic hypoglycemia of infancy and neonatal diabetes. We also have been devoted to the research on incretin, which is the current, important target for the treatment of diabetes. We recently are trying not only to develop the probe which enables β-cell imaging in vivo, but also to induce pancreatic β-cells from iPS cells. Publications: 215 original articles and 17 reviews Representative 10 publications: 1. Inagaki, N., Seino, Y., Takeda, J., Yano, H., Yamada, Y., Bell, G. I., Eddy, R. L., Fukushima, Y., Byers, M. G., Shows, T. B. and Imura, H. Gastric inhibitory polypeptide: structure and chromosomal localization of the human gene. Mol. Endocrinol. 3: 1014-1021, 1989. 2. Inagaki, N., Maekawa, T., Sudo, T., Ishii, S., Seino, Y. and Imura, H. c-Jun represses the human insulin promoter activity that depends on multiple cAMP response elements. Proc. Natl. Acad. Sci. USA. 89: 1045-1049, 1992. 3. Inagaki, N., Yoshida, H., Mizuta, M., Mizuno, N., Fujii, Y., Gonoi, T., Miyazaki, J. and Seino, S. Cloning and functional characterization of a third pituitary adenylate cyclase-activating polypeptide receptor subtype expressed in insulin-secreting cells. Proc. Natl. Acad. Sci. USA. 91: 2679-2683, 1994. 4. Inagaki, N., Tsuura, Y., Namba, N., Masuda, K., Gonoi, T., Horie, M., Seino, Y., Mizuta, M., and Seino, S. Cloning and functional characterization of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle, and heart. J. Biol. Chem. 270, 5691-5694, 1995. 5. Inagaki, N., Gonoi, T., Clement IV, J. P., Namba, N., Inazawa, J., Gonzalez, G., Aguilar-Bryan, L., Seino, S., and Bryan, J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea

Overseas Speakers receptor. Science 270: 1166-1170, 1995. 6. Inagaki, N., Gonoi, T., Clement IV, J. P., Wang, C.-Z., Aguilar-Bryan, L., Bryan, J., and Seino, S. A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels. Neuron 16: 1011-1017, 1996. 7. Yamada, K., Ji, J.-J., Yuan, H., Miki, T., Sato, S., Horimoto, N., Shimizu, T., Seino, S., and Inagaki, N. Protective role of ATP-sensitive potassium channels in hypoxia-induced generalized seizure. Science 292: 1543-1546, 2001. 8. Abudukadier, A., Fujita, Y., Obara, A., Ohashi, A., Fukushima, T., Sato, Y., Ogura, M., Nakamura Y., Fujimoto, S., Hosokawa, M., Hasegawa, H., and Inagaki, N. Tetrahydrobiopterin lowers fasting blood glucose levels by suppressing hepatic gluconeogenesis in an endothelial nitric oxide synthase-dependent manner in diabetic mice. Diabetes 62: 3033-3043, 2013. 9. Ayano-Takahara, S., Ikeda, K., Fujimoto, S., Hamasaki, A., Harashima, S.-I., Toyoda, K., Fujita, Y., Nagashima, K., Tanaka, D., and Inagaki, N. Glycemic variability is associated with quality of life and treatment satisfaction in patients with type 1 diabetes. Diabetes Care, in press. 10.Iwasaki, K., Harada, N., Sasaki, K., Yamane, S., Iida, K., Suzuki, K., Hamasaki, A., Nasteska, D., Shibue, K., Joo, E., Harada, T., Hashimoto, T., Asakawa, Y., Hirasawa, A., and Inagaki, N. Free fatty acid receptor GPR120 is higyly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology, in press.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Sarita Bajaj MD (Med), DM (Endo,AIIMS) Allahabad Director-Prof & Head of Medicine, MLN Medical College, Allahabad President South Asian Federation of Endo Societies (2013 onwards) President Women in Endocrinology and Diabetes (2013 onwards) Editor in Chief, ESI Manual of Endocrinology 2nd edition (2015) Syllabus Chair International Clinical Update Endocrinology 2014 Positions : Vice-President RSSDI (2013 onwards) Vice-President Endocrine Society of UP (2013 onwards)Vice-Chairman API-UP Chapter (2013 onwards) President Endocrine Society of India (2010-2011) President UP Diabetes Association (2007-2009) Vice President Diabetes India (2002-2008) Executive member Indian Thyroid Society (2013 onwards) Executive member RSSDI (2003 onwards) Executive Patron RSSDI-UP Chapter (2011 onwards) Executive member ISBMR-UP Chapter (2011 onwards) Vice Chairman API-UP Chapter (2013 onwards) Member on the Faculty of Medicine, IMS, BHU (Dept of Endo & Met) Awarded: WHO Fellowship in Endocrinology to visit Southern Illinois University, School of Medicine, Springfield, USA Fellowship of International College of Nutrition Rotary Vocational Excellence Award Fellowship of Uttar Pradesh Diabetes Association Award for Social Service Areas of Interest: Diabetes Education, Thyroidology, Growth disorders Publications: 103 in National and International Journals

Overseas Speakers

Achmad Rudijanto Cholil First Name: Achmad Rudijanto Last Name: Cholil Nationality: Indonesia Organization: PERKENI / ISE (Indonesian Society of Endocrinologiest) Position & Title: Staff of Internal Medicine Department, Endocrinology & Metabolic syndrom Division of Medical Faculty of Brawijaya university / Prof,.PhD Email:achmadrudijanto@yahoo.co.id / persadia_mlg@yahoo.com / perkeni_mlg@yahoo.com

2008 Philosophy doctor Of Brawijaya University 2008-2011 Chairman, PERSADIA / IDA (Indonesian Diabetes Association) 2012-2013 Chairman, AFES 2012-Now Chairman, PERKENI / ISE (Indonesian Society of Endocrinologiest) Representative 5 publications: 1. Achmad Rudijanto. The Expression and Down Stream Effect of Lectin Like-oxidized Low Density Lipoprotein Receptor-1 (LOX-1) in Hyperglycemic State. Indonesian Journal of Internal Medicine. Vol.39, No.1, January 2007. 2. Achmad Rudijanto. The Role of Vascular Smooth Muscle Cells on the Pathogenesis of Atherosclerosis. Indonesian Journal of Internal Medicine Vol.39, No.2, April 2007. 3. Achmad Rudijanto. Calcium Channel Blocker (Diltiazem) Inhibits Apoptosis of Vascular Smooth Muscle Cell Exposed to High Glucose Concentration Through Lectin-like Oxidized Low Density Lipoprotein Receptor-1 (LOX-1) Pathway. Indonesian Journal of Internal Medicine Vol. 42, No.2 April, 2010. 4. Production and Potency of Local Rambutan at East Java as a Candidate Phytopharmaca.Agrivita Vol 35 No.3 October 2013 5. The Physiological Response of Obese Rat model with rambutan peel extract treatment . Asian Pacific Journal of Tropical Disease.2014;4.S780-S785

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Young Kee Shong Academic Career 1977.03-1979.02 Premedical Course, Seoul National University 1979.03-1983.02 College of Medicine, Seoul National University (M.D.) 1984.03-1989.02 Graduate School, Seoul National University (Ph. D. in Medical Science) License 1983.03 1985.01 1987.04 1992.10 1997.03

Korean Medical Doctor (#26327) Special License for Medical Use of Radioisotope (#337) Korean Board of Internal Medicine (#2270) Korean Board of Endocrinology and Metabolism (#4-92-57) Korean Board of Nuclear Medicine (#99)

Professional Traning 1983.03-1984.02 Internship, Seoul National University Hospital (SNUH) 1984.03-1987.02 Residency, Department of Internal Medicine, SNUH 1985.10-1985.11 Special Training Course for Medical Use of Radioisotope, Korean Atomic Energy Research Institute 1987.03-1989.02 Fellowship, Endocrinology, SNUH 1989.03-1990.02 Fellowship, Endocrinology, Asan Medical Center (AMC) Professional Career 1990.03-1993.03 Lecturer, Asan Medical Center, University of Ulsan 1992.10-1993.12 Visiting Scientist, Charite, Standort Steglitz, Berlin, Germany 1993.04-1997.09 Assistant Professor, AMC, University of Ulsan 1997.10-2002.08 Associate Professor, AMC, University of Ulsan 2002.09- present Professor, AMC, University of Ulsan 1997.11-2000.10 Chairman, Department of Traditional Medicine, Asan Life Institute 1999.03-2001.02 Director, Medical Planning Team, AMC 2005.01-2006.12 Director, Asan Referral Center, AMC 1999.01-2003.12 Secretary/Treasurer, Korean Thyroid Association (KTA) 2002.01-2005.12 Secretary General, AOTA 2002.01-2010.12 Member, Program Organizing Committee, AOTA 2008.01-2009.12 Director, International Liason Committee, KTA 2009.01-2010.12 Director, Ethics Committee, Korean Endocrine Society (KES) 2010.01-2011.12 Chairman of the Board of Directors, KTA 2012.01-2013.12 Director without portfolio, KTA 2010.10-present Chairman, Program Organizing Committee, AOTA 2011.01-2012.12 Director, Mastercourse committee, KES 2013.01-2014.12 Director, International Liason Committee, KES 2013.01-present Editorial Board Member, THYROID 2013.01-present Editorial Board Member, EUROPEAN THYROID JOURNAL 16

Overseas Speakers 2013.10-present 2014.01-present 2015.01-present Award 2008.09 2009.05 2012.10

Editorial Board Member, CLINICAL ENDOCRINOLOGY Editorial Board Member, JAFES Chairman of the Board of Directors, Korean Endocrine Society

Genzyme Award, Korean Thyroid Association 2009 Endocrine Research Award, Korean Endocrine Society Nagataki-FUJIFILM award, AOTA

Publication Publications 115 peer-review articles. Representation 10 Article: 1. Jang EK, Song DE, Gong G, Baek JH, Choi YM, Jeon MJ, Han JM, Kim WG, Kim TY, Shong YK, Kim WB. Positive cytology findings and a negative histological diagnosis of papillary thyroid carcinoma in the thyroid: is it a false-positive cytology or a disappearing tumor? Eur Thyroid J. 2013 Sep;2(3):203-10. doi: 10.1159/000353624. Epub 2013 Aug 13. 2. Kwon H, Kim WG, Choi YM, Jang EK, Jeon MJ, Song DE, Baek JH, Ryu JS, Hong SJ, Kim TY, Kim WB, Shong YK. A cut-off Value of Basal Serum Calcitonin for Detecting Macroscopic Medullary Thyroid Carcinoma. Clin Endocrinol (Oxf). 2014 Jul 19. doi: 10.1111/cen.12562. [Epub ahead of print] 3. Lim HK, Baek JH, Lee JH, Kim WB, Kim TY, Shong YK, Hong SJ. Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer. Eur Radiol. 2014 Sep 9. [Epub ahead of print] 4. Kim TY, Kim WG, Kim WB, Shong YK. Current status and future perspectives in differentiated thyroid cancer. Endocrinol Metab (Seoul). 2014 Sep;29(3):217-25. 5. Kwon H, Kim H, Park S, Song DE, Kim WG, Kim TY, Shong YK, Kim WB. Solitary Skin Metastasis of Papillary Thyroid Carcinoma. Endocrinol Metab (Seoul). 2014 May 27. [Epub ahead of print] 6. Xing M, Alzahrani AS, Carson KA, Shong YK, Kim TY, Viola D, Elisei R, Bendlová B, Yip L, Mian C, Vianello F, Tuttle RM, Robenshtok E, Fagin JA, Puxeddu E, Fugazzola L, Czarniecka A, Jarzab B, O’Neill CJ, Sywak MS, Lam AK, Riesco-Eizaguirre G, Santisteban P, Nakayama H, Clifton-Bligh R, Tallini G, Holt EH, Sýkorová V. Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer. J Clin Oncol. 2014 Oct 20. pii: JCO.2014.56.8253. [Epub ahead of print] 7. Jang EK, Kim WG, Choi YM, Jeon MJ, Kwon H, Baek JH, Lee JH, Kim TY, Shong YK, Song DE, Kim WB Association between neck ultrasonographic findings and clinico-pathological features in the follicular variant of papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2014 Nov 17. doi: 10.1111/cen.12674. [Epub ahead of print] 8. Kwon H, Kim M, Choi YM, Jang EK, Jeon MJ, Kim WG, Kim TY, Shong YK, Song DE, Baek JH, Hong SJ, Kim WB. Lack of Associations between Body Mass Index and Clinical Outcomes in Patients with Papillary Thyroid Carcinoma. Endocrinol Metab (Seoul). 2014 Nov 26. [Epub ahead of print] 9. Suh CH, Baek JH, Ha EJ, Choi YJ, Lee JH, Kim JK, Chung KW, Kim TY, Kim WB, Shong YK. Ethanol ablation of predominantly cystic thyroid nodules: Evaluation of recurrence rate and factors related to recurrence. Clin Radiol. 2015 Jan;70(1):42-7. doi: 10.1016/j.crad.2014.09.008. Epub 2014 Oct 14. 10.Ji Hong M, Baek JH, Choi YJ, Lee JH, Lim HK, Shong YK, Hong SJ. Radiofrequency ablation is a thyroid function-preserving treatment for patients with bilateral benign thyroid nodules. J Vasc Interv Radiol. 2015 Jan;26(1):55-61. doi: 10.1016/j.jvir.2014.09.015. Epub 2014 Nov 18. 17

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Overseas Speakers

Than Than Aye M.B.,B.S, M.Med.Sc (Int.Med.), D.T.M & H (London), MRCP (UK) Dr.Med.Sc (Gen.Med.), FRCP (Edin),FRCP(London) Thesis in Doctorate course: Effectiveness of insulin therapy in type 2 diabetes patients Current position: Professor Emeritus, Previously Professor and Head (retired), Department of Medicine and Department of Endocrinology, North Okkalapa General Hospital University of Medicine 2, Yangon Member of : Member of Myanmar Medical Association Member of Internal Medicine Society,under Myanmar Medical Association Vice President of Myanmar Society of Endocrinology and Metabolism(MSEM) Vice President of Myanmar Diabetes Association (MmDA) Member of AFES Member of AACE,ADA,Endocrine Society After obtaining MRCP (UK), she trained in Diabetes and Endocrinology at Royal Infirmary Hospital of Edinburgh and Royal Infirmary Hospital of Hull in the UK in 1994 -1995.Since after backed home to Myanmar she has been playing an active role in educating medical students, practicing doctors and general practitioners by updating the knowledge in the field of Diabetes and Endocrinology .She has given ideas ,advices and encouragements to her post graduate trainees for their thesis and research particularly in the field of endocrinology. She is now leading and guiding the doctorate course on Endocrinology as she was honored as an Emeritus Professor in that university, although she has retired from the government service. She is actively practicing in the private sector, in Bahosi Hospital and Myint Thaw Dar Diabetes Center. She is trying to improve the medical knowledge of the public by writing articles in local Health journals.

Agenda

Bien J. Matawaran MD, FPCP, FPSEDM Fellow, Philippine College of Physicians Fellow, Philippine Society of Endocrinology, Diabetes and Metabolism e-mail: drbienj@yahoo.com or drbienj@gmail.com EDUCATIONAL ATTAINMENT BS Medical Technology (1988-1992) Doctor of Medicine (1992-1996) Medical Internship (May 1996 to April 1997) Internal Medicine Residency (Jan 1998 to Dec 2000) Fellowship in Endocrinology (Jan 2002 to December 2003) ACCREDITATIONS Certified Clinical Densitometrist Endocrinology & Metabolism Internal Medicine Physician

University of Santo Tomas, Faculty of Pharmacy University of Santo Tomas, Faculty of Medicine Dean’s Lister; Bene Meritus- Oral Revalida Santo Tomas University Hospital España, Manila, Philippines Santo Tomas University Hospital España, Manila, Philippines Section of Endocrinology & Metabolism University of Santo Tomas Hospital España, Manila, Philippines Chief fellow (January- June 2003) The International Society for Clinical Densitometry October 13 2007- October 13, 2012 Philippine Specialty Board of Endocrinology & Metabolism Philippine Society of Endocrinology & Metabolism July 2006 Philippine Specialty Board of Internal Medicine Philippine College of Physicians January 2001 Philippine Physician Licensure Examination August 1997

CURRENT POSITIONS Vice- President, Philippine Society of Endocrinology, Diabetes & Metabolism (since 2013) Vice Chair, Department of Medicine, Jose R. Reyes Memorial Medical Center (since 2012) Training Officer, Fellowship Training, Section of Endocrinology & Metabolism, UST Hospital (since 2010) Assistant Professor 2, Dept’ment of Biochemistry, Molecular Biology & Nutrition, UST Medicine & Surgery (since 2007) Member, Advocacy Committee, Philippine Society of Endocrinology & Metabolism (since 2007) Consultant, Section of Endocrinology, Diabetes & Metabolism, UST Hospital, España, Manila (since 2004) 19

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Editorial Staff, Hormone Hotspots (PSEM lay Publication) (since 2008) Medical Specialist 1, Department of Medicine, Jose R. Reyes Memorial Medical Center, Rizal Ave, Manila PROFESSIONAL MEMBERSHIP Diplomate and Fellow, Philippine Society of Endocrinology, Diabetes & Metabolism International Member, American Association of Clinical Endocrinologists Member, Endocrine Society, USA (2010-present) Member, Diabetes Philippines (formerly Philippine Diabetes Association) Diplomate and Fellow, Philippine College of Physicians POSITIONS HELD Secretary, Philippine Society of Endocrinology & Metabolism (2012-2013) Secretary, Philippine Specialty Board of Endocrinology, Diabetes & Metabolism (2012-13) Board of Director, Philippine Society of Endocrinology & Metabolism (2009-2012) Training Officer, Department of Medicine, Jose R. Reyes Memorial Medical Center (2009-2012) Secretary, Philippine Thyroid Association (2007-2009) Board of Directors, Philippine Thyroid Association (2006-2007) Member, Residency Training Committee, Department of Medicine, UST Hospital (2007-2010) Member, Medical Clerks Training Committee, Department of Medicine, UST Hospital (20082010) Member, Committee on Newsletter, UST Medical Alumni Association (2008-2010) Editorial Staff, Hormone Hotspots (PSEM lay Publication) (since 2008-2010) Member, Technical Review Committee, PSEM Research Grants (2005 & 2007) President- 86th Radioisotope Techniques & Training Course, Philippine Nuclear Research Institute, Quezon City, 2003 AWARDS AND RECOGNITION Plaque of Recognition for the Creation of The PSEM Hymn Dr. Nemencio Nicodemus and Dr. Bien J. Matawaran Philippine Society of Endocrinology & Metabolism Sofitel Hotel, Manila, February 3, 2007 Young Investigator Award American Association of Clinical Endocrinologists (AACE) Philippine Chapter Ayala Museum, Makati, August 26, 2006 Leadership Award- University of Santo Tomas Fellows’ Graduation CME Auditorium, UST Medicine Building, December 2003 1st Place- 4th Bayer Diabetes Debate, (UST- UP-PGH team) Philippine Diabetes Association, Inc.; Century Park Hotel Manila, November 25, 2003 ISSUE: Diagnostic criteria for type 2 DM PROPOSITION: “Resolve that the FBS for diagnosis of type 2 DM be below 126 mg/dL” Recipient of International Travel Grant Award- American Association of Clinical Endocrinologists 3rd Place Young Investigator Award Matawaran, BJ, Llorin, J, Gomez, HS. Pituitary Tuberculosis: Back with an old Foe 12th Annual Meeting and Clinical Congress American Association of Clinical Endocrinologists; San Diego, California, USA; May 14-18, 2003 20

Agenda One of the Best 15 papers- Free Communication Poster Session Matawaran, BJ, Udarbe, MP, Mercado- Asis, LB. Comparison of Pancreatic Insulin Response to Hyperglycemia Among Filipino Subjects in Various Metabolic Status 33rd Annual Philippine College of Physicians Convention; EDSA Shangri-la Hotel Pasig City, Philippines; May 2003 Grand Champion UST Hospital team- Philippine College of Physicians’ (PCP-Parke Davies) Quiz Contest EDSA Shangri-la Hotel Pasig City, Philippines; May 14, 1999

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Thavatchai Peerapatdit or Thavatchai Piraphatdist

Title: Associate Professor MD, FRCP(Thai), Thai sub board of Endocrinology Office: Department of Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine Siriraj Hospital, Mahidol University 2 Prannok Rd., Bangkoknoi, Bangkok 10700, Thailand. e-mail: thavatchai.pee@mahidol.ac.th or thavatc@hotmail.com Member of Professional Associations or Society Endocrine Society of Thailand Diabetes Association of Thailand Royal College of Physician of Thailand Medical Council of Thailand Present Positions Medical staff of Division of Endocrinology & Metabolism, Department of medicine, Faculty of Medicine Siriraj Hospital, Mahidol University President of the Endocrine Society of Thailand or EST (AD 2011-2013) Some Publications in English 1. Piraphatdist T, Sugawa H, Inoue D, Enomoto T, Mori T, Imura H. Possible binding site of thyrotropin binding inhibitor immunoglobulin (TBII) on the thyrotropin (TSH) receptor, which is different from TSH binding site. Biochem Biophys Res Commun. 1990 Oct 30;172(2):529-36 2. Peerapatdit T, Chaivichitmalakul P, Lertwatanarak R, Chobtangsilp S, Plengvidhya N, Sriussadaporn S, Nitiyanant W, Vannasaeng S. Craniopharyngioma : A review of 14 cases at Siriraj Hospital. Siriraj Med J 2006;58: 1091-4. 3. Peerapatdit T, Likidlilid A. MSc, Patchanans N, Somkasetrin A. Antioxidant status and lipid peroxidation end products in patients of Type 1 diabetes mellitus. J Med Assoc Thai 2006;89:S141-46. 4. Peerapatdit T, Likidlilid A, Poldee S, Sriratanasathavorn C. Plasma lipid peroxidation and antioxidiant nutrients in type 2 diabetic patients. J Med Assoc Thai 2006;89:S147-55. 5. Peerapatdit T, Chobtangsilp S, Lertwattanarak R. Effects of a long-acting somatostatin analog octreotide in a case of acromegaly. Intern Med J Thai 2005;21:61-4. 6. Peerapatdit T , Likidlilid A , Patchanans N, Tirawanchai N, Sriratanasathavorn C Glutathione and Glutathione Peroxidase in type 2 diabetic patients. Siriraj Hosp Gaz 2004;56: 53-62. 7. Mori T, Sugawa H, Piraphatdist T, Inoue D, Enomoto T, Imura H. A synthetic oligopeptide derived from human thyrotropin receptor sequence binds to Graves’ immunoglobulin and inhibits thyroid stimulating antibody activity but lacks interactions with TSH. Biochem Biophys Res Commun. 1991 Jul 15;178(1):165-72. 8. Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A. Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism. Clin Endocrinol. 2001 ;54:385-90. 9. Phoojaroenchanachai M, Sriussadaporn S, Peerapatdit T, Vannasaeng S, Nitiyanant W, Boonnamsiri 22

Agenda V, Vichayanrat A. Effect of maternal hyperthyroidism during late pregnancy on the risk of neonatal low birth weight. Clin Endocrinol 2001;54:365-70. 10. Plengvidhya N, Rathanavijitrasilp A, Sangruchi T, Nitiyanant W, Vannasaeng S, Piraphatdist T, Vichayanrat A. Primary thyroid carcinoma and thyrotoxicosis. Int J Clin Pract 1997;51: 471-6. 11. Sriussadaporn S, Ploybutr S, Peerapatdit T, Nitiyanant W, Vannasaeng S, Vichayanrat A. Efficacy of using basal plasma adrenocorticotropic hormone- radioimmunoassay(ACTH-RIA) level in the identification of the cause of Cushing’s syndrome. J Med Assoc Thai 1997;80:233-41. 12. Sriussadaporn S, Mekanandha P, Vannasaeng S, Nitiyanant W, Komoltri C, Ploybutr S, Yamwong P, Peerapatdit T, Vichayanrat A. Factors associated with diabetic foot ulceration in Thailand: A casecontrol study. Diab Med 1997;14:50-6. 13. Sriussadaporn S, Ploybutr S, Peerapatdit T, Plengvidhya N, Nitiyanant W, Vannasaeng S, Vichayanrat A. Nocturnal 8 mg dexamethasone suppression test: a practical and accurate test for identification of the cause of endogenous Cushing’s syndrome. Br J Clin Pract 1996;50:9-13. 14. Vannasaeng S, Ploybutr S, Nitiyanant W, Peerapatdit T, Vichayanrat A. Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of noninsulin-dependent diabetes mellitus. J Med Assoc Thai 1995;78:578-85. 15. Nitiyanant W, Vannasaeng S, Vichayanrat A, Sriussadaporn S, Piraphatdist T, Singalavanija A. Vascular complications and lipid disorders in IDDM in Thailand. Jap J Cons Med 1992;55:134-7. 16. Sriussadaporn Sutin; Phoojaroenchanachai Meta; Ploybutr Sirirat; Plengvidhya Nattachet; Peerapatdit Thavatchai; Nitiyanant Wannee; Vannasaeng Sathit; Vichayanrat Apichati. Hypercalcemia of malignancy: a study of clinical features and relationships among circulating levels of calcium, parathyroid hormone and parathyroid hormone-related peptide. J Med Assoc Thai. = Chotmaihet thangphaet 2007;90(4):663-71. 17. Santiprabhob Jeerunda; Likitmaskul Supawadee; Kiattisakthavee Pornpimol; Weerakulwattana Praewvarin; Chaichanwattanakul Katharee; Nakavachara Pairunyar; Peerapatdit Thavatchai; Nitiyanant Wannee Glycemic control and the psychosocial benefits gained by patients with type 1 diabetes mellitus attending the diabetes camp. Patient education and counseling 2008;73 (1):60-6. 18. Likidlilid A, Patchanans N, Peerapatdit T, Sriratanasathavorn C. Lipid peroxidation an antioxidant enzyme activities in erythrocytes of type 2 diabetic patients. J Med Assoc Thai. 2010 Jun; 93(6):682-93. 19. Jeerunda Santiprabhob, Pornpimol Kiattisakthavee, Supawadee Likitmaskul, Katharee Chaichanwattanakul, Jirapa Wekawanich, Hattaya Dumrongphol, Apiradee Sriwijitkamol, Thavatchai Peerapatdit, Wannee Nitiyanant. Glycemic control, quality of life and self-care behavior among adolescents with type 1 diabetes who attended a diabetes camp. Southeast Asean J Trop Med Public Health 2012; Vol 43 No.1: 172-184. 20.Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Rajesh Chaudhary, Atip Likidlilid, Thavatchai Peerapatdit, Damras Tresukosol, Sorachai Srisuma,Suphachai Ratanamaneechat and Charn Sriratanasathavorn. Cardiovascular Diabetology 2012, 11:36. 21.Associations of paraoxonase 2 A148G gene polymorphism on heart disease in type 2 diabetic patients. Hobang N, Peerapatdit T, Tresukosol D, Ratanamaneechat S, Likidlilid A. Thai J Genet 2013,S(1): 164-166. 22.A Prospective, Longitudinal, Multicenter, Observational Study to Assess Insulin Treatment Patterns in Diabetic Patients in Thailand: Results from the TITAN Study. Petch Rawdaree, Veerasak Sarinnapakorn, Somchai Pattanaungkul, Weerapan Khovidhunkit, Poj Tannirandorn, Thavatchai Peerapatdit. J Med Assoc thai 2014:97(11):1140-50. 23

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Manju Chandran MD, FACP, FACE, FAMS, CCD Dr Manju Chandran (MD, FACP, FACE, FAMS, CCD) is board certified in Endocrinology, Diabetes and Metabolism. She is an elected member of the Committee of Scientific Advisors (CSA) of the International Osteoporosis Foundation the Chair Elect of the Chapter of Endocrinology of the College of Medicine, Singapore, member of the Editorial Board of the Journal of the ASEAN Federation of Endocrine Societies (JAFES) and the immediate past President of the Endocrine and Metabolic Society of Singapore (EMSS). She also serves on the executive committee of the Osteoporosis Society of Singapore (OSS), played a key role in the launching of the Singapore FRAX

(R)

model and is an elected member of the Asia Pacific Panel of the International

Society of Clinical Densitometry (ISCD). Her research interests include Secondary Fracture Prevention, Epidemiology and Pharmaco-compliance of Osteoporosis, Renal Transplant Bone Disease and Rare Metabolic Bone Diseases. One of her studies on pharamaco-compliance of Osteoporosis recently won the IOF-ESCEO Young Investigator Award for 2013. She has widely published in international peer-reviewed journals and has been an invited speaker at numerous local, regional and international conferences in the field of Osteoporosis and Bone Metabolism.

Agenda

Howard Arthur Morris QUALIFICATIONS PhD (1970 (Univ Sydney), FAACB 1994 (AACB), FFSc(RCPA) 2011 (RCPA) AWARDS 2009 BioSA Industry Leader, BioSA Achievement Awards 2009 Louis V. Avioli Memorial Lecturer, American Society of Bone and Mineral Research. 2009 Finalist, South Australian Excellence in Research for Public Good 2012 Association of Clinical Biochemists (United Kingdom) International Lecturer EMPLOYMENT PRESENT POSITION 2010 to present Joint appointment Professor of Medical Sciences, University of South Australia and Senior Medical Scientist, Chemical Pathology Directorate, SA Pathology Research work focuses on steroid hormone regulation of bone metabolism and cancer with a team of research staff and postgraduate students. These studies involve collaborations with researchers at the University of Melbourne Austin Hospital, University of Adelaide, McGill University (Montreal), University of California San Francisco. EMPLOYMENT HISTORY 2007-2009 Director, Hanson Institute responsible for developing major research projects and new medical research directions for the campuses of Institute of Medical and Veterinary Science and Royal Adelaide Hospital: infrastructure to support the research of some 450 staff and 100 postgraduate students with external grants $AUD 35 million annually. As Chair, Large Animal Research Imaging Facility, awarded $30 million for node of the NCRIS-funded National Imaging Facility in conjunction with Uni of SA, Uni of Adelaide and IMVS National health and medical research Council 2006 Member, Grant Review Panel, Endocrinology and Diabetes 1988- present External Assessor Australian Research council 2012 Member, Excellence in Research Australia (ERA) Medical and Health Sciences Research Evaluation Committee INTERNATIONAL COMMITTEE MEMBERSHIPS 2012-2014 Vice-President, International Federation of Clinical Chemistry and Laboratory Medicine

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

2002 – 2008 2013 – 2016

Secretary, Scientific Division, International Federation of Clinical Chemistry and Laboratory Medicine Programme Advisory Committee, Vitamin D Workshop Incorporated

EDITORIAL RESPONSIBILITIES Co-editor (with PH Anderson and BEC Nordin) “Physiological Basis of Metabolic Bone Disease” CRC Press, Boca Raton, FL 2013 Guest Editor, Nutrients Special Issue ‘Osteoporosis Prevention’ 2010 Guest Editor, (with Dr Paul Anderson) Molecular and Cellular Endocrinology Special Issue “Vitamin D Metabolism: Implications for Biological Activities” 2011 International Editor, Annals of Clinical Biochemistry, 1994-2003 Editor, Clinical Biochemist Reviews, 1994-2002 Co-editor (with BEC Nordin and AG Need) “Metabolic Bone and Stone Disease, Third Edition” Churchill Livingstone, Edinburgh 1993. RESEARCH GRANTS Grants to a total value of $9.125 million have been awarded to support my research. NHMRC and ARC grants currently held: APP1029756 “Vitamin D Synthesis Within Osteoblasts Increases Bone Mineral By Regulating Remodelling: Is This The Link Between Vitamin D Status And Fractures?” Anderson PH, Morris HA, Turner A, Atkins GJ 2012 $202,003 2013 $202,003 2014 $202,003 APP1029926 “Control of Bone Remodelling By Osteoclastic Metabolism of Vitamin D” Atkins GJ, Anderson PH, Morris HA, Davey RA, Findlay DM. 2012 $223,700 2013 $223,700 2014 $223,700 APP 1003433 “Vitamin D activity to regulate bone remodelling and promote bone strength” Anderson PH, Morris HA, Davey RA, O’Loughlin PD 2011 $111,394 2012 $181,130 2013 $181,130 APP1009438 “Vitamin D and reducing the risk of breast cancer” Callen DF, Morris HA, Gill G. 2011 $179,551 2012 $179,551 2013 $179,551 LP120100519 “Towards a cost-effective therapy for osteoporosis using Australian indigenous emu oil” CF Xian, HA Morris C Gregory 2012 $150,000 2013 $150,000 2014 $150,000 TEACHING RESPONSIBILITIES Postgraduate: 1982-2013 Supervision of 15 B.Sc.(Honours) students 1994-2013 Supervision 13 Ph.D. theses

Agenda

Stephen L. Atkin MBBS, PhD Professor of Medicine sla2002@qatar-med.cornell.edu PROFILE Dr. Stephen L. Atkin joined Weill Cornell Medical College in Qatar (WCMC-Q) in January 2014 as Professor of Medicine. He has an established international reputation in diabetes and obesity research, encompassing both polycystic ovary syndrome and the metabolic syndrome, has led pharmaceutical and nutritional clinical trials teams for these studies in the U.K, and is regularly invited to speak at international forums and to participate in research panels for these conditions. Prior to coming to WCMC-Q, Dr. Atkin was Professor of Diabetes, Endocrinology, and Metabolism and Head of Academic Diabetes and Endocrinology at Hull York Medical School, University of Hull and Honorary Consultant in the Department of Diabetes and Endocrinology at Hull and East Yorkshire Hospitals. He has extensive experience teaching medical and graduate students and was the regional coordinator for the diabetes and endocrinology graduate training program for the Royal College of Physicians/Diabetes U.K. Endocrine Society covering a large part of central England. Under his leadership, the department became an internationally respected center for diabetes, endocrinology, obesity, and nutritional research. During his career, Dr. Atkin has received a number of important research awards, including recent funding from the Biotechnology and Biological Sciences Research Council, the Food Standards Agency, and the Higher Education Funding Council that amount to over nine million US Dollars. Additionally, he has led the Humber Obesity, Nutrition, Education, and Innovation (HONEI) project (www.honei.co.uk) that focuses on clinical and translational research on functional food in health and disease. He has published over one hundred and forty articles in peer-reviewed journals, including work in Diabetes Care, PLOS ONE, and the Journal of Clinical Endocrinology and Metabolism, and several book chapters and reviews. He is a grant referee for several major funding bodies, such as the Wellcome Foundation and the British Heart Foundation; a journal reviewer for several journals, including the Journal of the American Medical Association, Diabetes Care, and the Journal of Clinical Endocrinology and Metabolism; he is the series advisor on “rational testing” for the British Medical Journal and an Academic Editor for PLOS ONE and the International Journal of Endocrinology. SELECTED PUBLICATIONS 1. Kilpatrick ES, Rigby AS, Atkin SL, Barth JH. Glycemic control in the 12 months following a change to SI hemoglobin A1c reporting units. Clinical chemistry. 2013 Jun 21: doi: 10.1373/clinch em.2013.206334. [Epub ahead of print]. 2. Meneghini L, Atkin SL, Gough SC, Raz I, Blonde L, Shestakova M, Bain S, Johansen T, Begtrup K, Birkeland KI. The efficacy and safety of insulin degludec given in variable once-daily dosing intervals compared with insulin glargine and insulin degludec dosed at the same time daily: a 27

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes care. 2013 Apr;36(4):858-64. 3. Sathyapalan T, Shepherd J, Atkin SL, Kilpatrick ES. The effect of atorvastatin and simvastatin on vitamin D, oxidative stress and inflammatory marker concentrations in patients with type 2 diabetes: a crossover study. Diabetes, obesity & metabolism. 2013 Aug;15(8):767-9. 4. Sathyapalan T, Shepherd J, Kilpatrick ES, Coady AM, Atkin SL. Atorvastatin therapy Reduces Malondialdehyde in patients with Polycystic Ovary Syndrome. Journal of Clinical Endocrinology and Metabolism 2012;97(11):3951-5 5. Sathyapalan T, Manuchehri AM, Thatcher NJ, Rigby AS, Chapman T, Kilpatrick ES, Atkin SL. The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. The Journal of clinical endocrinology and metabolism. 2011 May;96(5):1442-9. 6. Sathyapalan T, Shepherd J, Arnett C, Coady AM, Kilpatrick ES, Atkin SL. Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome. Clinical chemistry. 2010 Nov;56(11):1696-700. 7. Ng JM, Cooke M, Bhandari S, Atkin SL, Kilpatrick ES. The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes care. 2010 Nov;33(11):2310-3 8. Kilpatrick ES, Rigby AS, Atkin SL. The role of blood pressure variability in the development of nephropathy in type 1 diabetes. Diabetes care. 2010 Nov;33(11):2442-7.

Agenda

Takashi Nomiyama, MD., PhD Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan Employment History 10/2012 to present Associate Professor, Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Fukuoka 10/2010 to 9/2012 Senior Assistant Professor, Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Fukuoka 7/2009 to 9/2010 Assistant, Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, Tokyo 9/2008 to 6/2009 Assistant, Department of Internal Medicine, Division of Diabetes and Endocrinology, Juntendo Tokyo Kotoh Geriatric Medical Center 2/2005 to 7/2008 Post-Doctoral Fellow, Department of Internal Medicine, Division of Endocrinology and Molecular Medicine, University of Kentucky College of Medicine 10/2004 to 1/2005 Assistant, Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, Tokyo 5/2002 to 9/2004 Post-Doctoral Fellow, Department of Medicine, Metabolism and Endocrinology, Juntendo University, School of Medicine, Tokyo 5/1995 to 4/1998 General Internal Medicine Residency Juntendo University Hospital, Tokyo Education Name/Location of University Juntendo University/Tokyo, Japan Juntendo University Graduate School/Tokyo, Japan

Degree 1995 2002

Year Conferred Medicine Diabetology

Field of Study MD PhD

Hobby: Kendo 6th Dan Publications Published more than 47 peer-review articles. Representative 10 publications: 1. Nomiyama T, Zhao Y, Gizard F, Findeisen HM, Heywood EB, Jones KL, Conneely OM, Bruemmer D. Deficiency of the NR4A Neuron-Derived Orphan Receptor-1 Attenuates Neointima Formation After Vascular Injury. Circulation 2009 Feb 3;119(4):577-86. 2. Nomiyama T, Bruemmer D. Liver X receptor as therapeutic targets in metabolism and atherosclerosis. Curr Atheroscler Rep. 2008 Feb;10(1):88-95 3. Nomiyama T, Perez-Tilve D, Ogawa D, Gizard F, Zhao Y, Heywood EB, Jones KL, Kawamori R, Cassis LA, Tschop MH, Bruemmer D. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest 2007 Oct 1;117(10):2877-2888 4. Nomiyama T, Igarashi Y, Taka H, Mineki R, Uchida T, Ogihara T, Choi JB, Uchino H, Tanaka

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Y, Maegawa H, Kashiwagi A, Murayama K, Kawamori R, Watada H, Deterioration of Insulin Stimulated Glucose Uptake by Peroxynitrite is Associated with Tyrosine-nitration of Insulin Receptor Substrate-1. Biochem Biophys Res Commun 2004 Jul 30;320(3):320:639-47 5. Nomiyama T, Tanaka Y, Piao L, Hattori N, Uchino H, Watada H, Kawamori R, Ohta S, Accumulation of Somatic Mutation in mitochondrial DNA and Atherosclerosis in Diabetic Patients. Ann NY Acad Sci. 2004 Apr;1011:193-204 6. Nomiyama T, Tanaka Y, Piao L, Nagasaka K, Sakai K, Ogihara T, Nakajima K, Watada H, Kawamori R, The polymorphism of manganese superoxide dismutase is associated with diabetic nephropathy in Japanese type 2 diabetic patients. J Hum Genet.2003 Mar;48(3):138-41 7. Nomiyama T, Tanaka Y, Hattori N, Nishimaki K, Nagasaka K, Kawamori R, Ohta S, Accumulation of somatic mutation in mitochondrial DNA extracted from peripheral blood cells in diabetic patients. Diabetologia. 2002 Nov;45(11):1577-83 8. Nomiyama T, Kawamori R, Hattori N., Pathogenesis and contribution of mitochondria to diabetes or deafness. Nihon Rinsho 2002 Apr;60 Suppl 4:273-7. (in Japanese) 9. Nakajima K, Tanaka Y, Nomiyama T, Ogihara T, Piao L, Sakai K, Onuma T, Kawamori R, Chemokine receptor genotype is associated with diabetic nephropathy in Japanese with type 2 diabetes. Diabetes. 2002 Jan;51(1):238-42. 10. Matsunaga H, Tanaka Y, Tanaka M, Gong JS, Zhang J, Nomiyama T, Ogawa O, Ogihara T, Yamada Y, Yagi K, Kawamori R, Antiatherogenic mitochondrial genotype in patients with type 2 diabetes. Diabetes Care. 2001 Mar;24(3):500-3 Awards 2004th Young Investigator Award of Japan Endocrinology Society 2006th Young Investigator Travel Award of 7th Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology 2012nd Outstanding research award of the Japanese Society of Constitutional Medicine Grants 2/2005 to 1/2007 Suzuki Manpei foundation Post Doctoral Grant 7/2007 to 6/2008 American Heart Association Post Doctoral Grant 2009th Grant from Ministry of Education, Sports and Culture of Japan (21790883) 2009th Grant from Suzuken Memorial Foundation

Agenda

Takashi Yoneda 1964 Born in Toyama 1984-1990, Medical School Kanazawa University, Medical Student 1990-1994, Graduate School of Medicine, Kanazawa University, Graduate Student 1994-1995, Medical Staff, Himi Municipal Hospital 1995-1999, Chief Doctor, Hoju Hospital 1999-2013, Assistant Professor, Kanazawa University Hospital, 2014-present, Associate Professor, Program Management Office for New Paradigms Establishing Centers for Fostering Medical Researchers of the Future, Kanazawa University Vice Chief, Division of Endocrinology and Metabolism, Kanazawa University Hospital

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Richard Joseph Auchus Current title and department: D Division, University of Michigan Medical School 2011-present EDUCATION: 1978-82 Massachusetts Institute of Technology, Cambridge, MA 1982 S.B. Chemistry 1982-88 Washington University, St. Louis, MO 1988 M.D. Medicine Ph.D. Pharmacology 1988-91 University of Iowa Hospitals & Clinics, Iowa City, IA Resident Internal Medicine 1991-93 UTHSC-San Antonio/Wilford Hall MC, San Antonio, TX Fellow Endocrinology 1993-95 Wilford Hall USAF Medical Center, Lackland AFB, TX Staff M.D. Endocrinologist 1995-96 University of California, San Francisco Res. Fellow Pediatric Endocr. PRINCIPAL POSITIONS HELD: 1981-82 Mass. Institute of Technology, Cambridge, MA Teaching Assistant in Chemistry 1984-85 Washington University, St. Louis, MO Teaching Assistant in Cell Biology 1984-87 Washington University, St. Louis, MO Teaching Assistant in Pharmacology 1993-95 Wilford Hall Medical Center, Lackland AFB, TX Staff Endocrinologist and Endocrinology Research and Education Coordinator 1996-99 University of CA, San Francisco Asst. Res. Endocrinologist, Pediatrics 1999-2005 University of TX, Southwestern Medical School Assistant Professor of Internal Medicine 2005-2008 University of TX, Southwestern Medical School Associate Professor of Internal Medicine 2008-2011 University of TX, Southwestern Medical School Professor of Internal Medicine 2011-now University of Michigan Medical School Professor of Internal Medicine HONORS AND AWARDS: 2014 Fellow, American College of Endocrinology RESEARCH AND CREATIVE ACTIVITY: ORIGINAL ARTICLES (173 published or in press): Representative 10 publications: 32

Agenda 2011 H.K. Ghayee, J. Rege, L.M. Watumull, F.E. Nwariaku, K.S. Carrick, W.E. Rainey, W.L. Miller, R.J. Auchus. Clinical, biochemical, and molecular characterization of macronodular adrenocortical hyperplasia of the zona reticularis: a new syndrome J Clin Endocrinol Metab 96:E243-E250. 2012 S. Monticone, N. Hattangady, K. Nishimoto, F. Satoh, R.J. Auchus, T.A. Williams, F. Mantero, H.K. Ghayee, J. Giri, R.J. Bollag, M. Edwards, C. Isales, W.E. Rainey. Effect of KCNJ5 mutations on gene expression in aldosterone-producing adenomas and adrenocortical cells. J Clin Endocrinol Metab 97:E1567–E1572. 2012 S. Monticone, R.J. Auchus, W.E. Rainey. Adrenal disorders in pregnancy. Nature Rev Endocrinol 8: 8:668-678. 2013 R.J. Auchus, W. Arlt. Approach to the patient: The adult with congenital adrenal hyperplasia. J Clin Endocrinol Metab 98:2645-2655. 2013 K.H. Chang, R. Li, Y. Lotan, C.G. Roehrborn, J. Liu, R. Vessella, P. Nelson, P. Kapur, R.J. Auchus, N. Sharifi. A genetic mechanism augments DHT synthesis to sustain castrationresistant prostate cancer. Cell 154:1074-1084. 2014 C.A. Marsh, R.J. Auchus. Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): Combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency. Fertil Steril 101:317-322. 2014 G. Sasaki, M. Zubair, T. Ishii, T. Mitsui, T. Hasegawa, R.J. Auchus. The contribution of serine 194 phosphorylation to steroidogenic acute regulatory protein function. Mol Endocrinol 28:1088-1096. 2014 R.J. Auchus, M.K. Yu, S. Nguyen, S.D. Mundle. Use of prednisone with abiraterone acetate in metastatic castration-resistant prostate cancer. The Oncologist 19:1231-1240. 2014 H.M. Peng, J. Liu, S.E. Forsberg, H.T. Tran, S.M. Anderson, R.J. Auchus. Catalytically relevant electrostatic interactions of cytochrome P450c17 (CYP17A1) and cytochrome b5. J Biol Chem 289:33838-33849. 2014 R.J. Auchus. The classic and nonclassic congenital adrenal hyperplasias. Endocr Pract (in press). COOPERATIVE GROUP TRIAL PUBLICATIONS (4): 2012 A. Colao, S. Petersenn, J. Newell-Price, J.W. Findling, F. Gu, M. Maldonado, U. Schoenherr, D. Mills, L.R. Salgado, B.M.K. Biller for the Pasireotide B2305 Study Group. A 12-month phase 3 study of pasireotide in Cushing’s disease. N Engl J Med 366:914-924. 2012 M. Fleseriu, B.M. Biller, J.W. Findling, M.E. Molitch, D.E. Schteingart, C. Gross; on behalf of the SEISMIC Study Investigators. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing’s syndrome. J Clin Endocrinol Metab 97:2039-2049. 2013 C.J. Ryan, M.R. Smith, J.S. de Bono, A. Molina, C.J. Logothetis, P. de Souza, K. Fizazi, P. Mainwaring, J.M. Piulats, S. Ng, J. Carles, P.F. Mulders, E. Basch, E.J. Small, F. Saad, D. Schrijvers, H. Van Poppel, S.D. Mukherjee, H. Suttmann, W.R. Gerritsen, T.W. Flaig, D.J. George, E.Y. Yu, E. Efstathiou, A. Pantuck, E. Winquist, C.S. Higano, M.E. Taplin, Y. Park, T. Kheoh, T. Griffin, H.I. Scher, D.E. Rathkopf; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138-148. 2014 S. Petersenn, J. Newell-Price, J.W. Findling, F. Gu, M. Maldonado, K. Sen, L.R. Salgado, A. Colao, B.M. Biller; Pasireotide B2305 Study Group. High variability in baseline urinary free cortisol values in patients with Cushing’s disease. Clin Endocrinol (Oxf) 80:261-269. 33

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Hirofumi Makino, M.D., Ph.D. PRESENT ADDRESS: Director, Okayama University Hospital 2-5-1 Shikata-cho, Okayama 700-8558, JAPAN E-mail: makino@md.okayama-u.ac.jp EDUCATION Collage/University: Okayama University Medical School (1969-1975) Medical Degree: Ph.D. in Okayama University Medical School (1983) PROFESSIONAL POSITIONS AND APPOINTMENTS Assistant Professor of Department of Medicine III, Okayama University Medical School, Okayama, Japan (1983-1993) Invited Professor at the Department of Pathology, Northwestern University Medical School, Chicago IL, U.S.A (1984-1986) Associate Professor of Department of Medicine III, Okayama University Medical School, Okayama, Japan (1994-1995) Professor and Chairman of Department of Medicine III, Okayama University Medical School, Okayama, Japan (1996-2000) Professor and Chairman of Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (2001-2014) President of The Japanese Society of Nephrology, (2008-2012) Dean, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences (2009-2010) Director, Okayama University Hospital (2012-present) HONORS/AWARDS: Okayama University Medical Prize, Yuki Prize, 1990 Young Investigator Award, Japanese Society of Clinical Electron Microscopy, 1994 Academic Award, The Kidney Foundation, Japan, 2008 Expert Investigator Award, The Japan Society for Diabetic Complications, 2008 BIBLIOGRAPHY: Published more than 389 peer-review articles.

Representative 13 publications:

1. Terami N, Ogawa D, Tachibana H, Hatanaka T, Wada J, Nakatsuka A, Eguchi J, Horiguchi CS, Nishii N, Yamada H, Takei K, Makino H. Long-term treatment with the sodium glucose cotranspoter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS ONE 9(6), e100777, 2014 2. Watanabe M, Nakatsuka A, Murakami K, Inoue K, Terami T, Higuchi C, Katayama A, Teshigawara S, Eguchi J, Ogawa D, Watanabe E, Wada J, Makino H. Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy. PLoS ONE 9(3), e92647, 2014 3. Kodera R, Shikata K, Takatsuka T, Oda K, Miyamoto S, Kajitani N, Hirota D, Ono T, Usui HK, Makino H. Dipeptidyl peptidase-4 inhibitor ameliorates early renal injury through its anti-

Agenda inflammatory action in a rat model of type 1 diabetes. Biochemical and Biophysical Research Communications 2014; 443:828–833 4. Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clinical science. 2013;124:139-152 5. Sugiyama K, Sada KE, Kurosawa M, Wada J, Makino H. Current status of the treatment of microscopic polyangiitis and granulomatosis with polyangiitis in japan. Clin Exp Nephrol. 2013;17:51-58 6. Sugiyama H, Yokoyama H, Sato H, Saito T, Kohda Y, Nishi S, Tsuruya K, Kiyomoto H, Iida H, Sasaki T, Higuchi M, Hattori M, Oka K, Kagami S, Kawamura T, Takeda T, Hataya H, Fukasawa Y, Fukatsu A, Morozumi K, Yoshikawa N, Shimizu A, Kitamura H, Yuzawa Y, Matsuo S, Kiyohara Y, Joh K, Nagata M, Taguchi T, Makino H, Committee for Standardization of Renal Pathological D, Committee for Kidney Disease Registry JSoNJ. Japan renal biopsy registry and japan kidney disease registry: Committee report for 2009 and 2010. Clin Exp Nephrol. 2013 7. Sato-Horiguchi C, Ogawa D, Wada J, Tachibana H, Kodera R, Eguchi J, Nakatsuka A, Terami N, Shikata K, Makino H. Telmisartan attenuates diabetic nephropathy by suppressing oxidative stress in db/db mice. Nephron Exp Nephrol. 2013;121:e97-e108 8. Nakatsuka A, Wada J, Iseda I, Teshigawara S, Higashio K, Murakami K, Kanzaki M, Inoue K, Terami T, Katayama A, Hida K, Eguchi J, Ogawa D, Matsuki Y, Hiramatsu R, Yagita H, Kakuta S, Iwakura Y, Makino H. Visceral adipose tissue-derived serine proteinase inhibitor inhibits apoptosis of endothelial cells as a ligand for the cell-surface grp78/voltage-dependent anion channel complex. Circulation research. 2013;112:771-780 9. Nakamura E, Otsuka F, Inagaki K, Tsukamoto N, Ogura-Ochi K, Miyoshi T, Toma K, Takeda M, Makino H. Involvement of bone morphogenetic protein activity in somatostatin actions on ovarian steroidogenesis. J Steroid Biochem Mol Biol. 2013;134:67-74 10. Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Ogawa A, Yamanari T, Kikumoto Y, Uchida HA, Kitamura S, Maeshima Y, Nakamura K, Ito H, Makino H. A decreased level of serum soluble klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS ONE. 2013;8:e56695 11. Makino H, Shikata K, Kushiro M, Hironaka K, Yamasaki Y, Sugimoto H, Ota Z, Araki N, Horiuchi S. Roles of advanced glycation end-products in the progression of diabetic nephropathy. Nephrol Dial Transplant. 1996;11 Suppl 5:76-80 12. Makino H, Kashihara N, Sugiyama H, Kanao K, Sekikawa T, Okamoto K, Maeshima Y, Ota Z, Nagai R. Phenotypic modulation of the mesangium reflected by contractile proteins in diabetes. Diabetes. 1996;45:488-495 13. Makino H, Shikata K, Hironaka K, Kushiro M, Yamasaki Y, Sugimoto H, Ota Z, Araki N, Horiuchi S. Ultrastructure of nonenzymatically glycated mesangial matrix in diabetic nephropathy. Kidney Int. 1995;48:517-526

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Robert J. Chilton MD, DO, FACC, FAHA, FACP Professor Department of Medicine, Division of Cardiology The University of Texas Health Science Center at San Antonio San Antonio, Texas Dr. Robert J. Chilton is Professor of Medicine, Director of the cardiac catheterization laboratories and Director of the electrophysiology laboratories at the University of Texas Health Science Center at San Antonio, Texas. He is a fellow of the American College of Cardiology, the American College of Physicians, American College of Osteopathic Internists, and American Heart Association. Dr. Chilton also chairs the Electrophysiology Board Examination for the American Osteopathic Association and presides over the San Antonio chapters of both the Cardiovascular Society and American Heart Association. In addition, Dr. Chilton is cardiology consultant to NASA. Dr. Chilton received his DO from the University of Osteopathic Medicine and Surgery, Des Moines, Iowa. He completed his internship at Wright-Patterson Air Force Base, Dayton, Ohio; his residency at the University of Oklahoma Health Science Center, Oklahoma City, Oklahoma; and a cardiology fellowship at the Wilford Hall United States Air Force Medical Center in San Antonio, Texas. Dr. Chilton is board certified in internal medicine, cardiovascular disease, electrophysiology and interventional cardiology. Over the past 20 years, Dr. Chilton has authored numerous articles, book chapters, and abstracts. He has delivered presentations globally on cardiology and diabetes. He has developed educational materials and has lectured widely, garnering several awards for his academic contributions, including several teaching awards, most notably the Outstanding Teacher award from the University of Texas Health Science Center at San Antonio. In 2010 he received the ACOI researcher of the year award on GLP1 and cardiovascular disease. He also served as a web master for vascular biology and lipid internet site. In addition, Dr. Chilton was an investigator or co-investigator in a host of clinical trials. Dr. Chilton has performed research in the fields of vascular biology, electrophysiology and interventional cardiology. He is currently is a review for American Journal of Cardiology, Diabetes Care and other journals. At present is deputy editor of clinical diabetes journal and catheterization and cardiovascular interventions journal. He is a fellow of the American Heart Association and American College of Physicians. 36

Agenda

Chul Woo Ahn, M.D., Ph.D. Mailing Address: Gangnam Severance Hospital Department of Endocrinology and Metabolism, Internal Medicine 612 Eonjuro, Gangnam-Gu, Seoul, South Korea E-mail: acw@yuhs.ac, endoahn@gmail.com Primary Area of Interest: Oxidative stress and diabetic complications,Genetic polymorphism and clinical pharmacology, Cell therapy Current Appointment: Professor at Department of Endocrinology and Metabolism, Internal Medicine Yonsei University College of Medicine, Seoul, Korea Training History and Hospital Affiliation 2013.-present: Professor Dept of Endocrinology and Metabolism, Internal Medicine Gangnam Severance Hospital, Seoul, Korea 2008.3-2013.2: Associate professor Dept of Endocrinology and Metabolism, Internal Medicine Gangnam Severance Hospital, Seoul, Korea 2007.5-2009.4: Visiting scholar Center for Endocrinology, Metabolism, and Molecular Medicine Northwestern University, Feinberg School of Medicine 2002.3-2008.2: Assistant professor Dept of Endocrinology and Metabolism, Internal Medicine Gangnam Severance Hospital, Seoul, Korea 1999.3–2002.2: Fellow Dept of Endocrinology and Metabolism, Internal Medicine Severance Hospital, Seoul, Korea 1995.3–1999.2: Resident Dept. of Internal Medicine Severance Hospital, Seoul, Korea 1994.3–1995.2: Intern Severance Hospital, Seoul, Korea Membership Korean Association of Internal Medicine Korean Endocrine Society, Director, Committee of Scientific Affairs of Korean Endocrine Society Korean Diabetes Society Korean Society of the Study of Obesity American Society for Clinical Pharmacology and Therapeutics American Diabetes Association 37

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

The Endocrine Society Education 1999 – 2002: PhD, Medical Science, Graduate School, Yonsei University 1996 – 1998: Master, Graduate School, Yonsei University 1985 – 1991: MD, Yonsei University College of Medicine Publications

Published more than 85 peer-review articles. Representative 10 publications: 1. Kim J, Park S, Kang HM, Ahn CW, Kwon HC, Song JH, Lee YJ, Lee KH, Yang H, Baek SY, Yoo SH, Kim SH, Kim H. Human insulin secreted from insulinogenic xenograft restores normoglycemia in type 1 diabetic mice without immunosuppression. Cell Transplant. 2012;21(10):2131-47. 2. HA JY, Kim MK, CHA YJ, Kim SK, YUN GY, Rhee K, Park JS, Cho ES, Ahn CW, Park JS. A Case of Adrenocortical Carcinoma Secreting Cortisol and Aldosterone. YUJM VOLUME 29, NUMBER 2, DECEMBER 2012 3. Jung HY, Kim CS, Nam J, Cho M, Park JS, Ahn CW, Kim KR. Change in Serum Adipocytokines after Recovery of Thyroid Function and Weight in Patients with Graves’ Disease. Korean J Obes. 2009 Jun;18(2):47-52. 4. WH Shim, EH Lee, YM Lee, HW Kim, SA Kim, SH Bum, ES Kim, MH Cho, JS Park, CW Ahn, BS Cha, KR Kim, HC Lee Glycemic Control during the Post-PTCA Period Impacts the Progression of Atherosclerosis as Determined through Follow-up Angiography of Patients with Type II Diabetes Korean Clinical Diabetes J 11:315-323, 2010 5. SH Beom, WH Shim, SW Hong, EH Lee, YM Lee, SA Kim, ES Kim, MH Cho, JS Park, CW Ahn, KR Kim. A Case of Insulinoma Diagnosed by a Selective Arterial Calcium Stimulation Test. Korean Clinical Diabetes J 11:243-246, 2010 6. JW Han, WH Shim, EH Lee, YM Lee, MG Kim, SA Kim, SH Beom, ES Kim, JS Yoo, JS Nam, MH Cho, JS Park, CW Ahn, KR Kim . Effects of Calpain-10 and Adiponectin Gene Polymorphisms on Insulin Secretion and Resistance in Patients with Type 2 Diabetes Mellitus. Korean Clinical Diabetes J 11:229-238, 2010 7. Nam JS, Kang HM, Kim J, Park S, Kim H, Ahn CW, Park JO, Kim KR, Transplantation of insulinsecreting cells differentiated from human adipose tissue-derived stem cells into type 2 diabetes mice. Biochem Biophys Res Commun. 2014 Jan 10;443(2):775-81 8. Kang S, Kyung C, Park JS, Kim S, Lee SP, Kim MK, Kim HK, Kim KR, Jeon TJ, Ahn CW, Subclinical vascular inflammation in subjects with normal weight obesity and its association with body fat: an 18 F-FDG-PET/CT study. Cardiovasc Diabetol. 2014 Apr 4;13:70 9. Kim MK, Ahn CW, Kang S, Ha JY, Baek H, Park JS, Kim KR, Association between Apolipoprotein B/Apolipoprotein A-1 and arterial stiffness in metabolic syndrome. Clin Chim Acta. 2014 Nov 1;437:115-9 10.Jee SH, Ahn CW, Park JS, Park CG, Kim HS, Lee SH, Park S, Lee M, Lee CB, Park HS, Kimm H, Choi SH, Sung J, Oh S, Joung H, Kim SR, Youn HJ, Kim SM, Lee HS, Mok Y, Choi E, Yun YD, Baek SJ, Jo J, Huh KB. Serum adiponectin and type 2 diabetes: a 6-year follow-up cohort study. Diabetes Metab J. 2013 Aug;37(4):252-61

Agenda

WonBae Kim, M.D., Ph.D. Office Address: Division of Endocrinology & Metabolism Department of Internal Medicine AsanMedicalCenter Pungnap-dong 388-1, Songpa-gu Seoul 138-736, Korea E-mail: kimwb@amc.seoul.kr Present Position: Professor, Department of Internal Medicine, University of UlsanCollege of Medicine ,Seoul, Korea Director, Division of Endocrinology & Metabolism, Department of Internal Medicine, AsanMedicalCenter, Seoul, Korea EDUCATION Premedical: Medical: Postgraduate: Degrees:

SeoulNationalUniversity College of Art and Science Seoul, Korea SeoulNationalUniversity College of Medicine Seoul, Korea SeoulNationalUniversity PostgraduateSchool Seoul, Korea M.D. M.S. (Internal Medicine) Ph.D. (Internal Medicine)

1981-1983 1983-1987 1994-1998 1987 1996 1998

PROFESSSIONAL APPOINTMENTS Internship 1987-1988 SeoulNationalUniversityHospital Seoul, Korea Resident Physician 1988-1991 Department of Internal Medicine SeoulNationalUniversityHospital Seoul, Korea Military Service: ROK Army Medical Officer 1991-1994 Medical Office, Ministry of National Defense Seoul, Korea Fellowship of Endocrinology & Metabolism 1994-1995 Department of Internal Medicine SeoulNationalUniversityHospital Seoul, Korea Physician 1995-2001 Department of Internal Medicine Seoul City Boramae Hospital Affiliated to Seoul NationalUniversityHospital Seoul, Korea Instructor 1996-1999 39

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Department of Internal Medicine SeoulNationalUniversityCollege of Medicine Seoul, Korea Visiting Scientist 1998-1998 Cell Regulation Section, NIDDK, NIH Bethesda, MD U.S.A. Assistant Professor 1999-2001 Department of Internal Medicine SeoulNationalUniversityCollege of Medicine Seoul, Korea Physician 2001- present Division of Endocrinology & Metabolism Department of Internal Medicine AsanMedicalCenter Seoul, Korea Associate Professor 2002- 2008 Department of Internal Medicine University of UlsanCollege of Medicine Seoul, Korea Visiting Fellow 2004-2005 Edison Biotechnology Institute OhioUniversity Athens, OH U.S.A. Professor 2008- present Department of Internal Medicine University of UlsanCollege of Medicine Seoul, Korea RESEARCH INTERESTS 1.Cancer biology: especially in cancer cell metabolism & mechanism of invasion & metastasis 2.Translational research: Thyroid cancer – markers of prognostic significance PUBLICATIONS Published more than 77 peer-reviewed Endocrine related manuscripts. Representative 10 Publications: 1. Han JM, Kim WG, Kim TY, Jeon MJ, Ryu JS, Song DE, Hong SJ, Shong YK, Kim WB.Effects of Low-Dose and High-Dose Postoperative Radioiodine Therapy on the Clinical Outcome in Patients with Small Differentiated Thyroid Cancer Having Microscopic Extrathyroidal Extension.Thyroid. 24:820-825, 2014 2. Ha EJ, Baek JH, Lee JH, Kim JK, Kim JK, Lim HK, Song DE, Sung TY, Kim TY, Kim WB, Shong YK.Core needle biopsy can minimise the non-diagnostic results and need for diagnostic surgery in patients with calcified thyroid nodules.EurRadiol. 24:1403-1409, 2014 3. Jang EK, Song DE, Sim SY, Kwon H, Choi YM, Jeon MJ, Han JM, Kim WG, Kim TY, Shong YK, Kim WB.NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma. Thyroid.24:1275-1281, 2014 4. Shin S, Park SE, Kim SY, Hyun MK, Kim SW, Kwon JW, Kim Y, Kim WB, Na DG, Park HA, Sheen SS, Yi KH, Chang HS, Cho JJ, Chung JH. Effectiveness of ultrasonographic screening for thyroid cancer: round-table conference in the national evidence- based healthcare collaborating agency (NECA) in conjunction with the Korean Thyroid Association. Asian Pac J Cancer Prev. 15:5107-5110, 2014 5. Jeon MJ, Kim TY, Kim WG, Han JM, Jang EK, Choi YM, Song DE, Yoon JH, Chung KW, Hong 40

Agenda SJ, Shong YK, Kim WB. Differentiating the location of cervical lymph node metastasis is very useful for estimating the risk of distant metastases in papillary thyroid carcinoma. Clin Endocrinol. 81:593-599, 2014 6. Kwon H, Kim WG, Choi YM, Jang EK, Jeon MJ, Song DE, Baek JH, Ryu JS, Hong SJ, Kim TY, Kim WB, Shong YK.A cut-off value of basal serum calcitonin for detecting macroscopic medullary thyroid carcinoma. Clin Endocrinol. 2014 Jul 19.doi: 10.1111/cen.12562. [Epub ahead of print] 7. Ha EJ, Baek JH, Lee JH, Kim JK, Kim JK, Lim HK, Song DE, Sung TY, Kim TY, Kim WB, Shong YK. Core needle biopsy can minimise the non-diagnostic results and need for diagnostic surgery in patients with calcified thyroid nodules. Eur Radiol. 24:1403-1409, 2014 8. Lim HK, Baek JH, Lee JH, Kim WB, Kim TY, Shong YK, Hong SJ. Efficacy and safety of radiofrequency ablation for treating locoregional recurrence from papillary thyroid cancer. Eur Radiol. 25:163-170, 2015 9. Yoon RG, Baek JH, Lee JH, Choi YJ, Hong MJ, Song DE, Kim JK, Yoon JH, Kim WB. Diagnosis of Thyroid Follicular Neoplasm: Fine-Needle Aspiration Versus Core-Needle Biopsy. Thyroid. 24:1612-1617, 2014 10. Jang EK, Kim WG, Choi YM, Jeon MJ, Kwon H, Baek JH, Lee JH, Kim TY, Shong YK, Song DE, Kim WB. Association between neck ultrasonographic findings and clinico-pathological features in the follicular variant of papillary thyroid carcinoma. Clin Endocrinol (Oxf). 2014 Nov 17. doi: 10.1111/cen.12674. [Epub ahead of print]

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 21, 2015 (Sat) 【Longevity Hall 】

Plenary Lecture-Endo Moderator: Tjin-Shing Jap

15:30~16:10

PL-Endo

Recent Advances in Pituitary Medicine Ken K.H. Ho Centres for Health Research, Princess Alexandra Hospital; Metro South Hospital and Health Service, Queensland Government, Australia

March 22, 2015 (Sun) 【1st Conference Room】

Plenary Lecture-DM Moderator: Wayne Huey-Herng Sheu

10:40~11:20

PL-DM

Physiology and Pathophysiology of Incretins: From Bench to Bedside and Vice Versa Nobuya Inagaki Department of Diabetes, Endocrinology and Nutrition Graduate School of Medicine, Kyoto University, Japan

March 21, 2015 (Sat) 【Longevity Hall】

08:55~09:00

DAROC-TADE Joint Symposium Better Management of Injection Therapy in Diabetes Opening Shih-Te Tu Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

Moderator: Chih-Yuan Wang 09:00~09:30

DT-1

Pathophysiology for Treatment with Insulin or GLP-1RA Jung-Fu Chen Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

Agenda Moderator: Yau-Jiunn Lee 09:30~10:00

DT-2

The Strategy for Psychological insulin Resistance Ming-Chia Hsieh Changhua Christian Hospital Diabetes e-Institute

10:00~10:20

Break

Moderator: Shih-Yi Lin 10:20~10:50

DT-3

The Future Model of DM Treatment about Team-Work and Insulin Treatment in Primary Medicine. Su Hsun Cheng An-Shin Clinic

Moderator: Wayne Huey-Herng Sheu 10:50~11:20

Panel Discussion

11:20~11:30

Closing Wayne Huey-Herng Sheu President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

March 21, 2015 (Sat) 【1st Conference Room】

09:30~09:35

Symposium-Endo-1 Current Status of Endocrinology in the Region Opening Tjin-Shing Jap President, The Endocrine Society of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taipei Veterans General Hospital

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Moderator: Ching-Chung Chang 09:35~09:55

SE-1-1

Endocrinology and Metabolism Subspecialty Training in Taiwan Tien-Shang Huang Department of Internal Medicine, National Taiwan University Hospital

Moderator: Tien-Chun Chang 09:55~10:15

SE-1-2

The Current Status of Endocrinology in India Sarita Bajaj President, South Asian Federation of Endocrine Societies Department of Medicine, MLN Medical College, Allahabad, India

Moderator: Jen-Der Lin 10:15~10:35

SE-1-3

The Current Status of Endocrinology in Indonesia Achmad Rudijanto President, Indonesian Society of Endocrinology Endocrinology and Metabolic Department, Faculty of Medicine Brawijaya University, Indonesia

Moderator: Tjin-Shing Jap 10:35~10:55

SE-1-4

The Current Status of Endocrinology in Korea Young Kee Shong Chairman of the Board, Korean Endocrine Society (KES) Division of Endocrinology, Asan Medical Center, Korea

Moderator: Hong-Da Lin 10:55~11:15

SE-1-5

The Current Status of Endocrinology in Myanmar Than Than Aye President, Myanmar Society of Endocrinology and Metabolism (MSEM)

Moderator: Ting-I Lee

Agenda 11:15~11:35

SE-1-6

The Current Status of Endocrinology in The Philippines Bien J. Matawaran Vice-President, Philippine Society of Endocrinology, Diabetes and Metabolism Department of Medicine, Jose R. Reyes Memorial Medical Center, Rizal Ave, Manila, The Philippines

Moderator: Harn-Shen Chen 11:35~11:55

SE-1-7

The Current Status of Endocrinology in Thailand Thavatchai Peerapatdit Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand

11:55~12:00

Closing Wayne Huey-Herng Sheu President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

March 21, 2015 (Sat) 【2nd Conference Room】

13:20~13:25

Symposium-DM-1 Diabetes Study and National Health Insurance Database in Taiwan Opening Chin Hsiao Tseng Department of Internal Medicine, National Taiwan University Hospital

Moderator: Chih-Jen Chang 13:25~14:05

SD-1-1

Application of National Health Insurance DATA in Disease Association Studies in Patients with Diabetes Chung-Yi Li Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University

Moderator: Ching-Chu Chen 45

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:05~14:45

SD-1-2

From Large Healthcare Database Studies to Clinical Practice - Path for Improving Care of Diabetic Patients and Individualizing Therapeutic Decision Making Chia-Hsuin Chang Institute of Preventive Medicine, College of Public Health, National Taiwan University Department of Internal Medicine, National Taiwan University Hospital

14:45~14:50

Closing Ching-Fai Kwok Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

March 21, 2015 (Sat) 【1st Conference Room】

Symposium-Endo-2 Recent Advances in Osteoporosis Moderator: Keh-Sung Tsai, Jung-Fu Chen

13:20~13:45

SE-2-1

Osteoporosis in Renal Failure: To Treat or not to Treat? Manju Chandran Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, DUKE-NUS Graduate Medical School

13:45~14:10

SE-2-2

Vitamin D: Molecular Actions across a Variety of Biological Systems Howard A Morris Department of Chemical Pathology, SA Pathology and School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia 5000 Australia

14:10~14:35

SE-2-3

Recent Advances in Osteoporosis Research in Taiwan Jung-Fu Chen Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

Agenda 14:35~14:50

Discussion

March 21, 2015 (Sat) 【2nd Conference Room】

16:10~16:15

Symposium-DM-2 New Treatments for Type 2 Diabetes: Roles of Incretin Therapy Opening Shih-Tzer Tsai Division of Endocrinology and Metabolism, Cheng Hsin Hospital

Moderator: Wei-Shiung Yang 16:15~16:55

SD-2-1

Journey to Individualized Insulin Therapy: From Clinical Trial to Real World Experience Stephen L. Atkin Medical Department, Weill Cornell Medical College in Qatar (WCMC-Q)

Moderator: Lu Chieh-Hsiang 16:55~17:35

SD-2-2

21st Century Breakthrough of Diabetology ~Beyond Glycemic Control~ Takashi Nomiyama Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Japan

17:35~17:40

Closing Dee Pei Division of Endocrinology and Metabolism, Cardinal Tien Hospital

March 21, 2015 (Sat) 【1st Conference Room】

Symposium-Endo-3 Primary Aldosteronism Moderator: Fen-Yu Tseng, Ming-Nan Chien 47

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

16:10~16:35

SE-3-1

The Genetic Study in Primary Aldosteronism Takashi Yoneda Division of Endocrinology and Metabolism, Kanazawa University Hospital, Japan

16:35~17:00

SE-3-2

The Pathophysiology of Primary Aldosteronism Kwan-Dun Wu Section of Nephrology, Department of Internal Medicine, National Taiwan University Hospital

17:00~17:25

SE-3-3

Diagnosis and Management Strategies for Primary Aldosteronism Richard Auchus Department of Internal Medicine,University of Michigan Medical School, USA

17:25~17:40

Discussion

March 22, 2015 (Sun) 【1st Conference Room】

09:00~9:05

Symposium-DM-3 Protection of Cardiovascular System and Kidney Beyond Glucose Control in Diabetes Opening Low-Tone Ho Department of Medical Research, Taipei Veterans General Hospital

Moderator: Lee-Ming Chuang 09:05~9:45

SD-3-1

New Therapies for Diabetes and Protection of Diabetic Kidney Disease Beyond Blood Glucose Hirofumi Makino Okayama University Hospital, Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan

Moderator: Jung-Fu Chen

Agenda 09:45~10:25

SD-3-2

Do We Need a New ARB, AziLSartan M for Better BP Control and Beyond Glucose Control in Diabetes? Robert J. Chilton Department of Medicine, Division of Cardiology The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

10:25~10:30

Closing Tong-Yuan Tai Department of Endocrinology and Metabolism, Taipei Jen-Chi Hospital

Symposium-Endo-4

March 22, 2015 (Sun) 【2nd Conference Room】

Pituitary Disease-Update Moderator: Ching-Chung Chang, Harn-Shen Chen

09:00~09:20

SE-4-1

A Few Things about Pituitary Adenoma Pathology Donald Ming-Tak HO Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital

09:20~09:40

SE-4-2

Recent Advances in Pituitary Disease: Hypophysitis Justin Ging-Shing Won Department of Endocrinology and Metabolism, Taipei Veterans General Hospital

09:40~10:00

SE-4-3

Surgical Treatment of Pituitary Tumors Chiung-Chyi Shen Department of Neurosurgery Surgical, Taichung Veterans General Hospital

10:00~10:20

SE-4-4

Stereotactic Radiosurgery for Pituitary Tumors Xiao Furen Division of Neurosurgery, National Taiwan University Hospital

10:20~10:30

Discussion

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 22, 2015 (Sun) 【1st Conference Room】

13:20~13:25

Symposium-DM-4 DAROC-TSOC Joint Symposium Guideline: an Update Opening Wayne Huey-Herng Sheu President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

Moderator: Jyuhn-Huarng Juang 13:25~14:05

SD-4-1

2015 Guidelines of the Taiwan Society of Cardiology and the Taiwan Hypertension Society for the Management of Hypertension Chern-En Chiang General Clinical Research Center, Division of Cardiology, Taipei Veterans General Hospital and National Yang-Ming University

Moderator: Shyi-Jang Shin 14:05~14:45

SD-4-2

Clinical Guideline of the DAROC for the Management of Diabetes Mellitus Hung-Yuan Li Department of Internal Medicine, National Taiwan University Hospital

14:45~14:50

Closing San-Jou Yeh President, Taiwan Society of Cardiology Department of Cardiology, Chang Gung Memorial Hospital

March 22, 2015 (Sun) 【2nd Conference Room】

Symposium-Endo-5 ESROC-KES Joint Symposium Moderator: Tjin-Shing Jap, Young Kee Shong

Agenda 13:20~13:40

SE-5-1

Metabolic Syndrome in Korea Chul Woo Ahn Department of Endocrinology and Metabolism, Internal Medicine Gangnam Severance Hospital, Seoul, Korea

13:40~14:00

SE-5-2

Graves’ Opthalmopathy: Management from Point of View of Endorinologist and Ophthalmologist Tien-Chun Chang Department of Internal Medicine, National Taiwan University Hospital

14:00~14:20

SE-5-3

Obesity and Thyroid Cancer Won Bae Kim University of ULSan College of Medicine, Department of Internal Medicine, Asan Medical Center, Seoul, Korea

14:20~14:40

SE-5-4

Metabolic Syndrome in Taiwan Dee Pei Division of Endocrinology and Metabolism, Cardinal Tien Hospital

14:40~14:50

Discussion

March 22, 2015 (Sun) 【1st Conference Room】 15:30~15:35

Symposium-DM-5 Comprehensive Eye Care in Diabetes Opening Yu-Yao Huang Division of Endocrinology and Metabolism, Linkou Chang Gung Memorial Hospital

Moderator: Chien-Wen Chou 15:35~16:00

SD-5-1

Epidemiology, Classification and Screening of Diabetic Retinopathy Shih-Jen Chen Department of Ophthalmology, Taipei Veterans General Hospital School of Medicine, National Yang-Ming University, Taiwan, R.O.C.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Moderator: Pi-Jung Hsiao 16:00~16:25

SD-5-2

Diabetes Mellitus and Diabetic Eye Disease Yan-Ling Chen Division of Endocrinology and Metabolism, Shin Kong Wu Ho-Su Memorial Hospital

Moderator: Chwen-Tzuei Chang 16:25~16:50

SD-5-3

Diabetic Retinopathy – Mechanisms, Treatments, and Neuronal Protections Ta-Ching Chen Department of Ophthalmology, National Taiwan University Hospital

16:50~17:00

Closing Chao-Hung Wang Division of Endocrinology and Metabolism, Mackay Memorial Hospital

March 22, 2015 (Sun) 【4th Conference Room】

Special Lecture Current Guideline of Thyroid Cancer Management Moderator: Pei-Wen Wang

10:00~10:30

SL-1

Personalized Management of Differentiated Thyroid Cancer: An Update of Guidelines and Literature Review Yen-Hsiang Chang Department of Nuclear Medicine, Kohsiung Chang Gung Memorial Hospital

Agenda

March 21, 2015 (Sat) 【2nd Conference Room】 09:00~09:05

2013 DM Research Grant Report Opening Boniface J. Lin Division of Endocrinology and Metabolism, Taitung Saint Mary's Hospital

Moderator: Chien-Ning Huang 09:05~09:25

DR-1

Glucagon-Like Peptide-1 Prevents ß CelLS from Apoptosis through Improving Mitochondrial Function and Decreasing ER Stress via Suppressing Sustained AMPK Activation by Methylglyoxal Tien-Jyun Chang Department of Internal Medicine, National Taiwan University Hospital

Moderator: Ta-Jen Wu 09:25~09:45

DR-2

The Role of Serum Prothymosin-α in Diabetes Mellitus Horng-Yih Ou Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital

09:45~10:00

Panel Discussion and Closing Lee-Ming Chuang Department of Internal Medicine, National Taiwan University Hospital

March 21, 2015 (Sat) 【4th Conference Room】 13:20~13:25

Oral Presentation-DM Opening Kun-Wu Tsan Division of Endocrinology and Metabolism, West Garden Hospital

Moderator: Ming-Chia Hsieh 53

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

13:25~13:33

OD-01

EXERCISE AND THE RISK OF PAINFUL NEUROPATHY IN PATIENTS WITH TYPE 2 DIABETES SHEN-SHU CHIANG, CHIA-LIN LEE, SHI-YI LIN, SHEU-JANE LIU, JUN-SING WANG, YEN-MIN SONG, I-TE LEE, CHIA-PO FU, WAYNE HUEY-HERNG SHEU Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.

13:33~13:41

OD-02

HIGH DIABETES MELLITUS PREVALENCE AMONG NEWLY-DIAGNOSED TUBERCULOSIS PATIENTS IN AN ASIAN POPULATION: A NATIONWIDE POPULATION-BASED STUDY 1

YU-CHENG CHEN, 2SHI-DOU LIN, 3PO-YEN KO

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital Yunlin Branch, Yunlin, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan

Moderator: Yi-Der Jiang 13:41~13:49

OD-03

HYPOGLYCEMIA IS A NOT RARE IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES AS ASSESSED BY CONTINUOUS GLUCOSE MONITORING YIN-CHUN CHEN, YU-YAO HUANG, JUI-HUNG SUN, CHUNG-HUEI HUANG, YU-TING YE, YA-HUI WU, SHIUE-HUA CHIOU, CHIA-HUNG LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

13:49~13:57

OD-04

INPATIENT GLYCEMIC CONTROL – THE EXPERIENCE IN AN ACADEMIC TEACHING HOSPITAL SHI-DOU LIN, JENG-FU KUO, SHIH-TE TU, MING-CHIA HSIEH Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital

Agenda Moderator: Cheering Lin 13:57~14:05

OD-05

ASSOCIATION OF GLUCOKINASE REGULATOR (GCKR) GENETIC VARIANT AND METABOLIC SYNDROME IN TAIWANESE ADOLESCENCE 1

CHANG-HSUN HSIEH, 1YI-JEN HUNG, 2,3NAIN-FENG CHU, 2 FU-HUANG LIN, 4DEE PEI, 1CHIEN-HSING LEE

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Taitung Hospital, DOH. Taiwan. 4Division of Endocrinology and Metabolism, Cardinal Tien Hospital, New Taipei City, Taiwan

14:05~14:13

OD-06

THE ASSOCIATION BETWEEN BODY MASS INDEX AND ALL-CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES: A 5.5-YEAR PROPECTIVE ANALYSIS JENG-FU KUO, SHIH-TE TU, SHI-DOU LIN, YUNG-SHENG CHANG, YU-FANG CHENG, MING-CHIA HSIEH Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Moderator: An-Tsz Hsieh 14:13~14:21

OD-07

ASSOCIATION AMONG FIBRINOLYTIC PROTEINS, METABOLIC SYNDROME COMPONENTS, INSULIN RESISTANCE AND SECRETION IN SCHOOL CHILDREN IN TAIWAN 1

CHUNG-ZE WU, 2NAIN-FENG CHU, 3YUH-FENG LIN, 4 LI-CHIEN CHANG, 5DEE PEI, 6JIN-SHEUN CHEN 1

Division of Endocrinology and Metabolism, 3Division of Nephrology,Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University; 2Taitung Hospital; 4School of Pharmacy, National Defense Medical Center; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Xindian; 6Division of Nephrology, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:21~14:29

OD-08

DOES THE PAY-FOR-PERFORMANCE PROGRAM REDUCE THE RISK OF VASCULAR DISEASE COMPLICATIONS FOR PATIENTS WITH TYPE 2 DIABETES IN TAIWAN? 1

HUI-MIN HSIEH, 2,3,5SHYI-JANG SHIN, 4HERNG-CHIA CHIU

Department of Public Health; 2School of Medicine; 3Center of Lipid and Glycomedicine Research; 4Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University; 5Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital

Moderator: Chang-Hsun Hsieh 14:29~14:37

OD-09

DETECTING MUTATIONS IN NEONATAL DIABETES AND TYPE 1B DIABETES USING EXOME SEQUENCING 1,11,12,13

YANN-JINN LEE, 1,4CHI-YU HUANG, 1,4WEI-HSIN TING, 2,3 FU-SUNG LO, 5,11DAO-CHEN LIN, 6CHAO-HSU LIN, 7 BIWEN CHENG, 8YILEI WU, 9CHEN-MEI HUNG, 10 HSIN-JUNG LI, 4,12HORNG-WEI YANG, 12CHIUNG-LING LIN, 12 TZU-YANG CHANG, 1CHON-IN CHAN 1

Department of Pediatric Endocrinology, MacKay Children’s Hospital; Department of Pediatrics, Chang Gung Memorial Hospital; 3Department of College of Medicine, Chang Gung University; 4Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management; 5Department of Endocrinology and Metabolism, Sijhih Cathay General Hospital; 6Department of Pediatrics, MacKay Memorial Hospital HsinChu Branch; 7Department of Pediatrics, MacKay Memorial Hospital Taitung Branch; 8Department of Pediatrics, Changhua Christian Hospital; 9Department of Pediatrics, Hsinchu Cathay General Hospital; 10Department of Pediatrics, St. Martin De Porres Hospital; 11Institute of Biomedical Sciences, MacKay Medical College; 12 Department of Medical Research, MacKay Memorial Hospital Tamsui District; 13 Department of School of Medicine, Taipei Medical University 2

14:37~14:45

OD-10

CILOSTAZOL INHIBITS HIGH GLUCOSEINDUCED VASCULAR SMOOTH MUSCLE CELL DYSFUNCTIONS THROUGH RAGE PATHWAY 1

CHIEN-HSING LEE, 2YI-SHING SHIEH, 1CHANG-HSUN HSIEH, 1YI-JEN HUNG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Oral Diagnosis, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Agenda 14:45~14:50

Closing Der-Chung Shen Division of Endocrinology and Metabolism, Chung Shan Hospital

Oral Presentation

March 21, 2015 (Sat) 【4th Conference Room】

English Section Moderator: Hwu Chii-Min

16:10~16:18

O-01

FACTORS ASSOCIATED WITH FIBROBLAST GROWTH FACTOR 19 INCREMENT AFTER ORAL GLUCOSE LOADING IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY 1

JUN-SING WANG, 1CHIA-LIN LEE, 2WEN-JANE LEE, 1 I-TE LEE, 1SHIH-YI LIN, 3WEN-LIENG LEE, 3 KAE-WOEI LIANG, 1WAYNE H-H SHEU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

Moderator: Hong-Da Lin 16:18~16:26

O-02

THE CONCOMITANT ASSOCIATION OF THYROID DISORDERS AND MYASTHENIA GRAVIS 1

YU-PEI LIN, 1CHEN-LING HUANG, 2PHUNG-ANH NGUYEN, 3 WEN-SHAN JIAN, 1,4,5CHUNG-HUEI HSU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 3School of Health Care Administration, Taipei Medical University, Taipei, Taiwan; 4Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 5 School of Medicine, College of Medicine, Taipei Medical University

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Moderator: I-Te Lee 16:26~16:34

O-03

HIGH GLUCOSE CAUSES RENAL INJURY VIA GLYCOSYLATION OF RBP4 RECEPTOR SIGNALING 1

ZHAO-HONG CHEN, 2KUN-DER LIN, 2MEI-YUEH LEE, 3 TUSEY-JIUAN HSIEH, 2,3PI-JUNG HSIAO, 2,3SHYI-JANG SHIN 1

Graduate Institute of Medicine, 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 3Center of Lipid and Glycomedicine Research, Kaohsiung Medical University.Kaohsiung, Taiwan

Moderator: Chih-Yuan Wang 16:34~16:42

O-04

CHARACTERIZATION AND ANALYSIS OF DIFFERENTIATED THYROID CANCER PATIENTS WITH POSITIVE THYROGLOBULIN ANTIBODY POST THYROIDECTOMY 1

DANIEL HUENG-YUAN SHEN, 1YI-FENG CHEN, 1 CHENG-HAN HOU, 1LI-FAN LIN, 2MING-LANG SHIH, 1 CHENG-YI CHENG 1

Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.; 2Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.

Moderator: Yi-Jen Hung 16:42~16:50

O-05

PROTEOMIC ANALYSIS OF FATTY LIVER TISSUES INDUCED BY HIGH-FAT DIET AND REVERSE ALTERATION WITH CANNABINOID RECEPTOR TYPE 1 ANTAGONIST TREATMENT IN MOUSE MODEL 1

CHIN-CHANG CHEN, 2YUNG-PEI HSU, 3 CHING-FAI KWOK, 1YAN-JIE LIN, 3KUANG-CHUNG SHIH, 1,2,3,4 LOW-TONE HO 1

Institute of Physiology, National Yang-Ming University, Taiwan, ROC; 2 Department of Medical Research, Taipei Veterans General Hospital, Taiwan, ROC; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, ROC; 4School of Medicine, National Yang-Ming University, Taiwan, ROC

Agenda

Moderator: Hong-Da Lin 16:50~16:58

O-06

CAN WE DISTINGUISH FOLLICULAR CARCINOMA FROM FOLLICULAR ADENOMA BY REGULARITY OF NODULAR MARGIN? 1,2

KUO-CHIN HUANG, 2,3CHWEN-TZUEI CHANG, 2,3 CHING-CHU CHEN, 2,3RONG-HSING CHEN, 2,3 TZU-YUAN WANG, 3WEI-LUN HUANG, 3 YI-CHIH HUNG, 3CHING-CHUNG CHANG 1

Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taiwan, R.O.C.; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taiwan, R.O.C.; 3Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taiwan, R.O.C

Moderator: Hung-Yuan Li 16:58~17:06

O-07

STATIN USE LOWERS THE INCIDENCE OF PARKINSON’S DISEASE IN PATIENTS WITH TYPE 2 DIABETES. -A STUDY USING THE NATIONAL HEALTH INSURANCE DATABASE 1,4

K-D LIN, 2,3,4P-J HSIAO, 4M-Y LEE, 2,3,4S-J SHIN

Graduate Institute of Medicine, 2School of Medicine, College of Medicine, Center of Lipid and Glycomedicine Research, Kaohsiung Medical University, 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C.

Moderator: Chih-Yuan Wang 17:06~17:14

O-08

RESPONSE OF DIFFERENT DEGREE PEDIATRIC GROWTH HOROME DEFICIENCY DURING REPLACEMENT THERAPY GAO BING-RU, 1,2CHEN PIN-FAN, 1LIAN WEI-CHENG, 1 YAN SHIH-TANG, 1CHEN TING-CHANG 1

Division of Endocrinolgy and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital, Taiwan 2Shool of Medicine, Tzu Chi University, Hualien, Taiwan

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Moderator: Hong-Da Lin 17:14~17:22

O-09

RADIOACTIVE IODINE-REFRACTORY DIFFERENTIATED THYROID CARCINOMA - DATA FROM KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL 1

PEI-WEN WANG, 2YEN-HSIANG CHANG, 1 I-CHIN HUANG, 1CHING-JUNG HSIEH 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Department of Nuclear Medicine, Kohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, kaohsiung, Taiwan 2

Moderator: Chih-Hsun Chu 17:22~17:30

O-10

LOW-DENSITY LIPOPROTEIN CHOLESTEROL ESTIMATION WITH VARIOUS FORMULAE CHING-YUN HU, CHIA-LIN LEE, CHIA-PO FU, JUN-SING WANG, I-TE LEE, YEN-MIN SONG, SHI-YI LIN, WAYNE HUEY-HERNG SHEU Endocrinology and Metabolism Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan

March 22, 2015 (Sun) 【2nd Conference Room】

Oral Presentation-Endo Moderator: Jen-Der Lin, Ging-Shing Won

15:30~15:38

OE-01

ANGIOTENSIN II ENHANCES ENDOTHELIN1-INDUCED VASOCONSTRICTION THROUGH UPREGULATING ENDOTHELIN TYPE A RECEPTOR 1,4

YAN-JIE LIN, 2,4CING-FAI KWOK, 1,3CHI-CHANG JUAN, 4 YUNG-PEI HSU, 2,4KUANG-CHUNG SHIH, 1 CHIN-CHANG CHEN, 1,2,3,4LOW-TONE HO 1

Institute of Physiology, National Yang-Ming University, Taipei, Taiwan Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan 3Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan 4Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan 2

Agenda 15:38~15:46

OE-02

THE POWER OF SERUM URIC ACID IN PREDICTING METABOLIC SYNDROME ALLEVIATED WITH AGING IN CHINESE ELDERLY 1,2

JUI-HUNG CHEN, 3DEE PEI, 1YI-JEN HUNG, 1 CHANG-HSUN HSIEH, 4YEN-LIN CHEN 1

Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan; 3Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 4Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

15:46~15:54

OE-03

BMI AND PREOPERATIVE PLASMA ALDOSTERONE CONCENTRATION AS CRITICAL PREDICTORS RATHER THAN POTASSIUM LEVEL FOR HYPERTENSION CURE IN PRIMARY ALDOSTERONISM. 1

CHIA-HUI CHANG, 1SHI-WEN KUO, 2YAO-CHOU TSAI, 3 VIN-CENT WU, 1YA-HUI HU 1

Division of Endocrine and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Taiwan; 2 Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Taiwan; 3 Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital.

15:54~16:02

OE-04

RISK FACTORS OF DISTANT METASTASIS IN FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA 1

YAN-RONG LI, 1JEN-DER LIN, 1SZU-TAH CHEN, 2 CHUEN HSUEH, 3TZU-CHIEN CHAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, R.O.C. 2Department of Pathology, Chang Gung Memorial Hospital, Taiwan, R.O.C. 3Department of General Surgery, Chang Gung Memorial Hospital, Taiwan, R.O.C.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

16:02~16:10

OE-05

ASSOCIATION OF MEAN ARTERIAL PRESSURE AND MORTALITY IN DIABETES PATIENTS WITH NORMAL ANKLE-BRACHIAL INDEX YU-HSUAN LI, I-TE LEE, SHI-YI LIN, WAYNE HUEY-HERNG SHEU Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taiwan.R.O.C.

16:10~16:18

OE-06

HIGHER SERUM TOTAL BILIRUBIN CONCENTRATION IS ASSOCIATED WITH LOWER RISK OF CHRONIC KIDNEY DISEASE IN AN ADULT POPULATION 1

ANG-TSE LEE, 2,3,4YA-YU WANG, 1,4SHIH-YI LIN, 5 JIIN-TSAE LIANG, 1,4,6WAYNE HUEY-HERNG SHEU, 1 YUH-MIN SONG, 2WEN-DAU CHANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2 Department of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 3 Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan; 4 School of Medicine, National Yang Ming University, Taipei, Taiwan; 5 Division of Biochemistry, Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 6 School of Medicine, National Defense Medical Center, Taipei, Taiwan.

16:18~16:26

OE-07

SERUM STIMULATED THYROGLOBULIN LEVELS AT THE TIME OF 131I ABLATION THERAPY IS A GOOD PROGNOSTIC MARKER TO PREDICT LONG-TERM STRUCTURAL PERSISTENT DISEASE IN WELL-DIFFERENTIATED THYROID CARCINOMA FENG-CHIH SHEN, CHING-JUNG HSIEH, I-CHIN HUANG, PEI-WEN WANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Kohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, kaohsiung, Taiwan

Agenda 16:26~16:34

OE-08

ELASTOGRAPHY OF THYROID ULTRASONOGRAPHY PREDICT RECURRENCE OF GRAVES’ DISEASE 1,3,4

CHWEN-TZUEI CHANG, 2,3KUO-CHIN HUANG, 1,3 RONG-HSING CHEN, 1,3,4TZU-YUAN WANG, 1 WEI-LUNG HUANG, 1YI-CHIH HUNG, 1,3 CHING-CHU CHEN, 1CHING-CHUNG CHANG 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taiwan, R.O.C; 2Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taiwan, R.O.C.; 3School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taiwan, R.O.C.

16:34~16:42

OE-09

AMIODARONE - ASSOCIATED THYROID DYSFUNCTION 1

HSIAO-LIEN CHEN, 2PAI-LIEN CHEN, 1 HUAN-WEN CHEN, 3PEI-LING CHAN 1

Division of endocrinology and Metabolism, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.; 2Division of endocrinology and Metabolism, Department of Internal medicine, Luo Dong Saint Mary’s Hospital ,Taiwan, R.O.C.; 3Department of Nursing, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.

16:42~16:50

OE-10

EPIMEDIUM EXTRACTS INDUCED C2C12 PROLIFERATION AND HYPERTROPHY 1

YI-AN LIN, 2MEI-CHICH HSU, 3SZU-TAH CHEN

National Taiwan Sport University; 2 Kaohsiung Medical University; Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

March 21, 2015 (Sat) 【1st Conference Room】

Luncheon Symposium-1 DPP4 Inhibitor Sponsor: MSD Moderator: Harn-Shen Chen

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

12:00~13:00

LS-1

DPP4 Inhibitors: Have We Optimized Their Role in the Treatment of Patients with Type2 Diabetes? Hung-Yuan Li Department of Internal Medicine, National Taiwan University Hospital

March 21, 2015 (Sat) 【2nd Conference Room】

Luncheon Symposium-2 Sponsor: AstraZeneca Moderator: Lee-Ming Chuang

12:00~12:30

LS-2-1

Beyond Hyperglycemic Control: What's New from SAVOR Study Chia Hung Lin Division of Endocrinology and Metabolism, Linkou Chang Gung Memorial Hospital

Moderator: Pi-Jung Hsiao 12:30~13:00

LS-2-2

New Medications on the Horizon: SGLT2 Inhibitors Chih-Yuan Wang Department of Internal Medicine, National Taiwan University Hospital

March 21, 2015 (Sat) 【3rd Conference Room】

Luncheon Symposium-3 Standards of Medical Care in Diabetes 2015 “NO GOAL” in Dyslipidemia Treatment Sponsor: Pfizer Moderator: Shih-Te Tu

Agenda 12:00~13:00

LS-3

Why Dose ADA aLSo Endorse no Goal in Dyslipidemia Treatment after 2014 ACC/AHA and NICE Lipid Guidelines? Tsung-Hsien Lin Department of Cardiology, Kaohsiung Medical University Chung-Ho Memorial Hospital

March 21, 2015 (Sat) 【4th Conference Room】

Luncheon Symposium-4 Statin For Diabetic & Pre-Diabetic Dyslipidemia Sponsor: Tanabe Moderator: Wayne Huey-Herng Sheu

12:00~12:05

Opening Wayne Huey-Herng Sheu President, The Diabetes Association of the R.O.C. (Taiwan) Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

12:05~12:35

LS-4-1

New Insights In The Treatment of Diabetic Dyslipidemia Chau-Chung Wu Department of Internal Medicine, National Taiwan University Hospital

12:35~12:50

LS-4-2

Pitavastatin Treatment for Cardiovascular Disease --Vascular Protection Effects Liang-Yu Lin Division of Endocrinology and Metabolism, Taipei Veterans General Hospital

12:50~13:00

Discussion

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 22, 2015 (Sun) 【2nd Conference Room】

Luncheon Symposium-5 The Evolving Paradigm in T2D Treatment Sponsor: Lilly & Boehringer Ingelheim Moderator: Wayne Huey-Herng Sheu

12:00~13:00

LS-5

21st Century Breakthrough of Diabetology~ Beyond Glycemic Control~ Takashi Nomiyama Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Japan

March 22, 2015 (Sun) 【3rd Conference Room】

Luncheon Symposium-6 TZD Across the CV Continuum Sponsor: Takeda Moderator: Lee-Ming Chuang

12:00~13:00

LS-6

Do We Still Need Actos for the Treatment of Type2 Diabetes? Robert J Chilton Department of Medicine, Division of Cardiology, The University of Texas Health Science Center at San Antonio, Texas, USA

March 22, 2015 (Sun) 【4th Conference Room】

Luncheon Symposium-7 Meet the Experts: A Thorough Discussion on Incretin Based Therapy Sponsor: Novartis

Agenda

Moderator: Shih-Te Tu 12:00~12:05

Opening Remarks Shih-Te Tu Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

12:05~12:30

LS-7-1

Master the Incretin Based Therapy: Focused on DPP4i Nobuya Inagaki Department of Diabetes, Endocrinology and Nutrition, Kyoto University Hospital, Japan

12:30~12:55

LS-7-2

Incretin Therapy Focused on DPP4i: The Relationship of Ectopic Fat Chih-Yuan Wang Department of Internal Medicine, National Taiwan University Hospital

12:55~13:00

Closing Remarks Shih-Te Tu

Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

March 22, 2015 (Sun) 【1st Conference Room】

Satellite Symposium-1 Journey to Individualized Insulin Therapy: From Clinical Trial to Real World Experience Sponsor: Novo Nordisk Moderator: Wayne Huey-Herng Sheu

08:00~09:00

SS-1

Journey to Individualized Insulin Therapy: From Clinical Trial to Real World Experience Stephen Atkin Medical Department, Weill Cornell Medical College in Qatar (WCMC-Q)

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 22, 2015 (Sun) 【2nd Conference Room】

Satellite Symposium-2 Sponsor: Tshbiopharm Moderator: Kuo-Yang Wang

08:00~09:00

SS-2

After HPS2-THRIVE and IMPROVE-IT TriaLS, How can We Maximize CV Events Reduction at the Beginning of 2015? Focus on Lipid Treatment Tsung-Hsien Lin Department of Cardiology, Kaohsiung Medical University Chung-Ho Memorial Hospital

March 22, 2015 (Sun) 【3rd Conference Room】

Satellite Symposium-3 Sponsor: ApexBio Moderator: Jung-Fu Chen

08:00~09:00

SS-3

Effectiveness of Telehealth Programs for Improving Diabetes Management Ming-Chia Hsieh Changhua Christian Hospital Diabetes e-Institute

March 22, 2015 (Sun) 【4th Conference Room】

Satellite Symposium-4 Sponsor: Otsuka Moderator: Shih-Te Tu

08:00~08:05

Opening Shih-Te Tu Taiwanese Association of Diabetes Educators Division of Endocrinology and Metabolism, Lukang Christian Hospital

Agenda 08:05-08:30

SS-4-1

The Impacts of Cilostazol on Macro- and Microvascular Disease in Type 2 Diabetes Chien-Hsing Lee Division of Endocrinology and Metabolism, Tri-Service General Hospital

08:30~08:55

SS-4-2

Optimal Antiplatelet Therapy for the Secondary Prevention of Stroke in Asian Patients Jiann-Shing Jeng Department of Neurology, National Taiwan University Stroke Center ICU, National Taiwan University Hospital

08:55-09:00

Closing Shih-Te Tu Taiwanese Association of Diabetes Educators Division of Endocrine and Metabolism, Lukang Christian Hospital

March 21, 2015 (Sat) 【6th & 7th Conference Room 】

Poster Presentation-Endo-1 Moderator: Hing- Chung Lam

14:50~15:30

PE-01

THYROID TUBERCULOSIS 1,2

TSUNG-JU CHUANG, 1JHIH-SYUAN LIOU, 1 YI-JEN HUNG, 1CHANG-HSUN HSIEH 1

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PE-02

PRIMARY ADRENAL INSUFFICIENCY DUE TO ISOLATED ADRENAL CRYPTOCOCCOSIS IN A IMMUNOCOMPETENT MAN SUCCESSFULLY TREATED WITH ORAL FLUCONAZOLE 1

YI-CHIH HUNG, 1CHING-CHU CHEN, 1TZU-YUAN WANG, 2 MAO-WANG HO 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C;2Division of Infection Disease, Department of Internal Medicine, China Medical University Hospital Taichung, Taiwan, R.O.C

14:50~15:30

PE-03

PROLACTINOMA PRESENTING AS DELAYED PUBERTY: A CASE REPORT 1

YI-LUN CHIANG, 1SZU-HUI LEE, 1PEI-CHI CHEN, 1 YEN-LING CHEN, 1CHUNG-YEN HUANG, 1,2 HONG-DA LIN, 1SHIH-MING LAI 1

Division of Endocrinology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Taipei-Veterans General Hospital , Taipei

14:50~15:30

PE-04

THE THYROID HORMONE RESISTANCE SYNDROME: A CASE REPORT 1

SHIH-HUI HUANG, 1CHUNG-YEN HUANG, 1 SHIH-MING LAI, 1YEN-LING CHEN, 1PEI-CHI CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin Kong Wu Ho-Su Memory Hospital, Taiwan, R.O.C.

14:50~15:30

PE-05

SUBACUTE THYROIDITIS PRESENTING AS DIFFUSE UPTAKE OF THYROID GLAND ON 18F-FDG PET/CT: A CASE REPORT 1

CHEN-TI WANG, 1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1 SHU-JU KU, 1JU-CHUN HUANG, 1KUO-BIN TSENG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine, I-Shou University, Kaohsiung, Taiwan

Agenda 14:50~15:30

PE-06

A CASE OF CUSHING’S SYNDROME WITH BILATERAL ADRENAL TUMOR 1

SHIH-TANG YAN, 1,2PIN-FAN CHEN

Divison of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

14:50~15:30

PE-07

HYPERPROLACTINEMIA ASSOCIATED WITH UNRUPTURED ANEURYSM: CASE REPORT WEI-TSEN LIAO, MING-JE TSAI, CHUN-CHUAN LEE Division of Endocrinology & Metabolism, Department of Internal Medicine, Mackay Memorial hospital, Taiwan, R.O.C.

14:50~15:30

PE-08

SEVERE HYPERTENSION IN A PATIENT WITH PRIMARY ALDOSTERONISM WITHOUT SUPPRESSED RENIN TZU-YUAN WANG, CHING-CHU CHEN, CHWEN-TZUEI CHANG, RONG-HSING CHEN, WEN-LIANG HUANG, KUO-CHIN HUANG, YI-CHIH HUNG Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

14:50~15:30

PE-09

CAN ROBOTIC THYROIDECTOMY APPLIED TO THYROID CARCINOMA WITH LUNG METASTASES? 1

HSIAO-WEN CHANG, 2YI-FENG CHEN, 1 CHANG-HSUN HSIEH, 2DANIEL HUENG-YUAN SHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan; 2Department of Nuclear medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PE-10

HYPERTRIGLYCERIDEMIA INCREASES THE SEVERITY OF THROMBOCYTOPENIA IN DENGUE INFECTED PATIENTS 1,3

MEI-YUEH LEE, 2CHUNG-YUAN CHEN, 3 KUN-DER LIN, 3YU-LI LEE, 1,3WEI -HAO HSU, 3 PI-JUNG HSIAO, 3SHYI-JANG SHIN 1

Department of Internal Medicine,Kaohsiung Municipal Hsiao-Kang Hospital; 2Chin-Pin Clinic, Kaohsiung; 3Division of Endocrinology and Metabolism , Kaohsiung Medical University Hospital

14:50~15:30

PE-11

INITIAL FALSE NEGATIVE ALDOSTERONE-TORENIN RATIO IN PRIMARY ALDOSTERONISM WITH SEVERE HYPOKALEMIC RHABDOMYOLYSIS- A CASE REPORT 1

YI-WEI WU, 1YA-HUI HU, 2YAO-CHOU TSAI, 1 SHI-WEN KUO 1

14:50~15:30

PE-12

ADRENAL LYMPHOMA: A CASE REPORT 1

LI-WEI HSIAO, 1CHIA-LIN LEE, 2CHIEH-LIN TENG, 1 SHI-YI LIN, 1WAYNE HUEY-HERNG SHEU 1

Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taiwan; 2Division of Hematology and oncology, Department of Medicine, Taichung Veterans General Hospital, Taiwan

14:50~15:30

PE-13

THYROIDITIS AND HYPERCALCEMIA AFTER UNILATERAL ADRENALECTOMY FOR CUSHING’S SYNDROME : A CASE REPORT 1

YU-WEI CHEN, 1CHIA-PO FU, 2WEN-MING CHEN, 1 SHI-YI LIN, 3WAYNE H-H SHEU 1

Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan;2Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 3Professor and Chairman, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Agenda 14:50~15:30

PE-14

THYROGEN, RECOMBINANT HUMAN TSH (RHTSH) - INDUCED HYPERCALCEMIC CRISIS IN A PATIENT WITH FOLLICULAR THYROID CARCINOMA : A CASE REPORT AND REVIEW OF THE LITERATURE CHIEN-AN CHOU, SZU-TAH CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C

March 22, 2015 (Sun) 【6th & 7th Conference Room】

Poster Presentation-Endo-2 Moderator: Daniel Hueng-Yuan Shen

14:50~15:30

PE-15

A CASE OF RETROPERITONEAL MASS LESIONS: PARAGANGLIOMA 1

CHIN CHOU YANG, 3CHING WEI CHANG, 2 CHUN LU LIN, 1YA CHUN HSIAO, 2CHUN CHUAN LI, 1 YA CHUN HSIAO, 2CHUN CHUAN LI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan; 3Division of GastrOEnterology, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan

14:50~15:30

PE-16

A CASE REPORT – PAPILLARY THYROID CANCER POST THYROIDECTOMY FOLLOWED BY LYMPHADENOPATHY CAUSED BY CASTLEMAN’S DISEASE 1

YI-HONG ZENG, 2SHIH-PING JHENG, 3DAO-YUAN WANG, 1 CHUN-CHUAN LEE 1

Division of Endocrinology and Metabolism, department of internal medicine, Mackay Memorial Hospital, Taiwan, ROC.; 2Department of General Surgery, Mackay Memorial Hospital, Taiwan, ROC.; 3Department of Pathology, Mackay Memorial Hospital, Taiwan, ROC.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PE-17

FALSE-NEGATIVE 99MTC SESTAMIBI PARATHYROID SCAN IN PATIENT WITH PARATHYROID ADENOMA: A CASE REPORT CHIH-HUNG LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan, R.O.C.

14:50~15:30

PE-18

SYNCHRONOUS PAPILLARY THYROID CARCINOMA AND SECONDARY HYPERPARATHYROIDISM: CASE REPORT 1

HSIAO-LIEN CHEN, 2MING-YU LAI

Division of Endocrinology and Metabolism, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.

14:50~15:30

PE-19

EXOME SEQUENCING OF A CASE WITH MIXED ADRENAL CORTICOMEDULLARY ADENOMA 1

LI LUN CHUANG, 2DAU YANG HWANG, 3 SHAN-YIN TSAI, 1WEI-WEN HUNG, 1KUN-DER LIN, 1,4 SHYI-JANG SHIN, 1,4PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, 2Department of Nephrology, Department of Pathology, Kaohsiung Medical University Hospital; 4 School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3

14:50~15:30

PE-20

ELECTRONEGATIVE LDL IMPAIRS KIDNEY THROUGH DAMAGE OF STRA6 SIGNALING 1

ZHAO-HONG CHEN, 2LIANG-YIN KE, 2 HUA-CHEN CHAN, 2CHU-HUANG CHEN, 2,3,4 SHYI-JANG SHIN 1

Graduate Institute of Medicine, 2Center of Lipid and Glycomedicine Research, 3School of Medicine, College of Medicine, Kaohsiung Medical University; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C.

Agenda 14:50~15:30

PE-21

CHYLOTHORAX AS A RARE PRESENTATION IN GRAVES’ DISEASE 1

LEE I-SHUAN, 1,2LEE TING-WEI, 1CHANG CHUN-JEN, 1 LEE TING-I, 1FAN CHI, 1CHIEN YU-MEI, 1 CHOU CHUAN-LIANG, 1LIU HAN-WEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University- Wan Fang Hospital; 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University

14:50~15:30

PE-22

ACUTE DECOMPENSATION OF METHYLMALONIC ACIDEMIA IN AN ADULT PATIENT-A CASE REPORT 1.2

PIN-FAN CHEN, 1BING-RU GAO, 1.2WEI-CHENG LIAN, 1 SHIH-TANG YAN, 1TING-CHANG CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

March 21, 2015 (Sat) 【6th & 7th Conference Room】

Poster Presentation-DM-1 Moderator: Shih-Yi Lin

14:50~15:30

PD-01

PATIENT-REPORTED OUTCOMES FROM A 104WEEK, PHASE 3, RANDOMISED, PLACEBOCONTROLLED STUDY COMPARING ONCE-WEEKLY DULAGLUTIDE TO SITAGLIPTIN AND PLACEBO IN METFORMIN-TREATED PATIENTS WITH TYPE 2 DIABETES; THE ASSESSMENT OF WEEKLY ADMINISTRATION OF DULAGLUTIDE IN DIABETES (AWARD-5) TRIAL 1

THOMAS LEW, 2M REANEY, 3M YU, 4O ADETUNJI, 5 Z MILICEVIC 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, UK; 3Eli Lilly and Company, Toronto, Canada; 4Eli Lilly and Company, Basingstoke, UK; 5Eli Lilly and Company, Vienna, Austria

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-02

PATIENT-REPORTED OUTCOMES WITH ONCEWEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE (AWARD-2) 1

THOMAS LEW, 2M REANEY, 3M YU, 2 BRUNT K VAN BRUNT, 4V PETCHNER, 5CP HAYES 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, UK; 3Eli Lilly and Company, Toronto, Canada; 4Eli Lilly and Company, Paris, France; 5Eli Lilly and Company, Indianapolis, IN, USA

14:50~15:30

PD-03

INSULIN LISPRO LOW MIXTURE TWICE DAILY VERSUS BASAL INSULIN GLARGINE AND PRANDIAL INSULIN LISPRO ONCE DAILY IN EAST ASIAN AND CAUCASIAN TYPE 2 DIABETES MELLITUS PATIENTS 1

THOMAS LEW, 2JH HAN, 3D EDRALIN, 4R DUAN, 5A RODRIGUEZ

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; Lilly Korea Ltd, Seoul, Korea; 3Eli Lilly, Pasig City, Philippines; 4Eli Lilly and Company, Indianapolis, IN, USA; 5Lilly Spain, Alcobendas, Spain 2

14:50~15:30

PD-04

SIMILAR EFFICACY AND SAFETY WITH LY2963016 INSULIN GLARGINE COMPARED WITH LANTUSR INSULIN GLARGINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2DM): THE ELEMENT 2 STUDY 1

JOYCE YEH, 2JULIO ROSENSTOCK, 3PRISCILLA HOLLANDER, 4ANJU BHARGAVA, 5LIZA ILAG, 5ROBIN K. POLLOM, 5WILLIAM J HUSTER, 5MELVIN PRINCE 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; Dallas Diabetes and Endocrine Center, Dallas, TX, USA; 3Baylor Endocrine Center, Dallas, TX, USA; 4Iowa Diabetes and Endocrinology Center, Des Moines, IA, USA; 5Eli Lilly and Company, Indianapolis, IN, USA 2

Agenda 14:50~15:30

PD-05

PREDICTION OF GLUCOSE EFFECTIVENESS WITH ROUTINE MEASUREMENTS IN CHINESE 1

DEE PEI, 2CHUN-TIEN LIN, 3YEN-LIN CHEN

Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, ROC; 2 Division of Endocrinology, Department of Internal Medicine,Shuang Ho Hospital, School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC; 3Division of Pathology, Cardinal Tien Hospital, Medical School, Fu Jen Catholic University, New Taipei City, Taiwan, ROC

Moderator: Yi-Jen Hung 14:50~15:30

PD-06

NOT ALL COMBINATION THERAPY OF METFORMIN AND STATINS CAN DECREASE HEPATOCELLULAR CARCINOMA IN DIABETIC PATIENTS IN TAIWAN HSIN-HUNG CHEN Institute of Public health and Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Metabolism & Endocrinology, Changhua Christian Hospital, Changhua, Taiwan; Nantou Christian Hospital

14:50~15:30

PD-07

THE ASSOCIATION OF HEMATOGRAM WITH METABOLIC SYNDROME IN THE YOUNG-OLD, OLD-OLD AND OLDEST-OLD POPULATIONS 1, 2

TSUNG-JU CHUANG, 1YI-JEN HUNG, 3DEE PEI, 4 YEN-LIN CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Taipei, Taiwan 4 Department of Pathology, Cardinal Tien Hospital, Taipei, Taiwan

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-08

SODIUM GLUCOSE COTRANSPORTER 2 (SGLT2) INHIBITION WITH EMPAGLIFLOZIN REDUCES MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES 1

DAVID CHERNEY, 2MAXIMILIAN EYNATTEN, 3 SØREN LUND, 3STEFAN KASPERS, 3SUSANNE CROWE, 3 HANS WOERLE, 3THOMAS HACH 1

Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Boehringer Ingelheim PharmaceuticaLS, Inc., Ridgefield, CT, USA; 3 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 2

14:50~15:30

PD-09

EFFECT OF EMPAGLIFLOZIN COMPARED WITH GLIMEPIRIDE AS ADD-ON TO METFORMIN FOR 2 YEARS ON THE AMOUNT AND DISTRIBUTION OF BODY FAT IN PATIENTS WITH TYPE 2 DIABETES 1

GABRIEL KIM, 2MARTIN RIDDERSTRÅLE, 3 KNUT ANDERSEN, 4CORDULA ZELLER, 1 HANS WOERLE, 1ULI BROEDL 1

Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany Steno Diabetes Center, Gentofte, Denmark 3Boehringer Ingelheim Norway KS, Asker, Norway 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany 2

14:50~15:30

PD-10

EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST LIRAGLUTIDE ON MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION IN RATS 1, 3

MEI-YUEH LEE, 2KUN- PAO TSAI, 4JONG-HAU HSU, 4 JIUNN-REN WU, 3KUN-DER LIN, 3PI-JUNG HSIAO, 3 SHYI-JANG SHIN, 5JWU-LAI YEH 1

Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 2Department of Pathology; 3Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital; 4Department of Pediatrics; 5Department of Pharmacology, School of Medicine, Kaohsiung Medical University

Agenda Moderator: Hung-Yuan Li 14:50~15:30

PD-11

C-REACTIVE PROTEIN IS ASSOCIATED WITH INTRAOCULAR PRESSURE INDEPENDENTLY OF METABOLIC SYNDROME I-TE LEE, WAYNE H-H SHEU, JUN -SING WANG, SHIH-YI LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

14:50~15:30

PD-12

EFFECT OF METFORMIN ON BONE LOSS IN OVARIECTOMIZED RATS FED WITH HIGHFRUCTOSE DIET 1

JIANN-LIANG LIN, 1YI-JING SHEEN, 2SHIH-YI LIN, 3 TSUNG-HAN TENG, 4ZIH-CYUN LIN, 4SHU-CHI CHIANG, 5 SHIH-MING HUANG, 2WAYNE HUEY-HERNG SHEU, 4 HUI-TING YANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital; 3Department of Pathology, St. Martin De Porres Hospital; 4Department of Nutrition, China Medical University; 5Department of Pathology, Taichung Hospital, Ministry of Health and Welfare

14:50~15:30

PD-13

A SUCCESSFULLY TREATED CASE OF EXTREMELY HYPERGLYCEMIC CRISIS ACCOMPANIED WITH RHABDOMYOLYSIS, STAGHORN STONE AND ACUTE KIDNEY INJURY CHIA-LUEN HUANG, I-REN HUNG, CHIENG-HSING LEE Division of Metabolism and Endocrinology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-14

CORRELATION BETWEEN PERIODONTAL DISEASE AND CLINICAL FEATURES IN TYPE 2 DIABETIC PATIENTS 1

JHIH-SYUAN LIU, 1CHIEN-HSING LEE, 1KAI-YUEN HSU, 2 YI-SHING SHIEH, 1CHANG-HSUN HSIEH, 1YI-JEN HUNG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; 2Dental Department of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

14:50~15:30

PD-15

THE LEVELS OF GROWTH ARREST-SPECIFIC PROTEIN 6 (GAS6) ARE REDUCED IN PATIENTS WITH TYPE 2 DIABETIC UREMIA 1

SHENG-CHIANG SU, 2YU-JUEI HSU, 1YI-JEN HUNG, 1 CHIEN-HSING LEE 1

Division of Endocrinology and Metabolism, 2 Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Moderator: Chih-Hsun Chu 14:50~15:30

PD-16

THE LINK OF IN VIRTUAL SCREENING TO HEALTH INSURANCE DATABASE IN THE CHEMICAL GENETIC STUDY OF OBESITY 1

CHIEH-HUA LU, 2WU-CHIEN CHIEN, 3LI-JEN TSAI, 4 PO-SHIUAN HSIEH 1

Division of Endocrinology and Metabolism, Tri-service general hospital; School of Public Health, National Defense Medical Center; 3Ching Kuo Institute of Management and Health; 4Graduate Institute of Physiology, National Defense Medical Center 2

14:50~15:30

PD-17

PROLONG HYPOGLYCEMIA ASSOCIATED WITH LONG ACTING INSULIN ANALOGUE INJECTIONA CASE REPORT WEI-HSIN HSU, I-MIN PAN Department of Internal Medicine, Division of Endocrinology, Tainan SinLau Hospital, Tainan, Taiwan, R.O.C.

Agenda 14:50~15:30

PD-18

ASSOCIATION BETWEEN PLASMA GROWTH ARREST-SPECIFIC PROTEIN 6 AND COMPONENTS OF METABOLIC SYNDROME 1

PENG-FEI LI, 2FU-HUANG LIN, 1CHANG-HSUN HSIEH, 1 YI-JEN HUANG, 1CHIEN-HSING LEE 1

Division of Endocrinoy and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 School of Public Health, National Defense Medical Center, Taipei, Taiwan

14:50~15:30

PD-19

COMPARSION OF BRACHIAL-ANKLE PULSE WAVE VELOCITY (BAPWV) IN POOR-GLYCEMIC CONTROL TYPE 2 DIABETES PATIENTS IN EASTERN-SOUTHERN TAIWAN 1

KAT-YIEN NGU, 1SHIH-MING CHUANG, 1YUE QIU HUANG, 2CHUN-QUAN LI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taitung branch; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei

14:50~15:30

PD-20

DIABETIC KETOACIDOSIS DEVELOPMENT IN A YOUNG WOMAN WITH THE STIFF PERSON SYNDROME 1

HUNG-YU HUANG, 2RONG-HSING CHEN, 1,3MING-KUEI LU, 1,3CHON-HAW TSAI 1

Department of Neurology, China Medical University Hospital; 2Department of Endocrine and Metabolism, China Medical University Hospital; 3School of Medicine, Medical College, China Medical University

March 22, 2015 (Sun) 【6th & 7th Conference Room】

Poster Presentation-DM-2 Moderator: I-Te Lee

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-21

E-SELECTIN AS A MARKER OF ENDOTHELIAL DYSFUNCTION IN METABOLIC SYNDROME AND GENDER DIFFERENCES IN THE EXPRESSION OF E-SELECTIN AND OTHER MARKERS OF INFLAMMATION. WEN-HAO TANG, FENG-CHIH KUO, FU-HUANG LIN, CHANG-HSUN HSIEH, YI-JEN HUNG, CHIEN-HSING LEE Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chen-Kung Rd.,Nei-Hu, Taipei, Taiwan

14:50~15:30

PD-22

DIABETIC PATIENT OUTCOMES BY DIFFERENT SPECIALTIES CARE: A 5-YEAR OBSERVATIONAL STUDY IN A MEDICAL CENTER TZU-YUN YU, CHIA-LIN LEE, JUN-SING WANG, CHIA-PO FU, I-TE LEE, YEN-MIN SONG, SHIH-YI LIN, WAYNE HUEY-HERNG SHEU Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

14:50~15:30

PD-23

ORAL GLUCOSE LOWERING WITH LINAGLIPTIN PLUS METFORMIN IS A VIABLE INITIAL TREATMENT STRATEGY IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES AND MARKED HYPERGLYCAEMIA 1

BAPTIST GALLWITZ, 2STUART A. ROSS, 3 A. ENRIQUE CABALLERO, 4STEFANO DEL PRATO, 5 DIANE LEWIS-D’ AGOSTINO, 6ZELIE BAILES, 7 SANDRA THIEMANN, 6SANJAY PATEL, 7 HANS-JUERGEN WOERLE, 5MAXIMILIAN VON EYNATTEN 1

Dept. Medicine IV, Universitätsklinikum Tübingen, Tübingen, Germany; LMC Endocrinology Centres, University of Calgary, Calgary, AB, Canada; 3 Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA; 4 Department of Endocrinology and Metabolism, Section of Diabetes, University of Pisa, Pisa, Italy; 5BOEhringer Ingelheim PharmaceuticaLS, Inc., Ridgefield, CT, USA; 6BOEhringer Ingelheim Ltd, Bracknell, UK; 7 BOEhringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany 2

Agenda 14:50~15:30

PD-24

RISK OF HYPOGLYCEMIA IN PEOPLE RECEIVING LINAGLIPTIN: POOLED DATA FROM 1489 ADULTS AGED ≥65 YEARS WITH TYPE 2 DIABETES MELLITUS 1

KAMLESH KHUNTI, 2MICHAEL NAUCK, 3 ATSUSHI ARAKI, 4SUSANNE CROWE, 4YAN GONG, 4 DOUGLAS CLARK, 5MAXIMILIAN VON EYNATTEN, 4 HANS-JUERGEN WOERLE 1

University of Leicester, Leicester, UK; 2Diabetes Center Bad Lauterberg, Bad Lauterberg im Harz, Germany; 3Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; 4BOEhringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5BOEhringer Ingelheim PharmaceuticaLS Inc., Ridgefield, CT, USA

14:50~15:30

PD-25

IGG4 RELATED DISEASE IN A PATIENT WITH DIABETES MELLITUS WU LUNG CHUANG, DONG-HWA TSAI, SHU-YI WANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Moderator: Jun-Sing Wang 14:50~15:30

PD-26

EMPHYSEMATOUS PYELITIS WITH PNEUMONEPHROSIS IN TYPE 2 DIABETES PATIENT 1

CHIU CHIH-HUANG, 2WANG SHU-Y, 3TSAI DONG-HWA

14:50~15:30

PD-27

EFFECT OF PITAVASTATIN ON GLUCOSE CONTROL AND LIPID PROFILE IN TYPE 2 DIABETIC PATIENTS CHUNG-HUEI HUANG, YU-YAO HUANG, BREND RAY-SEA HSU Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-28

A 31-YEAR-OLD TAIWAN WOMAN HAD FULMINANT TYPE 1 DIABETES MELLITUS FANG-CHUAN HUANG, HON-KE SIA, SHI-DOU LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

14:50~15:30

PD-29

INDICATOR ANALYSIS FOR RESPONSIVENESS TO GLUCAGON-LIKE PEPTIDE RECEPTOR AGONIST, LIRAGLUTIDE IN TAIWANESE TYPE 2 DIABETIC PATIENTS I-WEN CHEN, YU-YAO HUANG, SZU-TAH CHEN, SHINYUAN HUNG, CHIA-HUNG LIN, BREND RAY-SEA HSU Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

14:50~15:30

PD-30

RELATION OF BODY MASS INDEX, C-REACTIVE PROTEIN AND MORTALITY IN INPATIENTS OF CARDIOVASCULAR WARD 1

YI-TING KUO, 2I-TE LEE, 2JUN-SING WANG, 2 CHIA-LIN LEE, 2SHIH-YI LIN, 2WAYNE HUEY-HERNG SHEU 1

Department of Internal Medicine, Taichung Veteran General Hospital, Wancian Branch, Chiayi, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veteran General Hospital, Taichung, Taiwan, R.O.C.

14:50~15:30

PD-31

MEASURABLE GLUCOSE IMPACT MITOCHONDRIAL QUALITIES VARIATION WITH CONFOCAL MICROSCOPY 1

HONG-WEI SHEN, 1YUNG-SHENG CHANG, 1 PEI-YU CHENG, 1SHIH-TE TU, 1,2SHIH-LI SU, 2 CHIN-SAN LIU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.; 2 Vascular Medical Research Laboratory, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.

Agenda 14:50~15:30

PD-32

THE ANALYSIS OF OUTCOME AND MORTALITY IN DIABETIC PATIENTS WITH NECROTIZING FASCITIS IN SOUTHEAST TAIWAN SHIH-MING CHUANG, KAT-YIEN NGU, YUEN-CHIU HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine,Mackay Memorial Hospital, Taitung

Moderator: Kun-Der Lin 14:50~15:30

PD-33

SUCCESSFUL MANAGEMENT OF TYPE 2 DIABETES MELLITUS WITH MORBID OBESITY AND INSULIN ANTIBODIES-A CASE REPORT 1.2

PIN-FAN CHEN, 1BING-RU GAO, 1.2WEI-CHENG LIAN, 1 SHIH-TANG YAN, 1TING-CHANG CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

14:50~15:30

PD-34

M&OUML; NCKEBERG’S ARTERIOSCLEROSIS IN A DIABETIC PATIENT WITHOUT HYPERLIPIDEMIA YI-HSIN LIN, CHIH-HSUNG HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Taiwan Adventist Hospital, Taiwan, R.O.C

14:50~15:30

PD-35

PAY-FOR-PERFORMANCE PROGRAM REDUCE THE INCIDENCE OF DKA AND HHS IN DIABETIC PATIENTS 1

HUI-MIN HSIEH, 2,3,5SHYI-JANG SHIN, 4 HERNG-CHIA CHIU 1

Department of Public Health; 2School of Medicine, College of Medicine; Center of Lipid and Glycomedicine Research; 4Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University; 5 Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Taiwan 3

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

14:50~15:30

PD-36

10~YEAR FOLLOW-UP OF GLYCEMIC CONTROL DURING HOLIDAY TIME IN PATIENTS WITH TYPE 2 DIABETES 1,3

TSENG-HUI KAO, 2,4TZU-EN WU, 1,2HARN-SHEN CHEN, 1 CHUN-JUI HUANG 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital ,Taiwan,R.O.C.; 2Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan,R.O.C.; 3Division of Endocrinology and Metabolism, Department of Medicine, Taipei City Hospital Yangming Branch,Taiwan,R.O.C.; 4Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan,R.O.C.

14:50~15:30

PD-37

THE IMPACT ON RENAL FUNCTION FOR PARTICIPATING DIABETES SHARED-CARE NETWORK IN TYPE 2 DIABETES PATIENTS 1

TZU-HSING HUNG, 2JIUN-YIAN LIN, 2PI-YUAN WONG, 2 I-CHUAN LIN, 2I-JU LIEN, 2CHUNG-HSUEH CHUNG, 2 TONG-YUAN TAI 1

Department of Family Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.

14:50~15:30

PD-38

ASSOCIATION BETWEEN FRAMINGHAM STROKE RISK SCORE AND SUBCLINICAL ATHEROSCLEROSIS IN ELDER TYPE 2 DIABETIC PATIENTS WITHOUT CARDIOVASCULAR DISEASE 1

YI-MEI WANG, 2WEN-JANE LEE, 3WAYNE H-H SHEU

March 21-22, 2015 【The Gallery Outside the 6th & 7th Conference Room】

2015 Award Winners

Abstract PL-Endo

Recent Advances in Pituitary Medicine Ken K. Y. Ho Centres for Health Research, Princess Alexandra Hospital and the University of Queensland, Brisbane, Queensland, Australia

The last decade(s) has seen major developments in molecular genetics, cell biology, systems biology, pharmacotherapy and information technology collectively bringing major advances to all areas of medicine. This is no more evident than in pituitary medicine. My presentation will focus on major contributions in the literature in the last 2 years. The material spans basic to clinical advances across pathogenesis, epidemiology and therapy of pituitary disease. The selection includes elucidating the causation of craniopharyngiomas, identification of prolactin receptor defect phenotype, understanding the basis of pituitary tumour senesence, therapeutic perspectives for acromegaly, Cushing’s Disease and adult hyposomatotrophism and uncovering a pathogenic link between prolactin and post-partum cardiac dysfunction.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PL-DM

Physiology and Pathophysiology of the Incretins: From Bench to Bedside and Vice Versa Nobuya Inagaki Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Japan

Gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones released from enteroendocrine K-cells and L-cells, respectively, in response to nutrient ingestion to potentiate glucoSE-stimulated insulin secretion. GIP and GLP-1 are thought to play an important role in early phase glucoSE-induced insulin secretion in normal subjects. However, GIP signaling is down-regulated inβ-cells of diabetic subjects with impaired early phase glucoSEinduced insulin secretion, which is especially common in Japan. Presently, incretin-based therapy that augments incretin action is widely used in treatment of type 2 diabetes in Japan, where its effects are pronounced. The prevalence of obesity is increasing in Asia as it is elsewhere. In Japan, increased fat intake is supposed to underlie increasing obesity. Under condition of normal glucose tolerance, fat intake is a strong stimulant of GIP secretion and a chronic high-fat diet induces obesity through GIP hypersecretion. On the other hand, reduction of GIP secretion or signaling in mice alleviates obesity and lessens the degree of insulin resistance under high-fat diet conditions. To clarify the mechanism by which fat ingestion stimulates GIP secretion, we established GIP-GFP knock-in (GIP-GFP) mice to visualize K-cells by EGFP. By microarray analysis of K-cells isolated from these mice, we have identified fatty acid binding protein (FABP)-5, which is expressed exclusively in K-cells in small intestine. In addition, we found that GPR120 is abundantly expressed in the K-cells of upper small intestine. We also found that these molecules are involved in fat-induced GIP secretion. We have identified regulatory factor X 6 (Rfx6), a transcriptional factor, which is expressed exclusively in K-cells in small intestine, and found that Rfx6 is involved in transcription of the GIP gene and that its expression is up-regulated by chronic HFD loading. Regulation of these molecules may therefore open the way to novel therapeutic approaches to prevention of high-fat induced obesity.

Abstract DT-1

Pathophysiology for Treatment with Insulin or GLP-1RA Jung-Fu Chen Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

台灣的糖尿病人口在近幾年，隨著飲食與運動習慣的改變而快速成長，已達一百四十萬以上，大部份是 2 型糖尿病，2 型糖尿病的血糖治療在藥物方面已增加其複雜性。胰島素從 β-cells 的胰島素，每日釋出約 50unit。一旦被 β-cells 分泌出來，又分解為單分子、以利於擴散進入血管。一般的作用是減少糖異生機制 (Gluconeogenesis) ，減低蛋白質分解 (Proteinolysis) 及降低脂肪分解 (Lipolysis)，而增加氨基酸 (Amino acid) 的攝取，蛋白質的合成，三酸甘油脂的儲存。胰島素分泌不足可發現在糖尿病人身上，β cells 組織體縮小約 20-40%，而 β cells 功能則失掉 50%。檢定胰島素敏感性 (insulin sensitivity) 及 β cells 功能，每年約穩定的減低 4%，相對的 A1c 會增高。削弱的胰島素分泌、常因胰島素對抗而惡化，轉而削弱葡萄糖攝取，進而造成葡萄糖使用低效率，終致細胞以脂肪及蛋白質取代葡萄糖來消耗。糖尿病患的胰島素對抗 (insulin resistance) 很複雜，在肌肉，來自胰島素刺激的糖原 (glycogen) 產量減少，及胰島素受體減低，特別是在肥胖人的肝臟、骨骼肌、脂肪組織。所以胰島素對抗也是引發肝臟增生葡萄糖產量的主因。 Glucagon-like peptide (GLP-1) 和 gastric inhibitory polypeptide (GIP ) 為 incretin 荷爾蒙，具有刺激胰島素分泌的作用。除了刺激胰島素分泌的作用外，這些 incretin 還有促進 β 細胞生長及分化的作用、減少 β 細胞凋零死亡、以及經中樞神經糸統降低食物攝取的作用。這些胜類的促胰島素分泌作用是受血中葡萄糖濃度所影響 ( 即葡萄糖依賴性 )，較不會有低血糖的副作用。第 2 型糖尿病病人的臨床特徵為其胰島素分泌減少以及胰島素作用不好。而第 2 型糖尿病病人 incretin 效果不正常。主要原因是第 2 型糖尿病病人的 GLP-1「分泌」和「作用」較差所致。incretin 荷爾蒙有降血糖的作用已被發現了約 50 年，但一直無法在臨床上應用。主要原因是葯物特性不穩定，很快就會被 dipeptidyl peptidase IV (DPP IV) 分解。最近發展的 GLP-1 葯物是希望藉由結構修飾後可抵禦 DPP IV 分解，而能在血清有較長的半衰期和作用，臨床上已應用於糖尿病之治療。

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DT-2

The Strategy for Psychological Insulin Resistance Ming-Chia Hsieh Changhua Christian Hospital Diabetes e-Institute

糖尿病是我們最熟知的慢性疾病，在二十一世紀罹患率增加最快速的疾病，目前全球約有一億五千萬病患，根據 IDF 世界糖尿病組織估計，到西元 2025 年，全世界糖尿病患將再增加一倍以上，罹病人口會超過三億人。美國糖尿病學會也指出，美國約有一千八百二十萬人有糖尿病，目前罹病人數仍持續增加中。根據我國中央健保局的資料，糖尿病總患者人數為一百萬零三百六十八人，其中男性有四十八萬四千六百九十五人，女性則有五十一萬五千六百七十三人，約佔全國人口數的 4.45%。糖尿病為國人十大死因的第四位，糖尿病死亡率是所有疾病增加幅度最大者，達百分之九，值得國人警惕。糖尿病增加趨勢以女性更為明顯，女性十大死因排名中，糖尿病從三年前的第五位，前年的第四名到去年的第三名，己是連續四年排名向前竄升。現代的文明社會，人民生活與飲食習慣很大的轉變，多吃高熱量且精緻的食物，運動的習慣減少，相對肥胖人口逐漸增加，糖尿病患者也愈來愈多。近年來國人糖尿病有年輕化趨勢，中小學生提前出現第二型糖尿病的病例愈來愈多，這就是飲食生活習慣所造成。由於罹患糖尿病後約二十年會出現視網膜、腎臟、神經和血管病變，而這些併發症不但造成患者健康危害也是成為死亡率增加的危險因子，從國家健康保險支出上，這些醫療照護上亦是極大的負擔。糖尿病治療照護團隊，對於糖尿病治療有重大的任務，糖尿病患者血糖控制，除了飲食與生活習慣的改善，藥物介入的治療更是重要，我們都知道當被診斷為糖尿病時，其胰臟功能僅剩下 50%，隨著病程的演進其胰島素分泌逐漸下降，因此除了口服藥物的治療外，因醫學科技的發展目前有需多有效的針劑藥物協助病人控制血糖，例如 : 胰島素與 GLP-1 腸泌素。針對病人狀況給予適合的針劑治療，能有效降低血糖，改善整體 HbA1C，達到減緩糖尿病持續惡化的成效並獲得健康的生活糖。但病人一聽到針劑治療就想到要打針，擔心打針非常不方便之外，病人擔心自我病情是否惡化，而在針劑治療上，其醫師需要有相當豐富的經驗與藥物的認知，例如 : 目前胰島素有非常多的類型與比例，若無法了解胰島素的作用，對於胰島素處方的信心即減少，加上使用胰島素除了解類型與比例，另外每日病人的劑量、飲食、生活型態、都須考量，掌握這複雜的因子是為了避免患者在胰島素治療中發生低血糖。往往低血糖發生後病人對於胰島素治療發生恐懼，也會造成醫師處方胰島素的信心，而拒絕接受胰島素。相對新的針劑 GLP-1 腸泌素，醫療人員也需要了解這類型的藥物與適合的病人，如何針對治療方式與副作用的衛教，讓病人接受這類型的治療，因此針劑治療不僅是處方而已，而是需要一個專業團隊的介入照護，如此針劑治療才能達到有效與安全地協助病人血糖控制。本次演講藉由治療的經驗與糖尿病的管理，分享如何藉由專業團隊，從病人的胰島素或 GLP-1 衛教著手改善其認知，在病人接受針劑治療後，藉由衛教師對注射方式、劑量調整、SMBG 進行教育。而飲食攝取與控制也是會影響針劑治療的成效，其營養師這時就必須介入給予病人正確的飲食觀念。胰島素與 GLP-1 這類型針劑治療看似複雜其實不困難，只要掌握幾項關鍵，落實個人化治療觀念，針劑治療是能有效協助病人長期穩定血糖達到與糖尿病共存的健康人生。

Abstract DT-3

The Future Model of DM Treatment about Team-Work and Insulin Treatment in Primary Medicine. Su Hsun Cheng An-Shin Clinic

糖尿病是一種複雜的慢性病，病程長且併發症多，需要跨專科領域組成的照護團隊才能協助病人控制好。Dr. Wagner 提出慢性病照護模式 (Chronic Care Model)，此模式是以醫病雙方為核心，醫療提供者要能建立一個有準備 (prepared)、前瞻的 (proactive) 照護團隊，並提供病患獲得充足資訊 (informed) 而能自主 (activated) 的管理，如此因無雙方障礙的互動而產生更具建設性的協合決策 (collaborative decision making) 及發展出以關係為基礎的治療同盟 (therapeutic alliance)，而使健康結果 (health outcome) 更好。所以醫療提供者必需能建立一個以實證基礎指引為臨床決策依據，提供給病人有計劃、以病人為中心的照護，並提供資源給病人做自我管理，並能監控團隊照護品質時時做照護上的修正。過去基層診所在加入糖尿病共同照護上常有以下問題和困境：就診規模低 ; 醫師習慣傳統急性病的看診模式，不易調整成團隊合作的慢性病模式；運作技術不足；行政作業成本高；資訊系統導入障礙；無法提升病患自我照護的能力。而基層診所在導入糖尿病共同照護模式都是經過人員認證、建立團隊照護系統以及品質監控機制的過程。目前基層診所多半透過診所的看診作業系統處理日常看診和健保申報作業 ; 透過紙本病歷記錄或以各縣市免費的糖尿病共同照護網作業系統提供糖尿病的 3R's 個案管理，並提供 DQIP 和 DQPR 等報表做照護品質監控。但是面對糖尿病照護的複雜性，基層診所加入糖尿病照護後即使已解決照護人力建立團隊，仍然有許多問題：如 1. 目前使用的看診或糖尿病照護作業系統無法提供資訊整合，有效率且有計畫的提醒團隊：病人何時該回診及處置項目、逾期沒回診的病人。 2. 照護團隊間的整合溝通問題：系統無法把醫師依 guideline 擬定的治療計畫與病人所有相關資料 ( 病歷記錄、檢驗、護理及營養衛教記錄 ) 整合在一起，而照護團隊常常是各做各的，無法有效溝通整合。 3. 醫師對病人常只能以橫斷面的資訊來做決策，資訊系統無法將病人過去至今所有的檢驗、血壓、BMI 等數據資料呈現縱斷面的呈現，提供照護團隊做為調整照護計劃的參考。 4. 對於打胰島素的病人，即使已說服病人做 Structured SMBG test，仍然只能靠門診會晤或電話追蹤詢問並做劑量或飲食調整的指導，無法做到 Realtime 及異常管理。

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

5. 團隊和病人間溝通及資訊分享：支持病人自我管理的資源不足，無法提供病人的血糖、血壓、體重、甚至飲食等長期的記錄，讓這些記錄除了提供照護團隊外，也能讓病人家屬知道，協助病人一起努力。 6. 糖尿病病人要學習很多知識和技術 ( 飲食、SMBG、insulin 施打技術……)，即使有面對面個人或團體的衛教，當病人有問題時，除了門診或電話外，可能有學過卻無法應用 ( 學 7 成，只能應用 3 成 )，若能透過 IT 科技即時反映病人問題並由團隊做介入 , 並提供病人即時及所需的衛教資訊，協助解決其問題，做到即時掌握問題、縮短介入時間、降低病人學習障礙。如果能解決這些問題，就能提供病人充足資訊 (informed) 而能提升其自主 (activated) 管理能力；也能提升醫療團隊提供有準備 (prepared)、前瞻的 (proactive) 照護。本診所努力引進資訊科技，希望能做到 5Rs of Organized Care：Recognize、Register、 Resource、Relay、Recall。目前有： 1. 嘗試將所有病歷、檢驗、衛教記錄電子化並做整合。 2. 建立「遠距健康管理平台」提供病人在診所外的血糖、血壓、飲食、運動等記錄，可以透過電話線、網路、智慧型手機或平板的 APP 上傳至診所雲端，並對異常數據由診所衛教師進行即時的介入與指導。此平台有前台和後台，前台的資料提供病人和家屬使用，後台是提供團隊間分享照護資訊並能提供衛教資訊增進病人自我管理。

Abstract SE-1-1

Endocrinology and Metabolism Subspecialty Training in Taiwan Tien-Shang Huang Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital

Endocrinology and Metabolism board began to be certified as a subspecialty of Internal Medicine since 1988 in Taiwan. After Board certified in Internal medicine, it requires two years training in Endocrinology and Metabolism division of an accredited teaching hospital to be qualified for certification in this subspecialty. The certification process includes a paper test and an oral examination. There is no definite curriculum, but it usually includes the following trainings. 1. Administrative training: Manage the Endocrinology and Metabolism ward, such as admission and dischange of patients; corresponding to NHIB (National Health Insurance Bureau), Endocrine Society、Diabetic Association and TJCHA (Taiwan Joint cornmission on Hospital Accreditation), etc; arrange Clerk、Intern、PGY training course; arrange ward round; attend the department meeting. 2. Teaching training: In charge of Morning meeting, Clerk、Intern、PGY and Resident teaching include correct medical record, feedback, bedside teaching; Endocrine conference; Metabolism conference; medical Grand Round; minisymposium, etc. 3. Clinical skill training: Diabetic complication screening, ultrasound examination of thyroid and neck, Fine needle aspiration of thyroid, lymph node and tumor, Cytology examination of aspirate and stump smear. 4. Clinical training: Familiar with Endocrine and Metabolism diseases’ diagnosis, differential diagnosis, endocrine tests, various guidelines and aware the individualized therapy, Consultation training, In ward and out patient clinic training. Complete the required protofolio. 5. Research training: Every fellow has to participate one attending’s research project and presents (oral or poster) in National or international meeting. Every fellow has to publish at least one paper before the end of training.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SE-1-2

The Current Status of Endocrinology in India Sarita Bajaj President, South Asian Federation of Endocrine Societies Department of Medicine, MLN Medical College, Allahabad, India

India has a long tradition of formal medical education, dating back to the times of Ayurveda. Formal post graduate endocrinology training in the country, too, is nearing a half century of existence, but has gained importance only in the last 3 decades. Bioassays were required for diagnostics which was the major block for development in this branch. The first post graduate fellowship programme, labeled DM (Doctor of Medicine), was begun in 1968 at Chandigarh (a Union Territory). In 1971 the Endocrine Society of India (ESI) was set up in Mangalore. To date, there are about 1000 life members. As of today (January 2015), a total of 23 institutes offer a DM programme, spread over the length and breadth of the country. Fifty five seats are available for DM courses in 22 departments each year, excluding the autonomous All India Institute of Medical Sciences, New Delhi, which has an intake of 12 students spread over three years Indian medical education is rigorous and competitive. A 5.5 year undergraduate course (4.5 years of study, followed by 1 year of clinical internship) leads to the award of an MBBS (Bachelor of Medicine, Bachelor of Surgery) degree. Interested students compete for admission to a three year long MD (Doctor of Medicine) programme in Internal Medicine or Paediatrics. After completing this post graduate course, students again appear for national entrance examinations to the three year DM or DNB (Diplomate National Board) course. Thus, it takes a minimum of 11.5 years, assuming no breaks in study, to become an endocrinologist in India. Endocrinology training in India includes comprehensive education in clinical skills, laboratory endocrinology (including biochemistry, radioimmunoassay and nuclear medicine) and research. There is no central curriculum for the country. Indian endocrinology students are able to compete with the rest of the world at various platforms. Indian trainees are now a common sight at international meetings, presenting their data, asking questions sharing their knowledge, and improving their skills. These interactions help enhancement of endocrinology in the country.

Abstract SE-1-3

Introduction: The Endocrinology and Metabolism training program offers 2-3 years clinically and research program for individuals who are interested in career development inclinicalor research of endocrinology and metabolism.The program provides didactic and self-directed teaching for clinical and research skills Applicants must have an Internal Medicine Specialist degree from an accredited domestic or foreign institution, and have a strong commitment to well manage of patients or research in the field of Endocrinology, Diabetes, and Metabolism Endocrinologist training: We offer the incoming endocrinology subspecialty resident a comprehensive program leading to eligibility for the Indonesian College of Internal Medicine certification in Endocrinology and Metabolism The Program is to provide comprehensive training in the management and research of the broad spectrum of endocrine diseases and diabetes. After completion of our 2-year program, the trainee will be well prepared to pursue a career in Clinical Endocrinology or undertake further research training. Hospitals: There are eleven University in Indonesia provides Endocrinology and Metabolism training. The academic hospital of the University is the main hospital for Endocrinology and Metabolism training program. This hospital provides tertiary level care in the field of endocrinology and metabolism. Other training sites include the hospital as networking of university academic hospital that provides secondary care of endocrinology and metabolism. Core Competencies: In the University of Brawijaya Indonesia, the core competencies of the trainee will cover all area of: 1. Medical knowledge (basic, clinical and contextual knowledge). 2. Intellectual and Interpersonal skills (procedures and communication) 3. Professionalism 4. Evidence based practice 5. Systems based practice Clinical training: The clinical training program covers all areas of endocrinology with the major focus on diabetes, thyroid diseases, dyslipidemia, and obesity. In the first year, the fellows spend mostly of their time on inpatient care and consultations, less part of time on outpatient and ambulatory care and procedures skill. In the second year, the time is allocated for research and continues the clinical inpatient and outpatient care work. 97

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Research training and publication: The trainee must do research and should present or publish his/her work on research at national or international level, at least once during period of training. The research focus may in the field of clinical or basic endocrinology. They also should publish of two or more case report during traineeship program, and all are encouraged to present at national or regional meeting. Courses, Seminars and Teaching activity: The trainee has to participate in endocrine meeting each year at a local, regional or international level and must have at least one-month (1-3 months) endocrine rounds at endocrinology center abroad.The trainee must be participate actively in departmental or divisional teaching activities to teach junior staff, medical students and other medical personnel. Supervision of Training: Heads of Departments or Consultants who are accredited Endocrinologists should supervise training. Exit Evaluation in Endocrinology: The evaluation will be carried out in several ways for each level. The supervisor’s repot and logbook are in order. They must demonstrate competency in endocrinology and metabolism cases management including in endocrine emergency handling through case report and structured exit evaluation. National Board Examination by Indonesian College of Internal Medicine in Endocrinology and Metabolism, carry out at the end of program. Certification: Certification of completing the program, will be given by university and cetificate of competencies given by Indonesian College of Internal Medicine in Endocrinology and Metabolism Keyword: endocrinology training, Indonesia

Abstract SE-1-4

The Current Status of Endocrinology in Korea Young Kee Shong Chairman of the Board, Korean Endocrine Society (KES) Division of Endocrinology, Asan Medical Center, Korea

Korean Endocrine Society is youngest medical speciality group in Korea. It was founded at 1982 as with approximately 150 members. Since then it had annual meeting regularly. Thyroid Research Group was incorporated to KES at 1986, although later in 2008, Korean Thyroid Association became an independent organization again with endocrinologists, surgeons, nuclear medicine physicians and radiologists. So far KES hosted the 4th AOTA meeting at 1989 and the 11th AOCE meeting at 1998. Since 2013, KESD is organizing Seoul International Congress of Endocrinology and Metabolism (SICEM) annually and in this year this congress will be held at early May. KES publishes society journal named “Endocrinology and Metabolism: EnM” in English. It is published quarterly and welcomes submission from any country over any related topic. It is indexed in PubMed, PubMed Central and so on. KES is very willing to collaborate with sister societies in our region. KES welcomes participation to SICEM, submission of manuscript to EnM and would be happy to support research stay in Korea. Korea has two different educational system for medical doctors. The first one is 2+4 system. High school graduate enters pre-medical course of 2 years then goes to college of medicine. After 4-yearstudy, they graduate and get medical license if they pass National License Examination. Another is 4+4 system. College graduate with various bachelor degree may enter medical school. After 4-year study, they graduate and get medical license if they pass National License Examination. Those who has medical license and completed one-year rotating internship may apply for residency for speciality. Resident training lasts usually 4 years. After residency, they apply examination for speciality board certification. Those who are board certified in Internal Medicine may apply fellowship for subspeciality training. It usually last two years fellowship with various clinical and research activities. After completion of fellowship, they are eligible for the examination.

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Current Status of Endocrinologist in Myanmar Than Than Aye President, Myanmar Society of Endocrinology and Metabolism (MSEM) Department of Medicine and Department of Endocrinology, North Okkalapa General Hospital University of Medicine 2, Yangon, Myanmar

Myanmar has been challenged by the burden of endocrine diseases, mainly Type 2 Diabetes Mellitus which is one of the commonest non-communicable diseases (NCD) in Myanmar .There are other endocrine disorders such as Thyroid diseases and various endocrine disorders which are common but being underdiagnosed and not being effectively managed .The endocrinologists training has been inadequate in Myanmar for so many reasons. It was due to weaknesses in the health system and government bureaucracy previously. There was an inadequate production of specialists and the priority has been given to production of general physicians, according to the needs of the country. Only a few selected doctors had a chance to get training abroad for specialties through scholarship program. Although they had been trained for endocrinology, mainly from U.K., they were appointed as general physician with special interest in endocrinology. There are about 30 Specialists with special interest in endocrinology. After 2010 General Election, Myanmar has undergone major political change with the opening of Myanmar’s doors. Many specialists are now having more chances of attending international conferences and short courses to update their knowledge and practice. With the initiative of leading Endocrinologists the Department of Endocrinology and Metabolism was founded in University of Medicine 2 , Yangon in 2012. Post graduate course on Endocrinology (Dr.Med Sc) has been started in 2014.The selection criteria are those who have obtained the M Med Sc (Internal Medicine) and also got through the selection exam (both theory and viva). The training program and curriculum will be presented.

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Abstract SE-1-6

The Current Status of Endocrinology in The Philippines Bien J. Matawaran Vice- President, Philippine Society of Endocrinology, Diabetes and Metabolism Department of Medicine, Jose R. Reyes Memorial Medical Center, Rizal Ave, Manila, The Philippines

The Philippines is an archipelago of 7,107 islands inhabited by just over a hundred million people scattered unevenly in both urban and rural areas. Together with the economic difficulties of most developing countries like the Philippines compounded by the geographic challenges of our islands, the demands for skilled and trained endocrinologists is truly a staggering task to overcome. Based on the latest National Nutrition and Health Survey (NNHeS) done 2013, the prevalence of hypertension is 22 percent and diabetes mellitus at around 5.4 percent. These two most common non-communicable diseases are the bread and butter of endocrinologists in the country. Though the Philippines has established the Philippine Society of Endocrinology and Metabolism since 1962 and is now in the first few years of our sixth decade, the number of board certified endocrinologists is still disproportionate to the number of patients and locations in the Philippines. Currently we have 225 board-certified endocrinologists designated as full fellows (192) and diplomates (33). In addition, we also have associates members (36) that are board-eligible and 39 fellows-in-training. For several years, endocrinologists usually come from 5 training institutions in Manila--- University of the PhilippinesPhilippine General Hospital (UP_PGH), Makati Medical Center (MMC), University of Santo Tomas Hospital (USTH) and St. Luke’s Medical Center (SLMC). But because of the great demand for most internal medicine residency, we now have three additional institutions for training, The Medical City (TMC) and Chinese General Hospital (CGH), both from Manila and Chong Hua Hospital (CHH) in Cebu City. Fellowsin training are allowed to enter training after completion of a 3 year residency program in internal medicine and after passing the specialty board of the Philippine Specialty Board of Internal Medicine (PSBIM). Endocrinology fellowship is a 2- year in-hospital program in an accredited fellowship-training program and board eligibility is after completion of this trainings plus proof of a published research in a reputable peer-reviewed journal. Though less frequent, there are endocrinologists who completed training abroad and after evaluation of the minimum requirement set by the Philippine Specialty Board of Endocrinology and Metabolism (PSBEM) based on the core curriculum of training, foreign graduates are likewise allowed to take the specialty boards given every 2 years only. Even though we are trying to increase the number of well-trained endocrinologists, there are certain challenges and threats within the Philippine medical setting where other groups are calling themselves as sub-specialists or diabetologists, who unfortunately have no valid training in endocrinology and even internal medicine. We do acknowledge the need for better knowledge and management of diabetes especially by primary care physicians and generalists, however proper representation and accreditation should be a priority so as not to confuse other medical practitioners and more so our patients. In this light, as we move forward as a society and to reiterate our training and expertise in diabetes we now call ourselves as the Philippine Society of Endocrinology, Diabetes and Metabolism. More than just a name change, this is our commitment to ensure that each member of our society are truly well-trained, accredited and skilled in the practice of endocrinology and this assurance will translate to better patient care and outcome.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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The Current Status of Endocrinology in Thailand Thavatchai Peerapatdit President, The Endocrine Society of Thailand Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand

As of December 31st, 2014, there are only 218 endocrinologists among the 48,116 practicing physicians in Thailand, who can give medical care to the population of about 67.2 million. Of all the practicing physicians, 22,797 stay in Bangkok. Fellowship training in endocrinology and metabolism in Thailand is a 2-year program to get the Diploma of the Thai Subspecialty Board of Endocrinology and Metabolism, administered by the Endocrine society of Thailand(EST), under the Royal College of Physician of Thailand (RCPT) and Medical Council of Thailand. To be enrolled, graduated doctors must have a certificate of 3-year training from Board of Internal Medicine. Now there are 8 training centers with 49 trainers for endocrinology fellowship training, which can produce about 16-17 endocrinologists per year. Every year, there are also about 2-3 endocrinologists, who finished training from the USA Endocrine Society, entering the process to be qualified as endocrinologists in Thailand. Most of the endocrinologists work in medical schools and public hospitals. EST holds an annual meeting around November. Members can attend all the activities, both academic and non-academic, free of charge. During the year, we have inter-hospital endocrine conference every two months, hosted by the training centers in Bangkok. Thai endocrinologists can keep their knowledge up-to-date by attending the activities from EST, RCPT, Diabetes Association of Thailand, and other activities in USA, European countries, and regional meetings.

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Abstract SD-1-1

Over the past years, my co-authors and I published, using Taiwan’s National Health Insurance (NHI) data, a number of epidemiological studies that described the co-morbidity in patients with diabetes. These co-morbidities covered a wide range of diseases including macro- / microvascular events, neoplasm, urological / nephrological disease, neurological disorders, and psychological illnesses. Strengths of application of NHI data in epidemiological studies include population-based study design, large study sample, and lesser likelihood of selection bias. However, the accuracy of disease diagnosis and lack of certain data such as laboratory and lifestyle variables always limit the causal inference of the study findings. In this lecture, I will present first our previous studies that provided local data on the co-morbidity of patients with diabetes. Two bi-directional studies that explored the association of type 2 diabetes with depression and acute pancreatitis, respectively will then be presented in order to illustrate the usefulness of using Taiwan’s NHI data in such design. Some perspectives of claim data based studies on diabetes will also be discussed.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD-1-2

From Large Healthcare Database Studies to Clinical Practice Path for Improving Care of Diabetic Patients and Individualizing Therapeutic Decision Making 1,2

Chia-Hsuin Chang, 1Mei-Shu Lai, 1,2Lee-Ming Chuang

Institute of Preventive Medicine, College of Public Health, National Taiwan University; 2Department of Internal Medicine, National Taiwan University Hospital

Large healthcare databases compile tremendous amount of various patients' diagnostic and treatment records, far greater than the limited experiences of any physician or hospital. How to make the best use of these data to facilitate individual patient's therapeutic decision making and to improve outcome of care will become an important issue. We analyzed Taiwan National Health Insurance claims database to evaluate patterns and determinants of first-line and second-line anti-diabetic therapy, regional differences, prescription quality, and cost. Cardiovascular outcomes associated with use of metformin as compared with acarbose as the first-line therapy, and among several dual oral anti-diabetic regimens in combination with metformin as the second-line therapy were examined. In addition, we used data mining technique and Bayesian hierarchical rule modeling to evaluate 3 months incidence of severe cardiovascular events, including myocardial infarction, heart failure, and stroke, among individual type 2 diabetic patients with different risk profiles while receiving different oral anti-diabetic agents, including metformin, sulfonylurea, glinide, alpha-glucosidase inhibitor, pioglitazone, and DPP4-inhibitor. We propose that a diabetes registry which includes patients’ important lifestyle factors, clinical information, and medical records is in urgent need in Taiwan in order to monitor treatment cost, improve quality of care, and facilitate individual therapeutic decision making.

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Abstract SE-2-1

Osteoporosis in Renal Failure: To Treat or not to Treat? Manju Chandran Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, DUKENUS Graduate Medical School Chapter of Endocrinology, College of Medicine, Singapore Immediate Past President, Endocrine and Metabolic Society of Singapore (EMSS)

Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Practically speaking, osteoporosis is diagnosed by one of two ways: a low trauma fracture which is unexplained by any other cause of bone fragility or when there is a reduction in bone quantity as measured by BMD by dual energy X-ray absorptiometry (DXA). The diagnosis of osteoporosis in Chronic Kidney Disease (CKD) however is fraught with uncertainties. Patients with CKD could have alternations in bone quality due to increased or decreased bone turnover, impaired mineralization, or a combination of these and/or decreases in BMD. This means that techniques, such as BMD testing, to evaluate fracture risk due to osteoporosis may not be as useful in patients with CKD as they are in the general population. Patients with CKD-MBD may have one of 4 metabolic bone diseaSE- High turnover bone disease (Osteitis Fibrosa Cystica), Low turnover bone disease (Adynamic bone disease), Mixed Osteodystophy, and Osteomalacia. The differentiation between these bone diseases is not simple and straightforward and can conclusively be done only by bone biopsy and histomorphometry. In addition to and independent of alterations in bone quality and quantity, CKD patients are more likely to fracture, because they are at an increased risk for falls from muscle weakness and impaired balance secondary to poor nutrition, inactivity, myopathy, and peripheral neuropathy. The treatment of osteoporosis in CKD is also beset with difficulties. Most anti osteoporosis agents are currently contraindicated in patients with creatinine clearance less than 30 ml/ min/m2. In addition to the potential for worsening of renal function, the very real worry of worsening possible adynamic bone disease and thereby causing fractures with the use of potent anti resorptives exist. This presentation will aim to address the issues surrounding the diagnosis of osteoporosis in CKD as well as will the difficulties surrounding its treatment and will explore some of the currently available treatment options of this difficult disease.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Vitamin D: Molecular Actions Across a Variety of Biological Systems Howard A Morris Department of Chemical Pathology, SA Pathology and School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia 5000 Australia

Reports describing health risks due to inadequate vitamin D status continue to generate considerable interest. Recent research on the various molecular activities of the vitamin D system provides evidence of its capability to exert biological effects across a wide range of tissues similar to other nuclear receptor hormones. These activities include endocrine and paracrine or autocrine actions, vitamin D metabolism in a wide range of tissues and modulation of gene expression by interaction of the nuclear vitamin D receptor with other gene transcription factors. The endocrine action of 1,25-dihydroxyvitamin D plays critical roles in the maintenance of plasma calcium and phosphate through actions at the intestine to increase calcium absorption, renal tubular reabsorption and bone resorption. 25-hydroxyvitamin D metabolism to 1,25-dihydroxyvitamin D occurs in the kidney to maintain plasma levels as well as in a wide range of tissues where it does not contribute to plasma levels but exerts only local activities. The three major bone cell types, osteoblasts, osteocytes and osteoclasts, can all metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Vitamin D activities in the skeleton include endocrine actions to stimulate bone resorption and inhibit bone formation. Current research indicates that local synthesis of 1,25-dihydroxyvitamin D within osteoblasts together with adequate dietary calcium stimulates bone formation. Thus dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient. The nuclear vitamin D receptor exerts its classical action when 1,25-dihydroxyvitamin D binds by dimerising with the retinoid X receptor to bind to DNA sequences known as vitamin D response elements. Such binding results in recruitment of a large number of proteins making up the transcriptional complex to modulate messenger RNA transcription of vitamin D responsive genes. The 1,25-dihydroxyvitamin D-nuclear vitamin D complex can also initiate the cytoplasmic MAP kinase signalling pathway to enhance gene transcription. The nuclear vitamin D receptor can bind to other transcription factors such as β-catenin or Fox0 to regulate β-catenin or Fox0 responsive genes respectively. These transcriptional regulators are important in cell proliferation and this is a particular mechanism by which vitamin D can inhibit cell proliferation. This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. It also informs the design of such trials. Vitamin D interacts with dietary calcium intake to modulate bone mineral homeostasis. With a low dietary calcium intake For example many systematic reviews and metaanalyses. 106

Abstract SE-2-3

Recent Advances in Osteoporosis Research in Taiwan Jung-Fu Chen Division of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital

A growing elderly population is expected globally (Silver Aging Tsunami) and osteoporotic fractures now become a major epidemic , and the heavy burden of hip fractures on health care system will continue to exacerbate. Taiwan just caught the 9th worldwide role but 1st in Asia with annual incidence of hip fractures in women and men according to the hip fracture map of IOF (2012). According to the Nutrition and Health Survey in Taiwan (NAHSIT 2004-2008), the BMD study showed that the prevalence of femoral neck osteoporosis in individuals aged over 50 was 10.7% for men, and 12.1% for women. The prevalence increased to 22.57% and 41.17% respectively. Using Taiwan’s National Health Insurance claim data,we have showed the rising annual incidence of hip fractures did stabilize and decline progressively since 2005; but owing to the size of aging population, the number of hip fractures is expected to inflate yearly from 18,338 in 2010 to 50,421 in 2035—a 2.7fold increase. Furthermore there are many studies revealing the association with co-morbidity, such as diabetics did have HR 1.66 for fracture, also with higher post fracture deep wound infection, septicemia, and mortality, and the overall HRs for major osteoporotic fracture were 1.24 in men and 1.18 in women with CVD , especially cerebrovascular disease (HR 1.31) and heart failure (HR1.18). We do have seen greater hip fracture risk in Individuals with dementia (HR1.92), sleep disorders (HR 2.74), Parkinson’s disease (HR 2.71), schizophrenia (HR 1.57), dementia (HR 1.92), inflammatory bowel disease (HR 1.31), repeatedly addressing the importance of patient-centered comprehensive care. Unexceptionally adherence to osteoporotic regimens was still sub-optimal ,the majority of patients’ decreased adherence just within the first year,and although varieties of anti-fracture medicines are reimbursed by govemental insurance, efficacy and some SAE are proved and needed scheduled monitoring. However Taiwan NHI data showed the gap that only 27 % of hip fracture patients received BMD tests and only 34 % received drug treatment. The awareness of osteoporosis management among Taiwan patients and physicians still needs to be improved.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Journey to Individualized Insulin Therapy: From Clinical Trial to Real World Experience Stephen L. Atkin Medical Department, Weill Cornell Medical College in Qatar (WCMC-Q)

Diabetes is a chronic disease requiring ongoing medical care and well patient self-management. In addition to lifestyle modification, oral hypoglycemic agents, and glucagon-like peptide-1 receptor agonist -based therapy, exogenous insulin injection is essential in type 1 diabetes and becomes vital in patients with long-term type 2 diabetes who could not achieve optimal glycemic control. One of the risks that concerns insulin treatment most is hypoglycemia. Therefore, optimal insulin regimen should reduce the risk of hypoglycemia while improving glycemic control. As the disease progress, basal insulin initiation provides a remarkable benchmark, and rapid-acting prandial insulin doses can easily be added when optimization is needed. From certain perspectives of simplicity and convenience, premix insulin regimens could be another effective option for insulin intensification therapy. In addition to achieve glycemic control as one of the diabetes management goal, weight management and hypoglycemia risk should also be considered. Personalized diabetes treatment goal is recommended to both physicians and patients.

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21st Century Breakthrough of Diabetology ~Beyond Glycemic Control~ Takashi Nomiyama Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, Japan

Because the aim of glycemic control is not only lowering blood glucose level and HbA1c but also to improve quality of life and life span of patients through preventing complications, we need to choose anti-diabetic agents which could provide tissue-protective effect beyond glycemic control. To improve glycemic control including HbA1c and glucose level is minimal requirement for us in the present era. We should treat patients with diabetes for their future. Accordingly, glycemic control is a kind of life planning of patients. Incretin therapy has emerged as one of the most popular treatments for patients with type 2 diabetes, because of not only its’ efficacy and safety in glycemic control but also tissue-protective effect independent on glucose lowering effect. We have previously reported that Exendin-4, a GLP-1 receptor agonist, could improve atheroma formation (Diabetes 2010) and neointima formation (BBRC 2011). Further, we have recently reported anti-cancer effect of Exendin-4 (Diabetes 2014). In addition, DPP4 inhibitor linagliptin acts as vascular-protective agent through inhibition of DPP-4, anti-oxidative stress effect and direct effect on vascular smooth muscle cells (Cardiovasc Diabetol 2014). These data suggest that incretin therapy might be able to improve future of patients with type 2 diabetes beyond glycemic control. On the other hand, SGLT2 inhibitor is also new anti-diabetic agents. A lot of benefits are estimated, such as body eight reduction. However, we need to be careful to use this, especially in Asian patients with type 2 diabetes whose main phenotype is insulin deficiency. Almost 100 years have passed after the discovery of insulin. Anti-diabetic agents should evolve from just a glucose lowering agent into the partner of patients with diabetes to improve their future.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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The Genetic Study in Primary Aldosteronism Takashi Yoneda Division of Endocrinology and Metabolism, Kanazawa University Hospital, Japan

KCNJ5 gene mutations are reported to be frequently identified in aldosterone producing adenomas (APA). We performed genetic study in 27 APAs (9 micro- and 15 macro- APAs) and identified somatic KCNJ5 mutations in 20 of 27 APAs (83.3%). The prevalence of KCNJ5 mutation in micro- and macro-APAs was 78% (7/9) and 87% (13/15), respectively and there was no significant difference in the prevalence (P=0.09). We examined clinical characteristics difference between patients with micro- and macro-APAs. Serum potassium level in the patients with macro APAs (3.2±0.8mEq/L, n=13) was lower than that of micro-APA (4.0±0.6 mEq/L, n=7) (p<0.05). There were no significant differences in age (54±13 vs 49±14 years old.), blood pressure (156±16/91±14 vs 156±36/96±20 mmHg), plasma aldosterone concentration (164±73 vs 259±141 pg/mL) and plasma renin activity (0.3±0.2 vs 0.3±0.2 ng/mL/h) between micro- and macro-APAs with KCNJ5 gene mutations. Tumor size did not seem to be related to clinical characteristics other than serum potassium level. We also identified some interesting cases with APA harboring somatic KCNJ5 mutations such as two cases with recurrence of primary aldosteronism in remaining adrenal gland long after adrenalectomy, a case of multiple aldosterone producing microadenomas with different mutations of KCNJ5 gene, and two cases with unilateral APA demonstrating diagnostic discrepancy in AVS between with and without ACTH stimulation.

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Pathophysiology of Primary Aldosteronism Kwan-Dun Wu Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; TAPAI Study Group

Using aldosterone-renin ratio as screening test has increased the incidence of primary aldosteronism (PA) since the last three decades. Genetic mutations were identified in several subtypes of PA, e.g., hybrid gene in glucoticoid remendiable hyperaldosteronism, KCNJ5 somatic mutations in APA etc. Also linkage study suggested several candiadate genes. However, the pathogenesis of PA or its tumorgenesis is still unclear. We have demonstrated that dopamingergic regulation plays an important role in aldostereone production and cell proliferation of adrenocortical cells. Recently, we also revealed a dysregulation of microRNAs in PA patients. The finding may provide a therapeutic potential. Several mechanisms, in addition to high blood pressure, are proposed to explain the high incidence of cardiovascular diseases in patients with primary aldosteronism (PA). In vitro and in vivo studies demonstrate that aldosterone can induce insulin resistance, and PA is associated with metabolic syndrome. Aldosterone may increase intercellular adhesion molecule-1 expression of endothelial cell and promotes leukocyte adhesion through activating minorocorticoid receptor. Aldosterone has rapid non-genomic effects in the human vasculature. We have demonstrated that PA patients had lower numbers of circulating EPCs and endothelial colony forming unit than EH. Adrenalectomy or treatment with spironolactone can increase the number of EPCs in PA patients. This indicates impairment of the repair of endothelial damage may be a crucial factor of the development of CVD in PA.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Diagnosis and Management Strategies for Primary Aldosteronism Richard Auchus Department of Internal Medicine,University of Michigan Medical School, USA

Primary aldosteronism (PA) is the most common secondary cause of hypertension, accounting for 5-8% of all hypertensive adults. It is estimated that <1% of all patients with PA are ever screened for the disease. Obstacles to screening for PA include poor awareness of the disease, misunderstanding of diagnostic pitfalls, fear of embarking on the workup, and limited access to expertise in adrenal vein sampling (AVS). AVS remains the gold standard for distinguishing unilateral disease, largely caused by aldosterone-producing adenomas (APA) from bilateral disease, which is almost always due to idiopathic hyperaldosteronism (IHA). I will review the important principles and practical approaches to screening, confirming and subtyping PA. I will also review important advances for improving the success of AVS. Finally, recent advances in genetics of PA have provided insight to the pathogenesis of APA, and these advances might guide additional therapeutic strategies.

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The most problematic issue in clinical nephrology is relentless and progressive increase in the patients with end-stage renal disease (ESRD) in worldwide. Among various kidney diseases, the impact of diabetic nephropathy on the increasing population with chronic kidney disease (CKD) and ESRD is enormous. Diabetic nephropathy is characterized by accumulation of extracellular matrix in glomeruli, called exudative, diffuse and nodular lesions. They are finally followed by glomerulosclerosis and interstitial fibrosis, and in such situation, the patients inevitably undergo dialysis therapies and renal transplantation to survive. We have been emphasizing the importance of chronic inflammation and oxidative stress in the progression of diabetic nephropathy and the identification of key molecules would facilitate to the development of new therapeutic strategies. We focused and emphasized on the anti-inflammatory and anti-oxidative effects of glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidaSE-4 (DPP4) inhibitors, which ameliorated the progression of diabetic nephropathy in rodent models. We also recently investigated the beneficial role of sodium glucose cotransporter-2 (SGLT2) inhibitors on the progression of diabetic nephropathy using various animal models and reported SGLT2 inhibitors primarily ameliorates oxidative stress and inflammation in proximal tubular cells. New therapies such as incretin-related drugs and SGLT2 inhibitors would have the additional benefit in the protection of diabetic nephropathy beyond blood glucose control.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Do We Need a New ARB, Azilsartan M for Better BP Control and beyond glucose control in Diabetes? Robert J. Chilton Department of Medicine, Division of Cardiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Hypertension affects an estimated 25 - 30% of the adult population of the world. Despite the availability of antihypertensive treatments, hypertension remains inadequately controlled, with slightly less than half of patients who receive treatment successfully achieving blood pressure (BP) goals. While there are many drug classes available to reduce BP, drugs that modulate the renin-angiotensin-aldosterone system (RAAS) are more commonly used because of their efficacy, coupled with one of the lowest side effect profiles. Moreover, within the RAAS classes, those that inhibit the action of angiotensin II by binding directly to the angiotensin type 1 (AT1) receptor (ie, angiotensin receptor blockers [ARBs]) are the best tolerated of all antihypertensive drug classes. Some ARBs have shown efficacy in reducing mortality in patients with heart failure and post–myocardial infarction as well as slowing progression of diabetic nephropathy. Azilsartan medoxomil (AZL-M) is an ARB in development for the treatment of hypertension. It is a prodrug that is rapidly hydrolyzed to its active moiety, azilsartan. The current study assesses the antihypertensive efficacy and safety of the angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ³130 mmHg and £170 mmHg were studied; 142 received placebo and the remainder received 20mg, 40mg, or 80mg AZL-M or 40mg OLM-M. Mean age of participants was 58±11 years, baseline mean 24-hour SBP was 146 mmHg. DoSE-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mmHg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40mg was non inferior to OLM-M 40mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M. Data from this study suggest that AZL-M (Edarbi) 80 mg is more effective in reducing SBP than the highest approved dose of OLM-M, which is considered to be more effective than others in the ARB class. Moreover, the data from the current study have been validated internally by consistency of clinic and ABPM measurements. Outcome studies are needed to assess whether these differences in BP efficacy will be borne out in reduction of cardiovascular events. 114

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A Few Things About Pituitary Adenoma Pathology Donald Ming-Tak Ho Department of Pathology and Lab. Medicine, Taipei Veterans General Hospital Department of Pathology, National Yang Ming U. School of Medicine

Pituitary adenomas are benign neoplasm of adenohypophysial cells and consist of 10% of surgically removed intracranial neoplasms. The classification of pituitary adenomas has been evolved through histologic classification, ultrastructral classification, and immunohistochemical classification. In our institute, we adopt immunohistochemical classification using immunohistochemical staining of all pituitary hormones, i.e., PRL, GH, ACTH, FSH, LH, and TSH to classify pituitary adenomas since 1985. It was found that gonodotroph adenoma and plurihormonal adenoma are the most commonly encountered tumors, the former consists of around 1/3 of cases and the latter consists of slightly more than 1/4 of the pituitary adenomas in our surgical pathology file. In this presentation, the key features of these two tumors are presented based on the observations of our materials. As though the majority of pituitary adenomas are slow growing tumors, some are more aggressive and have a faster growth rate. By using MIB-LI, the most useful proliferative marker to date, the growth velocity of pituitary adenomas could be estimated. The presentation is based on our published materials and detailed information could be obtained from the references listed below. References: 1. Ho DM, Hsu CY, Ting LT, Chiang H. The clinicopathological characteristics of gonadotroph cell adenoma: A study of 118 cases. Hum Pathol 1997; 28: 905-11. 2. Ho DM, Hsu CY, Ting LT, Chiang H. Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification. Histopathology 2001; 39:310-9. 3. Hsu CY, Guo WY, Chien CP, Ho DM*. MIB-1 labeling index correlated with magnetic resonance imaging detected tumor volume doubling time in pituitary adenoma. Eur J Endocrinol 2010; 162:1027-33. (*corresponding author)

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Recent Advances in Pituitary Disease: Hypophysitis Justin Ging-Shing Won Division of Endocrinology and Metabolism, Department of Medicine, Taipei-Veterans General Hospital, Taiwan, R.O.C.

Hypophysitis, a rare but increasing recognized case of pituitary dysfunction, is a chronic inflammation of the pituitary and can be classified according to etiology, anatomic location, or histopathology. Etiology distinguishes hypophysitis into primary (or idiopathic) or secondary depending on whether the cause of the disease is unknown or identifiable. In terms of the anatomical regions affected, hypophysitis is also subdivided into 3 subtypes: adenohypophysitis- involving mainly the anterior lobe, infundibuloneurohypophysitis- involving mainly the stalk and posterior lobe, and panhypophysitis- involving both structures. Histologically, primary hypophysitis is further classified into 2 main forms of hypophysitis: lymphocytic (1962) and granulomatous (1916). During the past 2 decades, however, the clinicopathological spectrum of primary hypophysitis has expanded with the addition of 3 new forms: necrotizing (1993), xanthomatous (1999), and IgG4 plasmacytic (2004). Primay lymphocytic hypophysitis, the most common subtype, is histologically characterized by diffuse lymphocytic infiltration with predominance of T cells, particularly CD4 cells. It is more common in young adult women and usually presents with symptoms originating from compression of sellar structures- headaches or visual disturbances, deficiency of anterior pituitary hormone production, with ACTH deficiency being the most frequent (32%), or diabetes insipidus (DI). Granulomatous hypophysitis, the second most common subtype, affects males and females in equal proportion, and presents initially with symptoms/signs of mass effects from an enlarged pituitary gland, and later with 2 clinical manifestations; namely, central DI and panhypopituitarism. Histologically, it is characterized by multinucleated giant cells that from true granulomas with palisading histiocytes, surrounded by numerous lymphocytes, mainly T cells, and some plasma cells. Xantomatous hypophysitis is more common in women and is characterized by infiltration of foamy histiocytes and macrophages, accompanied by plasma cells, and lymphocytes. Only 4 cases of necrotizing hypophysitis has been reported till now so far. IgG4 plasmacytic hypophysitis, also called IgG4-related hypophysitis, is more common in men and advanced ages, presenting with central DI, ACTH deficiency, and ones from sellar compression due to an enlargement of the anterior pituitary and/or stalk as shown on sellar MRI. Histologically, it is characterized by the infiltration with numerous plasma cells, mainly the IgG4 plasmacytic form and predominantly produce antibodies of the IgG4 subclass. In this section, we will briefly review each subtype of hypophysitis and will share our experiences with 2 histologically proven cases of lymphocytic adenohypophysitis and another clinically proven case of IgG4-related hypophysitis.

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Surgical Treatment of Pituitary Tumors Chiung-Chyi Shen Minimally Invasive Neurosurgery, Taichung Veterans General Hospital, Taiwan, R.O.C.

Since Schloffer’s first description, the surgical treatment of pituitary tumors underwent significant evolution in the past century. To date, endonasal transsphenoidal microsurgery is the surgical treatment of choice for over 90% of pituitary tumours, but still transcranial operations are needed even in experienced hands in the large pituitary tumours with minor intrasellar components. Due to its excellent visualization through the endoscope, the implementation of intra-operative magnetic resonance (MR) imaging, minimal invasive endonasal endoscopic microsurgery for pituitary tumor has become widespread recently. The combination with stereotactic neuronavigational techniques offers accurate localization and superior anatomical details to help remove the tumor radically. We will discuss the different techniques, methods for removal various types of pituitary tumors. The use of vasoconstrictors and any form of nasal packing was unnecessary. The inferior margin of the middle turbinate and choana were a consistent surgical landmark leading to the sella. The use of an intraoperative fluoroscopic C-arm was also eliminated. The adoption of a nasal spectum, variously angled suction cannulas and suction-coagulators has made the operation easier and faster. As experience increased, the operation time progressively shortened and mucosal trauma became minimal. Minimal complications and no mortality related to the approach were encountered in any patients in the follow-up period. In microadenomas, the success rate reported from expert authors approaches 80%. Generally speaking, patients with non-functioning pituitary adenomas, acromegaly, ACTH-secreting and TSH-secreting adenomas are excellent candidates for primary surgical treatment. Re-operations are generally associated with less favourable outcomes. In prolactinomas, the primary therapy is medical; however, when dopamine agonists are not well tolerated or inefficient, an operative treatment should be considered. Although alternative medical treatments exist in acromegaly and thyrotropinomas, surgical treatment is relatively cheap. Conclusion: The endonasal endoscopic transsphenoidal microsurgery for pituitary tumors provide adequate visualization of operative fileds and wide exposure of the tumor. It can increase the total-resection rate in both microadenoma and macroadenoma with minimal morbidities. Key words: Endonasal, Endoscopic, Transsphenoidal, Pituitary Macroadenoma,

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Stereotactic Radiosurgery for Pituitary Tumors Xiao Furen Division of Neurosurgery, National Taiwan University Hospital

Surgery remains the treatment of choice in management of pituitary tumor except some prolactinoma. However, total adenomectomy is not achievable in some situation. Conventional radiotherapy had been used as one of adjuvant therapies. Although it is effective to control the lesion but the treatment field is relatively large and the course takes several weeks. Stereotactic radiosurgery (SRS) was used to replace the role of conventional radiotherapy. Single fraction or hypofraction SRS provides precise coverage of the tumor with low radiation dose to surrounding normal tissue. For nonfunctional tumor, the tumor control rate is high. For the growth hormone secreting tumor, the endocrinological normalization takes several years with a successful rate around 60%. As the majority of prolactinoma respond well to dopamine agonist, SRS is less frequently used. The success of SRS to ACTH secreting tumor was reported to be 80%, as fast as 2 years. In order to protect the vision, at least 2mm distance between the lesion and optic apparatus is desired in single fraction SRS. Hypopituiatrism occurs in some cases. SRS is applied to treat the pituitary tumor with good tumor control, both in volume and in endocrinology. Preservation of vision and pituitary function can be achieved with proper patient selection and careful dose planning.

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It has been almost 5 years since the publication of the 2010 hypertension guidelines of the Taiwan Society of Cardiology (TSOC). There is new evidence regarding the management of hypertension, including randomized controlled trials, non-randomized trials, post-hoc analyses, subgroup analyses, retrospective studies, cohort studies, and registries. More recently, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) published joint hypertension guidelines in 2013. The panel members who were appointed to the Eighth Joint National Committee (JNC) also published the 2014 JNC report. Blood pressure (BP) targets have been changed; in particular, such targets have been loosened in high risk patients. The Executive Board members of TSOC and the Taiwan Hypertension Society (THS) aimed to review updated information about the management of hypertension to publish an updated hypertension guideline in Taiwan. We recognized that hypertension is the most important risk factor for global disease burden. Management of hypertension is especially important in Asia where the prevalence rate grows faster than other parts of the world. In most countries in East Asia, stroke surpassed coronary heart disease (CHD) in causing premature death. A diagnostic algorithm was proposed, emphasizing the importance of home BP monitoring and ambulatory BP monitoring for better detection of night time hypertension, early morning hypertension, white-coat hypertension, and masked hypertension. We disagreed with the ESH/ESH joint hypertension guidelines suggestion to loosen BP targets to <140/90 mmHg for all patients. We strongly disagree with the suggestion by the 2014 JNC report to raise the BP target to <150/90 mmHg for patients between 60-80 years of age. For patients with diabetes, CHD, chronic kidney disease who have proteinuria, and those who are receiving antithrombotic therapy for stroke prevention, we propose BP targets of <130/80 mmHg in our guidelines. BP targets are <140/90 mmHg for all other patient groups, except for patients ≥80 years of age in whom a BP target of <150/90 mmHg would be optimal. For the management of hypertension, we proposed a treatment algorithm, starting with life style modification (LSM) including S-ABCDE (Sodium restriction, Alcohol limitation, Body weight reduction, Cigarette smoke cessation, Diet adaptation, and Exercise adoption). We emphasized a low-salt strategy instead of a no-salt strategy, and that excessively aggressive sodium restriction to < 2.0 gram/day may be harmful. When drug therapy is considered, a strategy called “PROCEED” was suggested (Previous experience, Risk factors, Organ damage, Contraindications or unfavorable 119

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

conditions, Expert’s or doctor’s judgment, Expenses or cost, and Delivery and compliance issue). To predict drug effects in lowering BP, we proposed the “Rule of 10” and “Rule of 5”. With a standard dose of any one of the 5 major classes of anti-hypertensive agents, one can anticipate approximately a 10-mmHg decrease in systolic BP (SBP)(Rule of 10) and a 5-mmHg decrease in diastolic BP (DBP)(Rule of 5). When doses of the same drug are doubled, there is only a 2-mmHg incremental decrease in SBP and a 1-mmHg incremental decrease in DBP. Preferably, when 2 drugs with different mechanisms are to be taken together, the decrease in BP is the sum of the decrease of the individual agents (approximately 20 mmHg in SBP and 10 mmHg in DBP). Early combination therapy, especially single-pill combination (SPC), is recommended. When patient’s initial treatment cannot get BP to targeted goals, we have proposed an adjustment algorithm, “AT GOALs” (Adherence, Timing of administration, Greater doses, Other classes of drugs, Alternative combination or SPC, and LSM + Laboratory tests). Treatment of hypertension in special conditions, including treatment of resistant hypertension, hypertension in women, and perioperative management of hypertension, were also mentioned. The TSOC/THS hypertension guidelines provide the most updated information available in the management of hypertension. The guidelines are not mandatory, and members of the task force fully realize that treatment of hypertension should be individualized to address each patient’s circumstances. Ultimately, the decision of the physician decision remains of the utmost importance in hypertension management.

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Clinical Guideline of the DAROC for the Management of Diabetes Mellitus Hung-Yuan Li Department of Internal Medicine, National Taiwan University Hospital

The prevalence of diabetes increased gradually in recent years. In 2012, it is estimated that there were 1.5 million people with diabetes in Taiwan. In this talk, I will introduce the clinical guideline of the DAROC for the management of diabetes mellitus published in 2015. In this edition, revisions were done in following topics, including screening of diabetes, diagnosis of gestational diabetes, treatment goal of blood pressure control, glycemic control, and lipid control. Treatment algorithm is also updated to include new class of anti-diabetic agents and new results from clinical trials. For screening of diabetes, 3 methods are recommended, based on the service provided by Ministry of Health and Welfare, Taiwan Diabetes Risk Score, and the recommendation of the American Diabetes Association. Screening algorithm with fasting plasma glucose and hemoglobin A1c is also provided. The diagnostic criteria for diabetes and pre-diabetes do not change. However, there are 2 methods to diagnose gestational diabetes, including 3-hour 100g OGTT and 2-hour 75g OGTT. The glycemic target for adults with diabetes is hemoglobin <7.0%. This target should be individualized according to different conditions in different patients. The updated algorithm recommend metformin as the first line oral anti-diabetic agent, if not contraindicated. Besides, SGLT-2 inhibitors are included in the algorithm. For clinical monitoring, screening of cancers is included, which is a service provided by the Health Promotion Administration, Ministry of Health and Welfare.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Metabolic Syndrome in Korea Chul Woo Ahn Department of Endocrinology and Metabolism, Internal Medicine Gangnam Severance Hospital, Seoul, Korea

Metabolic syndrome is a cluster of conditions including increased blood pressure, hyperglycemia, dyslipidemia, obesity which occur together under the common root of insulin resistance. Inadequate exercise, food, stress, and genetic susceptibility all contribute to insulin resistance, and it leads to the increased risk of diabetes and cardiovascular, cerebrovascular diseases. Insulin resistance and metabolic syndrome are inseparable, and the increase in insulin resistance results in cardiovascular, cerebrovascular events as well as the incidence of diabetes and hypertension. The cancer risk also has been shown to increase with the insulin resistance in Korea. The prevalence of metabolic syndrome is quite high in the Western countries, and about 50% of peopled aged over 60 years have metabolic syndrome The prevalence has been a rapid increase in Korea as well, and the reasons for such a rapid rise seem to be due to the over nutrition, westernized lifestyles, and other socioeconomic transitions. We are interested in treating metabolic syndrome because it is treatable. The treatment of metabolic syndrome can be divided into treating insulin resistance itself and treating each components of metabolic syndrome. To reduce insulin resistance, lifestyle modification is crucial with some additional help from pharmacotherapy. Also, many drugs are available for treating each component of metabolic syndrome. Several large scaled, prospective studies have demonstrated the effect of diet and exercise as well as some drugs reducing the risk of developing diabetes. However, many patients find it difficult to keep up with the behavioral modification, and new technologies may be helpful. Internet diabetic patient management using a short messaging service was effective in lowering body weight, HbA1c, fasting and postprandial glucose, and similar services using internet phone and smart phone provided similar effects. IT-based U-health service seems an effective way to guide the behavioral modification.

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Graves’ Ophthalmopathy: Management from Point of View of Endocrinologist and Ophthalmologist Tien-Chun Chang Department of Internal Medicine, College of Medicine and National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

Hyperthyroidism, Graves’ ophthalmopathy and pretibial myxedema are three major manifestations of Graves’ disease. TSH receptor antibody stimulates TSH receptors on the follicular cells of the thyroid to over-produce thyroid hormones, resulting hyperthyroidism. However, the etiology of Graves’ ophthalmopathy and pretibial myxedema is not so clear. It is quite clear that Graves’ ophthalmopathy is an autoimmune disease, and may be related to the action of T cells with TSH receptors on retrobulbar fibroblasts and adipocytes, and T cells produce cytokines to stimulate fibroblasts to secrete glycosaminoglycan which absorb water to make swelling of extraocular muscles and retrobulbar tissues. Orbital computed tomography is an important method to examine the morphologic change of Graves’ ophthalmopathy. In addition, the activity of Graves’ ophthalmopathy should be evaluated before medical treatment. Clinical Activity Score is an easy method to evaluate the clinical activity. The application of digital infrared thermal imaging in determining inflammatory state and follow-up effect of methylprednisolone pulse therapy through measurement of local heat in patients with Graves’ ophthalmopathy is also useful. The patient should be kept in euthyroid state at any stage. If it is in active stage, high dose of corticosteroid could be used. However, if the patients have B viral hepatitis, they should be treated with anti-viral agents first to avoid flare-up, although it is not necessary if the patients have C viral hepatitis. If it is inactive, but still has symptoms and/ or signs, surgery may be necessary. Retrobulbar fat removal, if possible, is a better way to relieve the orbital compression than orbital bone removal because postoperative diplopia less occurs. After decompression, muscle surgery and eyelid surgery could be considered if it is necessary. In addition, the management of Graves’ ophthalmopathy should be managed by team work to get the best result.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

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Obesity and Thyroid Cancer Won Bae Kim University of Ulsan College of Medicine, Department of Internal Medicine, Asan Medical Center, Seoul, Korea

Obesity is associated consistently with the development and progression of various cancers such as breast cancer, endometrial cancer, colon cancer, esophageal adenocarcinoma, prostate cancer, liver cell carcinoma, leukemia, non-Hodgkin lymphoma, and melanom. Moreover, several recent epidemiological studies observed a positive association between obesity and the prevalence of thyroid cancers. To see if obesity is associated with thyroid cancer we obtained data from 15,068 subjects that underwent a routine health checkup from 2007 to 2008 at the Health Screening and Promotion Center of Asan Medical Center. Thyroid ultrasonography was included in the checkup, and suspicious nodules were examined by ultrasonography-guided aspiration. Those with a prior history of thyroid disease or family history of thyroid cancer were excluded from this study. Of the 15,068 subjects screened by thyroid ultrasonography, 267 patients were diagnosed with thyroid cancer. The prevalence of thyroid cancer in women associated with a high body mass index (BMI, per 5kg/m2 increase) (odds ratios [OR]= 1.63, 95% CI 1.24–2.10, p<0.001), after adjustment of age, smoking status, and thyroid-stimulation hormone (TSH) levels. There was no positive correlation between the prevalence of thyroid cancer in men and a high BMI (OR=1.16, 95% CI 0.85–1.57, p=0.336). There was no association between age, fasting serum insulin, or basal TSH levels and thyroid cancer in both genders. Our study clearly showed that obesity was associated with an increase in prevalence of thyroid cancer, but serum TSH and insulin levels, known as risk factors for cancer, were not related to thyroid cancer. We retrospectively reviewed records of 1,189 patients who underwent a total thyroidectomy for PTCs of 1 cm or larger in size. All clinical outcomes were evaluated and compared based on BMI quartiles. There were no significant associations between BMI quartiles and primary tumor size, extrathyroidal invasion, cervical lymph node metastasis, or distant metastasis. However, an increased BMI was associated with an increase in mean age (P for trend < 0.001), multifocality (P for trend = 0.02), and advanced tumor-node-metastasis (TNM) stage (stage III or IV; P for trend 0.001). However, the increases in multifocality and advanced TNM stage were no longer significant when further assessed using multivariate analyses adjusted for age and gender (P = 0.07 and P = 0.77, respectively). Furthermore, were no differences in recurrence-free survival rates according to BMI quartile (P = 0.26). So, BMI was not associated with the aggressive clinicopathological features or recurrence-free survival rates of patients with PTC. These findings suggest that obesity may be involved in earlier stage of carcinogenesis rather than affecting progression of thyroid cancer. Additional studies are required to understand the mechanism(s) behind the association of obesity with thyroid cancer risk. 124

Abstract SE-5-4

Metabolic Syndrome in Taiwan Dee Pei Division of Endocrinology and Metabolism, Cardinal Tien Hospital

Companied with the increase prevalence of obesity, cardiovascular disease, stroke and diabetes have become the 3rd, 4th and 5th causes of death in Taiwan. Thus, early detection and prevention of these diseases become more important in recent two decades. Metabolic syndrome (MetS), first proposed by World Health Organization, serves the purpose of identifying subjects at risk. Ever since its publication, massive amount of studies were done. Based on the information derived from these researches, not only the prevalence of MetS is well known in different ethnic groups, but also its multirole is also elucidated. In Taiwan, the same trend of increased incidence of MetS is also noted. Although there are many good-quality researches done to investigate different aspects of MetS. However, there is limited number of nation-wild survey. Among them, the one published by Huang et al. could provide a good glance at the picture of MetS in Taiwan. They found out that, in 5936 participants (2815 men, 3121 women; age between 20-79.9 years), the age-standardized prevalence was 15.7% by using the modified ATP III criteria. The percentage of each abnormal MetS components were 30.2% for waist circumference, 27.6% for TG, 23.8% HDL-C, 29.9% for BP and 10.6% for glucose. The prevalence of MetS increases gradually with age with a peak found in the 70s (36.5%). Overweight had a profound impact on the occurrence of MetS. In subjects with BMI > 27 kg/m2, around 50% had MetS compared to 6.5% with a normal BMI. In another longitudinal study done in in Kinmen, higher triglyceride and waist circumference were the best independent predictors for future MetS and diabetes. In the same time, the China Health and Nutrition Survey done in 2009 showed a higher prevalence of MetS (21.3%). Similar to our findings, women, subjects with higher BMI, older and living in the urban had a higher prevalence than their comparators. Since Taiwanese and Chinese are the same race, their data are could also be referred. Since MetS has five different components. Each and every component has its unique effect on the cardiovascular diseases and diabetes. In the same time, it should also be noted that many nontraditional risk factors are also related to MetS. Being a complex and important syndrome, the MetS should further be emphasized.

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The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD-5-1

Objective: To review and update the epidemiology, classification and screeing of diabetic retinopathy (DR) and diabetic macular edema (DME). Materials And Methods: Literatures review including epidemiological studies and the national health institute databank studies in Taiwan as well as recent studies of treatment of DME. Results: Because of population growth and increase aging, prevalence of glycaemia and diabetes are rising globally. The global prevalence of any DR is 35% and 10% for vision threatening DR. The prevalence varied across different ethnic groups. Risk factors for DR included diabetes duration, HbA1c, blood pressure and type 1 DM. Classification of DR is important in order to establish adequate therapy. The International Clinical Disease Severity Scale was widely accepted for the classification of DR because it is simple to use, easy to remember, and based on scientific trials. It is a clinical examination and does not require special tests such as fluorescein angiography or optical coherent tomography (OCT). Fundus pictures, if available, are used to document, evaluate and follow the severity of DR. For screening purpose, single-field photographs centered at the macula are sufficient to identify patients with retinopathy for referral. Increase the photographic fields to 3 will be effective in determining the critical level of retinopathy for prompt referral. However, the hurdle for prevention of blindness in diabetic patients lies on screening and early detection of DR since 90% of the cases can be prevented from visual loss by proper management. The retina screening rate in patients with diabetes in Taiwan, the ways developed to improve the screening rate and decrease the time for diagnosis will be discussed in this talk. Conclusions: Visual loss from DR is largely preventable with proper screening based upon timely application of photocoagulation or intravitreal injection of anti-vascular endothelial growth factors. Fundus photography and standardized classification of DR allowed for communication and discussion between the endocrinologists and ophthalmologists. Recent technology of digital nonmydriatic fundus camera, automatic image detection of retinal pathology and telemedicine may facilitate the screening of DR.

126

Abstract SD-5-2

Diabetes Mellitus and Diabetic Eye Disease Yan-Ling Chen Division of Endocrinology and Metabolism, Shin Kong Wu Ho-Su Memorial Hospital

Diabetic eye disease refers to a group of eye problems that people with diabetes may face as a complication of diabetes. Diabetic retinopathy is the most frequent cause of new cases of blindness among adults aged 20–74 years. During the first two decades of disease, nearly all patients with type 1 diabetes and >60% of patients with type 2 diabetes have retinopathy. . In the younger-onset group, 86% of blindness was attributable to diabetic retinopathy. In the older-onset group, in which other eye diseases were common, one-third of the cases of legal blindness were due to diabetic retinopathy. Treatment modalities exist that can prevent or delay the onset of diabetic retinopathy, as well as prevent loss of vision, in a large proportion of patients with diabetes. The DCCT and the UKPDS established that glycemic and blood pressure control can prevent and delay the progression of diabetic retinopathy in patients with diabetes. In mild cases, treatment for diabetic retinopathy is not necessary. Regular eye exams are critical for monitoring progression of the disease. Strict control of blood sugar and blood pressure levels can greatly reduce or prevent diabetic retinopathy. In more advanced cases, treatment is recommended to stop the damage of diabetic retinopathy, prevent vision loss, and potentially restore vision.

127

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

SD-5-3

Diabetic Retinopathy – Mechanisms, Treatments, and Neuronal Protections Ta-Ching Chen, Chung-May Yang Department of Ophthalmology, National Taiwan University Hospital, Taiwan, R.O.C.

Diabetic retinopathy (DR) is one of the most common complications and leading cause of blindness in both developing and developed countries. Visual impairments may origin from diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR). Breakdown of blood-retinal barrier leads to DME. Treatments, including anti-VEGF agents, have achieved better results and some recovery of vision. Progression of neovasculization and fibrosis in PDR would lead to vitreous hemorrhage, macular traction, and retinal detachment. Extended laser and surgical vitrectomy are usually inevitable in these patients. However, these procedures just treat visible vascular changes in retina rather than prevent progressions. Nowadays, more and more evidences indicate that neurodegeneration may be the primary change in DR. Diabetes disturb the interaction of neuron and vasculatures and hamper the homeostasis necessary for retinal function. Subsequent vascular changes happen and the DR progresses. Profound neurodegeneration is often the final result despite adequate treatments. These changes suggest DR as a neurovascular disorder. Potential treatments toward neuroprotection may further regress the progression of disease at an earlier stage and prevent profound vision loss.

128

Abstract SL-1

Personalized Management of Differentiated Thyroid Cancer: An Update of Guidelines and Literature Review 1

Yen-Hsiang Chang, 1,2Pei-Wen Wang

Department of 1Nuclear Medicine and 2Internal Medicine, Kohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

In 2009, the American Thyroid Association established the guidelines regarding the management of differentiated thyroid carcinoma (DTC). More new studies have been published since then. According to the new evidences, the treatment of DTC has continued to modify and evolve. Not only guidelines in the US but also the European countries announced the changes in DTC management recently. We selected clinical questions regarding the management of DTC and revised them based on newly published data from western countries and unpublished ATA guidelines as well. More data have accumulated about conservative treatment of low-risk patients. In selective cases, observation of low-risk papillary microcarcinoma and lobectomy for low-risk papillary thyroid carcinoma (PTC) has become an acceptable alternative to total thyroidectomy. Thyroidectomy without prophylactic central neck dissection may be appropriate for small (T1 or T2), non-invasive, clinically node-negative PTC. Post-surgical radioactive iodine (RAI) ablation is almost routinely performed, however, recent studies showed that ablation is not beneficial for survival in low-risk patients. Recombinant human thyroid-stimulating hormone (rhTSH) has been recommended as the first line mode of TSH stimulation except for high risk patients or those with recurrent/metastatic disease. Although low-dose (30mCi) ablation showed similar ablation rate to high-dose ablation, long-term outcome has not yet been established. According to the follow-up of DTC patients, no single factor is capable of completely predicting the long-term outcomes. The concepts of “Dynamic risk assessment” have important implications on DTC management during follow-up. Evaluation of the efficacy of RAI therapy rely on anatomical information has been suggested. For those with radioiodine refractory disease, targeted therapy with small molecular inhibitor of tyrosine protein kinases (TKI) may improve progress-free survival. Recently, policy for treating DTCs has changed in many aspects. We have to continue to capture the new information with time to present the best treatments for DTC patients.

129

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

DR-1

Glucagon-Like Peptide-1 Prevents ß Cells from Apoptosis through Improving Mitochondrial Function and Decreasing ER Stress via Suppressing Sustained AMPK Activation by Methylglyoxal 1

Tien-Jyun Chang, 1,2Hsing-Chi Tseng, 1,2Lee-Ming Chuang

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Institute of Molecular Medicine, National Taiwan University Medical College, Taipei, Taiwan

Objective: Accumulation of methylglyoxal (MG) contributes to glucotoxicity, and leads to β-cell apoptosis. Glucagon-like peptide-1 (GLP-1) had the protective ability against β-cell apoptosis. However, the molecular mechanism of protecting β-cell from MG-induced apoptosis by GLP-1 remains unclear. In this study, we investigated the signaling pathway involved in the anti-apoptotic effect of GLP-1. Methods: Rat insulinoma cell line, RIN-m5F cells, was used. MTT assay, annexin V/PI staining, flow cytometry for sub-G1 fraction (DNA fragmentation), western blot of active form caspase 3 and phosphorylated JNK were used as indicators of apoptosis. Extracellular flux (XF) analyses for oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were applied to estimate the mitochondrial function. Western blots of phosphorylated JNK and eIF2αwere used as indicator of ER stress. Results: MG treatment of RIN-m5F cells induced decreased cell viability with increased apoptotic markers. Besides, MG-treated cells were under increased ER stress as revealed with enhancement in phosphorylated JNK and eIF2α. Mitochondrial dysfunction was also found in the MG-treated cells. Pretreatment of GLP-1 conferred anti-apoptotic effects on MG- treated beta cells by alleviating the above abnormalities. Besides, prolonged AMPK activation was found under chronic MG incubation. Pretreatment of GLP-1 improved ATP production and decreased ER stress upon MG treatment, thus reverting cytotoxic effect from the prolonged AMPK activation. Conclusion: GLP-1 protected β-cell from MG-induced apoptosis through improving mitochondrial function and decreasing ER stress, which may be caused by prolonged AMPK activation upon MG treatment. How this feature of GLP-1 on beta cell function or beta cell mass remains to be further evaluated.

130

Abstract DR-2

The Role of Serum Prothymosin-α in Diabetes Mellitus Horng-Yih Ou Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital

Insulin resistance, characterized by a reduced ability of insulin to regulate glucose homeostasis in target tissues, is an important pathophysiologic defect in type 2 diabetes. Previous studies indicated that inflammation plays an important role in the development of insulin resistance; inflammatory reactions disrupt insulin signal transduction and further decrease insulin sensitivity. Previous studies also showed that Toll-like receptor 4 (TLR-4), which is responsible for identifying the pathogenassociated molecular pattern (PAMP) of different pathogens in the original immunity against infection, will affect insulin sensitivity. The activation of TLR-4 can impair insulin sensitivity, disrupt the homeostasis of blood glucose, and then lead to development of diabetes. Prothymosin-α is a cytokine related to immune-modulation and cell proliferation. In immunemodulation, it is known that Prothymosin-α can compensate the defect of mixed lymphocyte reaction, increase the expression of MHC class II antigen, increase the IL-2 receptor expression in T lymphocytes, and enhance the ability of cytotoxicity in natural killer cells and LAK cells, as well as inhibit the growth of tumor by the indirectly increased secretion of TNF-α. Prothymosin-α also has a function to facilitate cell proliferation, and the level of Prothymosin-α is higher in tumor cells than that of normal cells. In addition, previous studies indicated that Prothymosin-α binds to TLR-4 to stimulate the production of interferons in cells and further kill the pathogens; however, the effects of Prothymosin-α on diabetes and insulin sensitivity are still unknown. Therefore, in this study, we hypothesize that Prothymosin-α may regulate insulin sensitivity and act as a biomarker of diabetes. To test this hypothesis, we enrolled 300 subjects with different glycemic status from the center of health care and diabetes clinic in the National Cheng Kung University Hospital. We found that subjects with newly diagnosed diabetes (NDD) had significantly higher Prothymosin-α levels than those of impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). Moreover, Prothymosin-α, diabetes, body mass index (BMI), and hypertriglyceridemia are independent predictive factors of HOMA-IR after adjustment for multiple confounding variables. Our results suggest that Prothymosin-α might play an important role in the pathogenesis of insulin resistance and diabetes.

131

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-01

Introduction: Diabetic neuropathy is one of the most common complications in the patients with type 2 diabetes mellitus (T2DM). Currently, there are no specific therapy that could improve the neuropathy except glycemic control. In recent years, few studies revealed that moderate intensity aerobic exercise could play a valuable role to slow down the progression of diabetic peripheral neuropathy. The aim of our study was to analysis the relationship between diabetic painful neuropathy (DPN) and exercise. Method: This cross-sectional study totally enrolled 2359 outpatients with type 2 diabetes who had completed the Douleur Neuropathique en 4 Questions (DN4) questionnaire from January 2013 to October 2013. The Patients’ characteristics, including age, sex, DM duration, anti-diabetic medication, anti-hypertensive and lipid-lowering medication, medication for diabetic neuropathy, HbA1c, systolic blood pressure, body weight and height, serum creatinine level, urine albumin to creatinine ratio, and daily exercise duration were recorded. A total score of DN4 questionnaire equal or greater than 4 was defined as having DPN. Linear regression was used to evaluate the correlation between duration of exercise and DN4 score. General linear model (GLM) was used to assess the effect of exercise and risk of painful neuropathy. Results: There were 179 patients with DPN, in whom 83 were men (46.4%), mean age 69.6±12.5 years old, BMI 25.5±4.1 kg/m2, diabetes duration 13.3±9.3 years, mean DN4 score 4.49±0.75, HbA1c 7.8±1.7%, insulin users 22.9%. It was found that longer daily exercise duration was associated with a lower mean DN4 score. The mean DN4 score was 0.74, 0.62, and 0.45 in the subjects with no exercise, daily exerciseduration ≦ 30 minutes, and daily exercise duration longer than 30 minutes, respectively (P for trend <0.001.) After adjusting the sex, age, diabetes duration, neuropathy medication usage, insulin user, oral anti-diabetics drugs, systolic blood pressure, body mass index, glycated hemoglobin, low-density lipoprotein, and estimated GFR, the risk of painful neuropathy was 3.38 times in the no exercise group(95% CI 1.54-9.79)in comparison with the group with daily exercise duration more than 30 minutes. Conclusion: The risk of painful neuropathy is markedly increased in the diabetic patients without exercise habits.

132

Abstract OD-02

HIGH DIABETES MELLITUS PREVALENCE AMONG NEWLYDIAGNOSED TUBERCULOSIS PATIENTS IN AN ASIAN POPULATION: A NATIONWIDE POPULATION-BASED STUDY 1

YU-CHENG CHEN, 2SHI-DOU LIN, 3PO-YEN KO

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital Yunlin Branch, Yunlin, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan

Aims: Our aims of this study were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated risk factors in an Asian population. Methods: The data for this study were obtained from the National Health Insurance Research Databaseand included 9831 newly-diagnosed TB individuals in the period from January 1, 2000 to December 31, 2010. The data were divided into a DM group and a non-DM group.We measured the prevalence and the associated risk factorsof DM,and amultivariate logistic regression modelwas used to estimate the adjusted odds ratios (ORs). Results: During the period between 2000 and 2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55-64 years had the highest risk of DM (OR=3.53), followedby those 45-54 years (OR=3.10), 65-74 years (OR=2.88), and ≥75 years (OR=2.30), compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were associated with a higher risk of DM (ORs=1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. The average number needed to screen to find one case of newly-diagnosed DM was 30.9. Conclusions: The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.

133

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-03

HYPOGLYCEMIA IS A NOT RARE IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES AS ASSESSED BY CONTINUOUS GLUCOSE MONITORING YIN-CHUN CHEN, YU-YAO HUANG, JUI-HUNG SUN, CHUNG-HUEI HUANG, YUTING YE, YA-HUI WU, SHIUE-HUA CHIOU, CHIA-HUNG LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Aims/Introduction: The objective of this study was to access hypoglycemia events among patients with poorly controlled type 2 diabetes using continuous glucose monitoring (CGM). Material and methods: Forty-seven outpatient subjects (age = 53.7 ± 11.8 years; HbA1c = 10.1 ± 1.3%) were monitored blood glucose using professional non-real time CGM over 4 days while maintaining their usual diet and daily activities. Self-monitoring of blood glucose (SMBG) data were also assessed. Results: Patients with poorly controlled diabetes showed frequent lack of awareness of hypoglycemic events as recorded by CGM (45% of hypoglycemic events below 70mg/dL, and 33% below 55mg/dL). Although hypoglycemic events could happen any time of a day, they were more common in the early morning between 2:00AM and 6:00AM. There was no statistical difference in gender, age, diabetes duration, body mass index, or rate of small vessel complications between patients with or without hypoglycemia. Similarly, the incidence of hypoglycemia did not differ according to type of anti-diabetic medicine, insulin dose, and glycohemoglobulin (HbA1c) level. By comparison to SMBG, CGM revealed a higher hypoglycemia detection rate. Conclusions: Hypoglycemia unawareness is not rare in poor controlled diabetes patients. Detection and avoidance hypoglycemia unawareness may be a key for control these patients. Key words: Continuous glucose monitoring; type 2 diabetes; unawareness of hypoglycemia;

134

Abstract OD-04

Background: Despite the awareness of the value of treating inpatient hyperglycemia and the announcement of the guidelines for managing hyperglycemia in inpatients, little is known about the glycemic control of Chinese patients during admission. Methods: The electronic informatics system was used to retrospectively extract data on inpatient point-of-care bedside glucose (POC-BG) tests for patients admitted from April to June 2012 to a medical center in Taiwan. Mean POC-BG values and hypoglycemia and hyperglycemia rates were calculated for intensive care unit (ICU) and general ward areas. The POC-BG values in different ICU areas and patient-day-weighted mean POC-BG values in different general wards were investigated. Results: A total of 3,002 patients with 70,303 POC-BG measurements were analyzed: 18,235 from the ICU and 52,068 from the general wards. Mean POC-BG was 193.2 mg/dL for the ICU and 192.7 mg/dL for the wards. Hospital hyperglycemia (>180 mg/dL) prevalence was 47.0% for the ICU and 46.4% for the wards. Hospital hypoglycemia (<70 mg/dL) prevalence was 1.9% for the ICU and 1.8% for the wards. In the ICU setting, those with lower mean POC-BG values were associated with a higher prevalence of hospital hypoglycemia. Patients in certain medical wards maintained a higher patient-day-weighted mean POC-BG level than the others during the first admission week. Conclusions: Hospital hyperglycemia is common, and POC-BG levels vary in different inpatient care settings. This information may facilitate the creation of a process for the development of an inpatient hyperglycemic program and improved glucose management in the hospital.

135

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-05

ASSOCIATION OF GLUCOKINASE REGULATOR (GCKR) GENETIC VARIANT AND METABOLIC SYNDROME IN TAIWANESE ADOLESCENCE 1

CHANG-HSUN HSIEH, 1YI-JEN HUNG, 2,3NAIN-FENG CHU, 2FU-HUANG LIN, 4 DEE PEI, 1CHIEN-HSING LEE 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Taitung Hospital, DOH. Taiwan. 4 Division of Endocrinology and Metabolism, Cardinal Tien Hospital, New Taipei City, Taiwan

Background: Glucokinase (GCK) plays an important role in the glucose regulation and interplayed by a glucokinase regulatory protein (GKRP) to maintain glucse concentration. The glucokinase regulator gene (GCKR) encodes for the GKRP and previous GWA studies showed that common genetic variants of the GCKR gene are associated with features of the metabolic syndrome (MetS). However, most of the studies have been explored in Westeran population and limited data in adolescent population of Asian. The study explores the genetic association of common genetic variant of GCKR gene with metabolic traits in Taiwan adolescent population. Methods: After multistage sampling, we enrolled 962 adolescents (468 boys and 494 girls). IDF criteria were applied to define MetS. Subjects had 3 or more of the following cardiometabolic abnormalities that occur in MetS: high blood pressure (BP), high fasting plasma glucose (FPG), triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), and obesity (by waist circumstance, WC; and body mass index, BMI). The characteristics of the MetS and its components associated with different alleles and genotypes of the GCKR rs780094 SNP were compared. Results: The boys had higher adiposity (including BMI and WC), SBP, FPG and lower HDL-C concentrations than girls and no difference was observed in DBP and TG levels. The girls had higher prevalence of CC genotypes than boys (p=0.017). Both genders did have similar allele frequencies in MetS and its components except boys with T-allele had higher prevalence of low HDL-C than C-allele (p=0.037). When gender is not considered, C-carried genotypes had lower prevalence rate of high WC and low HDL-C than non-C carried genotypes. The higher prevalence rate of low HDL-C and Mets were observed in T-carried genotype than non-T carried genotype. After adjusting age and pubertal stage, the odds ratio for low HDL-C prevalence rate in TT genotype was 2.10 (95% CI: 1.08–4.07) when compared with CC genotype in boy adolescents. Conclusions: The GCKR rs780094 polymorphism is associated with low HDL-C levels in boys of Taiwanese adolescents.

136

Abstract OD-06

Background: Ample data have illustrated a phenomenon of obesity paradox in patients with cardiovascular disease, which means that obesity patients have a better prognosis. However, studies on the association between obesity and mortality among Asian patients are limited, especially in patients with type 2 diabetes (T2DM). We investigate the association between body mass index (BMI) and allcause mortality in Taiwanese patients with T2DM in order to define the optimal body weight for health Materials and methods: A longitudinal cohort study of 2161 patients with T2DM and a mean follow up period of 66.7±7.5 months. Using Cox regression models, BMI was related to the risk of allcause mortality after adjusting all confounding factors. Results: A J-shaped association between BMI and all-cause mortality was observed among all the participants. Those in the BMI categories of less than 22.5 had a significantly elevated all-cause mortality as compared with participants with a BMI of 22.5 to 25.0, [BMI of 17.5~20.0, HR: 1.989 (p<0.0001); BMI of 20.0~22.5, HR: 1.286 (p=0.02)], as did those in the BMI categories of more than 30.0 comparing with participants with a BMI of 22.5 to 25.0 [BMI of 30.0~32.5, HR: 1.67 (p <0.0001); BMI of 32.5~35.0, HR: 2.632 (p<0.0001)]. This J-shaped association remained when we examined data by sex, age and smoking. Conclusions: Our study demonstrate a J-shaped relationship between all-cause mortality and BMI in patients with T2DM in Taiwan. As the knowledge of obesity increases, further study in other populations is needed in proof of our theory.

137

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-07

ASSOCIATION AMONG FIBRINOLYTIC PROTEINS, METABOLIC SYNDROME COMPONENTS, INSULIN RESISTANCE AND SECRETION IN SCHOOL CHILDREN IN TAIWAN 1

CHUNG-ZE WU, 2NAIN-FENG CHU, 3YUH-FENG LIN, 4LI-CHIEN CHANG, 5DEE PEI, 6 JIN-SHEUN CHEN 1

Background: Aspects of metabolic syndrome are associated with insulin resistance, and these patients are prone to atherosclerosis and cardiovascular disease. Fibrinolytic proteins participate in the process of atherosclerosis and intravascular thrombosis. The relationship between fibrinolytic proteins and metabolic syndrome has partly suggested in adult people. In the present study, we investigated the role of urokinase plasminogen activator (uPA), soluble receptors of uPA (suPAR) and plasminogen activator inhibitor-1 (PAI-1) in metabolic syndrome components, insulin resistance and secretion in school children. Methods: We enrolled 387 children (184 boys and 203 girls), mean age of 10.3±1.5 years, from elementary schools in Taipei. The children were divided into normal, overweight and obese groups according to the body mass index (BMI) percentile. All subjects received measurement of body anthropometry, blood pressure, fasting plasma glucose (FPG), total cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The levels of uPA, suPAR, and PAI-1 were measured by enzyme-linked immunosorbent assay (ELISA). Insulin secretion and resistance were assessed by homeostatic model assessment-β (HOMA-β) and -insulin resistance (HOMA-IR). Results: In boys, the obese group had higher levels of suPAR and PAI-1 than the normal group. On the other hand, the obese group in girls had higher levels of uPA, suPAR and PAI-1 than the normal group. For associations of fibrinolytic proteins and metabolic syndrome components in boys, PAI-1 is positively associated with BMI percentile (r=0.205), TG (r=0.217), HOMA-β (r=0.228) and HOMAIR (r=0.167), and negatively associated with HDL (r=-0.188). In girls, uPA is positively related to HOMA-β (r=0.161); suPAR is associated with BMI percentile(r=0.18), body fat (r=0.191) and hsCRP (r=0.169); PAI-1 is associated with BMI percentile (r=0.146), body fat (r=0.17), SBP (r=0.151), DBP (r=0.139), TG (r=0.152), and HOMA-β (r=0.158). After adjusting for age and BMI percentile in girls, uPA was still significantly positively related to HOMA-β; suPAR is positively associated with hsCRP; PAI-1 is positively associated with DBP. Conclusion: Changes in fibrinolytic proteins are associated with metabolic components and insulin secretion varying according to genders in children. This biochemical mechanism needs further exploration in future study. 138

Abstract OD-08

DOES THE PAY-FOR-PERFORMANCE PROGRAM REDUCE THE RISK OF VASCULAR DISEASE COMPLICATIONS FOR PATIENTS WITH TYPE 2 DIABETES IN TAIWAN? 1

HUI-MIN HSIEH, 2,3,5SHYI-JANG SHIN, 4HERNG-CHIA CHIU

Research Objective: To investigate the effectiveness of diabetes pay-for-performance program in Taiwan to reduce risk of diabetes related complications. The major outcome of interest was to compare the probability of incidence for high-severe and low-severe diabetes complications between P4P and non-P4P patients during the following-up period. Diabetes-related complications such as cerebrovascular diseases, cardiovascular disease, and peripheral vascular diseases were measured. Method: We conducted a longitudinal observational cohort study design using a nationwide diabetes P4P database and the National Health Insurance (NHI) administrative claims database in Taiwan for a 2007 to 2012 period. We included diabetes patients if he or she had primarily diabetes diagnosis (ICD-9-CM codes with 250.xx or A-code 181) in at least two outpatient visits or at least one inpatient hospitalization for each year during 2007 and 2008. Using the P4P database, we identified newly enrolled P4P patients as study P4P cohorts during the patient identification period and defined the date for each P4P patient as the date that they were first enrolled in the P4P program as index date. We then identified non-P4P diabetes patients as comparison groups if those patients were not found to be enrolled in the P4P program during the above-stated time period. To avoid potential confounding by selection bias and confounding factors, we used propensity score matching approach (PSM) to determine comparison groups. We defined incidence of a diabetes complication as the first event of that specific complication after following-up. In addition, we calculated total person-years for each patient. To compare between groups, we followed each P4P and non-P4P patient until the end of study date on December 31st, 2012. Any patient was censored if he or she dropped out of the insurance program, were diagnosed for a specific diabetes complication or had died. Complication incidence rates per 1,000 person-years for each complication were calculated. Principal Findings: Before matching, we included 34,710 P4P patients and 341,312 non-P4P diabetes patients. After PSM for 1 to 1 matching, however, the two groups were found to be similar. Diabetes complication incidence rates per 1,000 person-years were greater among P4P patients than non-P4P patients generally. However, when further looking at low and high level of severity, P4P patients tended to have non-significant difference of incidence rate in low-severe complications but smaller incidence rate in highsevere complications. For low-severe complications, for example, the HR for diabetes PVD was 1.179 (95%CI=1.107, 1.255). For high-severe complications, the HR for stroke was 0.782 (95%CI=0.747, 0.819) (p<0.001); and HR for myocardial infarction was 0.821 (95%CI=0.739, 0.911) (p<0.001). Conclusions: Compared with those do not enroll in the P4P program, enrolled P4P patients had similar risks of low-severe complications, while they had lower risks to develop high-severe complications. There is limited evidence on whether paying for quality of care results in improved outcomes, in terms of reduced complications. Our empirical findings provided evidences for the potential long-term benefit of pay-for-performance programs.

139

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OD-09

DETECTING MUTATIONS IN NEONATAL DIABETES AND TYPE 1B DIABETES USING EXOME SEQUENCING 1,11,12,13

YANN-JINN LEE, 1,4CHI-YU HUANG, 1,4WEI-HSIN TING, 2,3FU-SUNG LO, 5,11 DAO-CHEN LIN, 6CHAO-HSU LIN, 7BIWEN CHENG, 8YILEI WU, 9CHEN-MEI HUNG, 10HSIN-JUNG LI, 4,12HORNG-WEI YANG, 12CHIUNG-LING LIN, 12TZU-YANG CHANG, 1CHON-IN CHAN 1

Department of Pediatric Endocrinology, MacKay Children’s Hospital; 2Department of Pediatrics, Chang Gung Memorial Hospital; 3Department of College of Medicine, Chang Gung University; 4Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management; 5Department of Endocrinology and Metabolism, Sijhih Cathay General Hospital; 6Department of Pediatrics, MacKay Memorial Hospital HsinChu Branch; 7 Department of Pediatrics, MacKay Memorial Hospital Taitung Branch; 8Department of Pediatrics, Changhua Christian Hospital; 9Department of Pediatrics, Hsinchu Cathay General Hospital; 10Department of Pediatrics, St. Martin De Porres Hospital; 11Institute of Biomedical Sciences, MacKay Medical College; 12Department of Medical Research, MacKay Memorial Hospital Tamsui District; 13Department of School of Medicine, Taipei Medical University

Aim: We hypothesized that the mutations in neonatal diabetes and type 1B diabetes are genetically heterogeneous and able to be detected by exome sequencing. Research Design and Methods: Patients and parents - The DNA from 14 subjects (12 patients and parents of 1 patient) fulfilled the quality requirement for exome sequencing. These patients did not have anti-islet antibodies (anti-GAD65 antibody and anti-IA2 antibody). The diagnosis of neonatal diabetes and type 1B diabetes were based on clinical and laboratory evidence. Exome sequencing - Exome sequencing was performed by the National Genotyping Center at Academia Sinica, Taipei. We searched for candidate mutations by parallel sequencing of the exomes. Identified substitutions and insertions/deletions (indels) were filtered with the criteria: (a) not present in dbSNP 129 or 1000 genomes; (b) having one of the functional impacts: nonsense, missense, changing splice site, or coding indels; (c) homozygous. Results: Mutations in 5 genes (KCNJ11, INSR, INS, GCK, and ABCC8) were detected in 5 individual patients with NDM or T1BD. The diagnostic rate was 41.7% which is higher than those reported in literature. A patient with KCNJ11 mutation (c.602G>A) has benefited from oral sulfonylurea therapy with improved diabetes control. Conclusion: Our preliminary results show that exome sequencing is robust to detect mutations in patients with NDM or T1BD of heterogeneous genetic etiologies. Patients may benefit from the knowing their underlying mutations.

140

Abstract OD-10

CILOSTAZOL INHIBITS HIGH GLUCOSE-INDUCED VASCULAR SMOOTH MUSCLE CELL DYSFUNCTIONS THROUGH RAGE PATHWAY 1

CHIEN-HSING LEE, 2YI-SHING SHIEH, 1CHANG-HSUN HSIEH, 1YI-JEN HUNG

An emerging body of evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contribute to atherosclerosis. Previous reports demonstrate sustained HG and oxidative stress can enhance AGE/RAGE pathway that involved in diabetic micro- and macrovascular complications. Cilostazol is known as a clinical medicine in treating diabetic peripheral arterial occlusion disease (PAOD) by improving HG-induced vascular dysfunction. Our clinical data showed cilostazol treatment in type 2 diabetic patients not only improved PAOD but also associated with changes in serum soluble RAGE and endothelial markers. However, it is still remained unclear whether cilostazol improves the diabetes related atherosclerosis through the pathway of RAGE. In this study, we used human umbilical artery smooth muscle cell (HUASMC) to investigate whether cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism. First, our result revealed cilostazol decreased RAGE, VCAM-1 and ICAM-1 expression in HG cultured HUASMC and also improved proliferation, adhesion and migration of HUASMC. Second, the effects of cilostazol were mainly through inhibiting RAGE/ERK/NF-ƙB pathway and HG induced reactive oxygen species (ROS) production. We conclude that the data provide an additional mechanism underlying the antiatherosclerotic effect of cilostazol by influencing RAGE signal and the downstream molecules.

141

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O-01

FACTORS ASSOCIATED WITH FIBROBLAST GROWTH FACTOR 19 INCREMENT AFTER ORAL GLUCOSE LOADING IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY 1

JUN-SING WANG, 1CHIA-LIN LEE, 2WEN-JANE LEE, 1I-TE LEE, 1SHIH-YI LIN, 3 WEN-LIENG LEE, 3KAE-WOEI LIANG, 1WAYNE H-H SHEU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

Background: Fibroblast growth factor 19 (FGF-19) has been emerged as an important hormone in regulating glucose homeostasis. We investigated factors associated with FGF-19 increment after oral glucose loading (OGL) in patients undergoing coronary angiography. Materials and methods: Patients without known diabetes who were referred from our cardiovascular center for screening for abnormal glucose regulation (AGR) were recruited. From May 2011 to June 2013, a total of 240 outpatients were recruited and underwent a 75-g oral glucose tolerance test. Blood samples were collected before and 2 h after OGL for laboratory measurements. FGF-19 increment was calculated as FGF-19 2 h after OGL minus fasting FGF-19. Results: Overall, FGF-19 significantly increased after OGL (from 123 [78~201] to 141 [80~237] pg/ml, p=0.001). By age tertiles (≤54, 55~64, ≥65), FGF-19 significantly increased only in patients aged ≥65 (from 143 [98~209] to 189 [124~332] pg/ml, p<0.001). By glucose regulation status, FGF19 significantly increased in patients with normal glucose tolerance (from 117 [78~211] to 153 [106~325] pg/ml, p=0.014) and in patients with prediabetes (from 117 [73~179] to 123 [70~204] pg/ ml, p=0.043), but not in patients with diabetes (from 181 [102~243] to 178 [111~275] pg/ml, p=0.139). In multivariate regression analysis, FGF-19 increment was positively associated with age (β coefficient 3.37, 95% CI 1.46 to 5.29, p=0.001) and negatively associated with AGR (β coefficient -77.67, 95% CI -138.96 to -16.37, p=0.013). Conclusions: FGF-19 increment after OGL was positively associated with age and negatively associated with AGR in patients undergoing coronary angiography.

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Abstract O-02

THE CONCOMITANT ASSOCIATION OF THYROID DISORDERS AND MYASTHENIA GRAVIS 1

YU-PEI LIN, 1CHEN-LING HUANG, 2PHUNG-ANH NGUYEN, 3WEN-SHAN JIAN, 1,4,5 CHUNG-HUEI HSU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 3School of Health Care Administration, Taipei Medical University, Taipei, Taiwan; 4Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 5School of Medicine, College of Medicine, Taipei Medical University

Background: Myasthenia gravis (MG) is a neuromuscular disease caused by autoimmunity, which affect the neuromuscular junction, blocking synaptic neurotransmissions and resulting in clinically symptomatic muscle weakness. The association of MG with Graves’ disease (GD), an autoimmune thyroid disease (AITD) occasionally presenting with ocular myopathy and exophthalmos, was firstly reported by Rennie in 1908.In this study, we assessed the association of MG with thyroid disorders through a large population cohort study, and evaluated the co-occurrence rate of these 2 diseases and the strength of association. Materials and Methods: We collected the claims records of 10.8 million males and 10.6 million females from Taiwan’s National Health Insurance program for the January 2000–December 2002 period. We identified all patients with MG and thyroid disorders by referring to the International Classification of Disease, Clinical Modification, Ninth Revision [ICD-9-CM] codes. Thyroid disorders were further divided into morphological, functional, coexisting functional and morphological. The association of MG with thyroid disorders occurred only in the same person within the 3-year study period. The Q value was used to measure the strength of disease–disease associations. Results: We obtained 7965 MG and 520628 thyroid disorder records for analysis. The association rate of MG and diffuse toxic goiter was highest, followed by nontoxic nodular goiter, simple goiter, chronic lymphocytic thyroiditis, thyroid cancer, and toxic nodular goiter. Female and older patients have a higher rate than their male and younger counterparts, respectively. Functional abnormalities revealed a high rate of thyrotoxicosis and hypothyroidism in both sexes. We found the strongest association in males with chronic thyroiditis, toxic diffuse goiter, thyrotoxicosis, acquired hypothyroidism, thyroid cancer, and simple goiter. Intermediate association was observed in female with toxic diffuse goiter, in male with toxic and nontoxic nodular/multinodular goiters, in female with thyrotoxicosis, thyroid cancer and acquired hypothyroidism. Weak association was found in female with toxic nodular/multinodular goiter, chronic lymphocytic thyroiditis, simple goiter, non-toxic nodular/multinodular goiter. Conclusion: We identified the association of MG with all types of thyroid disorders, and observed a high association rate in female autoimmune thyroid disorders and in older, whereas males have a higher strength of association. Coexisting autoimmunity and genetic predisposition may play major roles in pathogenesis. 143

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O-03

HIGH GLUCOSE CAUSES RENAL INJURY VIA GLYCOSYLATION OF RBP4 RECEPTOR SIGNALING 1

ZHAO-HONG CHEN, 2KUN-DER LIN, 2MEI-YUEH LEE, 3TUSEY-JIUAN HSIEH, 2,3PIJUNG HSIAO, 2,3SHYI-JANG SHIN

Background: An increase of retinol-binding protein 4(RBP4) concentration has been demonstrated in subjects with type 2 diabetes. RBP4 can induce insulin resistance by activating JAK/STAT5. We also found that free RBP4 can cause apoptosis through the reduction of RBP4 binding activity with STRA6(stimulated by retinoic acid 6), in turn JAK2/STAT5/JNK/p38MAPK pathway in renal cells. We hypothesized that high glucose might cause kidney injury via O-link Nacetylglucosamine(O-GlcNAcosylation) modification of STRA6, RBP4 activity with STRA6, CRBP1 and RARα signaling. Method: The expression of STRA6, CRBP1, RARα, NOX4, Cnx, UGGT1, OST, OGT, caspase, collagen 1 and fibronectin were measured by Western blot analysis and O-GlcNAcosylation of STRA6, RBP4 binding with STRA6 was detected by immunoprecipitation method in high glucosecultured HEK cells and the kidneys of STZ-induced diabetic mice. Immunofluorescent method was done to detect O- GlcNAcosylation of STRA6, RBP4 binding with STRA6, and RNA silencing of NOX4, Cnx, UGGT1, OST and OGT were done to investigate the role of STRA6 O-GlcNAcosylation on high glucose-induced apoptosis and fibrosis. Transfection of CRBP1 gene were performed to investigate whether the reversal of CRBP 1 and RARα can reduce apoptosis and fibrosis, or affect O-GlcNAcosylation modification. Result: The expression of STRA6, NOX4, Cnx, UGGT1, OST, OGT, caspase, collagen 1, fibronectin and apoptotic cell number increased, while CRBP1 and RARα decreased in high glucosecultured HEK cells and diabetic mice. Immunoprecitated and immunofluorecsent experiments showed an increase of STRA6 O- GlcNAcosylation, and decreased activity of RBP4 with STRA6 after high glucose stimulation. RNA silencing of NOX4, Cnx, UGGT1, OST and OGT can reverse above changes. Transfection of CRBP1 gene can reverses the increased STRA6 O-GlcNAcosylation, the decreased binding activity of RBP4 with STRA6, the decrease of RARα, and these increases of NOX4, Cnx, UGGT1, OST, OGT, collagen 1, fibronectin, caspase activity, and apoptotic cell number. Conclusion: High glucose can cause kidney damage via activating O-GlcNAcosylation of STRA6, reducing RBP4 binding with STRA6, and decreasing CRBP1, RARα and finally enhancing apoptosis and fibrosis in diabetic mice. These results indicate that the activation of STRA6 O-GlcNAcosylation with reduced RBP4 binding with STRA6, the decreased expression of CRBP1, RARα is one novel molecular mechanism of diabetic nephropathy. 144

Abstract O-04

CHARACTERIZATION AND ANALYSIS OF DIFFERENTIATED THYROID CANCER PATIENTS WITH POSITIVE THYROGLOBULIN ANTIBODY POST THYROIDECTOMY 1

DANIEL HUENG-YUAN SHEN, 1YI-FENG CHEN, 1CHENG-HAN HOU, 1LI-FAN LIN, 2 MING-LANG SHIH, 1CHENG-YI CHENG 1

Background: Serum thyroglobulin (Tg) is a useful marker for surveillance of follicular-derived thyroid cancer after operation and radioiodine ablation therapy. However, it might be interfered by the presence of serum thyroglobulin antibodies (TA), resulting either under- or overestimation of Tg level. TA positivity occurring to more than 25% of thyroid cancer patients and its prevalence is greater than general population. In this study we intend to investigate the clinico-pathological features as well as serum Tg level in this subset of patients with positive TA. Method and Material: In 2013 we had consecutively 322 patients undergoing I-131 diagnostic/ therapeutic scans and 10 of them were excluded because of TA data not available. Thus 312 thyroid cancer patient charts were retrospectively examined regarding with serum TA and Tg level, pathological report (tumor size, local invasion, nodal involvement) and clinical course (recurrence, metastasis). Results: There were 63/312 (20.2%) of patients with detectable serum TA. It ranged from 4.18 to >1000 IU/ml (98.0+/- 172.7 IU/mL; normal reference <4.11 IU/ml). F:M = 50:13 and 58/63 (92%) were papillary type. 8/63 (12.7%) of TA-positive patient had documented Hashimoto’s thyroiditis and 2/63 (3.2%) had Graves’ disease. Although the correlation between TA concentration and tumor size was insignificant (R2=0.057), the cervical nodal involvement (33/63=52.4%) and extrathyroid extension (15/63=23.8%) were more frequently seen in the TA-positive group. Recurrence (9/63=14.3%) and distant metastases (7/63=11.1%) were noted and the incidence rate seemed not to differ greatly form the average. The serum Tg level in TA-positive patients ranged from <0.2 to 32320 ng/ml. Fifty-two (82.5%) of them had Tg <0.2 ng/ml. Interestingly, six (85.7%) out of those seven TApositive patients with distant metastases had detectable Tg>0.2 ng/ml and most of them showed Tg above 20 ng/mL. Conclusions: TA positivity is commonly seen in thyroid cancer patients. Co-existing Hashimoto’s thyroiditis or Graves’ disease can be one etiology. The impact of TA positivity on disease severity seems not significant while the observed higher frequency of extra-thyroid extension and cervical nodal involvement requires further study. Despite that TA positivity can cause unreliable serum Tg measurement, our preliminary results indicate the serum Tg might be detectable, albeit with great variation, in presence of distant metastases. 145

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O-05

PROTEOMIC ANALYSIS OF FATTY LIVER TISSUES INDUCED BY HIGH-FAT DIET AND REVERSE ALTERATION WITH CANNABINOID RECEPTOR TYPE 1 ANTAGONIST TREATMENT IN MOUSE MODEL 1

CHIN-CHANG CHEN, 2YUNG-PEI HSU, 3CHING-FAI KWOK, 1YAN-JIE LIN, 3 KUANG-CHUNG SHIH, 1,2,3,4LOW-TONE HO 1

Overactivity of cannabinoid receptor type 1 (CB1R) acts as a key role in increasing incidence of obesity associated metabolic disorders by inducing accumulation of lipid in the liver and resulting in the progression of nonalcoholic fatty liver disease (NAFLD). Tissue proteome analysis has been applied widely to investigate the bioinformatics on the mode of action and therapeutic mechanism. Therefore, we used diet-induced obesity (DIO) dependent fatty liver mouse model to gain insight into the potential pathways altered with CB1R, and carried out quantitative proteomic analysis of liver tissues. Male C57BL/6 mice were randomly assigned for 12 weeks to standard diet (STD), high-fat diet (HFD), or HFD with 1-wk treatment of CB1R antagonist AM251 at 5 mg/kg (AM). Subsequently, liver tissues were harvested and analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE). Protein expression profiles were evaluated by computer-assisted image analysis and proteins were identified using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). After statistical analysis, our results revealed that 8 protein spots were significantly either up- or down-regulated among the three groups (significant changes defined as > ± 2-fold). These 8 proteins included major urinary protein 1 (HFD/STD: -2.94, AM/HFD: 2.75), ATP synthase subunit β (HFD/ STD: -3.23, AM/HFD: 2.18), isocitrate dehydrogenase [NAD] subunit α (HFD/STD: 2.93, AM/HFD: -2.27), epoxide hydrolase 2 (HFD/STD: -3.85, AM/HFD: 2.87), glucosamine-fructose-6-phosphate aminotransferase 1 (HFD/STD: -2.27, AM/HFD: 2.73), zinc finger protein 2 (HFD/STD: -2.78, AM/ HFD: 2.25), 60S acidic ribosomal protein P0 (HFD/STD: 2.27, AM/HFD: -2.22) and S-adenosylmethionine synthase isoform tyPE-1 (HFD/STD: 2.87, AM/HFD: 2.38). These dysregulated and/or recorrective proteins were predicted to be involved in different metabolic processes, including glucose metabolic process, xenobiotic metabolic system, ATP synthesized process and uncoupling protein and tricarboxylic acid cycle system in mitochondria. Based on these findings, we provide evidences that expression of mitochondrial enzymes was dysregulated in hepatic steatosis under HFD condition and this dysregulation was alleviated after the CB1R antagonist treatment.

146

Abstract O-06

CAN WE DISTINGUISH FOLLICULAR CARCINOMA FROM FOLLICULAR ADENOMA BY REGULARITY OF NODULAR MARGIN? 1,2

KUO-CHIN HUANG, 2,3CHWEN-TZUEI CHANG, 2,3CHING-CHU CHEN, 2,3 RONG-HSING CHEN, 2,3TZU-YUAN WANG, 3WEI-LUN HUANG, 3YI-CHIH HUNG, 3 CHING-CHUNG CHANG 1

Introduction: Thyroid nodule is a common thyroid disease. Most thyroid nodules are benign, but about 5% of thyroid nodules are malignancy. Generally, we followed up patients’ nodular goiter by thyroid ultrasonography and fine needle aspiration cytology in clinical practice. But it was difficult to distinguish from follicular adenoma and follicular carcinoma by cytology only. We conducted a retrospective study to evaluate if thyroid ultrasonography is helpful to distinguish follicular carcinoma from follicular adenoma. Patient and Method: Patients who received thyroidectomy from Jan, 2001 to Dec 2013 in China Medical University Hospital that pathological report were follicular adenoma or follicular carcinoma were enrolled in this study. We compared patients’ age, sex, TSH, free T4, thyroglobulin, nodular size (including width, tall, and tall to width ratio), nodular margin and echoic density between the groups of follicular carcinoma and follicular adenoma. TSH was graded in 4 groups by <0.1, 0.1 to <0.34, 0.34 to 5.6, and >5.6 IU/L. Thyroglobulin was divided in the four grades based on Quartiles. Patients who were positive of anti-thyroglobulin antibody were excluded in this variable. Nodular margin and echoic density were divided into four grades (0, 1, 2, 3), which higher grade mean more irregularity and lower echoic density. Differences between the follicular carcinoma and follicular adenoma groups were compared by Student t-test for continuous variables and by χ2 test for categorical variables. Multivariate logistic regression model to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of variables which p value were <0.2. For ORs, p-values < 0.05 were considered statistically significant. Result: A total of 104 patients, who were 68 patients of follicular carcinoma and 36 patients of follicular adenoma, were enrolled in this study. Fifty sex patients of follicular carcinoma and total of follicular adenoma had received the examination of thyroid sonography before operation. Patients with follicular carcinoma were older, and their thyroid nodules’ margins were more irregularity. There were no difference in sex, TSH, Free T4, thyroglobulin, tumor size and echoic intensity. Multivariate logistic regression model showed statistic significant of nodular margin after adjust age, sex, nodular density, and tall. The odds ratio of grade 2 and grade 3 of modular margin were 4.8 folds and 38 folds compared with grade 0. Conclusion: Regularity of nodular margin detected by thyroid sonography would be a criteria to differentiate follicular carcinoma and follicular adenoma. Irregular nodular margin predicted increase risk of malignancy. 147

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O-07

STATIN USE LOWERS THE INCIDENCE OF PARKINSON’S DISEASE IN PATIENTS WITH TYPE 2 DIABETES. -A STUDY USING THE NATIONAL HEALTH INSURANCE DATABASE 1,4

K-D LIN, 2,3,4P-J HSIAO, 4M-Y LEE, 2,3,4S-J SHIN

Graduate Institute of Medicine, 2School of Medicine, College of Medicine, 3Center of Lipid and Glycomedicine Research, Kaohsiung Medical University, 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C.

Introduction: Parkinson’s disease (PD) is an age-related neurodegenerative disease, characterized by muscle rigidity, slowing of physical movement, behavioral abnormalities and autonomic impairment. All of which have a dramatic impact on quality of life in these elderly patients. The incidence of PD was reported higher in type 2 diabetic patients by NHRI database in Taiwan. The pathophysiology about diabetes and PD is variable, including suppression of central dopamine levels, inflammation, oxidative stress and cerebrovascular diseases. A number of the hypothesized pathogenesis of PD may be related to blood cholesterol. Statin has effects on lowering blood cholesterol level and anti-inflammatory effects especially in type 2 diabetic patients. We study the effects of statin use on PD incidence in type 2 diabetic patients by using NHRI database. Materials and Methods: A random sample of one million subjects covered by the NHI in 2005 was used. Incidence rate and relative risk of PD (ICD-9-CM 332.0) in type 2 diabetic patients (ICD-9CM 250.xx) were evaluated to investigate the risk factors including age, sex, statin use, hypertension, stroke and ischemic heart disease. Results: There are 58601 type 2 diabetic patients enrolled in our study. Statin use rate was lower in older patients (14.28% in patients older then 70 y/o v.s. 59.22% in patients between 40~60 y/o) and higher in female patients (53.53% v.s. 46.47%). The incidence rate of PD increased from 139.25 to 1022.35 per 100,000 person-years as the age increased from 40 y/o to older than 70 y/o. The crude hazards ratio was 4.67(4.11~5.29) in age 61~70 y/o group and 7.53(6.66~8.52) in age >70 y/o group referenced by the group of age 40~60 y/o. The multivariate adjusted relative risk increased with age. The relative risk was 3.78(3.31~4.32) in age 61~70 group and 5.13(4.47~5.89) in age >70 group referenced by age 40~60 group. The PD incidence rate was lower in statin users v.s. non-statin users. The crude HR of statin users was 0.53(0.48~0.57) and the multiple-adjusted relative risk is 0.71(0.64~0.79) referenced by non-statin users. The PD incidence rate was inverse correlated with statin dose duration day(DDD) in type 2 diabetic patients. The trend test for the relative risk of statin DDD with incidence of PD is significant (P<0.0001, X2=51.8515). Conclusion: Type 2 diabetic patients had higher risk of developing Parkinson’s disease. Statin use in type 2 diabetic patients protects them from having PD. The dose respond relative risk was invert correlated with incidence of PD in type 2 diabetic patients. 148

Abstract O-08

RESPONSE OF DIFFERENT DEGREE PEDIATRIC GROWTH HOROME DEFICIENCY DURING REPLACEMENT THERAPY GAO BING-RU, 1,2CHEN PIN-FAN, 1LIAN WEI-CHENG, 1YAN SHIH-TANG, 1CHEN TING-CHANG 1

Division of Endocrinolgy and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital, Taiwan; 2 Shool of Medicine, Tzu Chi University, Hualien, Taiwan

Aim: Pediatric growth horomone (GH) deficiency is one the the correctable cause of grwoth failure and can be cured by GH repalcement therapy. The indication of GH repalcement has been varified from GH level <10 ng/ml to <7ng/ml during GH provocative tests by National Health Insurance in Taiwan in Dec. 2011. We try to invesgate the responsiveness of two different groups of growth hormone deficiency according to the changes of GH levels in NHI criteria. Method: From year 2005 to 2013, 17 patients who diagnosed as growth horome deficiceny and received replacement therapy in Dalin Tzuchi General Hoispital were enrolled in this study. One patients were excluded. Of the remaining patients, we devided into group 1 ( GH <7 ng/ml) and group 2 (7-10 ng/ml) according to the GH value during endocrine provocative tests. The annual growth velosity and body weight change during replacment therapy were recorded and compared. In addition, the basic chemobiochemsty tests was also recorded and analysed. Results: A total 16 patients, aged 9.6±2.1 (mean±SD) years old were devided into group 1 (n=12) and group 2 (n=4) with mean follow-up period 3.0 ±1.4 years. The anunal growth velosity (adjusted mean±SEM) in group 1 v.s group 2 was 8.7±2.0 cm v.s 8.9±1.4cm (p=0.750); 6.6±0.7 cm v.s 8.0±1.3cm (p=0.005) and 6.0±2.6 cm v.s 6.5±1.7cm (p=0.259) in the first, second, or third year, respectively. Conclusion: Patients with higher degree of GH provocative tests have better response to GH therapy in the second year after GH replacement. There is a need of placebo-control group to strengthen this finding.

149

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

O-09

RADIOACTIVE IODINE-REFRACTORY DIFFERENTIATED THYROID CARCINOMA - DATA FROM KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL 1

PEI-WEN WANG, 2YEN-HSIANG CHANG, 1I-CHIN HUANG, 1CHING-JUNG HSIEH

Division of Endocrinology and Metabolism, Department of Internal Medicine, 2 Department of Nuclear Medicine, Kohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, kaohsiung, Taiwan

Background: Most cases of differentiated thyroid cancer (DTC) are curable with the use of surgery and radioactive iodine (RAI) ablation. However, when RAI becomes ineffective against DTC, ten-year survival is <10%. RAI-resistance is believed to be progressive tumoral de-differentiation over time and loss the ability of iodine uptake, organification and retention. The aim of this study was to evaluate the prevalence and clinical characteristics of patients who developed RAI resistance in Kaohsiung CGMH. Materials and Methods: Two cohort of DTC patients were analyzied: (1) a prospective study of 222 patients who had received 131I whole body scan (WBS) in the year of 2006 and (2) a retrospective review of 126 patients with distant metastasis and long term follow-up (9.6 ± 5.2 yr). RAI-refractory DTC was defined: (1) tumors did not take 131I at initial treatment or lost the ability during follow-up (2) disease progression despite significant uptake of 131I (3) 131I uptake retained in some lesions but not in others, and (4) persistent disease after the administration of a cumulative activity of 600 mCi. Results: In the prospective year 2006 131I WBS cohort, 44 patients were observed to have RAIrefractory disease in 2014, including 12 patients diagnosed before 2006, 5 in 2006 and 27 after 2006. The prevalence and incidence in year 2006 were 7.7% (17/222) and 2.4% (2/210) respectively. During the follow-up of 8 years, 15.2% (32/210) developed RAI resistance. RAI refractory cancer was more frequently observed in patients with older age, large tumor burden, and lesions detected by18F-FDG. In the retrospective metastasis cohort, 131I avidity was more frequently observed in patients with younger age, whose primary tumors without local invasion, and whose metastases detected at the first 131 I ablation. For papillary thyroid cancer patients, 84.8% showed 131I avidity, while 29.3% obtained disease remission with undetectable Tg. For follicular thyroid cancer patients, 90.6% showed 131I avidity, while 15.6% obtained disease remission. Patients whose diseases went into remission had a lower mean cumulative dose of 131I than those who did not (297±195mCi vs. 618±381mCi). Conclusion: There are about 15% patients with DTC developed RAI-refractory disease in our series. Risk factors include old age, invasive tumor behavior, and metastases detected by 18F-FDG. These patients need more careful evaluation and choice.

150

Abstract O-10

LOW-DENSITY LIPOPROTEIN CHOLESTEROL ESTIMATION WITH VARIOUS FORMULAE CHING-YUN HU, CHIA-LIN LEE, CHIA-PO FU, JUN-SING WANG, I-TE LEE, YENMIN SONG, SHI-YI LIN, WAYNE HUEY-HERNG SHEU Endocrinology and Metabolism Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan

Background: The Friedewald formula (FF) is the most often used formula for estimation of lowdensity lipoprotein cholesterol (LDL-C) in clinical trial and clinical practice. A simple new formula (NF) to estimate LDL-C had been recently developed by us and showed to have better accuracy than FF in subjects with total cholesterol (TC) levels between 100 and 299 mg/dL. This study was aimed to compare various published LDL-C estimation formulae with ours in a Chinese population. Methods: This is a cross-sectional study in outpatients who had full lipid profiles report at a medical center in central Taiwan from January 2004 to October 2014. All subjects had measurements of TC, triglyceride, high-density lipoprotein cholesterol, and directly-measured LDL-C in the same blood sample. Patients with TG level greater than 400 mg/dL were excluded. The mean differences of estimated and directly-measured LDL-C were compared between different formulae. Results: A total of 32, 753 subjects were included for analysis and the directly-measured LDL-C levels were 116±39mg/dL. The NF by us yield estimated LDL-C, which was equal to 0.75×TC–25. The mean estimated LDL-C levels were 104±42mg/dL, 114±35mg/dL, 109±41mg/dL, 97±40mg/ dL, 113±37mg/dL, 105±36mg/dL, 100±34mg/dLby using FF, NF, DeLong formula, Hattori formula, Chen formula and Cordova formula respectively, and mean differences with measured LDL-C were 12.1 ± 19.1mg/dL (p<0.001), 1.3±19.2mg/dL (p<0.001), 7.1±15.3mg/dL (p<0.001), 18.6±18.6mg/ dL (p<0.001), 3.1± 11.9mg/dL (p<0.001), 10.4±12.1mg/dL (p<0.001), 15.2±19.8mg/dL (p<0.001). In subjects with type 2 diabetes mellitus, the mean difference were 13.0±22.1 (p<0.001), 0.7±21.4 (p<0.001), 7.7±18.0 (p<0.001), 19.2±21.4 (p<0.001), 3.3±14.1 (p<0.001), 9.9±14.3 (p<0.001), 13.0±21.7mg/dL (p<0.001). In subjectswithouttype 2 diabetes mellitus, the mean difference were 11.1± 15.4 (p<0.001), 1.9±17.9 (p<0.001), 6.5±11.8 (p<0.001), 18.0±15.2 (p<0.001), 2.8±9.2 (p<0.001), 10.9±9.4 (p<0.001), 17.4±17.4 mg/dL (p<0.001). Conclusion: The NF had better performance than other formulae and was not affected by the diabetes mellitus diagnosis. Further study should be validated in different population.

151

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-01

ANGIOTENSIN II ENHANCES ENDOTHELIN-1-INDUCED VASOCONSTRICTION THROUGH UPREGULATING ENDOTHELIN TYPE A RECEPTOR 1,4

YAN-JIE LIN, 2,4CING-FAI KWOK, 1,3CHI-CHANG JUAN, 4YUNG-PEI HSU, 2,4 KUANG-CHUNG SHIH, 1CHIN-CHANG CHEN, 1,2,3,4LOW-TONE HO 1

Institute of Physiology, National Yang-Ming University, Taipei, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 4 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

Objective: Endothelin-1 (ET-1) is the most potent vasoconstrictor by binding to endothelin type A receptor (ETAR) in vascular smooth muscle cells (VSMCs). Angiotensin II (Ang II) and Ang II type one receptor (AT1R) react together as transient constrictor of VSMCs. The synergistic effect of ET-1 and Ang II on blood pressure has been observed in rats; however, the underlying mechanism remains unclear. We hypothesize that Ang II leads to enhancing ET-1-induced vasoconstriction through the activation of ETAR on VSMCs. Methods: The ET-1-induced vasoconstriction, 125I-ET-1 binding, and mRNA and protein of endothelin receptors were explored in the isolated endothelium-denuded aortae and A-10 VSMCs. Results: Ang II pretreatment enhanced ET-1-induced vasoconstriction and ET-1 binding to the aorta. Ang II enhanced mRNA and protein of ETAR, but not ETBR, in aorta and increased ET-1 binding, mainly to ETAR on A-10 VSMCs. Moreover, Ang II-enhanced ET-1 binding and ETAR expression were blunted reduced by AT1R antagonism or by PKC- or ERK-inhibitor individually. Conclusion: Ang II enhances ET-1-induced vasoconstriction by upregulating ETAR expression and ET-1/ETAR binding, which may be because of the AngII receptor/PKC/ERK signaling. These findings suggest the synergistic response of Ang II and ET-1 on the pathogenic development of hypertension.

152

Abstract OE-02

THE POWER OF SERUM URIC ACID IN PREDICTING METABOLIC SYNDROME ALLEVIATED WITH AGING IN CHINESE ELDERLY 1,2

JUI-HUNG CHEN, 3DEE PEI, 1YI-JEN HUNG, 1CHANG-HSUN HSIEH, 4YEN-LIN CHEN

Background: Although uric acid (UA) is not a traditional criteria for Metabolic syndrome (MetS), many studies had identified a positive association between UA and MetS in different age and ethnic population. However, the association between UA and MetS is not fully elucidated in the very aged population. Methods: We selected subjects aged 65 and older undergoing routine health checkups in Taiwan. After excluding subjects with taking medications known to influence components of MetS or UA, a total of 18,906 Chinese elderly were eligible for analysis. Modified Adult Treatment Panel III criteria were used to define MetS. All the participants were further divided into nine groups with gender specification according to the age (the young-old : 65 to 74, the old-old : 75 to 84 and the oldest-old : 85 and over) and UA level. UA level is assigned from lowest to highest tertile with UA Gr1:<5.7 mg/ dl, UA Gr2:5.7~6.7 mg/dl and UA Gr3:>6.7 mg/dl in male and Gr1:<4.9 mg/dl, UA Gr2:4.9~5.9 mg/ dl and UA Gr3:>5.9 mg/dl in female. A cross-sectional study was first performed to determine the correlation between UA and MetS. A longitudinal study then excluded subjects with MetS at baseline to explore the risk of MetS among different UA level of 3 aged populations. Results: Based on the demographic data, we found a graded positive association between UA and MetS components but alleviated with aging. Higher UA level have higher odds ratio (OR) of having MetS but the condition also eased up with aging (OR: 1.383 and 2.030 in male and 1.596 and 3.021 in female in UA Gr2 and UA Gr3 in the young-old group and OR: 2.303 in female in UA Gr2 and 1.922 in male and 2.690 in female in UA Gr3 in the old-old group with UA Gr1 as reference group). In the second part, the Kaplan–Meier plot showed that higher levels of UA would have higher risk of developing MetS in the young-old group of both genders (p<0.01 when UA Gr 3 compared with UA Gr1 and UA Gr 2, respectively). In addition, the Cox regression model further confirmed the results (UA Gr3 HR: 1.898 in male and HR: 1.832 in female). Conclusions: In conclusion, the preset study revealed that higher UA level in the young-old group in Chinese elderly had higher risk for developing MetS and being regard as an adjuvant tool for early awareness of MetS. However, the condition weakened with age greater than 75 years old.

153

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-03

BMI AND PREOPERATIVE PLASMA ALDOSTERONE CONCENTRATION AS CRITICAL PREDICTORS RATHER THAN POTASSIUM LEVEL FOR HYPERTENSION CURE IN PRIMARY ALDOSTERONISM. 1

CHIA-HUI CHANG, 1SHI-WEN KUO, 2YAO-CHOU TSAI, 3VIN-CENT WU, 1YA-HUI HU

Purpose: A few recent studies show possible predictors or critical prognostic factors affecting complete hypertension cure after adrenalectomy for primary aldosteronism (PA) including BMI, preoperative plasma aldosterone concentration (PAC), duration of hypertension, preoperative response to spironolactone, genotype, tumor size, etc. In this study, we demonstrated the clinical outcome after unilateral adrenalectomy in PA. We try to identify critical predictors for hypertension cure by statistical analysis. Methods: We reviewed the medical record of our patient group of 17 people who had been clinically confirmed (by ARB suppression test) to have PA and had undergone unilateral adrenalectomy between 2010 and 2014. The postoperative patients were divided into three groups based on blood pressure control namely cure group (anti-hypertension drugs all deactivated), improvement group (anti-hypertension drugs have reduced or have lower blood pressure in the same dosage), nonimprovement group (anti-hypertension drugs can’t be reduced). We analyzed the differences in BMI, PAC, potassium level, etc. in these three groups. Statistical analysis was performed using one-way ANOVA. Statistical significance was defined as a P value of <0.05. Result: There were 10 males and 7 females, with a mean age 54.6±9.4 years. There were 10 males and 7 females, with a mean age 54.6±9.4 years. There were 1 heart failure (5.8%), 5 CVA (29%), 3 CKD (17.6%), 7 DM (41.4%) and 16 hypokalemia (94.1%) in our population of 17 patients before operation. After operation, almost the patients who suffered from hypokalemia have been cured, but most of DM patients show no improvement. No any postoperative adrenal insuffiency was noted. The number of left side lesion was about 2.5 times of right side lesion (12:5). BMI show significant differences (P=0.029). Preoperative PAC show boderline differences (P=0.054) in these three groups but potassium level does not (P=0.307). Conclusion: We suggest that BMI and preoperative PAC can be critical predictors rather than potassium level for hypertension cure in primary aldosteronism but more PA population will be needed. There is no evidence of association between DM and PA in our database. 154

Abstract OE-04

RISK FACTORS OF DISTANT METASTASIS IN FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA 1

YAN-RONG LI, 1JEN-DER LIN, 1SZU-TAH CHEN, 2CHUEN HSUEH, 3TZU-CHIEN CHAO

Objective: Follicular variant of papillary thyroid carcinoma (FVPTC) is the most common subtype of papillary thyroid carcinoma. The previous study reveals its clinical behavior is a mixed type of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma (FTC). Locoreginal extension was lower in FVPTC than C-PTC; however, distant metastasis rate of FVPTC is higher than C-PTC. Unlike experiencing an indolent clinical course in most FVPTC cases, patients with distant metastasis have a worse prognosis. The aim of this study is to evaluate risk factors of distant metastasis in FVPTC post-operatively. Method: A retrospective review of total 359 patients with final pathological diagnosis of FVPTC treated in Chang Gung Memorial Hospital from January 2000 to January 2014 was performed. After excluding patients who had inadequate pathology specimen and did not attend regular follow-up for more than one year, 346 patients were finally included in this study. The following data were extracted from admission records for analysis: age, gender, primary tumor size, ultrasonographic findings, FNAC results, operative methods, histopathology, TNM staging, one-month post-operative serum Tg levels, causes of death, and survival status. Univariate and multivariate statistical analysis were performed to determine the significance of various factors. Statistical significance was set at a p value of 0.05 or below. Result: Of 346 patients with FVPTC, 19 (5.5%) patients had lymph node metastasis ; 32 (9.2%) patients had distant metastasis. Among the distant metastasis group, 25 (78.1%) patients were diagnosed initially and 7 (21.9%) patients were recurrent with distant metastasis during followup period. Two positive and one negative risk factors were predictive for distant metastasis by multivariable analysis: angiolymphatic invasion (odds ratio (OR) 3.069 , 95% confidence interval 1.004 to 9.384), extrathyroidal extension (OR 3.256, 1.04 to 10.194) and encapsulation (OR 0.384, 0.162 to 0.912). Conclusion: The presence of angiolymphatic invasion, extrathyroidal extension and encapsulation were associated with distant metastasis in FVPTC in this study. Post-operative investigation for distant metastases may be warranted in the presence of these two positive risk factors in FVPTC.

155

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-05

Objective: Peripheral arterial occlusive disease, defined as low ankle brachial index (ABI) value, is associated with an increased risk of all- cause mortality. In addition, arterial stiffness is also an important predictor for death. We aimed to investigate whether mean arterial pressure, measured by pulse volume recording, predicted mortality in a group of diabetes subjects with normal ABI values. Research Design And Methods: We retrospectively reviewed patient who had undergone assessment of ABI with pulse volume recording at the Division of Endocrinology and Metabolism in Taichung Veterans General Hospital since Jan, 2008. Pulse volume recording was estimated by upstream time (UT) of arterial wave and mean arterial pressure (MAP) during the measurement of ABI. The mortality data were collect ed to Dec, 2011. We plotted the Kaplan-Meier curves between high- and low- UT group, and the between high- and low- MAP group. Results: Based on the values of ABI at baseline, all subjects (n=361) were divided into 3 groups, including: low ABI (ABI <0.90, n=99), lower normal ABI (0.9≤ ABI <1.1, n=139) and higher normal ABI (1.1≤ABI <1.3, n=78) groups. Subjects in low ABI group showed a highest mortality rate among three categories [p<0.001]. Among the subjects with normal ABI (0.9≤ABI<1.3), the subjects was divided by mean value ( MAP=46%). High MAP (defined as MAP ≥46%) showed a higher risk of allcause mortality rate than those with low MAP (defined as MAP<46%) [p<0.001], but UT could not significantly predict the all-cause death [p=0.085]. Conclusions: Our findings showed that in the subjects with normal value of ABI, mean arterial pressure, but not UT, was associated with an increased risk of all cause mortality in the subjects with normal value of ABI.

156

Abstract OE-06

HIGHER SERUM TOTAL BILIRUBIN CONCENTRATION IS ASSOCIATED WITH LOWER RISK OF CHRONIC KIDNEY DISEASE IN AN ADULT POPULATION 1

ANG-TSE LEE, 2,3,4YA-YU WANG, 1,4SHIH-YI LIN, 5JIIN-TSAE LIANG, 1,4,6WAYNE HUEY-HERNG SHEU, 1YUH-MIN SONG, 2WEN-DAU CHANG 1

Background: Chronic inflammation is proposed to play a central role in the pathogenesis of chronic kidney disease (CKD) and serum bilirubin has anti-inflammatory effects. We investigated the association between serum total bilirubin concentration and CKD among an adult population. Design and setting: We conducted a cross-sectional study and collected anthropometric measurements, fasting blood test, lifestyle habits and medical history in a total of 3876 subjects attending the health examination. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Results: Serum total bilirubin concentrations were significantly lower in subjects with CKD than those without CKD (13.88±6.70 vs. 14.77±6.58 μmol/L in men; 10.41±5.55 vs. 11.53±5.02 μmol/ L in women). Multivariable linear regression analysis showed that total bilirubin concentration was positively associated with eGFR after adjusting for age, body mass index, lipids, lifestyle habits, medications, hypertension, diabetes, hyperuricemia and previous cardiovascular disease in women (p=0.048). Multivariable logistic regression revealed higher serum total bilirubin concentration (each 1.71 μmol/L increment) was associated with reduced risk of CKD: odds ratios were 0.94 (p=0.005) in men and 0.90 (p=0.015) in women, respectively. And multivariate-adjusted odds ratios for CKD comparing the fourth to the first total bilirubin quartile were 0.49 (p=0.001) in men and 0.35 (p=0.003) in women, respectively; stepwise additionally excluding subjects first with possible liver disease and second with advanced CKD (stage IV and V) showed consistent results. Conclusion: Higher serum total bilirubin concentration was associated with lower risk of CKD, regardless of other conventional CKD risk factors.

157

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-07

Introduction: This study was conducted to identify the prognostic factors for the prediction of long term disease status in patients with differentiated thyroid carcinoma (DTC) who received 131I ablation therapy after total thyroidectomy. We also want to access the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (sTg) at the first 131I ablation for the prediction of prognosis. Patients and methods: Patients with DTC (n=357) treated with total or near-total thyroidectomy followed by immediate 131I remnant ablation were retrospectively studied. Patients with anti-Tg autoantibodies were excluded. A minimum of 5 years of follow-up was required. Patients were classified as having: (i) no clinical evidence of disease (NED) if they achieved an unstimulated thyroglobulin (uTg) or sTg level < 0.5 ng/dL and had a normal neck ultrasound and/or cross-sectional imaging (CT, MRI); (ii) indeterminate (IND) response if they achieved an uTg level < 0.5 ng/dL (undetectable) or sTg level 0.5-2.0 ng/dL and had nonspecific findings by neck ultrasound and/or cross-sectional imaging; (iii) biochemical persistent disease (BPD) if they had an uTg level ≧ 0.5 ng/ dL or sTg level ≧ 2ng/dL and no findings or nonspecific findings on neck ultrasound or cross-sectional imaging; or (iv) structural persistent disease (SPD) if they had positive findings by neck ultrasound or cross-sectional imaging or had abnormal uptake on follow-up diagnostic whole body scan when available (not thyroid bed uptake) with any uTg or sTg level. Results: The female-to-male ratio was 4.0:1. The mean age was 41.5±12.7 years. During the 12.3 ±5.0 years of follow-up, 76.2% (n=273), 12.6% (n=45), 9.5% (n=34) and 1.4% (n=5) of the patients achieved NED, SPD, BPD and IND after initial therapy, respectively. Under univariate analysis, sTg levels at the first 131I ablation were an independent prognostic indicator for SPD (Tg cut-off value 13.5 ng/dL; sensitivity 71.4 %, specificity 77.4%). The other independent predictors of SPD were older age (OR 1.06, 95% CI [1.03-1.10]), male (OR 2.734 [1.42-5.25]) and presence of initial neck LNs metastasis (OR 2.47 [1.33-4.58]), local invasion (OR 2.28 [1.15-4.51]) and multiple foci (OR 2.17 [1.11-4.26]). After multivariate analysis, older age and high sTg are still the independent contributing factors. Conclusions: Stimulated serum thyroglobulin at the first 131I ablation and old age are good predictors of structural persistent disease for long-term prognosis. 158

Abstract OE-08

ELASTOGRAPHY OF THYROID ULTRASONOGRAPHY PREDICT RECURRENCE OF GRAVES’ DISEASE 1,3,4

CHWEN-TZUEI CHANG, 2,3KUO-CHIN HUANG, 1,3RONG-HSING CHEN, 1,3,4TZUYUAN WANG, 1WEI-LUNG HUANG, 1YI-CHIH HUNG, 1,3CHING-CHU CHEN, 1CHINGCHUNG CHANG

Purpose: To retrospectively evaluate efficacy of elastography of thyroid ultrasound predict recurrence of Graves’ dis after antithyroid agents management. Patients and Methods: Patients who received antithyroid agents for a period till to stable of clinical condition with lower dosage of antithyroid agents from Jan, 2003 to June 2014 in China Medical University Hospital. Total enrolled 102 subjects and divided to recurrent group and nonrecurrent group. Each group compared age, sex, TSH, free T4, TRH receptor Ab and picture of elastography in thyroid ultrasound. Statistics was Chi-square test, dependent test. P-values < 0.05 were considered statistically significant. Results: A total of 102 patients, who were divided into 25 patients in recurrent group and 77 patients in non-recurrent group. No evidence differentiation of age , sex, free T4, TSH, TSH receptor antibody, Acoustic Radiation Force Impulse (ARFI) in thyroid US were noticed between two groups. All p-values were over 0.05. Basic data in recurrent and non-recurrent group. Conclusions: No evidence data can support elastography of thyroid ultrasound or other items could predict recurrence of Graves’ disease after hold antithyroid agents.

159

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

OE-09

AMIODARONE - ASSOCIATED THYROID DYSFUNCTION 1

HSIAO-LIEN CHEN, 2PAI-LIEN CHEN, 1HUAN-WEN CHEN, 3PEI-LING CHAN

Objective: To determine the incidence of amiodarone-induced thyroid dysfunction in patients with amiodarone treatment. Research design and methods: We performed a retrospective review charts among patients from 2011/7/11 to 2012/12/31 who had been prescribed amiodarone for six consecutive months were identified through the computer based information integrated system. Patients treated with amiodarone for six months and at least one time check thyroid function test after amiodarone were included. Baseline characteristics, laboratoratory parameters were evaluated. Results: A totalof 144 patients were studied (mean age, 76+10 years (range, 51-90 year) were studied. Of the 144 patients, 51% (n=73) developed thyroid dysfunction:10%( n=14) became hyperthyroid and 40% (n=59) hypothyroid.Female sex more significant for thyroid dysfunction 45% than euthyroid 32 %. Conclusions: Amiodarone can cause hypothyroidism, or hyperthyroidism. During the first several months of treatment, there is often a transient period of mild hypothyroidism. A few patients remain hypothyroid, and fewer develop hyperthyroidism. Because there is no set time course for the development of thyroid abnormalities, it is important to evaluate and monitor thyroid function after starting amiodarone therapy.

160

Abstract OE-10

EPIMEDIUM EXTRACTS INDUCED C2C12 PROLIFERATION AND HYPERTROPHY 1

YI-AN LIN, 2MEI-CHICH HSU, 3SZU-TAH CHEN

National Taiwan Sport University; 2 Kaohsiung Medical University; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

Backgroud: Epimedium is commonly used as an aphrodisiac agent to improve sexual dysfunction in traditional Chinese medicine. Icariin, a natural flavonoid glucoside isolated from Epimedium extracts (EE), has been proved to exhibit an anabolic effect on in vivo as well as in vitro studies. Even so, the anabolic effect of EE on skeletal muscle has not been thoroughly investigated. Purpose: This study is to determine the effects of EE on the proliferation and differentiation of C2C12 cells, a well-established mice myoblast cell line. Methods: After exposure to EE for 72 hours, proliferation of the cells was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. For myotube development, EE was applied 3 days after differentiation media has been given. Myotube diameter was measured by computer-aided software before and after EE treatment. Western blots were used to assess the amounts of total and phosphorylated Akt and p70S6K proteins critical in the insulin-like growth factor-1 (IGF1) signaling pathway. Results: EE treatment enhanced myoblast proliferation at 24 hour under the range of 10 to 100 ug/ml. In addition, EE significantly facilitated myotube growth by increasing its diameter. Both Akt and p70S6K were significantly phosphorylated after EE stimulation, and this response could be abolished by phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitors. Conclusion: By using C2C12 cells, we found EE potentially facilitate myoblast proliferation and myotube hypertrophy. Our results suggest that PI3K/Akt and mTOR/p70S6K signaling pathway may play an important role in the EE-induced anabolic effect.

161

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-01

THYROID TUBERCULOSIS 1,2

TSUNG-JU CHUANG, 1JHIH-SYUAN LIOU, 1YI-JEN HUNG, 1CHANG-HSUN HSIEH

We presented a patient underlying thyroid cyst got pulmonary tuberculosis (TB) and then received treatment of anti-TB agents. Moreover, the thyroid cyst increased in size gradually despite repeated aspirations and progressed to acute thyroid abscess. Thyroid TB was diagnosed by acid fast stain of pus. However, resudial thyroid cyst remained but diminished in size after drainage of abscess and a 6-month duration of anti-TB agents therapy. Thyroid cysts are often benign with high recurrence rate and usually didn’t need aggressive treatment unless compressive symptoms. Nevertheless, they may be sensitive to TB infection and need aggressive treatment such as surgery as early as possible in patients with pulmonary TB with thyroid involvement to avoid progression to a thyroid abscess.

162

Abstract PE-02

PRIMARY ADRENAL INSUFFICIENCY DUE TO ISOLATED ADRENAL CRYPTOCOCCOSIS IN A IMMUNOCOMPETENT MAN SUCCESSFULLY TREATED WITH ORAL FLUCONAZOLE 1

YI-CHIH HUNG, 1CHING-CHU CHEN, 1TZU-YUAN WANG, 2MAO-WANG HO

Background: Cryptococcosis was commonly developed in immune compromised patients presenting with pulmonary cryptococcosis and meningitis. There are only a few reports describing isolated adrenal cryptococcosis in immunocompetent subjects. Furthermore, adrenal cryptococcosis is usually refractory to antifungal therapy alone and unilateral or bilateral adrenalectomy was often required in such cases. Case presentation: We present an individual who is a hepatitis c virus carrier with hyperpigmentation and reducing 20kg in weight within two years. He had non-bilious vomiting for three days before visiting emergency department. In addition to hyponatremia(Na:120 mmol/L) and hyperkalemia(K: 5.1 mmol/L), high serum adrenocorticotropic hormone (ACTH) (347 pg/mL) with low random serum cortisol (Cortisol:3.13 ug/dL) was observed. Contrast enhanced abdominal CT showed bilateral adrenal masses without enhancement. The serum cryptococcal antigen titer was elevated to 1:256 and adrenal cryptococcosis was confirmed by biopsy of the adrenal masses. He was diagnosed as having primary adrenal insufficiency due to adrenal cryptococcosis without central nervous system or lung involvement. After 10 months of oral fluconazole and cortisone acetate treatment, the serum cryptococcal antigen titer was 1:16 and high serum ACTH also subsided (ACTH: 25.1 pg/mL). Conclusion: To our knowledge, this is the first case report describing isolated adrenal cryptococcosis in an immunocompetent patient successfully treated with oral fluconazole. It is difficult to make the diagnosis of this rare disease prior to resection or autopsy. Therefore, adrenal cryptococcosis should be considered in patients with bilateral adrenal masses with primary adrenal insufficiency.

163

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-03

PROLACTINOMA PRESENTING AS DELAYED PUBERTY: A CASE REPORT 1

YI-LUN CHIANG, 1SZU-HUI LEE, 1PEI-CHI CHEN, 1YEN-LING CHEN, 1CHUNG-YEN

HUANG, 1,2HONG-DA LIN, 1SHIH-MING LAI 1

Division of Endocrinology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Taipei-Veterans General Hospital , Taipei

Prolactinomas are benign pituitary tumors that are frequently seen in females aged 20 to 50. In children and adolescents, pituitary adenomas are rare, and prolactinomas are the most common secretory tumors in these. As in adults, prolactinomas are also predominant in girls. The symptoms are heterogeneous and differ according to the prolactin level, tumor volume, age of onset and gender. We reported a case of prolactinoma presenting as delayed puberty and reviewed the literature of prolactinomas in young population. Case presentation: An 18-year-old boy was referred to our hospital with the chief problem of delayed puberty. His body weight was 68 kg, height 170 cm, arm span 169, upper segment 82 cm, and lower segment 88 cm. Physical examination revealed no axillary hair. Pubic hair and genital were underdeveloped (Tanner stage 3). Laboratory data showed high prolactin level (598.7 ng/mL) and low testosterone (1 ng/mL). The bone age survey revealed 14 years old. The magnetic resonance imaging (MRI) of sella revealed a pituitary tumor about 1.8 cm in diameter, with stalk deviation to right side. After undergoing cabergoline treatment, the prolactin level decreased in the first month and the testosterone level became normal after treatment for 3 months. His secondary sexual development improved gradually. Discussion: Clinical presentation with prolactinomas in childhood and adolescents varies by their age and gender. The symptoms include headache, visual field defects, galactorrhea, pubertal arrest and short stature. In girls, most of the symptoms are manifestation of reproductive axis abnormalities, such as amenorrhea and galactorrhea; while in boys, the mass effect symptoms are more common. In our case, medical treatment with cabergoline showed a good efficacy in controlling clinical symptoms and signs, and is safe for young population.

164

Abstract PE-04

THE THYROID HORMONE RESISTANCE SYNDROME: A CASE REPORT 1

SHIH-HUI HUANG, 1CHUNG-YEN HUANG, 1SHIH-MING LAI, 1YEN-LING CHEN, 1 PEI-CHI CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin Kong Wu Ho-Su Memory Hospital, Taiwan, R.O.C.

Impaired sensitivity to thyroid hormone is a rare inherited disease. Resistance of thyroid hormone (RTH) is the most common form of impaired sensitivity to thyroid hormone. It is an autosomal dominant disease. Most RTH is caused by mutation of THRβ gene, leading to the defect of thyroid hormone action. The hallmark of RTH is the paucity of symptoms and signs despite the presence of high serum T4 and T3 concentrations. The most common symptoms, if present, are goiter, tachycardia, and hyperactivity. Here, we present a case of suspect resistance of thyroid hormone. A 19-year-old man with symptoms of hand tremor and tachycardia was presented in June, 2014. Lab data showed elevated free T4 with nonsuppressed TSH. However, there were no pituitary tumor on MRI and no any other pituitary axis dysfunction. Thyroid echogram showed bilateral lobes were enlarged and thyroid scan showed diffusely increased tracer uptake. TRH stimulation test was also done and revealed exacerbated response. As a result, RTH was highly suspected. We had tried levothyroxin 0.1 mg/day but the TSH level had not been suppressed. Currently, only propranolol was prescribed for controlling his symptoms of hyperactivity and tachycardia. This case highlights that we should, in addition to pituitary TSH-secreting tumor, take RTH into consideration when we met a case of thyrotoxicosis with nonsuppressed TSH.

165

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-05

SUBACUTE THYROIDITIS PRESENTING AS DIFFUSE UPTAKE OF THYROID GLAND ON 18F-FDG PET/CT: A CASE REPORT 1

CHEN-TI WANG, 1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1SHU-JU KU, 1JU-CHUN HUANG, 1KUO-BIN TSENG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine, I-Shou University, Kaohsiung, Taiwan

Subacute thyroiditis is an inflammatory disease of the thyroid gland and is usually preceded by an upper respiratory tract infection and is thought to be caused by a viral infection or a postviral inflammatory process. The postviral inflammatory response leads to giant cell infiltration into the thyroid follicles resulting in disruption and collapse of thyroid follicles, and necrosis of follicular cells. This in turn causes pain and tenderness on palpation of thyroid. Radioiodine or technetium imaging study will show low uptake or a faint heterogeneous pattern of radionuclide uptake during the hyperthyroid phase. Ultrasonography of the thyroid appears to be normal or enlarged but is diffusely or focally hypoechogenic. Imaging studies of subacute thyroiditis shown on 18F-FDG PET/CT is scarce. We report a case of subacute thyroiditis presenting as diffuse uptake of thyroid gland on 18F-FDG PET/CT. The patient was a 49-year-old man who went for health examination due to symptoms of poor appetite, body weight loss 9kg in recent 3 months and poor concentration. 18F-FDG PET/CT revealed diffuse hypermetabolic process in both lobes of thyroid. Patient was then referred to Endocrinology and Metabolism outpatient department for further evaluation. Physical examination revealed tenderness of bilateral lobes of thyroid. Laboratory tests revealed elevated erythrocyte sedimentation rate (ESR: 54mm/hr; normal range: 0-20mm/hr), low thyroid-stimulating hormone (TSH: 0.06 uIU/ mL; normal range 0.35-4.94 uIU/ml), mild elevation of free-T4 (FT4: 1.54 ng/dL; normal range 0.7-1.48 ng/dL), elevation of thyroglobulin (Thyroglobulin: 157.14 ng/dL; normal range <50 ng/ dL), negative antimicrosomal antibody, negative thyroglobulin antibody and negative thyrotropin receptor antibody. Thyroid ultrasonography showed enlargement of bilateral thyroid lobes with illdefined irregular margin and hypoechoic hypovascular areas, compatible with subacute thyroiditis of both lobes. Thyroid fine needle aspiration was performed and the results of cytologic examination were consistent with subacute thyroiditis. Patient subsequently had a Tc99m thyroid scan and hardly shows visualization of the thyroid gland, which is also compatible with subacute thyroiditis. Oral prednisolone was prescribed and patient’s thyroid tenderness improved rapidly. Decreased uptake shown on Tc99m thyroid scan indicates disruption of the follicles of the thyroid. Diffuse uptake shown on 18F-FDG PET/CT was probable due to inflammatory changes of thyroid. Tc99m thyroid scan and 18F-FDG PET/CT can show different findings for subacute thyroiditis. Subacute thyroiditis in clinical practice is not rare. While 18F-FDG PET/CT is known to be helpful for making clinical decisions for thyroid lesions, there are still indeterminate clinical cases for diagnosing subcute thyroiditis. Therefore, clinical symptoms and other accompanying studies should be considered for diagnosis. 166

Abstract PE-06

A CASE OF CUSHING’S SYNDROME WITH BILATERAL ADRENAL TUMOR 1

SHIH-TANG YAN, 1,2PIN-FAN CHEN

Divison of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

Purpose: A 52-year-old man with Cushing’s syndrome was noted to have bilateral adrenal tumors. Initial ACTH data was still detectable (12.3 pg/dl, normal range 5-77, by RIA). Finally, unilateral functional adrenal tumor was proved. Abstract: A 52-year-old man came for leg weakness, rounding of face, and protruding of abdomen since 2 years ago, with weight gain 9 kg. Leg edema was noted from 3 months ago. He ever visited Ortho. Dr. for suspecting spondylosis. Abdominal CT revealed right adrenal nodule (12 mm) and left adrenal mass (around 3 cm in size) incidentally. So he was referred to our OPD. He was 79 kg weight and 175 cm height, BP 164/116 mmHg, with rounding of face, globular abdomen without striae, central obesity, without leg edema. Na: 145 and K: 3.6 mmol/L. Overnight dexamethasone suppression test (DST), 1 mg, showed cortisol level still 19.15μg/dl. The results of low-dose and highdose DST were 24.3 and 26.8μg/dl of morning cortisol, respectively. Baseline ACTH by RIA method was 12.3pg/ml by our lab. (repeat and the same) and caused diagnosis confusion. MRI of sella reported a small (4.9×4.4 mm) left pituitary tumor. We referred the case to Tai-Chung Veteran General Hospital, where the data of ACTH was undetectable. So the diagnosis of adrenal Cushing’s syndrome was more definite. NP-59 adrenal scan with SPECT showed uptake over left adrenal mass and no significant uptake over right adrenal tumor. Left adrenal mass was removed by laparoscopy uneventfully. After operation, significant reduction of weight, rounding face and protruding abdomen were noted. Blood pressure also became normal spontaneously. But he had symptoms of adrenal insufficiency and needed steroid supply for several months. Conclusion: A 52-year-old man with Cushing’s syndrome was noted to have bilateral adrenal tumors. Series of tests and image finding favored adrenal cause. However, initial inaccuracy of ACTH test leaded to diagnosis confusion. NP-59 adrenal scan helped to localize the side of functional tumor. After removal the tumor, symptoms much improved.

167

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-07

Prolactin level is regulated by hypothalamic-pituitary-prolactin axis. The dopamine produced in hypothalamus transports to the pituitary via hypothalamic hypophysial system and inhibits pituitary prolactin secretion. Stalk compression usually interrupts this pathway and leads to hyperprolactinemia. An 48-years-old woman was referred by OB/GYN clinic because of hyperprolactinemia (91.8 µg/L) which was treated with Cabergoline. Our investigation showed hyperprolactinemia (52.8 µg/L) but other pituitary hormones were within normal range. The MRI of the pituitary fossa showed a 1.8x2x2.1cm nodular lesion in suprasellar region with compression of pituitary gland and optic chaism. The differential diagnosis of the mass includes prolactinoma, or non-functional pituitary tumor with stalk compression that induces hyperprolactinemia. We also noted the tumor flow-void on T1WI & T2WI connecting to right ICA. Under the aneurysm arising from right ICA, the patient received angiography. Carotid artery aneurysm was confirmed by angiography and aneurysm surgery was performed. The symptoms of hyperprolactinemia was improved after surgery. The causes of hyperprolactinemia include physiologic cause, pathologic cause and pharmacologic cause. Among the pathological causes, the two most common etiologies are prolactinomas and decreased dopaminergic inhibition of prolactin secretion. Clinically, serum prolactin levels greater than 200 µg/L suggests the presence of a macroprolactinoma, and ranging from 25 to 100 μg/L usually indicates microadenoma or medication-induced hyperprolactinemia. However, a minimal to moderate elevation can also indicate secondary stalk interruption. Stalk compression caused by unruptured aneurysm is rare but very risky because it indicates large aneurysm which need aggressive treatment including surgery and adequate blood pressure control.

168

Abstract PE-08

Introduciton: Primary aldosteronism (PA), first described by Conn in 1955, is characterized by hypertension, increased aldosterone secretion and suppressed plasma renin activity (PRA). Previous reports indicate that primary aldosteronism is rarely to cause malignant or accelerated hypertension. Here we report a case of PA presented with severe hypertension without suppressed PRA. Case Report: A 27-year-old woman with a history of hypertension was refered to our hospital because of severe hypertension noted prior to tooth extraction. He had hypertension for 2 years without regular medications . Her blood pressure was 223/153 mmHg in supine position. His pulse rate 101/ min, respiratory rate 14/min and body temperature 36 ℃ .Physical examination revealed an acutely ill woman weighting 49 kg and measuring 159 cm tall. His heart beat was rapid without murmur and his breath sounds was clear. Neurologic examination was normal. Laboratory data consisted of the following: BUN 17 mg/dl, Cr 0.9 mg/dl, Na 137 mEq/L and K 2.8 mEq/L. PRA (plasma renin activity 1.73 ng/ml/hr , aldosterone 73.3 ng/ml. She received triple antihypertensive drug therapy. But her blood pressure still around 159/113mmHg. Two repeat assays of PRA and aldosterone were PRA 1.6 ng/ml/hr, aldosterone 76.8 ng/ml; PRA 2.6 ng/ml/hr, aldosterone 76.4 ng/ml separately. Persistent hypokalemia 3.2 mEq/L was found. Renal artery stenosis was highly suspected. A computed tomography (CT) scan showed a hypodense nodule of 1.2 cm of diameter in the left adrenal gland and patent both renal arteries. Unilateral left adrenalectomy was then performed due to considered PA . One yellowish adrenal gland tumor 1.0 x 1.0 cm of left adrenal gland was removed. The pathology showed cortical adenoma, which is compatible with Conn’s syndrome. Her blood pressure gradually returned to normal range with only one antihypertensive drug. Conclusion: PA can complicated with severe hypertension. A normal or even a high normal PRA does not necessarily exclude the diagnosis of PA. PA should be considered as a possible underlying cause of normal renin malignant hypertension.

169

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-09

CAN ROBOTIC THYROIDECTOMY APPLIED TO THYROID CARCINOMA WITH LUNG METASTASES? 1

HSIAO-WEN CHANG, 2YI-FENG CHEN, 1CHANG-HSUN HSIEH, 2DANIEL HUENGYUAN SHEN 1

Background: Robot-assisted trans-axillary endoscopic thyroidectomy (RTET) is an emerging surgical technique. Compared to the conventional thyroidectomy, it leaves no cervical scar and less neck discomforts. While Korean experience in RTET is impressive, the reproducibility and validity of its surgical completeness and oncological outcomes remains questionable elsewhere and the patient’s selection is still in debates. Herein we present a case of cytological suspected thyroid malignancy undergoing RTET while, post-operatively, without histological evidence of primary thyroid cancer but noted multiple lung metastases. Case presentation: A 49-year-old woman presented bilateral thyroid nodules, which was suspected to be papillary thyroid cancer (PTC) within right lobe via fine needle aspiration cytology. RTET was done in a local teaching hospital and the pathology indicated nodular goiter without malignancy. Due to post-operative hoarseness, she was referred to the ENT specialist, who recognized her pulmonary nodules via chest films incidentally. Lung metastases from follicular thyroid carcinoma were proved and then she was referred to our hospital for 131I therapy. 99mTc thyroid scan demonstrated left-sided thyroid remnant with appreciable uptake. 131I therapy (150 mCi) via rhTSH stimulation was utilized and post-therapeutic scan demonstrated those pulmonary lesions with iodine avidity. Four months after treatment, the lesional uptake disappeared and serum thyroglobulin (Tg) level subsided from 119.9 to <0.2 ng/ml and anti-Tg antibody also fell from 11.16 IU/ml to negative. Discussion: It is unusual to note cytological diagnosis of PTC not confirmed by subsequent histopathology and also uncommon to see evident lung metastases without primary thyroid cancer. It might be explained by the cytological features of PTC sometimes shared with other benign tumors (false positive finding) and/or primary lesion misdiagnosed (occult follicular thyroid cancer). Surgical incompleteness of RTET can also be one other concern. Contrast to Korea’s expert opinions, European study include BMI <22, unilateral small-sized nodules and low risk of malignancy as selection criteria of RT. Apart from controversy of RTET, we also face problems like limited case numbers and unfulfilled established surgeon training in Taiwan. From this case, we call for attention that RTET should only be opted when the risk of advanced thyroid cancer can be excluded.

170

Abstract PE-10

HYPERTRIGLYCERIDEMIA INCREASES THE SEVERITY OF THROMBOCYTOPENIA IN DENGUE INFECTED PATIENTS 1,3

MEI-YUEH LEE, 2CHUNG-YUAN CHEN, 3KUN-DER LIN, 3YU-LI LEE, 1,3WEI -HAO HSU, 3PI-JUNG HSIAO, 3SHYI-JANG SHIN 1

Department of Internal Medicine,Kaohsiung Municipal Hsiao-Kang Hospital; 2Chin-Pin Clinic, Kaohsiung; Division of Endocrinology and Metabolism , Kaohsiung Medical University Hospital

Background: The severity of thrombocytopenia is an indicator of the severity of dengue virus infection.We investigated whether hyperlipidemia especially hypertriglyceridemia is associated with thrombocytopenia in dengue-infected patients. Methods: We studied clinical characteristics of 644 patients with dengue infection at a Kaohsiung Medical University Hospital during the epidemic June 1, 2002 to December 31, 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. Results: Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p= 0.004 ), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Conclusion:Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

171

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-11

INITIAL FALSE NEGATIVE ALDOSTERONE-TO-RENIN RATIO IN PRIMARY ALDOSTERONISM WITH SEVERE HYPOKALEMIC RHABDOMYOLYSIS- A CASE REPORT 1

YI-WEI WU, 1YA-HUI HU, 2YAO-CHOU TSAI, 1SHI-WEN KUO

Division of Endocrine and Metabolism, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taiwan; 2Division of Urology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taiwan A 50-year-old female came to our neurology outpatient clinic for a sudden onset of right arm weakness which had occurred twice in 3 months. She had a history of hypertension under irregular medication for 7~8 years. Brain MRA was performed and revealed a right MCA aneurysm at M1-2 junction. She was referred to neurosurgery outpatient department. Surgery was suggested but the patient hesitated. However, the patient had severe neck pain with general weakenss and muscle pain 2 weeks later. Severe hypokalemia (1.7 mmol/L) with elevated creatine kinase level (6086 IU/L) was noted. After admission under the impression of hypokalemic rhabdomyolysis and hypertension, the patient was given potassium supplement and blood pressure control with carvedilol 6.25mg twice daily, amlodipne 5mg twice daily and telmisartan 80mg once daily. Because of her hypertension and hypokalemia, primary aldosteronism was highly suspected. Functional test was performed and the patient’s aldosterone-to-renin ratio (ARR) was 15 initially. Hypokalemia induced lab error was suspected. The patient’s creatine kinase level peaked at 27930 IU/L 3 days later. We gave the patient spironolactone and her hypokalemia and rhabdomyolysis improved. We repeated ARR after hypokalemia had been corrected and it was 324. Contrast adrenal computed tomography revealed a 1.9 cm left adrenal tumor. NP-59 SPECT/CT was performed and it showed a left adrenal gland tumor with increased NP-59 uptake, compatible with a functional adenoma. The patient was then referred to urology for left unilateral adrenalectomy . Pathology reported left corticol adenoma. At follow-up, her hypertension had been gradually improving and she was free of hypokalemic rhabdomyolysis. A 50-year-old female came to our neurology outpatient clinic for a sudden onset of right arm weakness which had occurred twice in 3 months. She had a history of hypertension under irregular medication for 7~8 years. Brain MRA was performed and revealed a right MCA aneurysm at M1-2 junction. She was referred to neurosurgery outpatient department. Surgery was suggested but the patient hesitated. However, the patient had severe neck pain with general weakenss and muscle pain 2 weeks later. Severe hypokalemia (1.7 mmol/L) with elevated creatine kinase level (6086 IU/L) was noted. After admission under the impression of hypokalemic rhabdomyolysis and hypertension, the patient was given potassium supplement and blood pressure control with carvedilol 6.25mg twice daily, amlodipne 5mg twice daily and telmisartan 80mg once daily. Because of her hypertension and hypokalemia, primary aldosteronism was highly suspected. Functional test was performed and the patient’s aldosterone-to-renin ratio (ARR) was 15 initially. Hypokalemia induced lab error was suspected. The patient’s creatine kinase level peaked at 27930 IU/L 3 days later. We gave the patient spironolactone and her hypokalemia and rhabdomyolysis improved. We repeated ARR after hypokalemia had been corrected and it was 324. Contrast adrenal computed tomography revealed a 1.9 cm left adrenal tumor. NP59 SPECT/CT was performed and it showed a left adrenal gland tumor with increased NP-59 uptake, compatible with a functional adenoma. The patient was then referred to urology for left unilateral adrenalectomy . Pathology reported left corticol adenoma. At follow-up, her hypertension had been gradually improving and she was free of hypokalemic rhabdomyolysis.

172

Abstract PE-12

ADRENAL LYMPHOMA: A CASE REPORT 1

LI-WEI HSIAO, 1CHIA-LIN LEE, 2CHIEH-LIN TENG, 1SHI-YI LIN, 1WAYNE HUEYHERNG SHEU 1

A 60-year-old old woman suffered from spiking fever for 3 days and initially visited the local hospital, where scrub typhus was impressed. After taking Doxycycline for one week, high fever still persisted, and the serology test result was negative. Finally, she came to emergency department of our hospital for further management. Incidentally, the abdomen computed tomography (CT) showed bilateral enlarged adrenal glands, both about 4.4cm. Therefore, she was admitted to our ward for adrenal incidentaloma and fever survey. At admission, the endocrine function tests showed that blood cortisol, ACTH, renin and aldosterone concentrations were all within normal limit, and therefore, the non-functional incidentaloma was impressed. The tumor survey of the other sites also showed negative findings. However, after a detailed review of her serial blood routine data, a progressively increased monocyte fraction was noted within 10 days after fever onset, and the peripheral blood smear demonstrated that monocyte was 9%, lymphocyte 21% and atypical lymphocyte 1%. Her LDH and ferritin level were increased to 946 U/L, and 1842 ng/ml, respectively, and an inverted albumin to total protein ratio was noted, A/G ratio=0.75. Then, we consulted the oncologist because of suspicion of hematological malignancy. The bone marrow biopsy proved to be diffuse large B cell lymphoma. A further adrenal mass biopsy was ever suggested, but the patient refused. Under the impression of adrenal lymphoma with bone marrow involvement, she received chemotherapy with R-CHOP+IT regimen for one cycle, and then shifted to R-hyper CVAD regimen for 3 cycles till now because of aggressive lymphoma pattern. After 4 months chemotherapy, her follow–up abdominal CT showed that bilateral adrenal glands size were both reduced to 1.2 cm, and the repeated bone marrow biopsy showed remission status.

173

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-13

THYROIDITIS AND HYPERCALCEMIA AFTER UNILATERAL ADRENALECTOMY FOR CUSHING’S SYNDROME : A CASE REPORT 1

YU-WEI CHEN, 1CHIA-PO FU, 2WEN-MING CHEN, 1SHI-YI LIN, 3WAYNE H-H SHEU

We reported a 46-year-old man with adrenal Cushing’s syndrom who developed thyroiditis complicated with symptomatic hypercalcemia after adrenalectomy. Initially, he was admitted to hour hospital for right adrenalectomy due to a cortisol-secreting adrenocortical adenoma in Jun, 2014. After adrenal surgery he was given glucocorticoid substitution, but later the patient discontinued steroid treatment and lost follow-up. In Jul, 2014, he began to suffer from fatigue, nausea, anorexia, vomiting and diffuse joint pain for weeks, and then was sent to ER due to drowsy consciousness and tremor of extremities on Jul 24, 2014. On admission, the patient’s GCS score was E3V4 M5, blood pressure was 138/85 mmHg, pulse rate 134/min, repiratory rate 19/min body temperature was 37.0 ° C. His height was 171 cm, weight 54 kg, and body mass index 18.4 kg/m2 .Laboratory tests showed that serum cortisol was les than 1μg/dl and ACTH was 34.4 pg/ml, correct serum calcium 13.9 mg/dl, PTH less than 3 pg/ml, free thyroxine (FT4) 42.10 pg/ml, and suppressed thyroid stimulating hormone (TSH) 0.006 uIU/ml. Serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were undetectable. The technetium thyroid scintigraphy found a complete absence of thyroid uptake, and thyroid ultrasound that revealed a diffusely hypoechogenic gland with low blood flow. According to these findings and the patient’s past history, he was diagnosis to have acute adrenal insufficiency and thyroiditis with hypercalcemia. Following steroid treatment his symptoms resolved gradually with improved consciousness. In addition, serum calcium level returned to 8.7 mg/dl on day 5 after steroid treatment, and FT4 level was 9.98 pg/ml and TSH level was 10.5 uIU/ml on day 87 after steroid treatment.

174

Abstract PE-14

Background: Follicular thyroid cancer (FTC) associated hypercalcemia is a rare condition coupling to increase mortality. The possible mechanisms of hypercalcemia in FTC are direct bone destruction and/or paraneoplastic effect. Through a different mechanism, rhTSH has been reported to induce hypercalcemia in far advanced thyroid cancer with massive residual cancer secondary to it’s thyrotropic effect on inducing hyperthyroidism. Here we present a case of hypercalemic crisis after administration of rhTSH for cancer treatment. Patient: A 50-year-old woman noted of inoperable recurrent FTC with pulmonary metastasis since 2011. Soft tissue mass and bone metastasis developed since 2014. rhTSH was prescribed for high dose radioactive iodine (RAI) therapy because patient could not tolerate her symptomatic hypothyroidism. Results: The patient was admitted to our hospital with severe nausea and vomiting the day after rhTSH administration. Laboratory data showed severe hypercalcemia >15mg/dL with low i-PTH(< 2.5pg/mL) and mild thyrotoxicosis [triiodothyronine (T3) 161.6 ng/dL, free thyroxine (FT4) 0.79 ng/ dL, TSH 0.009 µU/mL]. Plain X-ray revealed bony destruction of right scapula and right humerus. Patient was discharged with her total serum calcium level returned to normal range after massive fluid replacement, loop diuretics and intravenous bisphosphonate. Discussion: In the literature, rhTSH was reported to induce hypercalcemia in well differentiated thyroid carcinoma due to TSH induced hyperthyroidism or increased bone resorption by TSHenhanced tumor activity. In this case, we suspect that the hypercalcemic crisis may be associated with dehydration secondary to thyrogen induced nausea and vomiting. We report this case to remind doctors to be aware of possible sever complication of thyrogen to prepare patients for RAI treatment in far advanced well-differentiated thyroid carcinoma.

175

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-15

A CASE OF RETROPERITONEAL MASS LESIONS: PARAGANGLIOMA 1

CHIN CHOU YANG, 3CHING WEI CHANG, 2CHUN LU LIN, 1YA CHUN HSIAO, 2 CHUN CHUAN LI, 1YA CHUN HSIAO, 2CHUN CHUAN LI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan

Pheochromocytoma and paraganglioma are rarely seen cathecolamine-secreting neuroendocrine tumors. In our case, a retroperitoneal paraganglioma with a diameter of 5 cm was detected in a 71 years old man. After admission, he was found loss of consciousness suddenly. Myocarditis related to pheochromocytoma was the most possible reason of sudden collapse. The diagnosis of paraganglioma was made later in ICU, which would be subsequently removed. Pheochromocytoma or paraganglioma may cause hypertensive emergency which can lead to end organ damage. It should never been neglected in the differential diagnosis of retroperitoneal mass lesions, even though initial manifestations are not suggestive for the diagnosis. Case report: A 71 years old man presented with acute palpitation, abdominal pain, headache and dizziness in ER. He has history of hypertension for 4 years, and his condition remained stable while taking daily combination therapy with CCB, ARB, and B-blocker. Abdominal CT revealed a 5cm heterogeneous soft tissue mass occupied at right para-aortic region with anterior displacement of duodenum and pancreas head. He was admitted on Aug 20, 2014 under the tentative diagnosis of pancreatic tumor. On Aug 22 early morning, he was found loss of consciousness suddenly. After CPR and intubation with mechanical ventilator support, vital sign recovered. He was then transferred to ICU. Elevation of cardiac enzyme was noted. (Troponin-I: 12.67ng/mL, CK: 966IU/L, CKMB: 74.5ng/ mL). EKG revealed QS pattern and disappearance of R wave over anterior wall. Diagnostic cardiac catheterization was performed on Sep 10 and it revealed non-significant CAD. (RCA patent; LAD-D 50% stenosis；LCX hypoplasia) Fluctuating blood pressure was noted in ICU. We checked 24hr-Urine VMA and catecholamine for 2 days. The data revealed elevation of both VMA and catecholamine (VMA: 11.8, 13 mg/day, norepinephrine: 205.6, 168.7 ug/day). Correlated the clinical condition with laboratory data and CT findings, functional paraganglioma was highly suspected. Surgery is indicated. After discussion with the family, the patient was dischanged on Sep 27 and operation will be arranged later. Discussion: The terms of “pheochromocytomas” and “catecholamine-secreting paragangliomas” are referred to as catecholamine-secreting tumors that arise from the adrenal medulla and the sympathetic ganglia, respectively. Because of similar clinical presentations and treatments, some clinicians might use “pheochromocytoma” to refer to both of them. The classic triad of pheochromocytoma includes symptoms of episodic headache, sweating, and tachycardia. The pathogenesis of secondary hypertension and the role of catecholamines in the pathophysiology of pheochromocytoma have been well documented. Indeed, sustained or paroxysmal hypertension 176

Abstract is common, but about 5 to 15 percent of patients present with normal blood pressure. With high sensitivity, plasma metanephrines reamins the first-line test as diagnosis of pheochromocytomas. However, it is not available in some hospital. Another reliable method for diagnosis is measuring metanephrines and catecholamines in a 24-hour urine collection, both of them have high sensitivity and specificity. Adrenalectomy by an experienced surgeon is suggested as treatment of adrenal pheochromocytomas. However, surgical intervention does not always lead to long-term cure. Longterm monitoring is indicated in all patients, even those apparently cured. In our case, a 5cm heterogeneous retroperitoneal mass occupied at right para-aortic region was found in CT scan. In the differential diagnosis of retroperitoneal mass lesions, pheochromocytoma should never been neglected. The diagnosis was made later because of fluctuating blood pressure. The laboratory data revealed high levels of catecholamines and VMA in 24hr-urine studies. Correlated with the finding of CT scan, a paraganglioma is the most likely diagnosis, which would be subsequently removed. The diagnostic cardiac catheterization revealed no significant CAD. LVG demonstrated preserved LV systolic function. Myocarditis related to pheochromocytoma was suspected, although it has not been proven by tissue biopsy. Paraganglioma was the most possible reason of sudden collapse. In fact, unusual presentation of pheochromocytoma as acute myocarditis or cardiogenic shock has ever been reported. Also, the pathophysiology of cardiomyopathy due to pheochromocytoma has been tried to be explained. Furthermore, pheochromocytoma may also cause hypertensive emergency which can lead to end organ damage, including myocardial infarction. Although most clinicians could recognize the classic symptoms, the clinical presentation of pheochromocytoma may mimic severe diseases. If fewer symptoms were presented, early diagnosis may be more difficult. Patients with unrecognized pheochromocytoma presenting with critical illness such as sepsis, shock, or acute myocardial infarction may have poor prognosis. For clinicians, pheochromocytoma or paraganglioma should always be kept in mind even though initial manifestations are not suggestive for the diagnosis. References: 1. Shlomo Melmed, Kenneth S. Polonsky, Reed Larsen and Henry M. Kronenberg. Williams Textbook of Endocrinology, 12th Edition 2. Gaurav Agarwal, Dhalapathy Sadacharan, Aditya Kapoor, Aditya Batra, Preeti Dabadghao, Gyan Chand, Anjali Mishra, Amit Agarwal, Ashok K. Verma, and Saroj K. Mishra. Cardiovascular dysfunction and catecholamine cardiomyopathy in pheochromocytoma patients and their reversal following surgical cure: Results of a prospective case-control study. Surgery, Volume 150, Number 6, 2011 3. Xue-Ming Wu, Jien-Jiun Chen, Cho-Kai Wu, Lian-Yu Lin and Chuen-Den Tseng. Pheochromocytoma Presenting as Acute Myocarditis with Cardiogenic Shock in Two CasesInter. Med 47: 2151-2155, 2008 4. P.Kounatiadis, V.Kolettas, A.Megarisiotou, I.Stiliadis. Cardiomyopathy due to pheochromocytoma. Herz 2013, DOI 10.1007/s00059-013-3951-7 5. Soo Kyung Cho, Kye Hun Kim, Jae Yeong Cho, Hyun Ju Yoon, Hyung Wook Park, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, and Jong Chun Park. Pheochromocytoma as a Rare Hidden Cause of Inverted Stress Cardiomyopathy. J Cardiovasc Ultrasound 2014;22(2):80-83 6. Graham J. Fent*, Hazlyna Kamaruddin, Pankaj Garg, Ahmed Iqbal, Nicholas F. Kelland and Ian R. Hall. Hypertensive Emergency and Type 2 Myocardial Infarction Resulting From Pheochromocytoma and Concurrent Capnocytophaga Canimorsus Infection. The Open Cardiovascular Medicine Journal, 2014, 8, 43-47

177

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-16

A CASE REPORT – PAPILLARY THYROID CANCER POST THYROIDECTOMY FOLLOWED BY LYMPHADENOPATHY CAUSED BY CASTLEMAN’S DISEASE 1

YI-HONG ZENG, 2SHIH-PING JHENG, 3DAO-YUAN WANG, 1CHUN-CHUAN LEE

Introduction: Neck nodular lesion may origin from several structures. The raise of concern of malignancy would be noticed, particularly in the patient with history of head and neck cancer. We reported a case who had papillary thyroid cancer (PTC) and she had accepted total thyroidectomy. During follow up, neck nodular lesion was noted, and we performed a series of examination and considered it as PTC recurrence. However, pathology revealed Castleman’s disease (CD). Case Presentation: The 55 year-old woman had papillary thyroid cancer and she accepted radical thyroidectomy with unilateral neck lymph node dissection on 8th Aug, 2011 (pT3N0M0, stage 3). She also received radioiodine therapy (120mCi). Then she visited out-patient department of general surgery regularly and took Thyroxine. There was no thyroid remnant in sonography and Thyglobulin level was undectable. However, abnormal lymphnode was noted at left level IV (1.16cm*1.46cm) in April, 2013 (Figure 1). The result of fine needle aspiration revealed negative for malignant cells. Although I-131 whole body scan (Figure 2) reported no definite evidence of abnormal uptake in the thyroid bed, we arranged positron emission tomography (PET, Figure 3) because stimulated Tg is 3.93ng/ml (Table 1). However, it revealed the possibility of lymph nodes metastases in the bilateral submandibular, bilateral upper jugular, bilateral lower cervical, left lower posterior cervical, left supraclavicular regions. Thus, radical neck dissection was done on 21th Oct, 2013 and the operation finding is multiple enlarged lymph node along left level III to V. Several lymph nodes are dissected and the largest one measures 2.7*1.5*0.5cm in size. Sections show enlarged lymph nodes expanded by lymphoid follicles, showing germinal centers progressive transformation and hyalined vessels within follicles. Thin mantles surrounding the follicles are seen. CD21, Bcl-2 & Ki-67 stains support the diagnosis of Castlenan’s disease (Figure 4).

178

Abstract PE-17

Purpose: 99mTc sestamibi parathyroid scan is currently the radionuclide study of choice for preoperative parathyroid localization. But several factors could contribute to a false-negative result. We reported a case of primary hyperparathyroidism with false-negative 99mTc sestamibi parathyroid scan result. Method: A 66 y/o gentleman visited the out-patient clinic due to persisted malaise and back pain for months. Blood test revealed deteriorated renal function (BUN 44.2 mg/dL, creatinine 2.3 mg/dL) and hypercalcemia (corrected calcium 14.0 mg/dL). Urine protein electrophoresis was negative for light-chain proteins. Test for parathyroid function showed elevated i-PTH level (761 pg/mL). Result: Thyroid ultrasonography revealed a hypo-echoic lesion at left thyroid bed, which favored parathyroid adenoma. Spine X-ray showed no dislocation or fracture. The result of bone mineral density (BMD) study indicated osteoporosis (hip T-score -2.57). There was no evidence of co-existent pituitary or pancreatic lesion. However, the result of 99mTc sestamibi parathyroid scan was negative. Hydration, calcitonin and pamidronate were used to control persisted hypercalcemia, with limited response. Conclusion: After general surgeon consultation, left parathyroidectomy was performed. The pathology diagnosis was consistent with parathyroid adenoma. His symptoms relieved after the operation. Follow-up data showed decrement in i-PTH level (181 pg/mL), improvement of renal function (BUN 36.0 mg/dL, creatinine 1.8 mg/dL) and hypercalcemia (corrected calcium 8.8 mg/dL).

179

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-18

SYNCHRONOUS PAPILLARY THYROID CARCINOMA AND SECONDARY HYPERPARATHYROIDISM: CASE REPORT 1

HSIAO-LIEN CHEN, 2MING-YU LAI

Objective: Papillary thyroid carcinoma (PTC) is known to occur in association with primary hyperparathyroidism (HPT). Although, in secondary hyperparathyroidism (HPT), isolated cases have been reported and are often detected by surgery. We report two cases of thyroid cancer diagnosed at the time of parathyroidectomy for secondary HPT in patients with end-stage renal disease (ESRD). Case reports: Patient I - A 64 years old woman, with no personal or family history of neck irradiation, thyroid cancer,was admitted for a surgical parathroidectomy because of medically uncontrolled HPT. The patient had developed ESRD secondary to diabetes , and had been established on hemodialysis for 146 months at the time of admission. Investigation showed elevated alkaline phosphatase 355 U/l (35– 129), elevated PTH 2255 pg/ml(14–72), serum calcium 12.2 mg/dl (8.6–10.2), and phosphorus 7.8 mg/dl (2.7-4.5).Technetium 99m (Tc 99m) MIBI revealed persistent uptake in the upper and lower pole of right thyroid and lower pole of left thyroid.Thyroid ultrasonography revealed multiple nodule bilaterally.Right side nodule >1cm in diameter.The left lobe revealed 1.5cm nodule with calcification. Surgical total parathyroidectomy and left subtotal thyroidectomy. The final histologic analysis of the resected four parathyroid gland confirmed adenoma. The left thyroid gland had a focal follicular variant of PTC. Patient II - A 57 years old man with a history of ESRD secondary to polycystic kidney disease and on long-term hemodialysis for 120 months. Three months prior to his admission,he had biochemical evidence of HPT.Laboratory investigation demonstrated serum calcium 10.3mg/ dl (8.6–10.2), hyperphosphatemia 5.6 mg/dl (2.7-4.5), with a peak PTH level of 1440 pg/ml(14–72). Technetium 99m (Tc 99m) MIBI revealed persistent uptake in the upper pole of right thyroid. Thyroid ultrasonography revealed multiple nodule bilaterally.Right side nodule > 1cm in diameter.The left lobe two nodule > 2 cm in diameter. FNAB was performed from left side larger nodule and the cytology was benign. Surgical parathyroidectomy and left total thyroidectomy.The histological report diagnosed hyperplasia of the parathyroid glands of right and left upper parathyroid gland.The left thyroid had a focal follicular variant of papillary carcinoma (diameter 0.3 X 0.3X0.2cm) and nodule (2.5X 2.3X 2.0cm) revealed follicular adenoma with suspect capsule invasion.Regional lymph nodes were not affected. Conclusions: We suggest that the association of simultaneous pathology of the thyroid and parathyroid glands should be considered in uremic patients with secondary HPT. 180

Abstract PE-19

EXOME SEQUENCING OF A CASE WITH MIXED ADRENAL CORTICOMEDULLARY ADENOMA 1

LI LUN CHUANG, 2DAU YANG HWANG, 3SHAN-YIN TSAI, 1WEI-WEN HUNG, 1 KUN-DER LIN, 1,4SHYI-JANG SHIN, 1,4PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, 2Department of Nephrology, 3Department of Pathology, Kaohsiung Medical University Hospital; 4School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Mixed corticomedullary tumor is a single adrenal tumor containing both cortical and medullary cells intermixed throughout the entire neoplasm. It is extremely rare to be regarded as a new disease entity. Genetic mutation for the tumor formation is still unclear. We ever reported a 32-year-old female patient who has diagnosed with a huge mixed corticomedullary adenoma. She was clinically manifested with typical Cushing’s syndrome and pheochromocytoma diagnosed by biochemical and immunohistochemical evidences. For further evaluation of the possible gene mutation, the genomic DNA was extracted from blood and tumor together. High throughput next generation sequencing was performed by Illumina HiSeq system. Exome sequencings were performed on patient’s blood and adrenal tumor. Blood DNA was sequenced of more than 96 million reads with depth of 10-fold coverage of 96.8% and 30-fold coverage of 92.4%. Formalin fixed paraffin embedded tumor DNA was sequenced of >58 million reads with 10fold coverage of 92% and 30-fold coverage of 73.1%. The variants filtering criteria included minor allele frequency less than 1% from the database of dbSNP 141 and nonsynonymous variants. More than 1400 rare or unreported variants in both blood and tumor samples. After comparing these 2 variants set, more than 100 variants were found in the tumor but not in the blood, and more than 200 variants were found in the blood but not in the tumor. None of these variants was found to be the same with the reported mutations for pheochromocytoma (RET, VHL, NF1, SDHB, SDHC, SDHD, SDHA, TMEM127, KIF1B, PHD2 and MAX) or adrenal Cushing syndrome (PRKAR1A, ARMC5, hGR, GNAS, ENDRA, KCNJ5, and PDE11A). From our result, mixed corticomedullary adenoma of this case is really a diverse disease dissimilar to pheochromocytoma or adrenal Cushing syndrome. The true etiology may be secondary to an undiscovered mutation or existence of other mutations in the upper stream to stimulate growth of cortex or medulla cell origins of adrenal gland.

181

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-20

ELECTRONEGATIVE LDL IMPAIRS KIDNEY THROUGH DAMAGE OF STRA6 SIGNALING 1

ZHAO-HONG CHEN, 2LIANG-YIN KE, 2HUA-CHEN CHAN, 2CHU-HUANG CHEN, 2,3,4 SHYI-JANG SHIN 1

Background: Cardiovascular, cerebrovascular and kidney diseases have been remaining as the leading cause of death in Taiwan. Diabetes and dyslipidemia is the most important risks of these diseases. Increased serum retinol-binding protein 4 (RBP4) levels have been shown in subjects with diabetes, dyslipidemia, obesity, cardiovascular, cerebrovascular and chronic kidney disease (CKD). A multi-transmembrane receptor, called as “stimulated by retinoic acid 6 (STRA6)”, was identified as a specific membrane receptor for RBP4. We also found that free RBP4 can cause apoptosis through the reduction of RBP4 binding activity with STRA6 (stimulated by retinoic acid 6) and in turn through JAK2/STAT5/JNK/p38MAPK pathway in renal cells. Therefore, we reasonably hypothesized electronegative LDL (L5) might cause kidney injury via damages of STRA6 signaling. Method: The expression of STRA6, CRBP1, RAR, caspase 3, and collagen 1 were measured by western blot analysis in kidney of L5-injectied mice and human renal tubular epithelial cells. Immunofluorescent and immunochemical stain method were also done to detect STRA6 expression in kidney of L5-injectied mice and L5-stimulated human renal tubular epithelial cells. LOX1 knockout mice and LOX1 siRNA transfection were performed to investigate whether the reversal of CRBP 1 and RAR can reverse apoptosis and fibrosis in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. Result: The expression of caspase 3 and collagen 1 are remarkably increased, whileas STRA6, CRBP1 and RAR expression are reduced in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. Immunofluorescent and immunochemical stain method experiments also showed an decreased expression of STRA6 in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. However, LOX1 siRNA or LOX1 gene knockout reverse above changes induced by L5. Conclusion: L5 can cause kidney damage via damage of STRA6/CRBP1/RAR signaling and finally enhancing apoptosis and fibrosis in vivo and vitro. These results indicate that L5-impaired STRA6/CRBP1/RAR signaling is one novel molecular mechanism of diabetic nephropathy with dyslipidemia.

182

Abstract PE-21

CHYLOTHORAX AS A RARE PRESENTATION IN GRAVES’ DISEASE 1

LEE I-SHUAN, 1,2LEE TING-WEI, 1CHANG CHUN-JEN, 1LEE TING-I, 1FAN CHI, 1 CHIEN YU-MEI, 1CHOU CHUAN-LIANG, 1LIU HAN-WEN 1

Cardiovascular diseases, such as arrhythmia and heart failure are common complications in patients with poorly controlled hyperthyroidism. Here, we reported a patient presented with chylothorax, which is a rare manifestation of Graves’ disease. A 37-year-old woman was admitted because of abdominal fullness, legs swelling, and shortness of breath. The patient was diagnosed to have Graves’ disease about 9 years prior to this admission. However, she took 9 months of antithyroid drugs and lost follow-up afterward. Laboratory studies revealed severe thyrotoxicosis (TSH 0.007 uIU/ml, free-T4 > 7.77 ng/dl) associated with decompensated heart failure. After proper treatment, the patient got much improvement. However, on the fifth hospital day, the patient had fever and dyspnea. Chest X-ray showed acute onset of left pleural effusion. Pleural effusion analysis revealed transudative pleural effusion with high triglyceride levels in contents, the findings were consistent with chylothorax. Lymphoscintigraphy showed no evidence of thoracic duct leakage. But chest and abdomen CT scan demonstrated enlarged bilateral supraclavicular, axillary, mediastinal, and paraaortic lymph nodes. The patient underwent excisional biopsy for axillary lymphadenopathy and the pathological examination reported lymphoid hyperplasia. Survey for other common causes of chylothorax showed negative findings. Treatments for heart failure and hyperthyroidism led to a remarkable improvement in the clinical condition including a recovery of heart function and disappearance of chylothorax. From the literature review, there were only three patients with congestive heart failure and chylothorax that resulted from hyperthyroidism. Therefore, thyrotoxicosis should be included in the differential diagnosis in patients with unclear etiology of chylothorax.

183

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PE-22

ACUTE DECOMPENSATION OF METHYLMALONIC ACIDEMIA IN AN ADULT PATIENT-A CASE REPORT 1.2

PIN-FAN CHEN, 1BING-RU GAO, 1.2WEI-CHENG LIAN, 1SHIH-TANG YAN, 1 TING-CHANG CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

Objective: Methylmalonic academia (MMA) is a rare chromosome recessive inborn error with prevalence of 1 in 100,000 in Taiwan. Patients with MMA rarely grew up to be adults except having residual enzyme activity or cobalamin-responsive type. Toxic metabolites could cause neurological disorders, progressive renal and liver failure. Restricted high-protein diet with sufficient energy intake is the main treatment concept of MMA. Case report: we reported an adult case of MMA, presented with foods refusal, vomiting and confused consciousness after she had unrestricted high protein diet for days in Dec. 2012. At ER, metabolic acidosis, acute kidney injury and hyperammonemia were found. Intravenous 10% Dextrose fluid at 150% maintenance, intralipid 2gm/kg/day, and high dose of Vitamin B12 were adopted. The general condition and associated aberrant metabolic markers improved gradually. After suffering this episode, oral carnitine and high dose Vit. B12 keep using. There is not any acute metabolic decompensation till now. However, chronic renal disease and hyperuricemia persist. Conclusion: In patients with acute decompensation of methylmalonic academia, treatment of high dose of Vit. B12, carnitine, glucose and fat supplement with zero tolerance on protein consumption are essential. Key factors to determine acute decompensation are vomiting, high ammonia level and changes of acid-base homeostasis.

184

Abstract PD-01

PATIENT-REPORTED OUTCOMES FROM A 104-WEEK, PHASE 3, RANDOMISED, PLACEBO-CONTROLLED STUDY COMPARING ONCE-WEEKLY DULAGLUTIDE TO SITAGLIPTIN AND PLACEBO IN METFORMIN-TREATED PATIENTS WITH TYPE 2 DIABETES; THE ASSESSMENT OF WEEKLY ADMINISTRATION OF DULAGLUTIDE IN DIABETES (AWARD-5) TRIAL 1

THOMAS LEW, 2M REANEY, 3M YU, 4O ADETUNJI, 5Z MILICEVIC

Objective: To evaluate patient-reported outcome (PRO) data from the AWARD-5 trial. Materials and Methods: 1098 patients (mean age 54.1 years; HbA1c 8.1%; weight 86.4 kg; diabetes duration 7.1 years) were randomised to once-weekly dulaglutide 1.5 mg or 0.75 mg, sitagliptin 100 mg once daily, or placebo only (switched to sitagliptin after 26 weeks) in a 2:2:2:1 ratio. 831 (75.7%) completed the 12-month visit. PRO measures for Impact of Weight QoL-Lite (IWQoL-Lite) and EQ-5D were administered at baseline, 26, 52, 78 (only IWQoL-Lite), and 104 weeks (analysis LOCF ANCOVA). Results: Both dulaglutide doses showed a greater decrease (p<.001) vs sitagliptin in HbA1c at 52 and 104 weeks; dulaglutide 1.5 mg showed a greater decrease (p<.001) vs sitagliptin in body weight. Significant (p<.05) improvements from baseline were observed in EQ-5D visual analog scale (VAS) scores at 26 weeks (dulaglutide 1.5 mg, sitagliptin), 52 weeks (dulaglutide 1.5 mg), and 104 weeks (dulaglutide 1.5 mg, 0.75 mg, sitagliptin). EQ-5D UK population index scores did not significantly change from baseline (all groups). Significant improvements from baseline were observed in all groups in IWQoL-Lite total score as well as physical functioning and self-esteem domain scores (52, 78, 104 weeks). The improvement in total score was significantly larger with dulaglutide vs sitagliptin at 78 (dulaglutide 1.5 mg, dulaglutide 0.75 mg) and 104 (dulaglutide 1.5 mg) weeks. Some other domain scores also significantly improved with dulaglutide and sitagliptin postbaseline. Conclusion: Dulaglutide and sitagliptin showed improvements from baseline in EQ-5D VAS scores and IWQoL-Lite total scores. Improvement in IWQoL-Lite total scores (as well as work and physical functioning domain scores) was greater with dulaglutide vs sitagliptin.

185

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-02

PATIENT-REPORTED OUTCOMES WITH ONCE-WEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE (AWARD-2) 1

THOMAS LEW, 2M REANEY, 3M YU, 2BRUNT K VAN BRUNT, 4V PETCHNER, 5CP HAYES

Objective / Materials and Methods: This 78-week, Phase 3, open-label, randomized study compared the once-weekly GLP-1 receptor agonist dulaglutide 1.5 mg and dulaglutide 0.75 mg to glargine titrated-to-target in patients with type 2 diabetes on stable and maximal doses of metformin and glimepiride. Results: Dulaglutide 1.5 mg was superior in HbA1C (p<.001) and dulaglutide 0.75 mg was noninferior vs glargine at 52 weeks and 78 weeks. Dulaglutide was associated with weight loss, whereas glargine was associated with weight gain (p<.001); there was less hypoglycemia but more nausea with dulaglutide vs glargine (p<.05). Patient-reported outcome (PRO) instruments were administered at baseline and at 52 and 78 weeks; analysis of covariance models with country, baseline score, and treatment factors were used. At 52 and 78 weeks, significant (p<.05) improvements from baseline were demonstrated in both dulaglutide doses for EQ-5D visual analog scale (VAS) and low blood sugar survey (LBSS) behavior and worry measures and in dulaglutide 1.5 mg for ability to perform physical activities (APPADL) and impact of weight on self-perception (IW-SP). EQ-5D UK index scores decreased from baseline with glargine at 52 weeks (p<.05). Significant differences were observed between dulaglutide 1.5 mg and glargine for LBSS behavior and worry measures and APPADL at 52 and 78 weeks. Conclusion: Patients with type 2 diabetes, who added once-weekly dulaglutide injectable therapy to 2 oral antihyperglycemic medications, achieved glycemic benefit and, in comparison to glargine, greater improvement in some PROs.

186

Abstract PD-03

INSULIN LISPRO LOW MIXTURE TWICE DAILY VERSUS BASAL INSULIN GLARGINE AND PRANDIAL INSULIN LISPRO ONCE DAILY IN EAST ASIAN AND CAUCASIAN TYPE 2 DIABETES MELLITUS PATIENTS 1

THOMAS LEW, 2JH HAN, 3D EDRALIN, 4R DUAN, 5A RODRIGUEZ

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Lilly Korea Ltd, Seoul, Korea; 3Eli Lilly, Pasig City, Philippines; 4Eli Lilly and Company, Indianapolis, IN, USA; 5Lilly Spain, Alcobendas, Spain

Objective: This post-hoc analysis described efficacy and safety of insulin lispro low mixture (LM) twice daily versus bedtime insulin glargine plus prandial insulin lispro administered once daily before the largest meal (IGL) in East Asian (EA) and Caucasian type 2 diabetes mellitus patients who previously failed to reach glycemic targets on basal insulin glargine with metformin and/or pioglitazone. Materials and Methods: This Phase 4, randomized, open-label, multinational, multicenter trial included patients with glycosylated hemoglobin (HbA1c) between ≥7.5% and ≤10.5%, and fasting plasma glucose ≤6.7 mmol/L. Results: Baseline mean (standard deviation [SD]) HbA1c values were numerically similar between groups in EA (N=79) and Caucasian (N=278) patients (EA: LM=8.78% [0.71] vs IGL=8.72% [0.90]; Caucasian: LM=8.56% [0.78] vs IGL=8.51% [0.70]). Mean (SD) HbA1csignificantly (p<.001) decreased from baseline to 24 weeks for both treatments in both subpopulations (EA: LM=1.32% [0.96] and IGL=-0.89% [0.98]; Caucasian: LM=-1.24% [0.98] and IGL=-1.05% [0.97]). The proportion reaching HbA1c≤7% at Week 24 was LM=33.3% and IGL=22.9% for EA patients, and LM=37.2% and IGL=34.1% for Caucasian patients. Mean (SD) rate of hypoglycemia per 30 days was LM=0.74 (1.16) and IGL=1.22 (1.36) in EA patients, and LM=1.38 (2.04) and IGL=1.65 (2.43) in Caucasian patients. Mean (SD) change in weight gain was LM=0.62 kg (2.78) and IGL=0.51 kg (2.63) in EA patients, and LM=1.77 kg (2.91) and IGL=0.67 kg (3.09) in Caucasian patients. Conclusion: Improved glycemic control was observed in EA and Caucasian patients treated with either LM or IGL.

187

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-04

SIMILAR EFFICACY AND SAFETY WITH LY2963016 INSULIN GLARGINE COMPARED WITH LANTUSR INSULIN GLARGINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2DM): THE ELEMENT 2 STUDY 1

JOYCE YEH, 2JULIO ROSENSTOCK, 3PRISCILLA HOLLANDER, 4ANJU BHARGAVA, 5 LIZA ILAG, 5ROBIN K. POLLOM, 5WILLIAM J HUSTER, 5MELVIN PRINCE 1

Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Dallas Diabetes and Endocrine Center, Dallas, TX, USA; 3Baylor Endocrine Center, Dallas, TX, USA; 4Iowa Diabetes and Endocrinology Center, Des Moines, IA, USA; 5Eli Lilly and Company, Indianapolis, IN, USA

Objective: Even though LY2963016 (LY IGlar) and Lantus® (IGlar) are both insulin glargine products, with identical amino acid sequences, they are manufactured by distinct processes and must be shown to be clinically similar. Materials and Methods: A 24-week, Phase 3, randomized, double-blind, parallel study was performed to compare the efficacy and safety of LY IGlar and IGlar in 756 patients with T2DM on ≥2 oral antihyperglycemic medications (OAMs) who were insulin naïve (n=455, HbA1c ≥7.0% to ≤11.0%) or previously on IGlar (HbA1c ≤11.0%). The primary objective was to test the noninferiority (0.3% margin) of LY IGlar to IGlar as measured by change in HbA1c from baseline to 24 weeks. Results: Both treatment groups had within-group similarly significant (p<.001) decreases in mean HbA1c values (approx. -1.3%; endpoint HbA1c LY IGlar 7.04%, IGlar 6.99%; least-squares mean difference [95% confidence interval] 0.052 [-0.070, 0.175]). The change in HbA1c from baseline with LY IGlar was noninferior to IGlar. Noninferiority of IGlar to LY IGlar was also demonstrated; thus, the criteria for equivalence in clinical efficacy between LY IGlar and IGlar were met. There were no treatment differences in secondary efficacy or safety outcomes including hypoglycemia (21.3 versus 22.3 events/patient/year for LY IGlar and IGlar, respectively). Adverse event frequencies (LY IGlar 52%, IGlar 48%) were similar. The mean insulin dose at endpoint was 0.50 and 0.48 U/kg/day for LY IGlar and IGlar, respectively. Conclusion: LY IGlar compared with IGlar, used in combination with OAMs, provided equivalent efficacy and a similar safety profile in patients with T2DM.

188

Abstract PD-05

PREDICTION OF GLUCOSE EFFECTIVENESS WITH ROUTINE MEASUREMENTS IN CHINESE 1

DEE PEI, 2CHUN-TIEN LIN, 3YEN-LIN CHEN

Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, ROC; 2Division of Endocrinology, Department of Internal Medicine,Shuang Ho Hospital, School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC; 3Division of Pathology, Cardinal Tien Hospital, Medical School, Fu Jen Catholic University, New Taipei City, Taiwan, ROC

Aims: Glucose effectiveness (GE) is the capacity of glucose itself to increase glucose uptake and to inhibit endogenous hepatic glucose output under basal insulin level. Other than decreased insulin sensitivity (IS) and impaired insulin secretion, it also plays an important role on glucose balance in type 2 diabetes. In the study, we aimed to develop an equation for predicting GE. Methods: We enrolled 227 participants, from normal glucose tolerance to diabetes, in our study. Seventy five percent (171 subjects) were randomly assigned to the study group, whose data would be used to build the equation for estimating the GE. The remaining 56 participants comprised the validation group. A frequently sampled intravenous glucose-tolerance test was performed for all participants, and the IS, GE, and the acute insulin response after the glucose load were determined. Results: Age, triglyceride (TG) and fasting plasma glucose (FPG) were independently related to GE and thus were selected from multiple linear regression analysis. The following equation was made and we constructed the equation GE=(29.196-0.103×age-2.722×TG-0.592×FPG)×10-3. Using this same equation, GE was also calculated in the validation group. This calculated GE was significantly correlated with the measured GE (r=0.430, P=0.001). Conclusions: By using the equation based on the routine measurements, the GE could be predicted with acceptable accuracy(r=0.430).This method of predicting GE may help further clinicians’ understanding of the underlying pathological mechanisms in T2DM.

189

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-06

Objective: Based on previous studies, metformin or statins can decrease hepatocellular carcinoma (HCC) in diabetic patients. Our aim is to evaluate whether combination therapy can further reduce HCC in diabetic patients in Taiwan. Research Design and Methods: For this nested-case control study, we collected the Longitudinal Health Insurance Database 2000 (LHID2000), established by the Taiwan Bureau of National Health Insurance .Patients with newly diagnosed type 2 diabetes mellitus (DM), excluding those with histories of HCC prior to the date of DM diagnosis, were recruited to form a DM cohort. Diabetic patients developed HCC as case group and the date for HCC diagnosis as index date. Results: In general ,patients treated with statins showed a significantly decreased risk of HCC (OR=0.37; 95% CI=0.27–0.49) instead of patients treated with metformin(OR=0.84; 95%CI=0.651.08). Based on metformin use, patients treated with simvastatin, atorvastatin, and rosuvastatin showed significantly decreased risks of HCC (OR=0.35, 0.41, and 0.24; 95% CI=0.18–0.68, 0.24–0.71, and 0.08–0.74) instead of pravastatin ,fluvastatin and lovastatin. Interestingly, the comorbidities for patients with HCC were decreased in metformin combined with the two statins simvastatin and atorvastatin (OR=0.29 and 0.37; 95% CI= 0.11-0.76, and 0.16-0.85). Conclusion: Not all combination therapy of metformin and Statins can decrease the incidence of HCC in diabetic patients in Taiwan. Keywords: metformin; statins; hepatocellular carcinoma (HCC).

190

Abstract PD-07

THE ASSOCIATION OF HEMATOGRAM WITH METABOLIC SYNDROME IN THE YOUNG-OLD, OLD-OLD AND OLDEST-OLD POPULATIONS 1,2

TSUNG-JU CHUANG, 1YI-JEN HUNG, 3DEE PEI, 4YEN-LIN CHEN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Taipei, Taiwan; 4 Department of Pathology, Cardinal Tien Hospital, Taipei, Taiwan

Objectives: The prevalence of metabolic syndrome (MetS) increases with age and is associated with future occurrence of cardiovascular diseases (CVD) and diabetes. Previous studies found that abnormal hematogram components could predict future MetS. However, there was no study focused on different ages groups in the elderly, i.e. the young-old (YO), old-old (OO) and oldest-old (ODO) subjects. In this ten-year longitudinal study, we investigated the association between hematogram components and future MetS and diabetes in the aforementioned three aged groups. Methods: Subjects above 65 years were enrolled and divided into three groups by age ( youngold, 65-74; old-old, 75-84; oldest-old ≥85 years-old) of both sexes. All subjects were followed up until they developed MetS or until up to 10 years from the day of entry, whichever was earlier. By using multiple logestic regression, the hazard ratio (HR) of higher hemoglobin (Hb), white blood cell count (WBCC) and platelet (Plt) to have future MetS, diabetes and CVD were evaluated. Results: There were 7648 males and 7521 females in the YO group, 1963, 1573 in the OO group and 121, 81 in the ODO groups respectively. The prevalence of having MetS were 33.9%, 35.1%, 31.4%for males and 46.7%, 54.3%, and 62.9%for females at baseline. After 10 years follow-up,only higher WBCC and Hb levels (>5.0×103, 15 g/dL, respectively) was correlated to future MetS in YO males (HR: 1.612, 1.443, respectively). In female, only higher Hb (>13.7 g/dL) was associated with future MetS in YO and OO groups (HR:1.335 and 3.690, respectively). Finally, higher chances of diabetes could be noted with higher WBC in both males and females (HR: 1.589, 1.582, respectively) and higher Hb in females (HR: 2.273). Conclusion: In this large longitudinal study, focusing on the elderly, we have shown that predicting future MetS and diabetes in elderly by hematogram components is valuable only in youngold groups of both genders and old-old female.

191

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-08

SODIUM GLUCOSE COTRANSPORTER 2 (SGLT2) INHIBITION WITH EMPAGLIFLOZIN REDUCES MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES 1

DAVID CHERNEY, 2MAXIMILIAN EYNATTEN, 3SØREN LUND, 3STEFAN KASPERS, 3 SUSANNE CROWE, 3HANS WOERLE, 3THOMAS HACH 1

Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 3Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Objective: We examined the effect of 24 weeks’ treatment with empagliflozin on urine albumin to creatinine ratio (UACR) by pooling data from patients with T2DM and microalbuminuria (UACR 30–300 mg/g) who participated in four Phase III randomized placebocontrolled trials. Methods: Study population and design • Data were pooled from four Phase III trials in which 2477 patients with T2DM were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks as monotherapy, add-on to metformin, add-on to metformin plus sulfonylurea, or add-on to pioglitazone ± metformin.3-6 Patients who completed 24 weeks’ doubleblind treatment in the initial study could elect to continue their treatmentin a 52-week extension study. • 458 (18%) of the patients treated in these four trials (157 on placebo, 146 on empagliflozin 10 mg, and 155 on empagliflozin 25 mg) had microalbuminuria (UACR 30–300 mg/g) at baseline. • UACR was calculated from spot urine samples at study visits. Endpoints • Changes from baseline in HbA1c and systolic blood pressure (SBP) at week 24. • Percentage change in geometric mean (gMean) UACR from baseline to week 24. • The ratio of relative change from baseline in UACR over time. • Safety was assessed via reporting of adverse events (AEs) in the initial and extension studies (≥76 weeks). Analyses • Changes in HbA1c, SBP and UACR at week 24 were analyzed using analysis of covariance (ANCOVA). For HbA1c analyses, data following initiation of anti-diabetes rescue therapy were set to missing. For SBP and UACR analyses, data following a change in type or dose of antihypertensive medication were also set to missing (changes in dose were only captured in one trial). Missing data were imputed using the last observation carried forward (LOCF) approach. 192

Abstract Results: At week 24, empagliflozin 10 mg and 25 mg reduced UACR by 30% and 25%, respectively, compared with placebo (p<0.01) in patients with microalbuminuria at baseline. Change in UACR in all patients In the overall pooled population (n=2349; gMean [gCV] baseline UACR of 12.9 [217.1], 12.7 [215.2] and 13.6 [231.2] mg/g for the empagliflozin 10 mg, 25 mg and placebo groups, respectively), including patients with microalbuminuria, macroalbuminuria (UACR >300 mg/g) and normoalbuminuria (UACR <30 mg/g), the percentage change in gMean UACR compared with placebo was -10% (95% CI -3, -16%; p=0.009) with empagliflozin 10 mg and -10% (95% CI -3, -17%; p=0.005) with empagliflozin 25 mg at week 24. Safety Adverse events over ≥76 weeks in patients with microalbuminuria at baseline Conclusions: • Empagliflozin 10 mg and 25 mg reduced microalbuminuria when added to standard therapy in patients with T2DM. • Empagliflozin 10 mg and 25 mg significantly reduced HbA1c and SBP in patients with T2DM and microalbuminuria. • Empagliflozin was well tolerated in patients with T2DM and microalbuminuria. • Reduced albuminuria may be related to reduced intraglomerular pressure, as indicated by a reduction in renal hyperfiltration with empagliflozin in patients with T1DM. • Prospective studies are needed to examine the potential renal protective effects of empagliflozin in patients with T1DM and T2DM. • An ongoing cardiovascular outcome trial (EMPA-REG OUTCOME™; NCT01131676) is investigating the effect of empagliflozin in patients with T2DM and high cardiovascular risk.

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The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-09

EFFECT OF EMPAGLIFLOZIN COMPARED WITH GLIMEPIRIDE AS ADD-ON TO METFORMIN FOR 2 YEARS ON THE AMOUNT AND DISTRIBUTION OF BODY FAT IN PATIENTS WITH TYPE 2 DIABETES 1

GABRIEL KIM, 2MARTIN RIDDERSTRÅLE, 3KNUT ANDERSEN, 4CORDULA ZELLER, 1HANS WOERLE, 1ULI BROEDL 1

Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 2Steno Diabetes Center, Gentofte, Denmark; 3Boehringer Ingelheim Norway KS, Asker, Norway; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

Background and aims: In a randomized, double-blind, Phase III trial in patients with type 2 diabetes (T2DM), the SGLT2 inhibitor empagliflozin (EMPA) 25 mg qd as add-on to metformin for 104 weeks led to significant and sustained reductions in body weight compared with an increase in body weight with glimepiride (GLIM). Patients had the option to participate in a dedicated body composition sub-study in which we aimed to determine the effects of EMPA vs GLIM on the amount and distribution of body fat. Materials and methods: Body composition was evaluated in 91 randomised patients in the sub-study. Using whole body dual energy X-ray absorptiometry (DXA), changes from baseline to week 52 and week 104 in trunk fat, limb fat, total fat mass and fat-free mass were assessed in 62 patients (36 receiving EMPA and 26 receiving GLIM). Using magnetic resonance imaging (MRI), changes from baseline to week 52 and week 104 in abdominal visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) were assessed in 51 patients (29 receiving EMPA and 22 receiving GLIM). Changes from baseline were evaluated using mixed model repeated measures (MMRM) analyses. Results: In the 91 patients evaluated in the sub-study, baseline mean [SD] age was 55.7 [10.4] years, weight was 85.1 [14.7] kg, BMI was 31.9 [4.9] kg/m2 and 60% had BMI ≥30 kg/m2. EMPA significantly reduced trunk fat, limb fat and total fat mass vs GLIM at week 52 and week 104. EMPA also significantly reduced fat-free mass vs GLIM at week 52 but not at week 104 (table). Adjusted mean (SE) changes from baseline in abdominal VAT at week 52 were -15.5 (5.2) cm2 with EMPA compared with +10.0 (6.1) cm2 with GLIM (p<0.01) and at week 104 were 16.0 (8.4) cm2 with EMPA compared with +17.7 (10.0) cm2 with GLIM (p<0.05). Adjusted mean (SE) changes from baseline in abdominal SAT at week 52 were 29.9 (7.3) cm2 with EMPA compared with +25.8 (8.6) cm2 with GLIM (p<0.001) and at week 104 were 32.5 (9.2) cm2 with EMPA compared with +34.4 (10.7) cm2 with GLIM (p<0.001). Conclusion: When used as add-on to metformin, treatment with EMPA led to reductions in trunk fat, limb fat, abdominal VAT and SAT at week 52 and further reductions at week 104 compared with GLIM. Reductions in fat-free mass with EMPA vs GLIM were observed at week 52 but not at week 104. 194

Abstract PD-10

EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST LIRAGLUTIDE ON MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION IN RATS 1, 3

MEI-YUEH LEE, 2KUN- PAO TSAI, 4JONG-HAU HSU, 4JIUNN-REN WU, 3KUN-DER LIN, 3PI-JUNG HSIAO, 3SHYI-JANG SHIN, 5JWU-LAI YEH

Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 2Department of Pathology; Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital; 4Department of Pediatrics; 5 Department of Pharmacology, School of Medicine, Kaohsiung Medical University 3

Objectives: Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat type 2 diabetes, however, the effect of GLP-1R agonists on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated the pulmonary vasodilatory effects of liraglutide, a GLP-1 receptor agonist, on chronic monocrotaline (MCT) administration-induced PAH and pulmonary artery smooth muscle cells (PASMC) in rats. Materials and Methods: Two doses of liraglutide (75 and 200 μg/kg) i.p. twice daily for 21 days were tested in two rat models of MCT-induced PAH: prevention and treatment groups. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immunoreactivity of endothelial nitric oxide synthase (eNOS) in the pulmonary artery, endothelin-1 and cyclic guanosine monophosphate levels, eNOS, sGCα, PKG and ROCK2 protein expressions were measured in both lung tissue and PASMC. Cell migration and cell cycle by flow cytometry were also determined. Results: Pulmonary arterial pressure induced by MCT was reduced in both liraglutide prevention and treatment groups, with a reduction in mean arterial blood pressure and body weight, but no significant effect on mean heart rate and glucose level. Right ventricle and pulmonary vascular wall hypertrophy caused by MCT was also shown to be effectively reduced by liraglutide. The protein expression of Rho kinase was over expressed in the MCT-induced saline treated group and PASMC treated alone with platelet derived growth factor (PDGF), but decreased in eNOS, sGC and PKG, and liraglutide could reverse these expressions. The immunoreactivity of eNOS was decreased in the MCTtreated saline group, and this was improved by liraglutide. Conclusion: Liraglutide may have both preventive and treatment effects on MCT-induced PAH. The proposed mechanism of the inhibition of PAH by liraglutide may be due to activation of eNOS, sGCα and PKG in pulmonary arterial endothelium and inhibition of ROCK2 in PASMC.

195

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-11

Intraocular pressure (IOP) is associated with metabolic syndrome, a cluster of cardiovascular risk factors. Circulating levels of C-reactive protein (CRP) was reported, independent of metabolic syndrome, to be associated with cardiovascular disease. In the present study, we examined the effect of CRP on IOP in subjects with or without metabolic syndrome. A total of 1041 subjects underwent physical check-up in one of medical center in central Taiwan were enrolled. The levels of IOP was significantly higher in the subjects with metabolic syndrome than those without (14.1±3.0 vs. 13.4± 3.0 mmHg, P=0.002). The IOP were also significantly different among the subjects with different CRP tertiles. There was highest mean IOP in the subjects with metabolic syndrome and highest CRP tertile, while the lowest mean IOP in the subjects with lowest CRP tilter and without metabolic syndrome (P value for trend <0.001). In mulitivariate liner regression analysis, levels of CRP were independently associated with levels of IOP (95%CI between 0.080 and 1.297, P=0.027) even after adjustment for metabolic syndrome. In conclusion, systemic inflammation, reflected by serum CRP, might be associated with high IOP.

196

Abstract PD-12

EFFECT OF METFORMIN ON BONE LOSS IN OVARIECTOMIZED RATS FED WITH HIGH-FRUCTOSE DIET 1

JIANN-LIANG LIN, 1YI-JING SHEEN, 2SHIH-YI LIN, 3TSUNG-HAN TENG, 4ZIHCYUN LIN, 4SHU-CHI CHIANG, 5SHIH-MING HUANG, 2WAYNE HUEY-HERNG SHEU, 4 HUI-TING YANG 1

Aims: Osteoporosis is a silently progressive disease that confer a high burden of disease-related morbidity and mortality. Recent studies have reported bone loss in diabetic patients and the osteogenic potency of the anti-diabetic drug metformin in vitro. We aimed to investigate the role of metformin on bone mass in an ovariectomized (OVX) rats fed with high-fructose diet. Methods: Female Wistar rats at 6 weeks of age were randomly assigned to six groups: (1) the sham, (2) OVX, (3) high-fructose diet, (4) OVX + high-fructose diet,(5) OVX + metformin (300 mg/ kg/day), and (6) OVX + high-fructose diet + metformin (300 mg/kg/day) groups. Thirteen weeks after either sham surgery or bilateral ovariectomy, the rats were sacrificed. We collected serum biochemical data, including the levels of bone metabolism markers, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin, and pathologically examined resected cardiac and aortic specimens. Then, the femurs were harvested for micro-computed tomography. Results: The rats in the high-fructose diet groups presented with higher body weight, fasting blood glucose, insulin homeostasis model assessment of insulin resistance, and triglyceride levels but lower estrogen levels. Bilateral ovariectomy increased the body weight, serum low-density lipoprotein level, and fasting blood glucose level. Obvious aortic atherosclerotic changes were observed in the high-fructose diet groups, with or without ovariectomy. We found that the use of metformin improved the metabolic abnormalities in the fructose-fed OVX group, including body weight, fasting blood glucose level, serum low-density lipoprotein level, and triglyceride level; furthermore, metformin decreased the RANKL level (from 138.9±74.0 to 116.2±42.2 pg/mL) and significantly improved the bone volume percentages (from 17.8%±2.5% to 31.2%±3.5%, p<0.001) and the trabecular bone number (from 1.7±0.3 to 2.5±0.6 1/mm). In addition, metformin had no obvious benefit for the bone markers or morphology of the OVX rats without feeding with high-fructose diet. Conclusion: Our findings provide evidence that metformin has an inhibitory effect on bone loss in OVX rats fed with a high-fructose diet. Keywords: Fructose, Metformin, Osteoporosis, Receptor activator of nuclear factor kappa-B ligand (RANKL) 197

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-13

Background: We reported a 37-year-old man who demonstrated extremely high level of serum glucose (3355 mg/dL) complicated with diabetic ketoacidosis and hyperosmolar hyperglycemic state after excessive consumption of sweetened beverage within one day. His blood sugar levels were gradually decreased by aggressive fluid resuscitation and insulin infusion. However, the laboratory evaluation revealed elevated levels of creatinine, creatinine kinase and myoglobin on day 2. Simultaneously, a huge renal stone was found on abdominal plain film. The diagnosis of rhabdomyolysis, staghorn stone and acute kidney injury were made based on these laboratory tests. Interesting, his creatinine kinase concentration continued to rise and persisted with high levels for one week even blood glucose, ketoacidosis and renal function were recovered. Finally, this case was successfully survived after aggressive treatments. Conclusion: Rhabdomyolysis is an uncommon but underestimated complication of hyperglycemic crisis. Hence, physicians should be alerted to this under detected complication of hyperglycemic crisis which may lead to acute renal failure yet can be easily diagnosed by a readily available test—the creatinine kinase level.

198

Abstract PD-14

CORRELATION BETWEEN PERIODONTAL DISEASE AND CLINICAL FEATURES IN TYPE 2 DIABETIC PATIENTS 1

JHIH-SYUAN LIU, 1CHIEN-HSING LEE, 1KAI-YUEN HSU, 2YI-SHING SHIEH, 1 CHANG-HSUN HSIEH, 1YI-JEN HUNG 1

Introduction: Diabetes mellitus is currently considered as an established risk factor for periodontitis. In previous reports, the risk factors of periodontitis severity include poor glucose control, age and duration of disease in diabetic patients. In this study, we try to determine whether severity of periodontitis is associated with glycemic control, clinical features, biochemical variables or proinflammatory markers in our type 2 diabetic patients. Methods: A total of sixty-six type 2 diabetic adults were recruited from outpatient department at the Tri-Service General Hospital. All of them were collected general plus biochemical data, markers of the blood glucose level and oral X-ray. Results: Our data demonstrated no significant associations between glycemic control (fasting blood glucose and glycated hemoglobin) and marginal alveolar bone loss (crown to all tooth length ratio value). However, marginal alveolar bone loss revealed significantly positive correlation with age, high-sensitivity C-reactive protein (hsCRP) and missing teethes. The multiple logistic regression analysis also showed age, hsCRP and missing teethes were associated with marginal alveolar bone loss. Finally, the stepwise regression analysis indicated age and hsCRP were the major risk factors of the severity of marginal alveolar bone loss in our type 2 diabetic patients. Conclusions: Our study revealed that age and systemic inflammatory condition might have more significant roles than glycemic control in variations of periodontitis in our type 2 diabetic patients. Keywords: diabetes, periodontal disease, periodontitis,

199

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-15

THE LEVELS OF GROWTH ARREST-SPECIFIC PROTEIN 6 (GAS6) ARE REDUCED IN PATIENTS WITH TYPE 2 DIABETIC UREMIA 1

SHENG-CHIANG SU, 2YU-JUEI HSU, 1YI-JEN HUNG, 1CHIEN-HSING LEE

Division of Endocrinology and Metabolism, 2 Division of Nephrology, Department of Internal Medicine, TriService General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

Objectives: We aimed to not only investigate levels of growth arrest-specific protein 6 (Gas6), but also verify its unique role in patients with type 2 diabetic uremia. Methods: One hundred and nine adults were recruited including 23 subjects were type 2 diabetes with uremia and 56 patients were newly diagnosed type 2 diabetes without remarkable nephropathy as well as 30 adults with normal glucose tolerance without significant clinical co-morbidity served as control. Plasma Gas6 concentration and common anthropometric and biochemical variables were measured. Results: Plasma Gas6 levels were significantly lower in patients with type 2 diabetes than control, regardless of status of nephropathy. A trend of declined levels of Gas6 among three groups were also observed. Moreover, the Gas6 levels significantly inversely correlated with plasma creatinine, BUN and uric acid in all subjects. In multivariate logistic regression analyses, higher plasma Gas6 concentrations were significantly associated with a decreased risk of type 2 diabetic uremia even after adjusting for age, sex and fasting glucose. Conclusions: Our results suggest that plasma Gas6 levels are associated with type 2 diabetes and may play a potential role for developing diabetic nephropathy.

200

Abstract PD-16

THE LINK OF IN VIRTUAL SCREENING TO HEALTH INSURANCE DATABASE IN THE CHEMICAL GENETIC STUDY OF OBESITY 1

CHIEH-HUA LU, 2WU-CHIEN CHIEN, 3LI-JEN TSAI, 4PO-SHIUAN HSIEH

Division of Endocrinology and Metabolism, Tri-service general hospital; 2School of Public Health, National Defense Medical Center; 3Ching Kuo Institute of Management and Health; 4Graduate Institute of Physiology, National Defense Medical Center

Background: We are attempting to reduce obesity and the burden of obesity-associated comorbidities through drug discovery and to study the target mechanisms of drugs by virtual screening. We used forward chemical genetics by screening a chemical library to characterize abnormal fat accumulation by targeting specific proteins. We studied the library using a similar molecular approach to find possible targets of bioactive molecules. A connectivity map was created to link the signaling pathway and network using Pathway Studio and MetaCoreTM software to find potential targets for treatment. We selected Caenorhabditis elegans (C. elegans) and 3T3-L1 cells to screen in silico for active compounds and to find their targets. For detail regarding obesity-related comorbidities, we searched Taiwan’s national health insurance database to count its comorbidity types and their prevalence. Results: We found many active compounds which were similar with 15-lipoxygenase inhibitor, phospholipase A2 inhibitor, etc and compared the crosstalk of each target using Pathway Studio and MetaCore to find one important pathway, beta-transducin repeat containing (BTRC), which links with ubiquitin and glycogen synthase kinase-3beta (GSK3ß), and one unexplainable pathway, ephrin tyPE-A receptor 4 (EPHA4), which can involve fat accumulation. We found from the database that Taiwan has seen an increase in obesity and obesity-related comorbidities distributed across almost all fields of disease. Conclusions: This study represents a promising approach to study the target mechanisms of drugs by virtual screening and can link these mechanisms with obesity and its related comorbidities.

201

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-17

PROLONG HYPOGLYCEMIA ASSOCIATED WITH LONG ACTING INSULIN ANALOGUE INJECTION— A CASE REPORT WEI-HSIN HSU, I-MIN PAN Department of Internal Medicine, Division of Endocrinology, Tainan Sin-Lau Hospital, Tainan, Taiwan, R.O.C.

The action duration of long acting insulin analogues can last their hypoglycemic effect as long as 24 hours after subcutaneous injection. We report a case of prolong hypoglycemia up to 80 hours associated with insulin detemir injection. Case report: An 89-year-old woman with Type 2 DM, dementia, and bed sore was admitted under the impression of hypoglycemia, upper gastrointestinal bleeding, asthma, and hypothyroidism. She was just discharged with metformin and galvus, because she previously had experienced hypoglycemia with levemir subcutaneous injection. She has been taken augmentin, nexium, cortisone acetate, and eltroxin. As fingertip sugar showed 453 mg/dl at 9:30pm, 10 unit levemir was injected subcutaneously. One hour later (10:30 pm), an additional dose of levemir 30 units was injected at right thigh for another finger sugar result of 480 mg/dl. Follow-up blood glucose tests revealed 390 mg/dl at 11:30PM and 350mg/dl at 0:30AM on the next day. Unfortunately, an episode of hypoglycemia with blood glucose 60mg/dl and cold sweating was found at 6:00AM. After taking some milk and cubic sugar, blood glucose increased to100mg/dl. As the patient was still in confusion status at noon and blood sugar showed 50mg/dl, she was sent to emergency room where blood glucose revealed 41 mg/dl, insulin level 2820 mU/L and C-peptide level 1.3ng/ml. She was treated with a bolus dose of 50% glucose 40cc and continuous intravenous infusion of 10 % dextrose at a rate of 60cc per hour. In addition to close monitoring finger sugar and electrolytes, food intake of 1250 kcal/day through nasogastric tube was given. However, there are at least five episodes of hypoglycemia during 72-hour admission period. The long hypoglycemia duration with such a dose was rarely reported.

202

Abstract PD-18

ASSOCIATION BETWEEN PLASMA GROWTH ARREST-SPECIFIC PROTEIN 6 AND COMPONENTS OF METABOLIC SYNDROME 1

PENG-FEI LI, 2FU-HUANG LIN, 1CHANG-HSUN HSIEH, 1YI-JEN HUANG, 1CHIENHSING LEE 1

Division of Endocrinoy and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan

Background: Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and its receptors of the TAM (Tyro-3, Axl, Mer) family may be involved in the pathogenesis of obesity, systemic inflammation and insulin resistance. Our aim was to investigate the link between Gas6 protein and metabolic syndrome (MetS) components. Methods: In total, 205 adults (88 men and 117 women) were recruited in this study. Plasma Gas6 concentration, general and biochemical data were measured. They were divided into three groups according to plasma Gas6 concentration (lowest, Gas6(1); highest, Gas6(3)). The mean values of each MetS component for every group were compared in men and women separately. Results: Plasma Gas6 levels were not different between gender groups. Gas6 concentrations were declined parallel with various MetS components in all group.(P=0.017 for trend). In group comparison, only the high-density lipoprotein-cholesterol (HDL-C) was found to be significantly higher in Gas6(3) in all and female groups. Other components were not different. Plasma Gas6 values were significantly positively correlated with HDL-C and negatively correlated with fasting glucose levels. Conclusion: Our result first demonstrate positive correlation between Gas6 proteins values and HDL-C and reinforce the association with fasting glucose. The potential role of the Gas6/TAM system in the involvement of MetS deserves further attention. Keywords: Growth arrest-specific protein 6, Metabolic syndrome, Gender

203

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-19

COMPARSION OF BRACHIAL-ANKLE PULSE WAVE VELOCITY (BAPWV) IN POOR-GLYCEMIC CONTROL TYPE 2 DIABETES PATIENTS IN EASTERN-SOUTHERN TAIWAN 1

KAT-YIEN NGU, 1SHIH-MING CHUANG, 1YUE QIU HUANG, 2CHUN-QUAN LI

Objective: Brachial-ankle pulse wave velocity (baPWV), as an indicator of atherosclerosis in diabetes patients, was studied in 522 subjects randomly selected from outpatient department in Taitung Mackay Memorial Hospital. Research Design And Methods: Fasting blood glucose (FBS), lipid parameters (including total cholesterol, triglyceride, LDL and HDL), ankle brachial pressure index (ABI), and baPWV were measured in each subject between July-2014 and September-2014. ABI and baPWV were measured using the recently developed device, form ABI/PWV. All selected subjects were divided into two groups according HbA1c level: a conventional group consisting of subjects with HbA1c < 9.0 mg/ dl and a poor-controlled group consisting of subjects with HbA1c >9.0 mg/dl, and all subjects taking hypoglycemic agents. The parameters in the two groups were compared. Results: It was found that the baPWV value increased with increasing plasma glucose level. Significant differences were found between the baPWV values in the conventional and poor-controlled groups (1402 vs. 1570 cm/s, P=0.033). The results of multiple regression analysis showed that HbA1c was closely related to baPWV as well as to HDL level. Conclusions: The relationship between diabetes control and atherosclerosis remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in diabetes patients will result in the prevention of atherosclerosis progression.

204

Abstract PD-20

DIABETIC KETOACIDOSIS DEVELOPMENT IN A YOUNG WOMAN WITH THE STIFF PERSON SYNDROME 1

HUNG-YU HUANG, 2RONG-HSING CHEN, 1,3MING-KUEI LU, 1,3CHON-HAW TSAI

Department of Neurology, China Medical University Hospital; 2Department of Endocrine and Metabolism, China Medical University Hospital; 3School of Medicine, Medical College, China Medical University

Introduction: Stiff person syndrome is a rare and intriguing disease entity that was characterized with stiffness of the low back and lower limbs. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is one of the unique variants of stiff person syndrome. The accurate diagnosis of the disorder is of important not only for academic interest but also for the appropriate immunomodulation therapy of the disease. Case Report: This 35-year-old woman, elementary English teacher, with 48 kg of body weight and 19.2 kg/m2 of BMI, was admitted in November 2013 due to exacerbated difficulty in walking for 17 years. During the symptomatic period, which may usually last for about 2 months and remitted spontaneously, the ambulatory difficulty commenced intermittently, continuing for one to five minutes in duration, with preceding uncomfortable low trunk spasm with legs stiffness, which made her walk like a robot. The low back spasm following by legs stiffness is drawn out by psychological stress, unexpected noise or touch on the head, or crowded environment; it may present as triple flexion of legs at lying position, during walking, and while she is just arising from sitting. Excessive startles response to sound and touch on the upper trunk and head is fatigable and reappeared after a period of time. Double vision and left ptosis appeared since 2 years with spontaneous recovery of ptosis 6 months later. She was found to have hyper-reflexia of the lower limbs with clonus and flexor plantar responses. Limitation of the left eye downward and right eye upward gazing were detected. MRI for brainstem, and whole spinal cord was unremarkable. The serum levels of anti-glutamic acid decarboxylase (anti-GAD) antibodies were over 300 u/mL. During the follow up, she had improved ability of daily chores under daily diazepam and regular methylprednisolone pulse therapy with a four-month interval. However, nine months after the diagnosis of stiff person syndrome, she was diagnosed as diabetes melliatus and diabetic ketoacidosis with the presentation of progressive thirsty and body weight loss (from 48 kg to 40 kg of body weight) for three months. The HbA1c (13 %) level, flunctuated C-peptide level (<0.1 ng/ml, 1.04 ng/ml, in separated time), and marked response of C-peptide level to glucagon stimulation test suggested that she has possible type 1 diabetes, but the status of insulin dependence should be further elucidated. Conclusion: The patient has diagnosed as PERM by the appearance of intermittent lower trunk and legs stiffness in association with stimulus sensitive reticular reflex myoclonus, eye movement limitation and excessive startle response, and positive anti-GAD antibodies. Among the autoantibodies, the antiGAD antibody is the prototype of autoimmune-related SPS. It was found in about 80 % of newly diagnosed type 1 diabetes melliatus (T1DM), and almost half of SPS might be diagnosed as T1DM before or after the diagnosis of SPS in about five years. The possible associated comorbidities, such as diabetes mellitus, thyroid disorder, and autoimmune and paraneoplastic disorder, should be checked conditionally during follow-up. Since the immune modulation therapy may benefit the patients with stiff person syndrome, the correct diagnosis is important for the long term impact.

205

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-21

E-SELECTIN AS A MARKER OF ENDOTHELIAL DYSFUNCTION IN METABOLIC SYNDROME AND GENDER DIFFERENCES IN THE EXPRESSION OF E-SELECTIN AND OTHER MARKERS OF INFLAMMATION WEN-HAO TANG, FENG-CHIH KUO, FU-HUANG LIN, CHANG-HSUN HSIEH, YI-JEN HUNG, CHIEN-HSING LEE Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chen-Kung Rd.,Nei-Hu, Taipei, Taiwan

Objectives: Associations are established between metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction. We investigated associations between E-selectin and MetS and gender differences in biomarker expression. Patients: A convenience sample of 205 patients aged 20-75 years with/without MetS was recruited from outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Included patients had BMI < 35 kg/m2, no recent infection, no anticoagulant or diabetes medications. Pregnant or breastfeeding women, patients with liver disease, pancreatitis, previous malignancy, stroke or myocardial infarct, psychiatric disorders, alcoholism, or taking beta blockers, diuretics, cholestyramine or steroids were excluded. Measurements: Demographic, anthropometric and MetS index data were compared by gender. Markers of inflammation (TNF-α, IL-6, hsCRP) and endothelial dysfunction (E-selectin, ICAM1, VCAM-1) were measured and compared by gender. Associations were determined by correlation analysis and multivariate logistic regression. Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. Elevated E-selectin levels were significantly associated with number of MetS components in females (P<0.001) but not in males (P=0.125). In females, E-selectin levels in highest quartile (≥61.074 ng/ml) were significantly associated with increased MetS risk (OR=6.80, 95% CI=1.46 to 31.75; P=0.015) compared to lowest quartile levels (<30.24 ng/ml). Conclusion: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males.

206

Abstract PD-22

Background: In previous studies, endocrinologists have been reported to execute better glycemic control in diabetic patients than non-endocrinologists. This study was aimed to compare the outcome differences between endocrinologists and other subspecialists. Methods: Diabetic patients were enrolled from July 2006 to December 2006 in a medical center in central Taiwan. The patients were divided into two groups according to their main healthcare provider - either an endocrinologist (EN) or non-endocrinologist (non-EN). They were prospectively followed up for 5 years (till Dec 2011). Baseline characteristics, laboratory data, medications, and outcomes of the 1930 patients who were still alive one year after enrollment were analyzed. Results: A total of 1992 diabetic outpatients were recruited from Jul 2006 to December 2006. In comparison with non-EN group (n=813), the EN group (n=1117) is younger in age and has a lower mortality during the follow up period (EN group mortality=12.7%, non-EN group mortality = 18.9%, p<0.001). Comparing with non-EN subgroups, mortality was significantly lower in four of the EN subgroups: (1) diagnosis of hypertension (HR=0.612, 95% CI: 0.41-0.916, p=0.017), (2) using antihypertensive medications (HR=0.655, 95% CI: 0.444-0.967, p=0.033), (3) no coronary artery disease (non-CAD) (HR=0.658, 95% CI: 0.446-0.970, p=0.035), and (4) younger than 65 years-old (HR=0.406, 95% CI: 0.172-0.961, p=0.04). In addition, in the above four subgroups, more annual glycated hemoglobin(HbA1C) decrease was observed in (1) hypertensive patients (annual difference=0.1%, p=0.007), (2) using antihypertensive medications (annual difference=0.096%, p=0.011), (3) no coronary artery disease (non-CAD) (annual difference=0.068%, p=0.048), but annual HbA1C decrement did not significantly differ in patients aged less than 65 years old (annual difference=0.052%, p=0.319). Conclusion: Compared with diabetic patients cared by non-endocrinologists, greater annual HbA1C decrement and survival benefit were shown in three subgroups of patients cared by endocrinologists: (1) hypertensive patients (2) patients who receive antihypertensive medications (3) patients without CAD. However, in the subgroup aged less than 65 years old, survival difference was noted without significant difference in HbA1C decrement rates between these two groups. This may suggest factors other than HbA1C decrement rate as the cause of the survival benefit.

207

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-23

ORAL GLUCOSE LOWERING WITH LINAGLIPTIN PLUS METFORMIN IS A VIABLE INITIAL TREATMENT STRATEGY IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES AND MARKED HYPERGLYCAEMIA 1

BAPTIST GALLWITZ, 2STUART A. ROSS, 3A. ENRIQUE CABALLERO, 4STEFANO DEL PRATO, 5DIANE LEWIS-D’ AGOSTINO, 6ZELIE BAILES, 7SANDRA THIEMANN, 6 SANJAY PATEL, 7HANS-JUERGEN WOERLE, 5MAXIMILIAN VON EYNATTEN 1

Dept. Medicine IV, Universitätsklinikum Tübingen, Tübingen, Germany; 2LMC Endocrinology Centres, University of Calgary, Calgary, AB, Canada; 3Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA; 4Department of Endocrinology and Metabolism, Section of Diabetes, University of Pisa, Pisa, Italy; 5 Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 6Boehringer Ingelheim Ltd, Bracknell, UK; 7 Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Background and aims: Newly diagnosed type 2 diabetes (T2D) patients commonly present with marked hyperglycaemia. This condition has rarely been studied for novel oral diabetes drugs and insulin is often proposed as the preferred starting therapy. Materials and methods: We explored oral glucose-lowering combination therapy in newly diagnosed (≤12 months) T2D patients with marked hyperglycaemia (n=316) utilising prespecified exploratory subgroup analyses from a randomised double-blind study of initial combination of linagliptin+metformin versus linagliptin. Baseline mean±SD age and HbA1c was 48.8±11.0 years and 9.8±1.1%, respectively. The primary endpoint was HbA1c change from baseline to week 24. Results: Mean±SE HbA1c reduction was -3.4±0.2% versus -2.5±0.2% with linagliptin +metformin and linagliptin, respectively, in patients with baseline HbA1c ≥9.5%, and -2.1±0.2% versus -1.4±0.2% in patients with baseline HbA1c <9.5%. Similar HbA1c reductions occurred in all subgroups of age, body-mass index (BMI), renal function, race, and ethnicity. Hypoglycaemia was rare (1.9% and 3.2% of patients, respectively) with no severe episodes. Conclusion: In our analysis of newly diagnosed T2D patients presenting with marked hyperglycaemia, initial linagliptin+metformin elicited consistent HbA1c reductions across different subgroups. Oral glucose-lowering combination therapy may be a viable initial alternative to insulin for effective treatment of these patients.

208

Abstract PD-24

RISK OF HYPOGLYCEMIA IN PEOPLE RECEIVING LINAGLIPTIN: POOLED DATA FROM 1489 ADULTS AGED ≥65 YEARS WITH TYPE 2 DIABETES MELLITUS 1

KAMLESH KHUNTI, 2MICHAEL NAUCK, 3ATSUSHI ARAKI, 4SUSANNE CROWE, 4 YAN GONG, 4DOUGLAS CLARK, 5MAXIMILIAN VON EYNATTEN, 4HANS-JUERGEN WOERLE 1

University of Leicester, Leicester, UK; 2Diabetes Center Bad Lauterberg, Bad Lauterberg im Harz, Germany; Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA 3

Objectives: Risk of hypoglycemia (HYPO) in elderly patients with T2DM is a major concern, especially when drug regimens include either insulin (INS) or secretagogues (SECR). We pooled data from a global clinical trials program to further assess the safety, focusing on HYPO, of the DPP-4 inhibitor linagliptin (LINA). Methosd: Adults with T2DM aged ≥65 years who participated in 11 randomized, placebo (PBO)controlled, Phase III trials were included. Efficacy was assessed by change in HbA1c from baseline to Week 24 using the full analysis set (FAS). Incidence of confirmed HYPO (plasma glucose ≤70 mg/dL) or severe HYPO (requiring third-party assistance) was assessed in the treated set (TS) with consideration for background therapy: regimens including INS but no SECR, SECR but no INS, or neither therapy. Results: Overall, 1489 patients were treated (TS: LINA, n=948; PBO, n=541). Mean ± SD age was 70.9 ± 4.6 y (range, 65-91). In both treatment groups (FAS: LINA, n=936; PBO, n=530), mean baseline HbA1c was 8.1 ± 0.8%. Linagliptin significantly decreased HbA1c at Week 24 by a PBOadjusted mean (95% CI) of −0.60% (−0.69, −0.51; p <0.0001). Incidence of confirmed HYPO was 26.3% in the LINA group and 34.0% in the PBO group (RR: 0.77 [95% CI: 0.66, 0.91; p <0.05]). In the subgroup of patients receiving INS but no SECR (LINA, n=247; PBO, n=256), incidence was 53.4% vs. 55.9%, respectively (RR: 0.96 [CI: 0.82, 1.12; p ≥0.05]). In the subgroup receiving a SECR but no INS (LINA, n=309; PBO, n=126), incidence was 32.0% vs. 25.4% (RR: 1.26 [CI: 0.90, 1.77; p ≥0.05]). Finally, in those whose regimens included neither SECR nor INS (LINA, n=371; PBO, n=152), incidence was 1.3% vs 3.3% (RR: 0.41 [CI: 0.12, 1.39; p ≥0.05]). Overall, incidence of severe HYPO was low in both groups (LINA, 0.8%; PBO, 1.3%). Conclusions: In an elderly population, overall risk of HYPO was not increased when LINA was added to improve hyperglycemia, with lower incidence rates compared to PBO when LINA was given with background INS but higher rates with background SECR.

209

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-25

We report a rare case of IgG4 related disease in a patient with diabetes mellitus.A 48-year-old man with an seven-year history of diabetes mellitus presented skin rash after linagliptin use.He had been treated for diabetes mellitus with metformin for many years. Due to poor glycemic control, linagliptin was added at one year ago.Then he developed skin rash.Because it’s suspected adverse effects of DPP4-inhibitor drug, linagliptin was then withdrawed and metformin dose was titrated up. Then he presented gastrointestinal upset so that metformin dose was titrated down and repaglinide was added. Because he developed chronic diarrhea and weight loss, upper GI scope and liver sonography were arranged.Liver sonography revealed pancreas swelling with heterogenous parenchyma, common bile duct and intrahepatic duct dilatation, gall bladder wall thickness and one gall bladder polyp.Pancreatic cancer was suspected so that abdominal CT scan was arranged. Abdominal CT scan revealed relatively prominent pancreatic parenchyma with encapsulated appearance around the pancreatic body ; prominent and symmetric mural thickening of the common hepatic duct to the common bile duct, with dilated intrahepatic ducts.Due to suspect Ig G4 related disease, IgG and subgroups blood levels were checked.IgG and IgG4 levels were elevated and IgG1,IgG2,IgG2 were all within normal range.Then Ig G4 related disease was diagnosed. Prednisone was then administered. The patient’sGI upset and diarrhea gradually improved and IgG and IgG4 levels decreased after prednisone use which was suggestive of good response to steroid.

210

Abstract PD-26

EMPHYSEMATOUS PYELITIS WITH PNEUMONEPHROSIS IN TYPE 2 DIABETES PATIENT 1

CHIU CHIH-HUANG, 2WANG SHU-Y, 3TSAI DONG-HWA

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan This 54-year-old Taiwanese woman, with a history of diabetes mellitus for 7 years with oral anti-diabetic agents control and proliferative diabetic retinopathy under ophthalmology OPD following up. General weakness and fever were noted since 4 days before admission. She hold oral antidiabetic agents by herself. She ever came to LMD 7 days ago and urinary tract infection was suspected. Empiric antibiotics was used. Due to fever off and on, she was admitted to further survey. NO travel occupation contact cluster history was noted. PE: Pulmonary: symmetric expansion, no wheezes, rales, rhonchi. Abdominal: Normoactive bowel sounds. Soft, no tender, knocking pain: both kidney Lab: WBC HB Plet neutrophil lymphocyte Monocyte 17100/սL 11g/dl 266000/ սL 89.5% 3.5% 6.9% Bun Cre Na K GPT sugar 34mg/dl 1.7 mg/dl 124 5.0 11 675 Urine sugar Urine protein Urine WBC Epithelial cell >0.5g/dl 100 mg/dl 38.2/HPF 2/HPF Image: Renal echo: renal stone and hydronephrosis KUB: free air over bladder, urethral tube and pelvis Abdomen CT: extensive gas collection in the parenchyma and perinephric space of the left kidney; bilateral hydroureteronephrosis and pneumonephrosis According to laboratory exam, image studies, emphysematous pyelitis was diagnosed. Antibiotics with ertapenem for blood culture and urine culture revealed multiple drug resistant Escherichia coli. Due to hyperglycemia, initial insulin pump and then basal bolus insulin regimen were prescribed for blood sugar control. After completion of antibiotic treatment, with good glycemic control, symptoms of hydroureteronephrosis got improved gradually. She was discharged and received outpatient department follow up. Discussion: Emphysematous pyelitis is defined as isolated gas production inside the excretory system, secondary to acute bacterial infection. It is relatively benign entity, and needs accurate differentiation from emphysematous pyelonephritis, which is much morbid condition. It has excellent prognosis with good response to medical management. The incidence of emphysematous pyelitis in DM is unknown. Disease is more common in female2, associated with diabetes and urinary tract obstruction. The common pathogenic bacterium were Escherichia coli, Klebsiella pneumoniae, Aerobacter aerogenes and Proteus mirabilis. When diabetic patient with urinary tract infection, early survey such as renal echo or abdomen CT should be done. Empiric antibiotics should consider (1) clinic status ( severe sepsis or not) (2)previous antibiotics sensitivity and pathogenic bacterium (3)recurrent hospital admission or Foley’s tube using(4) common pathogenic bacterium in the area or this hospital (5) survey effection of emperic antibiotics per 3 days (6) Drugs resistance of pathogenic bacterium or not (7) antibiotics side effect and cast effection. Emphysematous pyelitis was a kind of special disease in DM poor control patient.

211

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-27

Background: Hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors are important for prevention of cardiovascular diseases in type 2 diabetic patient with dyslipidemia. Clinical data concerning the effect of statins on glucose metabolism in diabetics are limited. We investigated the effect of pitavastatin treatment on glycemic and dyslipidemic control in diabetic patients. Patients and Methods: Within the period of 1 August 2013 to 31 May 2014, 196 type 2 diabetic patients with dyslipidemia who started pitavastatin treatment were studied. They were either statinnaïve (statin-naïve group) or were treated with atorvastatin in the past (atorvastatin-switched group). Among them, the change of A1c levels were analyzed in 139 patients who had no adjustment of antidiabetic agents during study period. Clinical data were collected every 3 months. Results: Significant decrease of total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) was observed in the statin-naïve group (p<0.001). An increment of high-density-lipoprotein cholesterol (HDL-C) was observed in patients with baseline hypo HDL-C in both groups at 3 months. A correlation between the improvement of A1c and baseline A1c were noted in both groups (r= 0.23 and r=0.53 in statin-naïve group and atorvastatin-switched group, respectively). Further analysis by tertile baseline A1c levels revealed that the glycemic benefit of pitavastin treatment is significantly noted in relatively poorly-controlled diabetes group at 6 months of pitavastatin treatment in both groups (p=0.017 in the statin-naïve group, p=0.034 in the atorvastatin-switched group). Conclusions: Dislipidemic patients with type 2 diabetes can achieve not only improvement of lipid profile, but also better glycemic control when treated with pitavastatin. The latter effect is more prominent in the poorly-controlled patients. Further studies are needed to lucid the mechanism of glucose lowering effect of pitavastatin treatment.

212

Abstract PD-28

Fulminant type 1 diabetes is a new clinical entity in which the process of beta-cell destruction, and the subsequent progression of hyperglycemia and ketoacidosis, are extremely rapid with near normal HbA1C. Until now, this subtype of type 1 diabetes has only been reported in the Asian population, especially Japanese and Koreans. We report one case of fulminant type 1 diabetes mellitus in Taiwan. A 31-year-old Taiwan woman complained of nausea, vomiting and abdominal discomfort for 2 days and she had short of breath, polyuria and thirst just on the day of her admission to hospital. Flulike symptoms (cough, chills, fever) had developed five days. There was no weight loss (BMI: 26.7 kg/ m2,71 kg,163cm). Upon admission, her blood glucose levels were highly elevated (1029 mg/dL) and associated with severe ketoacidosis (urine ketone 2+; arterial blood pH: 7.035; arterial blood HCO3: 5.2 mEq/L, serum β-hydroxybutyrate:5.3 , normal<0.6 mmol/L). Hyperkalemia was also noted: K:7.7 mmol/L with EKG show sinus tachycardia with Peaked T waves and prolonged QRS, develop of nearing a sine wave appearance. HbA1c was normal at 5.6%. Her fasting serum C-peptide levels were below the detection limit (<0.1 ng/mL) at the time of admission and after metabolic decompensation. As for autoantibodies, anti-GAD antibody, and antithyroperoxidase antibodies were all negative, and serum pancreatic enzyme levels were elevated at the time of admission day 7 (lipase: 145 UI/L, normal range:19– 47;amylase:109 IU/L, normal range: 28–100). Abdominal CT revealed no significant abnormality. She was initially treated in the intensive care unit (ICU) with intravenous insulin and a large volume of intravenous normal saline for diabetic ketoacidosis. Her dyspnea, thirsty, polyuria nausea, vomiting and abdominal pain got improved after two days. She was subsequently treated with a daily injection of a long-acting insulin analogue along with three daily injections (at each meal) of a rapid-acting insulin analogue. She had no ‘honeymoon period’, and her HbA1c levels were up to 6.8 % 2 months later with 54 IU/day of insulin.

213

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-29

INDICATOR ANALYSIS FOR RESPONSIVENESS TO GLUCAGONLIKE PEPTIDE RECEPTOR AGONIST, LIRAGLUTIDE IN TAIWANESE TYPE 2 DIABETIC PATIENTS I-WEN CHEN, YU-YAO HUANG, SZU-TAH CHEN, SHIN-YUAN HUNG, CHIA-HUNG LIN, BREND RAY-SEA HSU Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Background: Liraglutide, a glucagon-like peptide receptor agonist (GLP-1 RA) is approved to use for a second-line glucose-lowering agent to maintain and improve glucose control in type 2 diabetic patients. Here, we compared the characteristics and parameters among Liraglutide responders and non-responders to identify possible indications for GLP-1 RA treatment. Design and Methods: This observational study included 94 patients with type 2 diabetes mellitus being treated with Liraglutide. Clinical characteristics and parameters were documented every 3 months at initiating Liraglutide treatment. All patients have used Liraglutide and followed up for 3 to 12 months. The adjustment of Liraglutide dosing or other antidiabetic agents was depended on clinical judgment. Those patients had benefit from liraglutide treatment for more than 1% of serum glycohemoglobin decrement was defined as responder group. The other patients without such effect were defined non-responders. Binary logistic regression analysis was used to compare between these 2 groups Results: Liraglutide treatment significantly decreases serum HbA1c (9.66±0.17% to 8.73±0.17%, P<0.001) and body mass index (30.43±4.75 to 29.89±4.54, P< 0.001) in the study patients. Forty-one of the 94 patients (43.6%) were reported as responders. Demographically, known diabetic duration was 9.90±5.16 years for responders and 13.52±5.97 years for non-responders (p=0.002); pre-treatment body mass index (BMI) was 33.27 ± 5.07 kg/m2for responders and 28.53 ± 3.60 kg/m2 for nonresponders (p<0.001); pretreatment HbA1c level was 10.15±1.62% for responders and 9.29±1.51% for non-responders (p=0.016); fasting C-peptide level was 4.15±2.21 ng/ml among responders and 2.39±1.22ng/ml among non-responders (p=0.011); triglyceride was 237.09±138.08 mg/dL among responders and 173.95±86.94 mg/dL among non-responders (p=0.024). Stepwise regression analysis demonstrated that baseline BMI (adjusted OR and 95% CI: 1.313, 1.136-1.517, p<0.001) and HbA1c (adjusted OR and 95% CI: 1.437, 1.017-2.029, p=0.040) may predict for Liraglutide response. Conclusion: We conclude that Liraglutide effectively maintained better glycemic control by reducing BMI and increasing C-peptide in type 2 diabetic patients. The response of Liraglutide was significantly associated with baseline body mass index and HbA1c, that is, patients with higher BMI and HbA1c may be a better Liraglutide responder. 214

Abstract PD-30

RELATION OF BODY MASS INDEX, C-REACTIVE PROTEIN AND MORTALITY IN INPATIENTS OF CARDIOVASCULAR WARD 1

YI-TING KUO, 2I-TE LEE, 2JUN-SING WANG, 2CHIA-LIN LEE, 2SHIH-YI LIN, 2 WAYNE HUEY-HERNG SHEU 1

Department of Internal Medicine, Taichung Veteran General Hospital, Wancian Branch, Chiayi, Taiwan, R.O.C.; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veteran General Hospital, Taichung, Taiwan, R.O.C.

Background: Obesity causes many serious medical complications that impair quality of life and lead to increase morbidity and mortality. Besides, several studies have linked obesity with elevated levels of C-reactive protein, which is associated with cardiovascular disease and mortality. Most of these studies enrolled subjects without cardiovascular disease. Recently, being overweight or obese is associated with lower mortality rates than for similar patients with normal BMI values in some chronic disease, such as cardiovascular disease, which is called “obesity paradox”. The study aim to evaluate the correlation of body mass index and C-reactive protein in patients with cardiovascular disease. Methods: This study enrolled 1456 subjects admitted to cardiovascular ward during March, 1999 to July, 2004. Relationships between body mass index and C-reactive protein with all-cause mortality were examined. Results: Be overweight or obese (BMI≥23) was found to associate with lower mortality compared to normal. Death subjects had higher level of mean C-reactive protein compared to survivor (1.09±1.58 v.s. 0.57±1.22, p<0.0001). However, mean C-reactive protein was found to be decreased with elevated body mass index level. (BMI<18.5:1.41±1.92, 18.5≤BMI<23:1.12±1.67, 23≤BMI<25:0.70±1.31, 25≤BMI<30:0.71±1.31, BMI≥30:0.65±1.17, p=0.0025). Conclusion: Obesity and inflammation may lead to cardiovascular disease. But in patients with developed cardiovascular disease, overweight, obese and chronic inflammation, such as the relationship of body mass index and C-reactive protein, may be different from normal subjects. C-reactive protein seemed to be a better predictor in mortality compared with body mass index in studies. The correlation of obesity and inflammatory marker in these patients still need further evaluation.

215

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-31

MEASURABLE GLUCOSE IMPACT MITOCHONDRIAL QUALITIES VARIATION WITH CONFOCAL MICROSCOPY 1

HONG-WEI SHEN, 1YUNG-SHENG CHANG, 1PEI-YU CHENG, 1SHIH-TE TU, 1,2SHIHLI SU, 2CHIN-SAN LIU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.; 2Vascular Medical Research Laboratory, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.

Aim: Assess the eﬀect of treatments with high glucose concentration on mitochondrial morphological changes in human renal mesangial cell Methods: Human renal mesangial cells are cultured in normal glucose (5mM) and high glucose (30 mM) medium. We had been using the XF24 seahorse to examine sequential electron flow through mitochondrial electron transport chain complexes which can be identified the status of mitochondrial dysfunction and modulation. The previous study applied the quality changes, including metabolic dysfunction and extracellular acidification. The morphological changes of mitochondrial had been done with same MES cell line by confocal microscopy. MitoTracker Green FM can detect the mitochondrial real activities without an affect mitochondrial membrane potential. Tetramethylrhodamine ethyl ester can disclose the apoptosis of cells with decade red color. Combine both stain made us recognizing the mitochondrial quality variations. Conclusion: Our experiments suggest that mitochondria quality variation of mesangial cell of kidney displays significant increase mitochondrial amounts. The apoptosis and membrane potential also enhanced. Glucose is the source of energy to provide mitochondrial essential functions which demonstrate as an increment of total mitochondrial amounts. For the purpose to keep balance, apoptosis also amplify.

216

Abstract PD-32

Objective: Necrotizing fasciitis (NF) is a life threatening insidiously advancing or sometimes fulminant soft tissue infection characterized by widespread fascial necrosis. Necrotizing fasciitis on thewhole is higher in patients with immunosuppressive conditions(such as diabetes mellitus and liver cirrhosis). Research Design and Methods: We invesigated 104 case of necrotizing fascitis(NF) with or without diabetes within recent 10 years(2004-2013) in Taitung Mackay Memorial Hospital. 48 case of NF(46.2%) with diabetes and most involvement over lower extremities(66.67%). All NF patients were divided into two groups according to diabetes history, all biochemical parameter, sequent complinactions and outcome in the two groups were compared. Results: It was found that the NF patients with diabetes have higher CRP(P=0.01), lower sodium(P=0.043), lower eGFR(P=0.019) as compared without diabetes. Elderly NF patient with T2DM has high mortality rate(35%) as compared younger patients (13%). Old-aged diabetes was increasing risk of moltality(Odds ratio: 2.54, 1.18-5.46, P=0.022) in NF patients. Conclusions: The relationship between diabetes control and NF remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in diabetes patients will change outcome of Necrotizing fascitias.

217

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-33

SUCCESSFUL MANAGEMENT OF TYPE 2 DIABETES MELLITUS WITH MORBID OBESITY AND INSULIN ANTIBODIES-A CASE REPORT 1.2

PIN-FAN CHEN, 1BING-RU GAO, 1.2WEI-CHENG LIAN, 1SHIH-TANG YAN, 1TINGCHANG CHEN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

Objective: Patients with type 2 diabetes mellitus have an option to receive bariatric surgery if BMI are over 32 kg/m2 and glycemic control are not quite well in Asia. The result, focusing on diabetes remission, is tremendously well if C-peptide level before operation is above 3.0 ng/ml, compared with medical control. Case report: We reported a case of severe obesity (height 180 cm, weight 118kg and BMI 36.4 kg/m2), who was diagnosed with type 2 diabetes since Nov. 2011 in Tai-Chung. At that time, high daily insulin requirement (over 1U/kg) was found and having insulin antibodies was told. The need of unusual high daily insulin requirement was confirmed by continuous subcutaneous insulin infusion (CSII). As a resulting increase in daily insulin doses by using insulin analogues over 300IU/day, He received RI 70U, 60U, 50U, 30U four times a day along with IVII 5U/hr to control finally before he received laparoscopic Sleeve Gastrectomy on 31 Oct. 2013. Six days after operation, diabetes remission has been found till now. Conclusion: In patients with type 2 diabetes with morbid obesity, who has insulin antibodies, bariatric surgery is the more favored choice than other medical methods and should be performed as soon as possible.

218

Abstract PD-34

M&OUML;NCKEBERG’S ARTERIOSCLEROSIS IN A DIABETIC PATIENT WITHOUT HYPERLIPIDEMIA YI-HSIN LIN, CHIH-HSUNG HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Taiwan Adventist Hospital, Taiwan, R.O.C

Mönckeberg’s arteriosclerosis, also called medial calcific sclerosis, is a form of arteriosclerosis or vessel hardening, where calcium deposits are found in the muscular middle layer of the walls of arteries (the tunica media). Its clinical significance and etiology are not well understood but may be associated with poorer prognosis. Probably it causes increased arterial stiffness, increased pulse pressure and resulting in exaggerated damage to the heart and kidneys. We described a 70-year-old female diabetic patient, without hyperlipidemia and calcium/phosphate imbalance, had gradually aggregative Mönckeberg’s arteriosclerosis from thoracic to abdominal aorta, which looked like “a pipestem” in X-ray radiograph, in 7 years follow-up. Key words: Mönckeberg’s arteriosclerosis, medial calcific sclerosis, diabetic

219

The

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-35

PAY-FOR-PERFORMANCE PROGRAM REDUCE THE INCIDENCE OF DKA AND HHS IN DIABETIC PATIENTS 1

HUI-MIN HSIEH, 2,3,5SHYI-JANG SHIN, 4HERNG-CHIA CHIU

Department of Public Health; 2School of Medicine, College of Medicine; 3Center of Lipid and Glycomedicine Research; 4Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University; 5 Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Taiwan

Introduction: The effectiveness of diabetes pay-for-performance program (P4P) in Taiwan and even in the world has not been elucidated. In this study, we compared the probability of incidence for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) between P4P and non-P4P patients during the 5-year period to assess the effectiveness of diabetes P4P. Methods: We conducted a longitudinal cohort study using a nationwide diabetes P4P database and the National Health Insurance (NHI) administrative claims database in Taiwan from 2007 to 2012. We included diabetic patients who had primarily diabetes diagnosis (ICD-9-CM codes with 250.xx or A-code 181) in at least two outpatient visits or at least one inpatient hospitalization during 2007 and 2008. Using the P4P database, we identified newly enrolled P4P patients as study P4P cohorts and the date when they were first enrolled as index date. We then identified non-P4P diabetic patients if they were not found in the P4P program in study period. To avoid potential confounding by selection bias and confounding factors, we used propensity score matching approach (PSM) to determine comparison group. Incidence rates per 1,000 person-years for DKA and HHS were calculated until the end of study date on December 31, 2012. Multivariate logistic regression and cox proportional hazard model were used to calculate HR for DKA and HHS in comparison between P4P and non-P4P patients. Results: Before matching, we included 34,710 P4P patients and 341,312 non-P4P diabetes patients. After PSM for 1 to 1 matching, the two groups were found to be similar in demographic characteristics, comorbidities (CCI index, categories) and institution of health care. Incidence rates per 1,000 person-years of DKA (2.69 vs 3.00) and HHS (2.09 vs 2.53) were lower in P4P patients than non-P4P patients. Using multivariate logistic regression, the HR for DKA was 0.900 (95% CI=0.813, 0.997) (p<0.044) and for HHS was 0.884(95% CI=0.787, 0.992) (p<0.036) between P4P and nonP4P groups. Using cox proportional hazard model, the HR for DKA was 0.796 (95% CI=0.717, 0.883) (p<0.001) and for HHS was 0.726(95% CI=0.643, 0.819) (p<0.001) between P4P and non-P4P groups. Conclusion: Our findings provided evidences for the potential long-term benefit of pay-forperformance programs for diabetic care on the incidence of DKA and HHS.

220

Abstract PD-36

10-YEAR FOLLOW-UP OF GLYCEMIC CONTROL DURING HOLIDAY TIME IN PATIENTS WITH TYPE 2 DIABETES 1,3

TSENG-HUI KAO, 2,4TZU-EN WU, 1,2HARN-SHEN CHEN, 1CHUN-JUI HUANG

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital ,Taiwan,R.O.C.; 2Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan,R. O.C.; 3Division of Endocrinology and Metabolism, Department of Medicine, Taipei City Hospital Yangming Branch,Taiwan,R.O.C.; 4Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan,R.O.C.

Objective: We carried out this follow-up study to investigate whether HbA1c gain during the Chinese New Year’s holiday exist every year and contribute to the substantial increase in HbA1c among patients with type 2 diabetes in the 10-years follow-up. Researche Design And Methods: We measured HbA1c in 108 patients with type 2 diabetes to determine the glycemic change during Chinese New Year's holiday from November 2000 to April 2001. In this 10-year follow-up, we collected the data from November 1st to the beginning of Chinese New Year’s holiday as the pre-holiday period, and from the end of the holiday to April 30th as the post-holiday period. Results: The significantly increment of HbA1c values after holiday period were seen in 2001, 2002, 2006 and 2008. Compared with the pre-holiday HbA1c in the first year, the pre-holiday HbA1c in the 10th year was increased significantly (0.57±1.52%, [95% CI, 0.17-0.96]). The time-weighted HbA1c levels were significantly higher in subjects with HbA1c increased in the upper half of the first year (8.02±0.30% vs. 7.69±0.28%, p=0.0003). Conclusions: The level of HbA1c increased significantly after Chinese New Year’s holidays for four times during the 10-years follow-up in which three times occurred during the 9-day vacation and another one occurred during a lower temperature in Taipei City. Longer holiday period and lower temperature are risk factors for poor glycemic control during Chinese New Year’s holidays.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

PD-37

THE IMPACT ON RENAL FUNCTION FOR PARTICIPATING DIABETES SHARED-CARE NETWORK IN TYPE 2 DIABETES PATIENTS 1

TZU-HSING HUNG, 2JIUN-YIAN LIN, 2PI-YUAN WONG, 2I-CHUAN LIN, 2I-JU LIEN, 2 CHUNG-HSUEH CHUNG, 2TONG-YUAN TAI 1

Department of Family Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.

Aims: To evaluate the impact of participation of diabetes shared-care network to renal function of type 2 diabetes patients. Methods: One hundred nine cases of type 2 DM patients, well controlled by entering DM sharedcare network (participants) for a certain period of time and thirty eight cases without entering (nonparticipants) were observed for 3.53± 0.57 years and 3.45±0.65 years, respectively. The mean ages were 64.7±10.4 years and 66.4±10.7 years, DM durations 9.72±7.33 years and 9.49±8.71years, gender distributions of male participants 44.0% and 42.1%, respectively. The differences of corresponding parameters between two groups were not significant. Their renal functions were expressed by eGFR, which was derived from yearly determination of serum creatinine levels. Resuts: The initial and final HbA1c values of the participants were 7.59±1.07 % and 7.17±1.12%, and respective values for the non-participants were 8.24±1.59 % and 7.38±1.35%. AT the beginning, the participants showed better glycemic control (p value=0.02, by Mann-Whitney U test), however, at the end of observation, HbA1c of both groups showed no significant difference. The initial and final eGFR of the participants were 74.70±17.97 mL/min/1.73 m2and 74.01±21.89 mL/min/1.73m2 and those of the non-participants were 71.65±20.78 mL/min/1.73 m2 and 68.03±20.64 mL/min/1.73m2, respectively. The change of eGFR of the participants was -0.87% (eGFR, final-initial/initial x100%) and that of the non-participants was -7.9%(p value=0.023, by Mann-Whitney U test). Conclusions: The earlier correction of glycemic control through entering the DM shared-care network may do a better job in preserving the renal function of diabetic patients.

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Abstract PD-38

ASSOCIATION BETWEEN FRAMINGHAM STROKE RISK SCORE AND SUBCLINICAL ATHEROSCLEROSIS IN ELDER TYPE 2 DIABETIC PATIENTS WITHOUT CARDIOVASCULAR DISEASE 1

YI-MEI WANG, 2WEN-JANE LEE, 3WAYNE H-H SHEU

Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, R.O.C. 2Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, R.O.C. 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, R.O.C. Objective: Stroke is the third leading cause of death in Taiwan. Diabetes greatly increases the risk of stroke. Framingham stroke risk score (FSRS) is a widely used tool to identify asymptomatic individuals who are at risk to stroke. Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of subclinical atherosclerosis. We aim to investigate the association between subclinical atherosclerosis and FSRS in elder Type 2 Diabetes Mellitus (T2DM). Methods: This cross-sectional study enrolled 68 T2DM participants (33 men and 35 women, with age of 67.5±4.8 years (mean±SD)) and 34 non-DM participants (16 men and 18 women, with age of 66.8±4.8 years (mean±SD)) without history of CVD and cerebrovascular disease, aged ≥60 years, was analyzed. The baPWV, FSRS, clinical variables, basic laboratory data, plasma lipid profile, coagulation, fibrinolytic, and inflammation parameters were measured for each participant. A modified version of the Framingham stroke Risk Profile (incorporating age, sex, systolic blood pressure (SBP), smoking status, hypertensive medication, DM, atrial fibrillation, left ventricular hypertrophy, and prior CVD) was used to assess 10-years risk of stroke. Multiple regression assessed the independent correlates of baPWV. Results: A significant increase of FSRS (15.8±8.6% vs. 6.7±4.9%; p<0.05), baPWV (16.4±2.3 m/sec vs. 14.9±1.9 m/sec; p<0.05), body mass index (BMI), heart rate (HR), SBP, pulse pressure (PP), haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), creatinine (cre), estimated glomerular filtration rate (eGFR), uric acid (UA), and homocysteine (Hcy) was present in the T2DM group, with a significant decrease of total cholesterol (TCHO), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and vitamin B12 (Vit B12) levels compared to non-DM group. Compared with the non-DM group, the T2DM group had significantly higher rate of hypertension (HTN) (77.9% vs. 35.3%; p<0.05), use of anti-hypertensive drugs (76.5% vs. 32.4%; p<0.05), dyslipidemia (DLP) (64.5% vs. 34.3%; p<0.05), use of lipid-lowering drugs (55.9% vs. 11.8%; p<0.05), and Smoking (27.9% vs. 11.8%; p=0.07). Among the T2DM group baPWV had significant positive correlations with the duration of diabetes (r=0.265, p<0.05), age (r=0.395, p<0.001), BMI (r= -0.321, p<0.01), SBP (r=0.639, p<0.001), DBP (r=0.451, p<0.001), PP (r=0.489, p<0.001), MAP (r=0.654, p<0.001), HbA1c (r=0.339, p<0.05), cre (r=0.308, p<0.05), eGFR (r= -0.329, p<0.01), Hcy (r=0.209, p=0.088), D-dimer (r=0.201, p=0.099), and FSRS (r=0.582, p<0.001). In a multiple linear regression analysis, FSRS (95% CI: 0.015-0.233; p=0.027), HR (95% CI: 0.001-0.929; p=0.045), and PP (95% CI: 0.009-0.100; p=0.02) were independently associated with baPWV in T2DM after adjustment for other risk factors. Conclusions: These results suggest that higher FSRS, HR, and PP are associated with baPWV in Elder T2DM patients without CVD.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-01

The Studies of Gas6/AxL and Glucose Metabolism, Atherosclerosis, Obestiy and Sex Hormones 1

Yi-Jen Hung, 1Chien-Hsing Lee, 2Yi-Shing Shieh, 1Fone-Ching Hsiao, 1 Chang-Hsun Hsieh 1

Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, Taipei, Taiwan

Protein growth arrest–specific 6 (Gas6) was the last addition to the family of plasma vitamin K– dependent proteins. Gas6 was cloned and characterized in 1993 and found to be similar to plasma anticoagulant protein S. It was recognized as a growth factor–like molecule, as it interacted with receptor tyrosine kinases of the TAM (Tyro-3, Axl, Mer) family. The Gas6/TAM system regulates an intriguing mix of processes, including cell survival and proliferation, cell adhesion and migration, blood clot stabilization, and inflammatory cytokine release. The role of the Gas6/TAM system has been found to be important in inflammation; hemostasis; autoimmune disease; nervous, reproductive, and vascular systems; and cancer. In our study, plasma Gas6 is associated with altered glucose tolerance, inflammation, and endothelial dysfunction. It may represent a novel independent risk factor of type 2 diabetes and a potential surrogate marker of inflammation and endothelial dysfunction. The Gas6 c.843+7AA genotype and A allele are less prevalent in type 2 diabetes, which may have a protective role for type 2 diabetes. Otherwise, in cellular study, we also found that high glucose can alter Gas6/Axl signaling and may through Akt and VEGF/VEGFR2 downstream molecules and suggests that Gas6/Axl may involve in high glucoSE-induced endothelial cell dysfunction. Gas6 expression is widespread in many tissues, including immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Preclinical studies indicate that Gas6 and its receptors of the TAM family may be involved in the pathogenesis of obesity and its complications. Therefore, our data showed that circulating Gas6 and sAxl were significantly higher in overweight and obese adolescents. Circulating Gas6 levels were significantly positively correlated with body mass index Z-score, waist circumference, body fat mass, among overweight and obese adolescents. GAS6 and AXL polymorphisms are associated with adiposity, systemic inflammation, and insulin resistance in adolescents, especially in boys. In addition, we also found that significantly higher Gas6 concentrations were observed in adult male rather than female and lower Gas6 levels in the postmenopausal compared to the premenopausal women. Plasma Gas6 levels were positively correlated with estradiol levels in the pre- and postmenopausal women. Plasma Gas6 is associated with sex hormones in female and ages in male, indicating a potential role of sex hormones and ages involving the Gas6/TAM system. How the Gas6/ TAM pathway is regulated by sex hormones or ages in cellular concentrations, whether the activation of GAS6 gene by estrogen and androgen. It still needs further studies to elucidate. 224

Abstract AP-02

Three-Dimensional Islet Graft Histology: Panoramic Imaging of Neural Plasticity in Sympathetic Reinnervation of Transplanted Islets Under the Kidney Capsule 1,2

Jyuhn-Huarng Juang, 3,4Shih-Jung Peng, 5Chien-Hung Kuo, 3,4,6 Shiue-Cheng Tang 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, R.O.C; 2Department of Medicine, College of Medicine, Chang Gung University, Taiwan, R.O.C.; 3 Connectomics Research Center, National Tsing Hua University, Taiwan, R.O.C.; 4Institute of Biotechnology, National Tsing Hua University, Taiwan, R.O.C.; 5Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Taiwan, R.O.C.; 6Department of Medical Science, National Tsing Hua University, Taiwan, R.O.C.

Microscopic examination of transplanted islets in an ectopic environment provides information to evaluate graft adaption. However, because of the dispersed nature of blood vessels and nerves, global visualization of the graft neurovascular network has been difficult. In this research we prepared transparent mouse islet grafts under the kidney capsule with optical clearing to investigate the sympathetic reinnervation via three-dimensional confocal microscopy. Nondiabetic and streptozotocindiabetic mice were used in syngeneic islet transplantation, with both groups maintaining euglycemia after transplantation. Triple staining of insulin/glucagon, blood vessels, and tyrosine hydroxylase was used to reveal the graft microstructure, vasculature, and sympathetic innervation. Three weeks after transplantation, we observed peri-graft sympathetic innervation similar to that in the pancreas. Six weeks after transplantation, prominent intra-graft, perivascular sympathetic innervation was achieved, resembling the pancreatic sympathetic innervation in situ. Meanwhile, a higher graft sympathetic nerve density in diabetic recipients compared with nondiabetic recipients, indicating the graft neural plasticity in response to the physiological difference of the recipients and the resolving power of this imaging approach. Overall, this new graft imaging method provides a useful tool to identify the islet neurovascular complex in an ectopic environment.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-03

High Glucose Induces Human Endothelial Dysfunction Through an Axl-Dependent Mechanism 1

Chien-Hsing Lee, 2,3Yi-Shing Shieh, 1Fone-Ching Hsiao, 1Feng-Chih Kuo, 4 Chih-Yuan Lin, 1Chang-Hsun Hsieh, 1Yi-Jen Hung 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Dentistry, National Defense Medical Center, Taipei, Taiwan; 3Department of Oral Diagnosis and Pathology, Tri-Service General Hospital, Taipei, Taiwan; 4Division of Cardiovascular Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

OBJECTIVE: The receptor tyrosine kinase Axl and its ligand growth arrest-specific protein 6 (Gas6) are involved in the diabetic vascular disease. The aim of this study was to explore the role of Gas6/Axl system in high glucose (HG)-induced endothelial dysfunction. METHODS: We investigated the effect of various glucose concentrations on Axl signaling in human microvascular endothelial cells (HMEC-1 s). RESULTS: Human plasma Gas6 value inversely correlated with glucose status, endothelial markers. HG decreased Gas6/Axl expression and increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) expression in HMEC-1 s. HG significantly decreased HMEC-1 s cell viability and tube formation and promoted monocyte-EC adhesion. Down-regulation of Akt phosphorylation was found in HG culture. Axl transfection significantly reversed HG-induced Akt phosphorylation, VCAM-1 expression and endothelial dysfunction. We also found additive changes in Axl-shRNA-infected HMEC-1 cells in HG culture. Furthermore, Axl overexpression in HMEC-1 s significantly reversed HG-induced vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression. In addition, significantly lower Axl and VEGFR2 expression in arteries were found in diabetic patients as compared with non-diabetic patients. CONCLUSIONS: This study demonstrates that HG can alter Gas6/Axl signaling and may through Akt and VEGF/ VEGFR2 downstream molecules and suggests that Gas6/Axl may involve in HG-induced EC dysfunction.

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Abstract AP-04

Cardiac Metabolism, Inflammation, and Peroxisome ProliferatorActivated Receptors Modulated by 1,25-Dihydroxyvitamin D3 in Diabetic Rats 1,2

Ting-I Lee, 3,4Yu-Hsun Kao, 5Yao-Chang Chen, 6Wen-Chin Tsai, 4,7 Cheng-Chih Chung, 4,7*Yi-Jen Chen 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 2 Department of General Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5 Department of Biomedical Engineering, National Defense Medical Center, Taipei, Taiwan; 6 Division of Cardiology, Tzu-Chi General Hospital, Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan; 7 Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

Background: High free fatty acid with reduced glucose utilization in diabetes mellitus (DM) impairs cardiac function. Peroxisome proliferator-activated receptors (PPARs) modulate myocardial lipid and glucose homeostasis. The active 1,25-dihydroxyvitamin D3 (1,25(OH) 2D 3) regulates oxidative stress and inflammation, which may play a key role in the modulation of PPARs. The aim of this study was to investigate whether 1,25(OH)2D3 can modulate the cardiac PPARs and fatty acid metabolism. Methods: Electrocardiogram, echocardiogram, and Western blot analysis were used to evaluate cardiac fatty acid metabolism, inflammation, and PPAR isoform expression in Wistar-Kyoto (WKY) rats, DM rats, and DM rats treated with 1,25(OH)2D3. Results: Compared to healthy rats, DM and 1,25(OH)2D3-treated DM rats had lower body weight. DM rats has larger left ventricular end-diastolic diameter, and longer QT interval than healthy or 1,25(OH)2D3-treated DM rats. Moreover, compared to healthy or 1,25(OH)2D3-treated DM rats, DM rats had fewer cardiac PPAR-α and PPAR-δ protein expressions, but had increased cardiac PPAR-γ protein levels, tumor necrosis factor-α, interleukin-6, 5’adenosinemonophosphate-activated protein kinaseα2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase 1, PPAR-γ coactivator 1-α, cluster of differentiation 36, and diacylglycerol acyltransferase2 protein expressions. Conclusions: 1,25(OH)2D3 significantly changed the cardiac function and fatty acid regulations in DM hearts, which may be caused by its regulations on cardiac PPARs and proinflammatory cytokines.

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th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

AP-05

Effects of Pitavastatin Versus Atorvastatin on the Peripheral Endothelial Progenitor Cells and Vascular Endothelial Growth Factor in High-Risk Patients: a Pilot Prospective, Double-Blind, Randomized Study 1,2

Liang-Yu Lin, 3Chin-Chou Huang, 4 Jia-Shiong Chen, 3Tao-Cheng Wu, 3 Hsin-Bang Leu, 3Po-Hsun Huang, 2Ting-Ting Chang, 3 Shing-Jong Lin, 2,3 Jaw-Wen Chen 1

Division of Endocrinology and Metabolism, 3Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Institute of Pharmacology, 4Cardiovascular Research Center, National YangMing University, Taipei, Taiwan

Background: Circulating endothelial progenitor cells (EPCs) reflect endothelial repair capacity and may be a significant marker for the clinical outcomes of cardiovascular disease. While some highdose statin treatments may improve endothelial function, it is not known whether different statins may have similar effects on EPCs. This study aimed to investigate the potential class effects of different statin treatment including pitavastatin and atorvastatin on circulating EPCs in clinical setting. Methods: A pilot prospective, double-blind, randomized study was conducted to evaluate the ordinary dose of pitavastatin (2 mg daily) or atorvastatin (10 mg daily) treatment for 12 weeks on circulating EPCs in patients with cardiovascular risk such as hypercholesterolemia and type 2 diabetes mellitus (T2DM). Additional in vitro study was conducted to clarify the direct effects of both statins on EPCs from the patients. Results: A total of 26 patients (19 with T2DM) completed the study. While the lipidlowering effects were similar in both treatments, the counts of circulating CD34+KDR+EPCs were significantly increased (from 0.021 ± 0.015 to 0.054 ± 0.044% of gated mononuclear cells, P < 0.05) only by pitavastatin treatment. Besides, plasma asymmetric dimethylarginine level was reduced (from 0.68 ± 0.10 to 0.53 ± 0.12 μmol/L, P < 0.05) by atorvastatin, and plasma vascular endothelial growth factor (VEGF) level was increased (from 74.33 ± 32.26 to 98.65 ± 46.64 pg/mL, P < 0.05) by pitavastatin. In the in vitro study, while both statins increased endothelial nitric oxide synthase (eNOS) expression, only pitavastatin increased the phosphorylation of eNOS in EPCs. Pitavastatin but not atorvastatin ameliorated the adhesion ability of early EPCs and the migration and tube formation capacities of late EPCs. Conclusions: While both statins similarly reduced plasma lipids, only pitavastatin increased plasma VEGF level and circulating EPCs in high-risk patients, which is probably related to the differential pleiotropic effects of different statins.

228

Abstract AP-06

Diabetes and Non-Hodgkin’s Lymphoma: Analyses of Prevalence and Annual Incidence in 2005 Using the National Health Insurance Database in Taiwan Chin Hsiao Tseng Department of Internal Medicine, National Taiwan University College of Medicine; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital

Background: The association between diabetes and non-Hodgkin’s lymphoma (NHL) is rarely studied and the risk associated with insulin use is not known. Materials and Methods: The crude and age-standardized trends of NHL incidence in the general population from 1979 to 2007 were first calculated. NHL prevalence and annual incidence in 2005 were calculated in 329,198 insurants aged ≥45 years from a random sample of 1,000,000 insurants of the National Health Insurance. Logistic regression evaluated the risk factors. Results: NHL incidence trends increased significantly in either sex. A total of 1,079 and 148 NHL cases were identified for prevalence and incidence analysis, respectively. The respective prevalence (per 100,000) for diabetic and non-diabetic subjects was 480.2 and 269.9 (P<0.01); and the respective incidence (per 100,000) was 70.9 and 35.3 (P<0.01). Odds ratio for diabetic versus non-diabetic subjects after adjustment for age, sex, occupation and living region was 1.51 (1.33-1.71) for prevalence and 1.48 (1.06-2.06) for incidence. In diabetic patients, the adjusted odds ratio for insulin users versus non-users was 1.63 (1.23-2.15) for prevalence and 2.52 (1.37-4.64) for incidence. Conclusions: NHL incidence is increasing in Taiwan. Diabetes and insulin use are associated with a higher risk.

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The

230

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Memo

The

232

th Annual Meeting of March 21-22, 2015 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

Abstract

104年會論文摘要集

Articles inside

Poster Presentation

2015 Award

Oral Presentation

Current Guideline of Thyroid Cancer Management

2013 DM Research Grant Report

Comprehensive Eye Care in Diabetes

ESROC- KES Joint Symposium

DAROC-TSOC Joint Symposium Guideline: an Update

Pituitary Disease-Update

Protection of Cardiovascular System and Kidney Beyond Glucose Control in Diabetes

Primary Aldosteronism

Current Status of Endocrinology in the Region

Recent Advances in Osteoporosis

Physiology and Pathophysiology of Incretins: From Bench to Bedside and Vice Versa

Board of Directors

Diabetes Study and National Health Insurance Database in Taiwan

Recent Advances in Pituitary Medicine

New Treatments for Type 2 Diabetes: Roles of Incretin Therapy

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