110年會

Easy & Powerful Choice

高效能，一錠達標 STELLAR

CRESTOR 10mg 平均能降低 45.8% 的 LDL-C，CRESTOR 20mg 平均能降低 52% 的 LDL-C Change in LDL-C from baseline (%) 0

-5

-10

-15

-20

Rosuvastatin

-30

-35

-40

-45

10 mg*

Atorvastatin

10 mg

Simvastatin Pravastatin

-25

20 mg

10 mg 10 mg

20 mg 20 mg

40 mg

40 mg

-50

-55

20 mg†

40 mg‡

-60

80 mg

80 mg

40 mg

-45.8%

-52%

* p<0.002 vs atorvastatin 10 mg; simvastatin 10, 20, 40 mg; pravastatin 10, 20, 40 mg ; † p<0.002 vs atorvastatin 20, 40 mg; simvastatin 20, 40, 80 mg; pravastatin 20, 40 mg ; ‡ p<0.002 vs atorvastatin 40 mg; simvastatin 40, 80 mg; pravastatin 40 mg Adapted from Jones PH et al. Am J Cardiol 2003;92:152–160

* Rosuvastatin 40mg is not indicated in Taiwan

冠脂妥 膜衣錠5，10，20毫克 CRESTOR 5, 10, 20mg Film-Coated Tablets ®

®

【適應症】高膽固醇血症，高三酸甘油酯血症。【用法用量】CRESTOR 每天服用一次，服藥時間早晚不拘，隨餐或空腹均可。高膽固醇血症（異型接合子家族型及非家族型）及混合型高脂血症 （Fredrickson IIa 型及IIb 型）：CRESTOR 的劑量 範圍是 5-20 mg 每天一次，並應根據治療目標及患者的反應，個別調整劑量。CRESTOR 的一般建議起始劑量是 10 mg 每天一次。需要降低低密度脂蛋白膽固醇較少程度的患者，應考慮以 5 mg 每天一次開始治療，這些患者包括有肌病促發因子者 和下列特殊族群，例如服用 cyclosporine 者、亞裔患者及重度腎功能不全的患者。有顯著高膽固醇血症（低密度脂蛋白膽固醇 > 190 mg / dL）且有積極血脂目標值的患者，可考慮以 20 mg 開始治療。開始 CRESTOR 治療及/或調整劑量之後，應 在 2-4 週內檢查血脂濃度並依照結果調整劑量。開始statin類藥物治療或由另一種 statin 改為 CRESTOR 時，首先應使用適當的 CRESTOR 起始劑量，然後才可以根據患者個別的治療目標調整劑量。患有異型接合子家族型高脂血症的小兒患者 （10-17歲）: CRESTOR 的一般劑量範圍是每天 5-20 mg，最大建議劑量是每天 20 mg。劑量應按照治療的建議目標個別調整。應以4週或更久的時間調整劑量。同型接合子家族型高膽固醇血症：建議劑量是 20 mg 每天一次。CRESTOR 應作為其 他降血脂治療（例如低密度脂蛋白血漿析離術）的輔助治療，或不能利用此類治療時的輔助治療。應從施行血漿析離術之前的低密度脂蛋白膽固醇濃度估計對治療的反應。亞裔患者的劑量：對亞裔患者宜考慮以 5 mg 每天一次開始。對於用 5 或 10 mg 每天一次的劑量無法適當控制高膽固醇血症的患者，考慮提高劑量時，必須注意亞洲人的 rosuvastatin 暴露量可能比白種人高。與Cyclosporine、Atazanavir/Ritonavir、Lopinavir/Ritonavir 或 Simeprevir 併用：對於使用 cyclosporine 的患者， CRESTOR 的劑量應以 5 mg 每天一次為限。對於使用 atazanavir 及 ritonavir, lopinavir 及 ritonavir 或 simeprevir 的患者，CRESTOR 的劑量應以 10 mg 每天一次為限。併行降血脂治療：與膽汁結合樹脂併用時，CRESTOR 降低低密度脂蛋白膽固 醇及總膽固醇的療效會增加。若與 gemfibrozil 併用，CRESTOR 的劑量應以 10 mg 每天一次為限。腎功能不全患者的劑量：輕度至中度腎功能不全患者無須調整劑量。對於有重度腎功能不全（CLcr< 30 mL/min/1.73 m2）而未接受血液透析的患 者，CRESTOR 應以 5 mg 每天一次開始治療，不可超過 10 mg 每天一次。【禁忌症】已知對本品任何成分過敏之患者；有活動性肝疾病之病患；懷孕或可能懷孕的婦女；授乳婦。【警語和注意事項】骨骼肌效應：HMG-CoA 還原酶抑制劑(包括 CRESTOR)曾有肌球蛋白尿(myoglobinuria)引起之橫紋肌溶解(rhabdomyolysis)、肌病(myopathy)及急性腎衰竭的案例報告，這個風險可能發生在任何一個用藥劑量之下，但在高劑量下(40mg)風險會升高。肝酵素異常和監測：使用本品可能引起病 人肝轉氨酶的持續升高，建議在開始治療之前，及在開始治療和每次調高劑量後 12 週都要做肝功能檢查，此後還要定期監測(例如每半年檢查一次)。併用 Coumarin 類的抗凝血劑：開始 CRESTOR 治療前應測量其 INR，在治療初期也應常常監測 INR。蛋白尿和血尿：對於在例行尿液檢查中，有不明原因、持續性蛋白尿及/或血尿之患者，應該要考慮降低 CRESTOR 的劑量。內分泌效應：醣化血色素(HbA1c)上升。當 CRESTOR 和可能會降低內生性類固醇荷爾蒙濃度或活性的藥品併用時(例 如 ketoconazole、spironolactone、cimetidine)，需謹慎小心。可逆性認知障礙：曾有少數上市後研究顯示，使用statin類藥品與認知功能障礙(如:記憶力減退、健忘、記憶障礙、認知混亂等)可能有關。該等認知功能問題通常是不嚴重的，且於停藥 後可恢復，其症狀發生及緩解時間不定。【不良反應】常見不良反應（發生率≧2%）：頭痛、肌肉疼痛、腹痛、衰弱無力、噁心、便祕。可能嚴重不良反應：橫紋肌溶解伴隨肌球蛋白尿、急性腎衰竭及肌病（包括肌炎）、肝臟酵素異常。 【使用前詳閱說明書警語及注意事項，詳細仿單資料備索。】【僅限醫藥專業人員參考，處方藥物請參考衛生福利部核准仿單說明書。】

衛署藥輸字第024597、024131、024129號 北市衛藥廣字第109080114號 TW-12344_CRE_08/07/2020

Contents FLOOR PLAN OF CONFERENCE ROOMS ................................................................... 2 DAILY PROGRAM SCHEDULE .......................................................................................... 6 OPENING REMARKS............................................................................................................. 9 BOARD OF DIRECTORS .....................................................................................................11 SPONSORS ............................................................................................................................ 12 MODERATOR & SPEAKER ............................................................................................... 13 AGENDA .................................................................................................................................. 14 ABSTRACT DAROC-TADE：DAROC-TADE Joint Symposium .................................................... 36 PL：Plenary Lecture (1-4) ................................................................................................. 40 MTP-D：Meet the Professor-Diabetes (1).................................................................. 45 MTP-E：Meet the Professor-Endocrine (1-2)............................................................. 46 SD：Symposium-Diabetes (1-9)............................................................................. 48 SE：Symposium-Endocrine (1-8) ............................................................................... 77 WE：Workshop-Endocrine................................................................................... 103 LS：Lunch Symposium (1-15) ..................................................................................104 OD：Oral Presentation-Diabetes (1-6) ......................................................................121 OE：Oral Presentation-Endocrine (1-6) ....................................................................129 PD：Poster Presentation-DM (1-30) .........................................................................135 PE：Poster Presentation-Endocrine (1-28) ...............................................................170 AP：2021 Award .......................................................................................................205 BP：廠商論文壁報展示 (1-6) ..................................................................................210 1

42

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

台大國際會議中心一樓平面圖

The

2

台大國際會議中心二樓平面圖

Floor Plan of Conference Rooms

3

42

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

台大國際會議中心一樓平面圖

The

2

台大國際會議中心二樓平面圖

Floor Plan of Conference Rooms

3

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

社團法人中華民國內分泌暨糖尿病學會 第 14 屆第 3 次會員大會暨學術研討會 節目表 March 27, 2021 (Saturday) Room 101

Room 301

Room 401

600 人

220 人

220 人

DAROC-TADE Joint Symposium

200 人

Room 202

Room 203

Room 205

80 人

80 人

70 人

LS6 百靈佳殷格翰

LS7 賽諾菲

LS8 友華

200 人

(10:00-12:00) WE Thyroid Cytology Workshop

主持人：許惠恒 歐弘毅 08:00-12:00 蔡育賢 唐德成 黃建寧 演講者：陳鴻震 王治元 陳忠信 陳念榮 LS1 12:00-13:00 阿斯特捷利康

Room 402AB Room 402CD

主持人：張天鈞 陳思達

演講者：詹一秀 陳亭竹

LS2 禮來

LS3 默沙東

LS4 諾和諾德

LS5 輝瑞先進

13:10-13:20

Opening (Room 101) ( 直播 )

13:20-14:05

PL1 Plenary Lecture-1 (DM) (Room 101) ( 直播 ) 主持人：黃建寧 演講者：Filip Knop

14:05-14:50

PL2 Plenary Lecture-2 (Endocrine) (Room 101) ( 直播 ) 主持人：曾芬郁 演講者：萬永亮

15:00-15:20

Break (Poster Stand -3 Floor Walkway) 海報展示評分 PD: 林嘉鴻、王俊興、李建興 PE: 蘇登煌、邱偉益、陳思綺 SE-2 ( 直播 ) SE-1 SD-2 ( 直播 ) Thyroid Reproductive Diabetic Medicine Kidney Disease: An Update

15:20-17:00

晚宴場佈

17:00-18:00

18:00-21:00

6

SD-1 Type 1 DM Atlas

SD-3 Adipocytes Biology & YL: Young Investigator

SE-3 Precision Medicine

主持人：陳思達 主持人：林宏達 主持人：辛錫璋 主持人：胡啟民 主持人：洪乙仁 主持人：劉鳳炫 王佩文 王治元 林時逸 杜思德 莊峻鍠 蔡克嵩 陳榮福 戴東原 曾慶孝 演講者：林偉哲 演講者：陳 明 演講者： 演講者：童怡靖 演講者： 演講者：張淑惠 諶鴻遠 郭仁富 Hiddo J.L. heerspink 林嘉鴻 Yu-Hua Tseng 陳瑜忻 張丞賢 黃尚玉 黃書恒 王俊興 楊偉勛 蘇登煌 杜業豐 林樹福 黃尚志 MTP-D ( 直播 ) Meet the ProfessorDiabetes

MTP-E1 ( 直播 ) Meet the ProfessorEndocrine 1

OD OE Oral Oral Presentation- PresentationDiabetes Endocrine

主持人：許惠恒 演講者：黃國晉

主持人：張慶忠 演講者：王鵬惠

主持人：蘇景傑 主持人：簡銘男 楊宜瑱 李亭儀 林昆德 歐弘毅

Welcome Dinner (Conference Room 101)

Daily Program Schedule

March 28, 2021 (Sunday) Room 101

Room 301

Room 401

600 人

220 人

220 人

200 人

(08:30-09:30) MTP-E2 Meet the ProfessorEndocrine 2

SE-4 ( 直播 ) Update on Medical Treatments for Osteoporosis/ Metabolic Bone Disorders in Taiwan

SD-4 ( 直播 ) SD-5 Issues in Application of Diabesity New Technology on DM Patients

08:00-09:40 主持人：莊立民 林慶齡 葉振聲 演講者：張以承 黃國晉 李威傑

Room 202

Room 203

Room 205

200 人

80 人

80 人

70 人

SE-5 Acromegaly

SD-6 Islet Biology, Transplantation and Stem Cells on Diabetic Treatment

Room 402AB Room 402CD

主持人：黃建寧 主持人：曾芬郁 主持人：蔡克嵩 主持人：施翔蓉 主持人：楊偉勛 陳榮福 歐弘毅 陳涵栩 李弘元 杜思德 何橈通 演講者：陳沛隆 演講者：陳靖博 演講者：葉乃誠 演講者：莊峻鍠 演講者： Robert Vigersky 黃兆山 黃博浩 Kun Ho Yoon 黃奕修 蔡克嵩 李政家 沈家寧 陳思羽

09:40-10:00

Break (Poster Stand -3 Floor Walkway)

10:00-10:45

PL3 Plenary Lecture-3 (DM)(Room 101) ( 直播 )

主持人：莊立民 演講者：林瑞祥

10:45-12:15

General Assembly 會員大會 (Room 101)( 直播 )

12:15-12:25

Group Picture 會員大合照 (1st Floor Square)

12:25-13:25 13:45-14:30

LS9 諾華

LS10 禮來／ 百靈佳殷格翰

LS11 賽諾菲

LS12 諾和諾德

PL4 Plenary Lecture-4 (Endocrine) (Room 101) ( 直播 )

14:30-14:50

LS13 安晟信

LS15 拜耳

主持人：王佩文 演講者：王逢興

Break (Poster Stand -3 Floor Walkway) SE-6 ( 直播 ) Endocrine Diseases Management during Pregnancy

SD-7 Therapeutic Nutritional Therapy on Diabetes Management

SE-7 Advances in Adrenal Diseases

SD-8 ( 直播 ) SD-9 Diabetes and Taiwan Cardiovascular Registration Disease Study

14:50-16:30 主持人：施翔蓉 主持人：杜思德 主持人：黃天祥 主持人：黃建寧 主持人：許惠恒 劉鳳炫 裴 馰 張慶忠 朱志勳 戴東原 陳清助 蔡世澤 陳榮福 胡啟民 演講者：林家宏 演講者：陳珮蓉 演講者：呂金盈 演講者：宋思賢 演講者：林時逸 黃君睿 莊武龍 李亭衛 李弘元 沈宜靜 林怡瑄 楊宜瑱 吳明諴 Jennifer Green 林軒維 張恬君 16:30-16:35

LS14 安進

SE-8 Growth and Development

主持人：羅福松 林建銘 演講者：劉士嶢 丁瑋信 童怡靖

Closing

7

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

直播課程整合如下 March 27, 2021 (Saturday) 直播 1 13:10-13:20

直播 2

OPENING PL1 Plenary Lecture-1 (DM)

13:20-14:05

主持人：黃建寧 演講者：Filip Knop PL2 Plenary Lecture-2 (Endocrine)

14:05-14:50

15:20-17:00

17:00-18:00

主持人：曾芬郁 演講者：萬永亮 SE-2 Thyroid

SD-2 Diabetic Kidney Disease: An Update

主持人：陳思達、王佩文 演講者：林偉哲、諶鴻遠、張丞賢

主持人：辛錫璋、林時逸、陳榮福 演講者：Hiddo J.L. Heerspink、黃書恒、黃尚志

MTP-D Meet the Professor-Diabetes

MTP-E1 Meet the Professor-Endocrine 1

主持人：許惠恒 演講者：黃國晉

主持人：張慶忠 演講者：王鵬惠

March 28, 2021 (Sunday) 直播 1

直播 2

SD-4 Issues in Diabesity

SE-4 Update on Medical Treatments for Osteoporosis/ Metabolic Bone Disorders in Taiwan

主持人：莊立民、林慶齡、葉振聲 演講者：張以承、黃國晉、李威傑

主持人：蔡克嵩、歐弘毅 演講者：陳靖博、黃兆山、蔡克嵩

08:00-09:40

PL3 Plenary Lecture-3 (DM) (Room 101) 10:00-10:45 主持人：莊立民 演講者：林瑞祥 10:45-12:15 General Assembly 會員大會 (Room 101) PL4 Plenary Lecture-4 (Endocrine) 13:45-14:30

主持人：王佩文 演講者：王逢興

14:50-16:30

8

SE-6 Endocrine Diseases Management during Pregnancy

SD-8 Diabetes and Cardiovascular Disease

主持人：施翔蓉、劉鳳炫 演講者：林家宏、黃君睿、林怡瑄

主持人：黃建寧、朱志勳、蔡世澤 演講者：宋思賢、李弘元、Jennifer Green

Opening Remarks

理事長致歡迎詞 回首 2020 年，受到新冠肺炎疫情影響，許多學會的重要活動受到波及 而延期。但因兩學會理監事與會員們的共同努力，我們仍然迅速調整會議進 行方式，順利成功地舉辦了年會、冬季會與 40 週年慶的各項活動。 目前新冠病毒疫苗雖已開打，但客觀上仍充滿許多不確定因素。今年 年會，原則上在防疫措施下採取實體會議，但學會也在各時段各準備一場線 上直播，以因應若有疫情突發時之不時之需，其他場次也將後製錄影，置於 學會網址供會員參考。今年年會承襲以往，兩會均安排精彩豐富的課程供會 員們學習。適逢胰島素發現 100 週年，Plenary lecture 特別邀請林瑞祥教授就 胰島素的發現、進展及臨床應用發表演講；也邀請丹麥的著名學者 Prof. Flip Knop 演講 Incretin 的發展與最新應用。此外萬永亮教授的腎上腺影像，以及 王逢興教授的題目有關骨骼脂肪的表觀基因控制在腸道與肌肉間的相互作 用，都令人非常期待。 去年我們與糖尿病衛教學會繼 2019 年出版 T2DM 年鑑之後，再度完成 Type 1 DM 年鑑，連同糖尿病登錄計畫的部分研究分析，此次也安排於年會 發表。另外，由副秘書長楊宜瑱醫師執筆完成的 DM 在 Covid-19 疫情中的 治療指引，也將於年會中發放供會員參考。 再度感謝所有理監事與會員們的共同努力參與，期待並預祝年會順利圓 滿成功！ 社團法人中華民國糖尿病學會 理事長 民國 110 年 3 月 27 日 9

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

理事長致歡迎詞 中華民國內分泌學會及糖尿病學會第 14 屆第 3 次 會 員 大 會 暨 學 術 研 討 會 於 110 年 3 月 27 日 及 28 日在台大醫院國際會議中心舉行，由內分泌學會負 責籌畫的學術節目包括邀請萬永亮教授及王逢興教 授 主 講 的 plenary lecture、 王 鵬 惠 教 授 及 陳 沛 隆 教 授 的 meet professor、 thyroid cytology workshop、以及 thyroid、reproductive medicine、precision medicine、osteoporosis and metabolic bone disease、acromegaly、endocrine diseases during pregnancy、adrenal diseases、growth and development 等八個 symposium、再加上內分泌的口頭論文報告及壁報比賽，節目內容十分精 彩。感謝所有的演講者及主持人，讓年會充滿了學術氣息。考量新冠肺炎 疫情的不確定性，今年的年會除了實體課程外，也籌畫了一些視訊的備案。 感謝今年負責場地規劃的糖尿病學會，也感謝所有會員對學會的支持。不 管疫情如何，我們永遠同心協力，為台灣的新陳代謝內分泌醫療而努力。 敬祝大家 平安健康。

社團法人中華民國內分泌學會 理事長 民國 110 年 3 月 27 日

10

Board of Directors

Board of Directors

（依照姓氏筆劃排序）

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

曾芬郁 Fen-Yu Tseng

Standing Executive Board

王佩文 Pei-Wen Wang

蔡克嵩 Keh-Sung Tsai

Executive Board

王治元 Chih-Yuan Wang 施翔蓉 Shyang-Rong Shih 陳涵栩 Harn-Shen Chen 歐弘毅 Horng-Yih Ou

李亭儀 Annie Lee 陳思達 Szu-Tah Chen 劉鳳炫 Feng-Hsuan Liu 簡銘男 Ming-Nan Chien

Standing Control Board

張慶忠 Ching-Chung Chang

Control Board

林宏達 Hong-Da Lin

Secretary General

吳婉禎 Wan-Chen Wu

Deputy Secretary General

王舒儀 Shu-Yi Wang 林志弘 Chih-Hung Lin 陳思綺 Szu-chi Chen

林怡君 Yi-Jyun Lin 周振凱 Chen-Kai Chou 邱偉益 Wei-Yih Chiu 蘇登煌 Deng Huang Su

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

黃建寧 Chien-Ning Huang

Standing Executive Board

杜思德 Shih Te Tu 陳榮福 Jung-Fu Chen

楊偉勛 Wei-Shiung Yang 蔡世澤 Shih-Tzer Tsai

Executive Board

朱志勳 Chih-Hsun Chu 林時逸 Shih-Yi Lin 洪乙仁 Yi-Jen Hung 陳清助 Ching-Chu Chen 裴 馰 Dee Pei

李弘元 Hung-Yuan Li 林慶齡 Ching-Ling Lin 胡啟民 Chii-Min Hwu 曾慶孝 Chin-Hsiao Tseng 蘇景傑 Ching-Chieh Su

Standing Control Board

許惠恒 Wayne Huey-Herng Sheu

Control Board

何橈通 Low-Tone Ho 葉振聲 Tjin-Shing Jap

Secretary General

張恬君 Tien-Jyun Chang

Secretary

王俊興 Jun-Sing Wang 李建興 Chien-Hsing Lee 林嘉鴻 Chia-Hung Lin

莊立民 Lee-Ming Chuang 戴東原 Tong-Yuan Tai 田凱仁 Kai-Jen Tien 林昆德 Kun-Der Lin 楊宜瑱 Yi-Sun Yang 11

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

The Endocrine Society and the Diabetes Association of the R.O.C (Taiwan) Would Like to Recongnize the Following for Their Support of the 42nd Annual Meeting 力大圖書有限公司

THE LEADER BOOK COMPANY LTD.

臺灣阿斯特捷利康股份有限公司

ASTRAZENECA TAIWAN LIMITED

安克生醫股份有限公司

AMCAD BIOMED CORPORATION

台灣諾和諾德藥品股份有限公司

NOVO NORDISK PHARMA (TAIWAN) LTD.

嘉德藥品企業股份有限公司

CHAR DEH DRUGS ENTERPRISE CO., LTD.

賽諾菲股份有限公司

SANOFI TAIWAN CO. LTD.

輝瑞大藥廠股份有限公司

PFIZER TAIWAN LTD.

台灣百靈佳殷格翰股份有限公司

BOEHRINGER INGELHEIM TAIWAN LTD.

台灣諾華股份有限公司

NOVARTIS (TAIWAN) CO., LTD.

美商默沙東藥廠股份有限公司台灣分公司

MERCK SHARP & DOHME (I.A.) CORP. TAIWAN BRANCH

友華生技醫藥股份有限公司

ORIENT EUROPHARMA CO., LTD.

台灣田邊製藥股份有限公司

TAIWAN TANABE SEIYAKU CO., LTD.

美商亞培股份有限公司台灣分公司

ABBOTT LABORATORIES SERVICES CORP. TAIWAN BRANCH

新加坡商必帝股份有限公司台灣分公司

BECTON DICKINSON HOLDINGS PTE. LTD. TAIWAN BRANCH

台灣禮來股份有限公司

ELI LILLY COMPANY (TAIWAN)

台灣安晟信有限公司

ASCENSIA DIABETES CARE TAIWAN, LTD.

台灣安進藥品有限公司

AMGEN TAIWAN LIMITED

台灣拜耳股份有限公司

BAYER TAIWAN CO., LTD.

12

Moderator & speaker

主持人、演講者列表 Prof. Jennifer Green Prof. Filip Knop Prof. Hiddo J.L. Heerspink Prof. Kun Ho Yoon Prof. Robert Vigersky Prof. Yu-Hua Tseng Prof. Ralph DeFronzo Prof. Alice Cheng Prof. Leigh Perreault 丁瑋信 王佩文 王治元 王俊興 王逢興 王鵬惠 朱志勳 何橈通 吳明諴 呂金盈 宋思賢 李弘元 李亭儀 李亭衛 李威傑 李建興 李政家 李貽恒 杜思德 杜業豐 沈宜靜 沈家寧 辛錫璋 林宏達 林怡瑄 林昆德 林建銘 林家宏 林時逸 林軒維 林偉哲 林瑞祥 林嘉鴻 林慶齡 林樹福 邱偉益 施翔蓉 洪乙仁 胡啟民 范綱志 唐德成 張天鈞 張以承 張丞賢 張恬君 張淑惠 張慶忠 張宏猷 莊立民 莊武龍 莊峻鍠

Duke University Medical Center Division of Endocrinology, Metabolism and Nutrition Professor of Endocrinology and Director of Center for Clinical Metabolic Research at Gentofte Hospital, University of Copenhagen University Medical Center Groningen, Netherlands Department of Endocrinology & Metabolism Seoul St. Mary's Hospital Chief Medical Officer, Medtronic Diabetes Professor of Medicine, Harvard Medical School Senior Investigator, Joslin Diabetes Center Professor of Medicine, Chief, Diabetes Division UTHSC, San Antonio TX St. Michael´ s Hospital, Credit Valley Hospital University of COLORADO Anschutz medical campus

馬偕兒童醫院兒童內分泌科 高雄長庚醫院新陳代謝科與核子醫學科 臺大醫院內科部代謝內分泌科 臺中榮民總醫院內科部新陳代謝科 高雄長庚紀念醫院醫學研究部 臺北榮民總醫院婦女醫學部 高雄榮總新陳代謝科 臺北榮民總醫院 新北市立土城醫院新陳代謝科 臺大醫院內科部代謝內分泌科 臺北榮民總醫院內科部心臟科 臺大醫院內科部代謝內分泌科 萬芳醫院 萬芳醫院 / 新陳代謝科 敏盛綜合醫院外科 松山班廷建興診所 臺北榮總神經外科 成大醫院內分泌新陳代謝科 醫療財團法人彰化基督教醫院 成大醫院內分泌新陳代謝科 臺中榮民總醫院 中研院生醫轉譯研究中心創服育成中心 尊德診所 臺北榮民總醫院 林口長庚醫院新陳代謝科 高雄醫學大學附設醫院內科部新陳代謝內分泌內科 三軍總醫院小兒內分泌科 新竹台大分院生醫醫院竹北院區內科部 臺中榮總高齡醫學中心 臺北榮民總醫院新竹分院內科部 高雄長庚放射診斷科 立達診所 林口長庚醫院內分泌暨新陳代謝科 國泰綜合醫院 / 內科部 / 內分泌新代科 新北市立土城醫院內分泌暨新陳代謝科 臺大醫學院內科部代謝內分泌科 臺大醫學院內科部代謝內分泌科 國防醫學院預防醫學研究所 臺北榮總內科部內分泌新陳代謝科 國立臺灣大學醫學院附設醫院新竹分院 臺北榮民總醫院內科部腎臟科 臺大醫院內科部及遠東聯合診所 臺大醫院內科部代謝內分泌科 高雄醫學大學附設醫院眼科 臺大醫院內科部 臺大流行病學與預防醫學研究所 中國醫藥大學附設醫院內科部內分泌新陳代謝科 林口長庚紀念醫院內分泌新陳代謝科 臺大醫院內科部代謝內分泌科 鹿港基督教醫院 長庚紀念醫院內分泌暨新陳代謝科

許惠恒 郭仁富 陳 明 陳沛隆 陳忠信 陳念榮 陳亭竹 陳思羽 陳思達 陳思綺 陳珮蓉 陳涵栩 陳清助 陳瑜忻 陳靖博 陳榮福 陳鴻震 曾芬郁 曾慶孝 翁瑄甫 童怡靖 黃天祥 黃兆山 黃君睿 黃尚玉 黃尚志 黃奕修 黃建寧 黃書恒 黃國晉 黃博浩 楊宜瑱 楊偉勛 萬永亮 葉乃誠 葉振聲 詹一秀 裴 馰 劉士嶢 劉鳳炫 董 欣 歐弘毅 蔡世澤 蔡克嵩 蔡育賢 諶鴻遠 戴東原 簡銘男 羅福松 蘇景傑 蘇登煌

臺北榮民總醫院 醫療財團法人彰化基督教醫院 醫療財團法人彰化基督教醫院院長室醫療長 臺灣大學基因體暨蛋白體醫學研究所 臺大醫院泌尿部 國立陽明交通大學微生物及免疫學研究所 臺大分院新竹醫院內科部內分泌新陳代謝科 三軍總醫院糖尿病衛教師 林口長庚紀念醫院內分泌新陳代謝科 臺北市立聯合醫院仁愛院區內分泌及新陳代謝科 臺大醫院營養室 臺北榮民總醫院內分泌暨新陳代謝科 中國醫藥大學附設醫院內科部智能糖尿病中心 國泰綜合醫院細胞學科主任暨內分泌新陳代謝科 高雄長庚紀念醫院腎臟科 高雄長庚紀念醫院內分泌暨新陳代謝科 生命科學研究發展司 臺東基督教醫院內分泌新陳代謝科 臺大醫院內科部代謝內分泌科 臺北醫學大學附設醫院新陳代謝科 臺大醫院小兒部 國泰綜合醫院內分泌新陳代謝科 林口長庚醫院內科部新陳代謝科 臺北榮民總醫院內分泌新陳代謝科 林口長庚醫院婦科暨不孕症科 高醫腎臟內科 林口長庚眼科部視網膜科 中山醫學大學附設醫院 市立大同醫院 / 內分泌新陳代謝科 臺大醫院北護分院 臺大醫院 / 外科部神經外科 中山醫學大學附設醫院內分泌暨新陳代謝科 臺大醫院內科部代謝內分泌科 長庚大學林口長庚醫院 / 影像診療部 奇美醫院內分泌新陳代謝科 為恭紀念醫院新陳代謝科 臺大醫院檢驗醫學部 輔大醫院新陳代謝科 臺大醫院小兒部 林口長庚紀念醫院 / 新陳代謝科 臺中榮總神經內科 成大醫院內科 振興醫院新陳代謝科及營養治療科 臺大醫院內科部及遠東聯合診所 國立成功大學醫學系泌尿學科 三軍總醫院核醫部甲狀腺多專科團隊 仁濟院 / 顧問 台北馬偕紀念醫院 林口長庚醫院兒童內分泌暨遺傳科 蘇景傑診所 臺大醫院內科部及遠東聯合診所

13

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

中華民國內分泌暨糖尿病學會 第 14 屆第 3 次會員大會暨學術研討會 日期：民國 110 年 3 月 27-28 日 地點：台大醫院國際會議中心

March 27, 2021 【Room 101】

Time

DAROC-TADE: Joint Symposium Topic

Speaker

Moderator

08:00-08:20 報到 08:20-08:30 OPENING REMARKS

許惠恒

TADE-1

08:30-09:10 科技部生科司未來展望與規劃

陳鴻震

許惠恒

TADE-2

09:10-09:50 胰島素百週年學會演講：甲狀腺疾病及 糖尿病智慧醫療新進展

王治元

歐弘毅

09:50-10:10 休息 TADE-3

10:10-10:50 ARISTOLOCHIC ACID AND UPPER TRACT UROTHELIAL CARCINOMA IN TAIWAN - STORY CONTINUED 馬兜鈴酸與上泌尿道上皮癌的故事連載

陳忠信

蔡育賢

TADE-4

10:50-11:30 THE INNATE REGULATING ROLE OF TREMS IN THE UUO NEPHRITIS 髓系細胞觸發受體在堵塞性腎炎中扮演 的先天免疫調節角色

陳念榮

唐德成

14

11:30-11:50 PANEL DISCUSSION

許惠恒 唐德成 歐弘毅 蔡育賢

11:50-12:00 CLOSING REMARKS

黃建寧

Agenda

March 27, 2021 【Room 101】

PL1: Plenary Lecture 1 (Diabetes)

Time

Topic

Speaker

13:20-13:25 OPENING PL1

黃建寧

13:25-14:05 INCRETIN DEVELOPMENT ( 預錄影片 )

March 27, 2021 【Room 101】

Filip Knop

Topic

Speaker

14:05-14:10 OPENING

【Room 101】

萬永亮

Topic

Speaker

10:00-10:05 OPENING

【Room 101】

林瑞祥

莊立民

PL4: Plenary Lecture 4 (Endocrine)

Time

Topic

Speaker

13:45-13:50 OPENING PL4

Moderator 莊立民

10:05-10:45 THE JOURNEY OF INSULIN DISCOVERY AND APPLICATION ON DIABETIC TREATMENT

March 28, 2021

曾芬郁

PL3: Plenary Lecture 3 (Diabetes)

Time

PL3

Moderator 曾芬郁

14:10-14:50 腎上腺影像之回顧和進展

March 28, 2021

黃建寧

PL2: Plenary Lecture 2 (Endocrine)

Time

PL2

Moderator

13:50-14:30 EPIGENETIC CONTROL OF BONE AND FAT METABOLISM: AN INTERPLAY BETWEEN GUT AND MUSCLE

Moderator 王佩文

王逢興

王佩文

15

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 27, 2021 【Room 301】

MTP-D: Meet the Professor - Diabetes

Time MTP-D

Topic

17:00-18:00 MANAGEMENT OF OBESITY

March 27, 2021

【Room 402AB 】

Speaker

Moderator

黃國晉

許惠恒

MTP-E1: Meet the Professor - Endocrine 1

Time

Topic

Speaker

Moderator

17:00-17:05 OPENING

張慶忠

MTP-E1 17:05-18:00 POLYCYSTIC OVARY SYNDROME (PCOS)

March 28, 2021 【Room 401】

王鵬惠

張慶忠

MTP-E2: Meet the Professor - Endocrine 2

Time

Topic

Speaker

Moderator

08:30-08:35 OPENING

曾芬郁

MTP-E2 08:35-09:30 內分泌疾病的基因診斷實例

March 27, 2021

【Room 402CD】 Time

陳沛隆

曾芬郁

SD1: Symposium-Diabetes 1 Type 1 DM Atlas

Topic

Speaker

15:20-15:25 OPENING REMARK

Moderator 胡啟民

SD1-1

15:25-15:55 台灣第 1 型糖尿病現況 發生率 , 盛行率 , 死亡率

童怡靖

胡啟民

SD1-2

15:55-16:25 台灣第 1 型糖尿病胰島素治療與併發症

林嘉鴻

杜思德

SD1-3

16:25-16:55 台灣第 1 型糖尿病醫療利用情形與照護 品質

王俊興

戴東原

ALL

戴東原

16:55-17:00 PANEL DISCUSSION 16

Agenda

March 27, 2021 【Room 402AB】

SD2: Symposium-Diabetes 2 Diabetic Kidney Disease : An Update

Time 15:20-15:25

Topic

Speaker

Moderator

OPENING

辛錫璋

SD2-1

15:25-15:55 SGLT2 INHIBITORS-EXTENDING THE USE FROM DIABETES TO NON-DIABETES( 預錄影片 )

Hiddo J.L. Heerspink

辛錫璋

SD2-2

15:55-16:25 UPDATE OF DKD IN TAIWAN FOCUS ON DKD TREATMENT GUIDELINE.

黃書恒

林時逸

SD2-3

16:25-16:55 DIABETIC KIDNEY DISEASE AND ESRD IN TAIWAN

黃尚志

陳榮福

ALL

陳榮福

16:55-17:00 PANEL DISCUSSION

March 27, 2021 【Room 202】

SD3: Symposium-Diabetes 3

Adipocytes Biology & YL: Young Investigator Research Lecture

Time 15:20-15:25

Topic

Speaker

OPENING

SD3-1

15:25-16:05 NOVEL INSIGHTS INTO THE THERAPEUTIC POTENTIAL OF THERMOGENIC FAT( 預錄影片 )

SD3-2 SD3-3

Moderator 洪乙仁

Yu-Hua Tseng

洪乙仁

16:05-16:35 METAINFLAMMATION OF ADIPOCYTES AND BEYOND

楊偉勛

莊峻鍠

16:35-16:55 THE ROLE OF METFORMIN AND ORGANIC CATION TRANSPORTER 2 IN MANAGEMENT OF RENAL CELL CARCINOMA

杜業豐

曾慶孝

16:55-17:00 PANEL DISCUSSION

曾慶孝

17

42

The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 28, 2021 【Room 101】

SD4: Symposium-Diabetes 4 Issues in Diabesity

Time

Topic

Speaker

Moderator

08:00-08:05 OPENING

莊立民

SD4-1

08:05-08:35 UPDATE OF GENETIC, BASIC, AND TRANSLATIONAL RESEARCHES OF TYPE 2 DIABETES AND OBESITY

張以承

莊立民

SD4-2

08:35-09:05 LIFE STYLE AND MEDICAL INTERVENTION OF DIABESITY

黃國晉

林慶齡

SD4-3

09:05-09:35 SURGICAL INTERVENTION FOR DIABESITY: A STORY OF 5%

李威傑

葉振聲

ALL

葉振聲

09:35-09:40 PANEL DISCUSSION

March 28, 2021 【Room 301】

Time

SD5: Symposium-Diabetes 5

Application of new technology on DM Patients Topic

Speaker

08:00-08:05 OPENING REMARK SD5-1

08:05-08:35 THE PARADIGM OF CGM AND CSII BASED ON ADVANCED A.I. TECHNOLOGY FOR ARTIFICIAL PANCREAS( 預錄影片 )

SD5-2

SD5-3

黃建寧 Robert Vigersky

黃建寧

08:35-09:05 THE ADVANCE OF A.I. FROM RETINA TO WHOLE BODY IN FUTURE HEALTH INDUSTRY

黃奕修

陳榮福

09:05-09:25 POST-PANDEMIC ERADIGITALIZATION FLIPS HEALTH EDUCATION OF DIABETES

陳思羽

杜思德

ALL

杜思德

09:25-09:30 PANEL DISCUSSION

18

Moderator

Agenda

March 28, 2021 【Room 202】

SD6: Symposium-Diabetes 6

Islet biology, transplantation and stem cells on diabetic treatment

Time

Topic

Speaker

Moderator

08:00-08:05 OPENING

楊偉勛

SD6-1

08:05-08:35 THE PERSPECTIVE OF ISLET TRANSPLANTATION ON THE TREATMENT OF TYPE 1 DIABETES

莊峻鍠

楊偉勛

SD6-2

08:35-09:05 ENGINEERING OF MICROCAPSULES FOR OVERCOMING BARRIERS FOR ISLET TRANSPLANTATION ( 預錄影片 )

Kun Ho Yoon

李弘元

SD6-3

09:05-09:35 CURRENT PROGRESS IN STEM CELL THERAPY FOR DIABETES MELLITUS

沈家寧

何橈通

09:35-09:40 CLOSING

March 28, 2021 【Room 301】

何橈通

SD7: Symposium-Diabetes 7

Therapeutic Nutritional Therapy on Diabetes Management

Time

Topic

Speaker

14:50-14:55 OPENING

Moderator 杜思德

SD7-1

14:55-15:25 CAN WE RELY ON NUTRITION SCIENCE FOR DIABETES AND CARDIOVASCULAR DISEASE?

陳珮蓉

杜思德

SD7-2

15:25-15:55 INTERMITTENT FASTING IN PATIENTS WITH DIABETES MELLITUS

莊武龍

裴 馰

SD7-3

15:55-16:25 PARADIGM SHIFTS IN NUTRITION THERAPY FOR TYPE 2 DIABETES

楊宜瑱

陳清助

ALL

陳清助

16:25-16:30 PANEL DISCUSSION

19

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nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 28, 2021 【Room 402AB】

SD8: Symposium-Diabetes 8 DM and CVD

Time

Topic

Speaker

Moderator

14:50-14:55 OPENING

黃建寧

SD8-1

14:55-15:25 ACCUMULATED CV DATA FROM SGLT2I OUTCOME TRIALS

宋思賢

黃建寧

SD8-2

15:25-15:55 ACCUMULATED CV DATA FROM GLP1 RA OUTCOME TRIALS

李弘元

朱志勳

SD8-3

15:55-16:25 OPTIMIZING DELIVERY OF GUIDELINEBASED CARE IN PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE ( 預錄影片 )

Jennifer Green

蔡世澤

ALL

蔡世澤

16:25-16:30 PANEL DISCUSSION

March 28, 2021

【Room 402CD】

SD9: Symposium-Diabetes 9

Time

Taiwan Registration Study

Topic

Speaker

14:50-14:55 OPENING SD9-1

14:55-15:15 RISK FACTOR CONTROL IN DIABETIC PATIENTS WITH CARDIOVASCULAR AND KIDNEY DISEASES - TAIWAN DIABETES REGISTRY STUDY

Moderator 許惠恒

林時逸

許惠恒

沈宜靜

戴東原

15:15-15:20 Q AND A SD9-2

15:20-15:40 FACTORS ASSOCIATED WITH QUALITY OF LIFE AMONG PATIENTS WITH DIABETES: THE TAIWAN DIABETES REGISTRY STUDY 15:40-15:45 Q AND A

20

Agenda SD9-3

15:45-16:05 TREATMENT GOAL ACHIEVEMENT AND ASSOCIATION WITH 10YEAR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RICK IN PATIENTS WITH TYPE 1 DIABETES MELLITUS IN TAIWAN

林軒維

陳榮福

張恬君

胡啟民

16:05-16:10 Q AND A SD9-4

16:10-16:30 THE EPIDEMIOLOGIC INVESTIGATION AND RISK FACTOR ANALYSIS OF DIABETIC KIDNEY DISEASE AMONG TYPE 1 DIABETES PATIENTS IN TAIWAN 16:30-16:35 Q AND A

March 27, 2021 【Room 401】

SE1: Symposium-Endocrine 1

Time

Reproductive Medicine

Topic

Speaker

15:20-15:25 OPENING

Moderator 林宏達

SE1-1

15:25-15:50 NEW DEVELOPMENTS IN REPRODUCTION AND GENETICS

陳 明

林宏達

SE1-2

15:50-16:15 UPDATE ON PREMATURE OVARIAN INSUFFICIENCY

郭仁富

林宏達

SE1-3

16:15-16:40 THE NEW ERA IN REPRODUCTIVE MEDICINE

黃尚玉

王治元

16:40-17:00 PANEL DISCUSSION

王治元

21

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 27, 2021 【Room 301】

SE2: Symposium-Endocrine 2 Thyroid

Time

Topic

Speaker

Moderator

15:20-15:25 OPENING

陳思達

SE2-1

15:25-15:50 CLINICAL IMPLICATION OF RADIOFREQUENCY ABLATION IN LOCALLY RECURRENT THYROID CANCER

林偉哲

陳思達

SE2-2

15:50-16:15 NOVEL TARGETED THERAPIES FOR THE TREATMENT OF ADVANCED THYROID CANCER

諶鴻遠

王佩文

SE2-3

16:15-16:40 NAVIGATION ASSISTED ENDOSCOPIC ORBITAL DECOMPRESSION FOR THYROID ORBITOPATHY

張丞賢

王佩文

16:40-17:00 PANEL DISCUSSION

March 27, 2021 【Room 203】

王佩文

SE3: Symposium-Endocrine 3

Time

Precision Medicine

Topic

Speaker

15:20-15:25 OPENING

Moderator 劉鳳炫

SE3-1

15:25-15:45 精準醫療的統計挑戰：長期健康醫療記 錄資料的整合分析

張淑惠

劉鳳炫

SE3-2

15:45-16:05 生物標記在甲狀腺結節診斷的應用

陳瑜忻

劉鳳炫

SE3-3

16:05-16:25 生物標記在甲狀腺癌預後的運用

蘇登煌

蔡克嵩

SE3-4

16:25-16:45 生物標記在甲狀腺癌治療的應用

林樹福

蔡克嵩

16:45-17:00 PANEL DISCUSSION

22

蔡克嵩

Agenda

March 28, 2021 【Room 402AB】

SE4: Symposium-Endocrine 4

Update on Medical Treatments for Osteoporosis/Metabolic Bone Disorders in Taiwan

Time

Topic

Speaker

Moderator

08:00-08:05 OPENING

蔡克嵩

SE4-1

08:05-08:30 UPDATE ON TREATMENT FOR SECONDARY HYPERPARATHYROIDISM IN DIALYSIS PATIENTS

陳靖博

蔡克嵩

SE4-2

08:30-08:55 NEW TREATMENT FOR OSTEOPOROSIS IN TAIWAN

黃兆山

歐弘毅

SE4-3

08:55-09:20 骨鬆長期治療之芻議

蔡克嵩

歐弘毅

09:20-09:30 PANEL DISCUSSION

March 28, 2021

【Room 402CD】

歐弘毅

SE5: Symposium-Endocrine 5

Time

Acromegaly

Topic

Speaker

08:00-08:05 OPENING

Moderator 施翔蓉

SE5-1

08:05-08:30 難治型肢端肥大症策略及未來趨勢

葉乃誠

施翔蓉

SE5-2

08:30-08:55 CONTEMPORARY SURGICAL MANAGEMENT OF ACROMEGALY

黃博浩

陳涵栩

SE5-3

08:55-09:20 LOWER-DOSE GAMMA KNIFE RADIOSURGERY FOR ACROMEGALY

李政家

陳涵栩

09:20-09:30 PANEL DISCUSSION

陳涵栩

23

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 28, 2021 【Room 101】

SE6: Symposium-Endocrine 6 Endocrine Diseases during Pregnancy

Time

Topic

Speaker

Moderator

14:50-14:55 OPENING

施翔蓉

SE6-1

14:55-15:20 MANAGING PROLACTINOMAS DURING PREGNANCY

林家宏

施翔蓉

SE6-2

15:20-15:45 THYROID DISEASE AND IODINE INTAKE IN PREGNANCY

黃君睿

劉鳳炫

SE6-3

15:45-16:10 PHEOCHROMOCYTOMA AND PREGNANCY

林怡瑄

劉鳳炫

16:10-16:30 PANEL DISCUSSION

March 28, 2021 【Room 401】

劉鳳炫

SE7: Symposium-Endocrine 7

Time

Advances in Adrenal Diseases Topic

Speaker

14:50-14:55 OPENING

Moderator 黃天祥

SE7-1

14:55-15:20 NEW PROGRESS IN THE DIAGNOSIS AND TREATMENT OF PRIMARY BILATERAL MACRONOCULAR HYPERPLASIA

呂金盈

黃天祥

SE7-2

15:20-15:45 UPDATE IN ADRENAL INCIDENTALOMA – INVESTIGATION AND MANAGEMENT

李亭衛

黃天祥

SE7-3

15:45-16:10 ADVANCES IN ADRENAL DISEASE:S STEROID PROFILING IN ADRENAL DISEASES

吳明諴

張慶忠

16:10-16:30 PANEL DISCUSSION AND CLOSING

24

張慶忠

Agenda

March 28, 2021 【Room 202】

SE8: Symposium-Endocrine 8 Growth and Development

Time

Topic

Speaker

14:50-14:55 OPENING

Moderator 羅福松

SE8-1

14:55-15:20 EVALUATION AND MANAGEMENT OF CHILDREN WITH SHORT STATURE

劉士嶢

羅福松

SE8-2

15:20-15:45 DIAGNOSIS AND MANAGEMENT OF PRECOCOUS PUBERTY

丁瑋信

羅福松

SE8-3

15:45-16:10 DELAYED PUBERTY

童怡靖

林建銘

16:10-16:30 PANEL DISCUSSION

March 27, 2021 【Room 402AB】

WE: Workshop – Endocrine Thyroid Cytology Workshop

Time

WE

林建銘

Topic

10:00-10:05

OPENING

10:05-11:55

THYROID CYTOLOGY

11:55-12:00

CLOSING

Speaker

Moderator 張天鈞

詹一秀 陳亭竹

張天鈞 陳思達

25

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS: Lunch Symposium

March 27-28, 2021 ROOM 101

ROOM 301

ROOM 401

ROOM 402AB

ROOM 402CD

ROOM 202

ROOM 203

ROOM 205

600 人

220 人

220 人

200 人

200 人

80 人

80 人

70 人

LS4

LS5

LS6

MARCH 27 LS1 12:00-13:00 阿斯特捷利康 MARCH 28 12:25-13:35

LS9 諾華

March 27, 2021

LS2

LS3

禮來

默沙東

LS10

LS11

禮來／百靈佳 賽諾菲 殷格翰

諾和諾德 輝瑞先進 百靈佳殷格翰

LS7

LS8

賽諾菲

友華

LS12

LS13

LS14

LS15

諾和諾德

安晟信

安進

拜耳

Topic

Speaker

Moderator

LS1

阿斯特 捷利康

NEW APPROACHES FOR CHRONIC KIDNEY DISEASE IN TYPE 2 DIABETES MANAGEMENT

Ralph DeFronzo

許惠恒

LS2

禮來

COMPREHENSIVE REVIEW ON RENAL SAFETY DATA FOR TRULICITY ON PATIENTS WITH TYPE 2 DIABETES

張宏猷

黃建寧

LS3

默沙東

SEE ASIA - SITAGLIPTIN AND ERTUGLIFLOZIN EFFICACY IN ASIAN T2DM PATIENTS

王治元

陳榮福

LS4

諾和諾德 NEW ERA OF CONVENIENT INSULIN REGIMENS: THE FIRST 2-IN-1 INSULIN CO-FORMULATION IDEGASP

王俊興

蔡世澤

LS5

輝瑞先進 1 糖尿病之血脂異常治療 2 糖尿病周邊神經病變之診斷與治療

葉乃誠 董 欣

胡啟民

LS6

百靈佳 殷格翰

OPTIMIZE T2D TREATMENT STRATEGY TO MAXIMIZE PERSISTENCE OF OAD

Alice Cheng

楊偉勛

LS7

賽諾菲

IMPORTANCE OF EARLY INSULINIZATION AND HOW TOUJEO HELPS

范綱志

翁瑄甫

LS8

友華

CURRENT CONCEPT OF LIPID LOWERING THERAPY

李貽恒

杜思德

26

Agenda

March 28, 2021

Topic

Speaker

Moderator

LS09

諾華

VERIFY THE ROLE OF EARLY COMBINATION : FOCUS ON BETA CELL PRESERVATION

翁瑄甫

李亭儀

LS10

禮來／ 百靈佳 殷格翰

EVOLUTION OF T2D CARE, MOVE FROM CONVENTIONAL TO COMPREHENSIVE THERAPY

蔡世澤

陳榮福

LS11

賽諾菲

ADVANCED IN INJECTABLE THERAPY: ADDRESSING THE NEED FOR INTENSIFICATION AND HOW WE MAKE IT SIMPLER

Leigh Perreault

莊立民

諾和諾德 ADVANCING DIABETES CARE WITH GLP-1 RECEPTOR AGONISTS

杜思德

王治元

PREVENTING HYPOGLYCEMIA BY USING TECHNOLOGY IN DIABETES SELF-MANAGEMENT

林慶齡

許惠恒 陳涵栩

LS12 LS13

安晟信

LS14

安進

RELENTLESS PROTECTION OF PROLIA (DENOSUMAB) IN ENDOCRINOLOGY

廖國盟

黃兆山

LS15

拜耳

PRECISION MEDICINE IN THYROID CANCER- UPDATED NTRK FUSION - TKI USE IN RAI-REFRACTORY DTC AND ATC

諶鴻遠

曾芬郁

27

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 27, 2021 【Room 202】

時 間

OD: Oral Presentation- Diabetes 題 目

演講者

主持人

OD-1

17:00-17:10 第 2 型糖尿病病人平均糖化血色素、糖化 血色素變異度與心衰竭的相關性

陳清助

蘇景傑

OD-2

17:10-17:20 探討第二型糖尿病與負面情緒、自主神經 活性和血糖控制之關聯性

林昆德

蘇景傑

OD-3

17:20-17:30 粒線體單被群組別比核基因遺傳變異在第 二型糖尿病病人的胰島素使用更有相關性

沈峰志

楊宜瑱

OD-4

17:30-17:40 第 2 型糖尿病患者慢性腎病變退行和進展 的預後模型

李建興

楊宜瑱

OD-5

17:40-17:50 藉由連續心電圖及血糖監測系統觀察低血 糖和心律變異性之關聯

許嘉容

林昆德

OD-6

17:50-18:00 利用資訊系統主動進行住院中高血糖會診 以改善醫療品質

謝靜蓉

林昆德

28

Agenda

March 27, 2021 【Room 203】

時 間

OE: Oral Presentation- Endocrine 題 目

演講者

主持人

OE-1

17:00-17:10 葛瑞夫茲症患者於即時性超音波應變彈性 影像之變化

賴昆佑

簡銘男

OE-2

17:10-17:20 甲狀腺刺激素受體抗體於冰存檢體中之安 定性

陳大期

簡銘男

OE-3

17:20-17:30 甲狀腺結節細針抽吸液基細胞學檢查應用 於以傳統抹片固定之甲狀腺細胞其病理學 BETHESDA 報告為無法診斷

林麗珊

李亭儀

OE-4

17:30-17:40 遠端轉移對濾泡型甲狀腺癌患者預後之 影響

吳明諴

李亭儀

OE-5

17:40-17:50 標靶藥物治療未分化甲狀腺癌病人的結果

李宜螢

歐弘毅

OE-6

17:50-18:00 接受放射碘治療前使用 THYROGEN 和 停用甲狀腺素對於甲狀腺癌病人的臨床經 驗 - 從南部醫學中心的經驗分享

蔡加睿

歐弘毅

29

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

March 27-28, 2021 【三樓走廊】

AP: 2021 Award 題 目

作 者

諾華優秀論文獎 AP-1

血清中 ANGPTL6 對高血糖之反應以及與第二型糖尿病風險之關係： 前瞻式世代研究

范綱志

AP-2

前胸腺素透過活化第一型膠原蛋白導致胎盤纖維化與妊娠期糖尿病的 發生

吳泓璁

諾和諾德優秀論文獎 AP-3

甲狀腺乳突癌中雄性賀爾蒙接受體異常表現與高癌症風險和甲狀腺外 侵犯相關

周振凱

AP-4

台灣第 1 型糖尿病人 HLA-DQ 基因型和抗轉麩醯胺酸酶 2 抗體的生 化學特性

李燕晉

30

Agenda

March 27-28, 2021

PD: Poster Presentation-Diabetes 主持人：林嘉鴻、王俊興、李建興 評分時間：MARCH 27 , 2021 15:00-15:20 ( 三樓走廊 ) 題 目

第一作者

PD01

懷孕前期使用 METFORMIN 治療第 2 型糖尿病的懷孕結果

林樹福

PD02

母體懷孕時脂質 , 胎盤生長因子與胎兒生長之關係

陳冠宇

PD03

糖尿病足潰瘍中不同金黃色葡萄球菌菌株與治療結果之關聯性分析

李瑞祥

PD04

第二型鈉 - 葡萄糖共同轉運蛋白抑制劑對腦血管事件的影響 : 統合分析

蔡文瑄

PD05

在罕見的胰島素瘤病例中進行連續葡萄糖監測（CGM）和 5 小時口 服葡萄糖耐量測試

顏琦恩

PD06

GLP-1 受體促效劑藉由調節膽酸的代謝平衡而改善高脂肪飲食相關 之脂肪肝

姜和均

PD07

從 GLP1-RA 的使用來看減重對糖尿病治療成效和病患滿意度之影響

沈振榮

PD08

新診斷第二型糖尿病患得到化膿性肝膿瘍的風險 : 台灣全國人口之世 代研究

王子源

PD09

GCK-MODY 4 歲前診斷 :

李燕晉

PD10

SGLT-2 抑制劑對糖尿病腎病變和體重控制之治療成效

沈振榮

PD11

老人身體質量指數與全因死亡風險之相關研究

賴韻如

PD12

透 過 REAL TIME CGM 的 介 入 評 估 新 診 斷 第 二 型 糖 尿 病 人 使 用 IGLARLIXI 在血糖穩定度及簡化治療的效果

林春杏

PD13

於中台灣某精神專科區域醫院門診應用糖尿病論質計酬計畫之效益評估

楊晉州

PD14

CEMIP-HBC DNA 質體疫苗干擾 WNT/Β-CATENIN 細胞訊息路徑 抑制高脂肪飲食小鼠腎臟纖維化

陳肇閎

31

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The

nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

題 目

第一作者

PD15

二肽基酶 -4 抑制劑對第二型糖尿病患者腎臟功能的影響

徐莞嘉

PD16

過氧化低密度脂蛋白活化 SARS-COV2 棘狀蛋白與跨膜絲胺酸蛋白 酶第 4 型親和性造成肝臟損傷

陳肇閎

PD17

第 2 型糖尿病患 SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR 2 與腎病變預後相關性研究

林亮羽

PD18

乳房葉狀瘤相關的非胰島細胞腫瘤性低血糖：病例報告與文獻回顧

楊幼琳

PD19

腰圍是第二型糖尿病患者肌肉表現的決定因素

江宜倫

PD20

使用 SARC-CALF 問卷與其他危險因素預測第 2 型老年人糖尿病的 肌少症風險

陳柏君

PD21

SGLT-2 抑制劑與正常血糖值糖尿病酮酸中毒症案例報告

劉哲瑜

PD22

ALIROCUMAB 治療後改善 LORLATINIB 所造成的高血脂―案例報告

陳芳瑜

PD23

肢端肥大症與糖尿病之雙向相關性研究

嚴元鴻

PD24

後腹腔單發性纖維瘤以低血糖為表現之病例報告

蔡依靜

PD25

SGLT-2 抑制劑治療 ALPELISIB(PI3K 抑制劑 ) 引起的嚴重高血糖― 案例報告

廖唐毅

PD26

健康族群中補充維生素 E 於代謝症候群要素之益處

吳國新

PD27

健康者服用蜂膠於白血球與代謝症候群要素之效益

張鳳如

PD28

睡眠時間越短，糖尿病前期風險越增。台灣社區的世代研究

余宜叡

PD29

LIRAGLUTIDE 與 EMPAGLIFLOZIN 在糖尿病心肌病變不同地調控 心臟代謝

董裡阮

PD30

案例報告 : 31 歲女生表現為新診斷第 2 型糖尿病合併脊髓炎

林玉怡

32

Agenda

March 27-28, 2021

PE: Poster Presentation- Endocrine 主持人：蘇登煌、邱偉益、陳思綺 評分時間：MARCH 27 , 2021 15:00-15:20 ( 三樓走廊 ) 題 目

第一作者

PE01

在卵巢的異位性腎上腺皮質癌 : 個案報告

蔡文瑄

PE02

ADAVOSERTIB 抑制 WEE1 用以治療未分化甲狀腺癌

呂毓苓

PE03

低劑量 LENVATINIB 使用於放射碘治療無效的甲狀腺癌之實際治療 經驗

姜和均

PE04

奶類與蛋之碘含量測定

王繁棻

PE05

ABIRATERONE 所引起之可逆性後部腦病症候群

陳冠樺

PE06

甲狀腺濾泡癌以頭皮腫塊表現―案例報告

吳崇暉

PE07

新型突變基因位點的腎源性尿崩症：病例報告與文獻回顧

楊幼琳

PE08

乳突狀甲狀腺微小癌風險增加趨勢：一家醫學中心的經驗

李麗青

PE09

個案報告 : 嚴重骨質疏鬆症合併低血磷症

許靖玫

PE10

以感應耦合電漿質譜儀測定尿碘之新方法及確效

黃君睿

PE11

放射碘治療前執行低碘飲食之患者依從性

黃君睿

PE12

異位頸部胸腺瘤 - 個案報告及文獻回顧

林子健

PE13

測定臺灣醬油之含碘量

黃君睿

PE14

孕婦甲狀腺功能亢進其新生兒甲狀腺腫合併功能低下：病例報告與文 獻回顧

楊幼琳

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題 目

第一作者

PE15

多次復發之轉移性分化型甲狀腺乳突癌的局部和全身性治療 : 病例報 告及文獻回顧

周依文

PE16

分化型甲狀腺癌合併骨轉移 - 三病例報告及文獻回顧

蔡雨言

PE17

異位性甲狀腺

黃婉婷

PE18

完全雄性素不敏感症候群

朱建宇

PE19

抑制 POLO-LIKE KINASES 以治療甲狀腺未分化癌

林樹福

PE20

以肺部隱球菌感染和多重脊椎骨折為臨床表現的庫欣氏症候群

林冠宇

PE21

甲狀腺細針穿刺細胞學檢查後前頸部血腫伴氣管受壓：內分泌檢查中 罕見但需謹慎以對的併發症

吳宗祐

PE22

家族性甲狀腺乳突癌 : 案例報告

林卉羚

PE23

促甲狀腺素分泌垂體腺瘤 - 案例報告與臺大醫院五年系列案例的臨床 特色與治療經驗分析

林均賢

PE24

腎上腺偶見瘤有自主性皮質醇分泌與罕見的病理表現

古麒正

PE25

同時分泌促甲狀腺素與生長激素之腦垂體腫瘤 - 病例報告

林祐霆

PE26

假性副甲狀腺低能症？！或偽 - 假性副甲狀腺低下症？？！

吳家德

PE27

利用射頻燒灼術治療局部侵犯之副甲狀腺癌之案例報告

陳維常

PE28

痔瘡和葛瑞夫氏症的關聯

陳信宏

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Agenda

March 27-28, 2021 【三樓走廊】

BP 1-6 廠商論文壁報展示 題 目

投稿單位

BP-01 按基線糖化血色素和身體質量指數評估研究中的 DULAGLUTIDE 劑 量的整體療效 : AWARD 11 的探索性次分析

禮來

BP-02 跟 口 服 SEMAGLUTIDE, 針 劑 SEMAGLUTIDE 和 DULAGLUTIDE 相關的病患偏好與健康效用

禮來

BP-03 嚴重低血糖相關對話和反應 (CRASH): 65 歲以上第一型糖尿病或是第 二型糖尿病接受胰島素治療的病患和照護者的調查

禮來

BP-04 DULAGLUTIDE 對第二型糖尿病病患腎臟相關結果 : REWIND 試驗 的事後檢定

禮來

BP-05 EMPAGLIFLOZIN 有助於第 2 型糖尿病和心血管疾病患者的胰島素劑 量持續降低： EMPA-REG OUTCOME 試驗

百靈佳 殷格翰

BP-06 EMPAGLIFLOZIN 對不同 BMI 類別的心腎結果和死亡率的影響： EMPA-REG OUTCOME 試驗亞洲患者次分析

百靈佳 殷格翰

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DAROC-TADE-1

科技部生科司未來展望與規劃 陳鴻震 科技部生命科學研究發展司／司長

紮實的基礎科學研究帶動多面向的應用科學研究發展，不僅讓我國在研究上維持優勢，亦 可將成果延伸到產業應用，對國家經濟的發展提供實質貢獻。生命科學研究發展司 ( 簡稱生科 司 ) 支援全國生物、醫學及農學學術研究、培育及延攬科研人才，透過補助大專院校及研究機 構從事學術研究，提升我國科技研發水準；另，也著眼國內外趨勢，推動涉及民生議題的專案 研究計畫，以提升科技對社會的貢獻；依據國家發展委員會推估，我國將於 2025 年成為超高 齡社會，因此，可以預見老年醫學及精準醫學研究的重要性，未來生科司持續奠基在我國優勢 領域及利基，投入精準健康相關研究外，全球變遷對全球生態系統之相關影響也將是投入的研 究焦點之一。

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Abstract DAROC-TADE-2

NEW ADVANCES IN SMART MEDICINE FOR THYROID DISEASES AND DIABETES MELLITUS CHIH-YUAN WANG, M.D., PH.D, EMBA Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University

在內分泌的領域當中，有兩種疾病是最常看到的內分泌系統疾病，就是糖尿病與甲狀腺 疾病。以糖尿病為例，過去 100 年最大的進展，就是胰島素的發明，以及新型口服糖尿病藥物 的出現，目的就是延長病患正常的生活壽命，以及改善病患的生活品質， 減少小血管及大血管 併發症，以及降低死亡率。在於血糖監測方面，連續血糖監測儀，是一個劃時代的進展，病人 自我血糖監測進步到以人工智慧來做管理。甲狀腺疾病相關的研究領域中，甲狀腺消融術，是 臨床上取代傳統手術的重要發展，而人工智慧甲狀腺超音波診斷，對於良性惡性結節的判讀， 目前顯然已經超越臨床醫師的判讀能力。甲狀腺癌症的治療，也從過去分子生物學機轉的研究 中，找到了標靶療法及免疫療法，隨之而來，是如何改變甲狀腺癌症追蹤的生物指標， 因為甲 狀腺癌患者， 大多數因為細胞分化良好而能夠長時間存活，如何在術後數十年存活的歲月中， 找到穩定的甲狀腺癌追蹤指標，也有許多新的發展。

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DAROC-TADE-3

ARISTOLOCHIC ACID AND UPPER TRACT UROTHELIAL CARCINOMA IN TAIWAN - STORY CONTINUED

馬兜鈴酸與上泌尿道上皮癌的故事連載 CHUNG-HSIN CHEN Department of Urology, National Taiwan University Hospital 台大醫院泌尿部

台灣每年約有新診斷泌尿上皮癌 (urothelial carcinoma) 六千人，其中有近四成為上泌尿道 泌尿上皮癌 (upper urinary tract urothelial carcinoma)，其發生率約為 4 人每十萬人每年。看似不 高，但是台灣的上泌尿到泌尿上皮癌發生率已是美國的 5 到 10 倍，也比周邊國家的發生率高 上數倍。追究其原因可能有很多，但是目前發現有近三分之一的病例與中草藥中的馬兜鈴酸 (aristolochic acid) 暴露相關，其證據除了流行病學上的相關性研究，也有來自病人腎臟組織、 腫瘤組織上馬兜鈴酸的印記。這些馬兜鈴酸引起的上泌尿道泌尿上皮癌病人擁有許多臨床上的 特色 : 相對年輕、女性居多、少吸菸史與腎功能較差。這些特色反映出馬兜鈴酸與個人飲食和 生活習慣可能有關。其他研究也顯示馬兜鈴酸的印記也出現在其他腫瘤上，例如腎臟的腎細胞 癌與肝細胞癌等等。因此，馬兜鈴酸影響的範圍比學者原先的預期還要大。 近年，我們團隊也發現原先認為以無機砷為主要致癌物質的砷汙染區，其部分泌尿上皮癌 也為馬兜鈴酸所造成。以病例與流行病學雙線研究，證實無機砷與馬兜鈴酸對於上泌尿道泌尿 上皮癌的發生有相加效應。可喜的是我們也終於觀測到上泌尿道泌尿上皮癌的發生率開始緩慢 回落，顯示 2003 年禁止馬兜鈴酸相關中草藥的使用，已在 15 年後逐步看到成果。

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Abstract DAROC-TADE-4

THE INNATE REGULATING ROLES OF TREMS IN THE UUO NEPHRITIS NIEN-JUNG CHEN Associate Professor, Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan; Director, Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan

Chronic kidney disease (CKD) is a kidney inflammatory disease, and the high prevalence and incidence of end stage renal disease (ESRD) in Taiwan is an urgent concern. The triggering receptor expressed on myeloid cells (TREM) family is involved in the pathogenesis of many inflammatory diseases, and we investigated the inflammatory regulation contributed by TREMs in a murine CKD disease model, unilateral ureteral Obstruction (UUO), which provides a chance to examine the pathogenesis of CKD within two weeks. In the past decade, we adapted the UUO surgery in the wild type mice and the established TREM deficient mice, and compared the pathogenesis and histological changes in the renal tissues. Our data implicated that TREM-1 plays a pro-inflammatory role and promotes the M1 macrophage polarization, subsequently mediates the renal inflammation, tissue damage, and finally leading to the renal fibrosis. In comparison, TREM-2 plays an anti-inflammatory role, losing TREM-2 in mice exacerbates the renal damage due to an enhancement of neutrophils infiltration in effected kidneys. We observed that TREM2 expressed on Dendritic cells contributes to the induction of iNOS and the downstream NO production. It has been shown that NO play a crucial role on modulating the function of RORγt, the key transcriptional regulator of Th17 function.

Nitrosylation of RORγt depresses the Th17 activation, further leads to the deduction of IL-17 and the downstream chemokine (CCL3) production, subsequently downregulates the infiltration of neutrophils in the inflamed kidneys upon UUO. Taken together, our results demonstrate that TREM1 and TREM2 play opposite roles in inflammatory regulation, it would be a novel topic to develop the drugs against the TREM-1 function or stimulate the TREM-2 mediated iNOS-NO for Th17 suppression in future for the human CKD therapy.

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PL-2

IMAGING OF ADRENAL LESIONS: A REVIEW AND AN UPDATE YUNG-LIANG WAN Department of Medical Imaging and Intervention Linkou Chang Gung Memorial Hospital, Chang Gung University

Noninvasive cross section imaging, such as ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging have been playing a critical role in the detection, characterization, and lateralization of adrenal lesions. The differentiation of a malignant from a benign adrenal mass is crucial in the management and treatment of a patient. Thus, a thorough understanding of the basic principle, advantages, and limitations may help a physician and a radiologist to optimize the application of various imaging modalities in a patient with suspected adrenal lesions. The following are the key points in this presentation 1. The basic principles and comparison of different cross section imaging are as shown in Table 1. On ultrasonograms, the echogeneities of the scanned objects depend on the difference of the acoustic impedance of the two media forming the interface. The higher the discrepancy in the acoustic impedance, the higher the reflection coefficients or the echogeneity. On the CT images, the attenuations of the scanned objects depend on their densities. The higher the density of an object, the higher the attenuation (whiteness). On the MRI, the signal intensities depend on the longitudinal relaxation time (T1), transverse relaxation time (T2), flip angle, proton density, and the flow of the scanned tissue (Table 1).

2. A drenal masses can be divided into benign (predominantly adenoma, hyperplasia, pheochromocytoma, cyst, hemorrhage, myelolipoma, tuberculosis, hemangioma, and ganglioneuroma) and malignant (mainly metastases, adrenal cortical carcinoma, lymphoma, neuroblastoma) masses.

3. Clinical manifestations and laboratory data are essential for the accurate diagnosis of the adrenal masses, especially in cases associated with functional disorders.

4. Suggestive signs of malignancy. One has to consider the possibility of malignancy when a mass is associated with any one of the following findings: a mass larger than 6 cm in diameter (except for pheochromocytoma), with irregular or indistinct border, invasiveness to the adjacent viscera or vessels, the presence of a mass in the contralateral adrenal gland, mass, metastases, or enlarged nodes elsewhere.

5. The differential diagnoses of the diffuse enlargement of the adrenal gland include lymphoma, hemorrhage, hyperplasia, and metastasis (mainly from cancer of the lung, pancreas, and kidney).

Lesions that may involve both adrenal glands comprise hyperplasia, metastases, lymphoma, pheochromocytoma (10%) and granulomatous diseases.

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Abstract 6. An adrenal mass with fat components may feature characteristic findings on sonograms, CT images, and MR images.

7. Adenoma, which may frequently be present as an incidentaloma, is the most common adrenal tumor. Washout evaluation of the adrenal masses on the dynamic contrast-enhanced CT is an efficient technique in differentiating the adenomas from the metastases.

8. Chemical shift MR imaging is a useful tool to identify the fat content within a mass. The lack of signal loss on the out-of-phase MR images is suggestive of metastases rather than adenoma. DWI is not useful to differentiate the adrenal lesions.

9. Glucose metabolic imaging or 18F-FDG-PET/CT plays a vital role in the differentiation of the adrenal metastasis from a benign adrenal mass in lung cancer patients, with excellent diagnostic performance. It could be considered as a second-stage imaging study for evaluation of the indeterminate adrenal lesions.

10. Image-guided intervention may play a critical role in specific clinical settings.

12. A hyperpolarized carbon 13 (HP 13C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway specific investigation of the dynamic metabolic and physiologic processes that were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations of metabolism that are central to a variety of diseases. Prospective studies are required to investigate its role in the adrenal imaging and the differentiation of the malignancies from the benign masses.

Table 1. Comparison of Imaging Modalities:

Factors

Principle

US

CT (abdomen)

Acoustic Densities impedance

MRI T1, T2, flip angle, proton density, flow

Description

Echogeneity

Attenuation

Signal intensity

Duration

5-10 mins

3-7 mins

30-45 mins

Cheaper

Expensive

Cost

Cheap

Dimensions

2 or 3

3

3

Soft tissue

Poor

Poor detail

Excellent

Bone

Poor

Excellent detail

Poor

Radiation

None

10 mSv

None

Contrast Media

Limited (MB)

Common Iodine

Common Gd

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PL-3

再訪胰島素發現始末 林瑞祥 立達診所

Paul Langerhans(1847-1888) 在 1869 年發表的論文中描述在胰臟內有一小團一小團功能不 明的細胞。1888 年 Langerhans 去世後不久，Laguesse 稱這群細胞為 islets of Langerhans。 1889 年 Joseph von Mering 告訴 Oskar Minkowsky 胰臟內的消化酵素可能幫助消化小腸內 的食物，但沒人願意切除動物的胰臟來證明這件事，因為切除胰臟後很快就死亡。Minkowsky 的手術技巧很好，1888 年曾手術切除天鵝肝臟，術後活一段時間。於是和 von Mering 談話後， 當天切除狗的胰臟。過兩天照顧狗的工友告訴 Minkowsky 那隻開刀過的狗到處跑，到處撒尿。 Minkowsky 的老師是當時德國出名的糖尿病泰斗 Bernhard Naunyn。Minkowsky 立刻驗尿，證 明尿裡有糖。既然切除胰臟後血糖升高，胰臟內應含有使血糖下降的成分。此後 20-30 年， Minkowsky 和其他有經驗的研究者投入尋找胰島素的行列，但都失敗。 1920 年 7 月 1 日 28 歲的骨科醫師 Frederic Grant Banting 在加拿大 Ontario 州 London 市開業。 第一個月只有一位病人上門，生理學賺了 4 塊錢。第二個月也好不了多少。於是十月開始在當 地的 University of Western Ontario 的解剖學科和外科擔任兼職的助教。 生理學的教授約 Banting 醫師在 12 月底給學生上一堂碳水化合物的課。剛好 Banting 自己訂的雜誌 Surgery Gynecology and Obstetrics 的 11 月號在 10 月底到手。其中有一篇由病理學家 Moses Barron 寫的研究報告：「特 別參照胰臟結石症，討論郎氏小島與糖尿病的關係」。Barron 注意到胰管結石後，各種消化酵 素滯留在胰臟內活化，破壞製造消化酵素的細胞，但是郎氏小島因與胰島沒有連結，沒受影響。 Banting 讀完 Barron 的論文後推想過去三十年大家失敗的原因可能是抽取糖尿病有效物質時，被 消化酵素破壞殆盡。當天半夜 Banting 醒來在小本子上疾書：「結紮狗的胰管，讓狗活到腺胞退 化變性，只剩胰小島。然後嘗試抽取內分泌物質」。接受同事的建議，Banting 回母校 Toronto 大學醫學院找生理學教授 John R.R. MacLeod。由於 Banting 沒有研究經驗，MacLeod 起初不看 好 Banting 的研究計畫，但拗不過再三的請求，同意 1922 年暑假回故鄉蘇格蘭期間，讓 Banting 利用生理學研究室做實驗。MacLeod 特別安排攻讀生化和生理學四年級的學生 Charles Best 協 助 Banting 做實驗。1921 年 5 月中旬 Best 考完畢業考試後第二天立即開始做實驗。經過多次失 敗，逐漸改善分離胰臟的方法和結扎胰管的方法，終於取出萎縮的胰臟，剪成碎片，在乳鉢內 利用生理鹽水和海砂研磨。萃取液用紗布過濾後，靜脈注射事先切除胰臟的狗。血糖從 360 降 到 320 mg/dl。再注射抽取液，血糖更降。成功了！起先 Banting 及 Best 稱胰島素為 Isletin。後 來 MacLeod 教授建議採用 1910 年 Jean de Meyer 起的名子 Insulin( 拉丁文 Insula，島 )。

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Abstract 1921 年 12 月底，Banting 和 Best 到 Connecticut 州 New Heaven 市參加美國生理學會年會， 正式向外宣佈發現胰島素。1922 年一月，利用當時在 Toronto 大學生化學科擔任客座教授的 J.B.Collip 協助純化的胰島素，給即將陷入酮酸中毒的 14 歲男童 Leonard Thompson 注射，成功 的救回一命。Banting 和 Best 取得胰島素的專利，並把專利以一元賣給 Toronto 大學。後者組 織胰島素委員會，統籌胰島素的品質管理，提供專利使用權給任何合法的藥廠。1923 年醫學 或生理學的 Novel 獎頒給 Banting 和 MacLeod。Banting 領獎後宣布，他領受的獎金的一半送給 Charles H.Best。不服輸的 MacLeod 馬上宣布將他領受的獎金的一半送給 J.B.Collip。

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PL-4

EPIGENETIC CONTROL OF BONE AND FAT METABOLISM FENG-SHENG WANG, MS, PHD Department of Medical Research; Core Laboratory for Phenomics & Diagnostics; Center for Mitochondrial Research & Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan

Osteoporosis puts the elderly at an incredibly high risk of fracture, which accounts for the leading cause of limb disability or premature death of the elderly around the globe. Aging, estrogen deficiency, metabolism syndrome, and glucocorticoid overmedication etc., are common etiological factors of the development of osteoporotic diseases. Bone mass loss together with marrow adiposis is a prominent pathological feature of osteoporotic skeleton. The adverse conditions drive mesenchymal stem cells away from bone-forming cells and toward adipocytic cells, slowing bone mineral acquisition to accelerate bone turnover. Accumulating evidence reveals a plethora of epigenetic pathways, including DNA methylation, histone modification, and non-coding RNA, etc. are correlated with the development of osteoporosis, as well as control the differentiation capacity and fate of osteogenic progenitor cells.

Of epigenetic regulators, DNA methyltransferases (DNMTs), histone lysine demethylases (KDMs), histone deacetylases (HDACs), and the microRNA-29a (miR-29a) family are indispensable in bone and fat metabolism in skeletal tissue. miR-29a loss was correlated with human senile osteoporosis.

Osteoblast-specific miR-29a knockout mice showed low bone mass, sparse trabecular microstructure, and marrow adiposis. Mice overexpressing osteoblastic miR-29a developed less age, estrogen deficiency, and glucocorticoid-mediated osteoporosis and fatty marrow. The osteoblastic microRNA also influences energy metabolism and abdomen fat deposition. miR-29a targeted Dnmt3b-mediated DNA methylation to regulate long-chain fatty acid metabolism, peroxisome autophagy, brown/white adipocyte formation in bone marrow, as well as modulated Hdac4-mediated histone enrichment in adipokine and myokine transcription. We also revealed that Kdm loss in osteoblasts dwarfed postnatal bone development, accelerating marrow fat accumulation and abdomen adipose development. This speech throws new light onto the mechanism by which epigenetic pathways regulate bone homeostasis and adipose development and highlight the perspective of remedial effects of epigenetic regulators to osteoporosis, joint disorders, and fat metabolism.

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Abstract MTP-D

MANAGEMENT OF OBESITY K-C HUANG 1Department of Family Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

Obesity is related to many comorbidities such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, non-alcoholic fatty liver diseases, osteoarthritis, and some kinds of cancer.

Furthermore, obesity per se also increases all-causes mortality. Furthermore, the prevalence of obesity increases thereby it becomes a worldwide health problem. Appropriate weight reduction can reduce the obesity-related health burden. Lifestyle modification remains the core stone in the management of obesity. Restricted balanced diet and increased physical activity are encouraged in stages of weight reduction and maintenance. Pharmacotherapy may be considered if subjects are suffered from obesityrelated comorbidities or high degree of obesity. In Taiwan, Xenical and Saxenda are two available antiobesity drugs. Weight change issue should be also assessed in advance when managing comorbidities.

Bariatric surgery is indicated if the subjects fail to reduce adequate body weight with lifestyle modification and pharmacotherapy. In the future, long acting or oral form GLP-1 agonists or other gut hormones will be on the market to assist obese people to control their body weight.

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MTP-E1

POLYCYSTIC OVARY SYNDROME PENG-HUI WANG Department of Obstetrics and Gynecology, Taipei Veterans General Hospital and Institute of Clinical Medicine, National Yang Ming Chiao Tung University

Polycystic ovary syndrome (PCOS) is a common endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and multiple small subcapsular cystic follicles in the ovary during ultrasonography, and affects 5–10% of women of reproductive age. PCOS is frequently associated with insulin resistance (IR) accompanied by compensatory hyperinsulinemia and, therefore, presents an increased risk of type 2 diabetes mellitus (DM). The pathophysiology of PCOS is unclear, and several hypotheses have been proposed, often based on the concept that ovarian steroidogenesis requires gonadotropin stimulation and the subsequent dysregulation or dysfunction of the hormone, metabolism, and homeostasis systems, such as consequent unopposed estrogenemia, IR, compensatory hyperinsulinemia, chronic inflammatory reaction, proinflammatory cytokines, and oxidative stress.

Among these hypotheses, IR and hyperandrogenism may be the two key factors. The first line of treatment in PCOS includes lifestyle changes and body weight reduction. Achieving a 5–15% body weight reduction may improve IR and PCOS-associated hormonal abnormalities. For women who desire pregnancy, clomiphene citrate (CC) is the front-line treatment for ovulation induction. Twenty five percent of women may fail to ovulate spontaneously after three cycles of CC treatment, which is called CC-resistant PCOS. For CC-resistant PCOS women, there are many strategies to improve ovulation rate, including medical treatment and surgical approaches. Among the various surgical approaches, laparoscopic ovarian drilling (LOD) has been proposed as an alternative treatment, resulting in an overall spontaneous ovulation rate of 30–90% and final pregnancy rates of 13–88%.

These benefits are more significant for women with CC-resistant PCOS. LOD, mediated mainly by thermal effects, produces a series of morphological and biochemical changes. These changes include the formation of artificial holes in the very thick cortical wall, loosening of the dense and hard cortical wall, destruction of ovarian follicles with a subsequently decreased amount of theca and/or granulosa cells, destruction of ovarian stromal tissue with the subsequent development of transient but purulent and acute inflammatory reactions to initiate the immune response, and the continuing leakage or drainage of “toxic” follicular fluid in these immature and growth-ceased pre-antral follicles. All these factors contribute to decreasing local and systemic androgen levels, the following apoptosis process with these pre-antral follicles to atresia; the re-starting of normal follicular recruitment, development, and maturation, and finally, the normalization of the “hypothalamus–pituitary–ovary” axis and subsequent spontaneous ovulation.

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GENETIC DIAGNOSIS OF ENDOCRINE DISEASE 1,2,3

P-L CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, 2Department of Medical Genetics, National Taiwan University Hospital, Taiwan, R.O.C. 3Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taiwan, R.O.C.

Precision medicine, according to the National Institutes of Health (NIH), USA, is “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person”. Under this approach, diagnostic testing is often employed for diagnosis and/or for selecting appropriate therapies based on the patient’s genetic content. Given that the genetic models of diseases (for example, single gene disease vs. complex disease) can vary from diseases to diseases, the most appropriate method for genetic testing therefore will also keep evolving. In addition to traditional platforms (such as Sanger sequencing, multiplex ligationdependent probe amplification (MLA), array CGH, etc.), next-generation sequencing (NGS) has been revolutionizing the field of genetic testing during the latest years.

In this presentation, the principles of precision medicine and the state-of-the-art methodologies of clinical genetic testing will be illustrated. Several important endocrine diseases will be covered, including multiple endocrine neoplasia (MEN) type 1, MEN type 2, pseudohypoparathyroidism (PHP) type 1a and type 1b, pheochromocytoma/paraganglioma (PPGL), primary aldosteronism, thyroid cancer, mitochondrial disease, antithyroid drug-induced agranulocytosis, congenital adrenal hyperplasia (CAH), congenital hypothyroidism, etc.

However, genetic diagnosis is far from perfect and NGS is no panacea. Several critical challenges need to be addressed. In this talk, the speaker will present his views and experience in clinical genetic testing, especially focusing on the challenges and possible solutions.

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SD1-1

OVERVIEW OF TYPE 1 DIABETES IN TAIWAN: THE INCIDENCE, PREVALENCE AND MORTALITY RATE YI-CHING TUNG Division of Pediatric Endocrinology, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

Type 1 diabetes (T1D) only consists 0.7% of diabetes population in Taiwan. However, these patients have onset at the young age and require lifelong insulin therapy.

Material: The Database of Taiwan National Health Insurance from 2000 to 2016.

Incidence: The number of new-onset T1D cases in Taiwan is about four to five hundred per year.

Current incidence data reveals a trend towards younger age onset, increase by 30% in children. The standardized incidence of T1D in the general population is 2.23/105 person-year, and 6.70/105 personyear in the early adolescents. However, we still found forty percent of T1D having their onset in the adulthood.

Prevalence: The prevalence of T1D in all age groups is increasing. There are more females than males having T1D. The standardized prevalence of T1D in the general population is 49.3/105 persons, and 81.54/105 persons in the late adolescents. Ninety percent of adults with T1D have been diagnosed for more than 5 years. Therefore, the transitional care from pediatrics to adults should include patient education on potential chronic complications.

Mortality Rate: The standardized mortality ratio in T1D patients is three times higher than those of the general populations. In T1D patients, the most common cause of death is diabetes mellitus.

Other causes include cancer, cardiovascular disease and cerebral vascular disease. Men with T1D had the higher mortality rate, and this may be associated with higher cardiovascular risks in these male patients.

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Abstract SD1-2

INSULIN TREATMENT OF TYPE 1 DIABETES AND DIABETIC COMPLICATIONS IN TAIWAN CHIA-HUNG LIN1,2 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan City33302, Taiwan 2 Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City33302, Taiwan

The treatment guidelines suggest multiple daily injections (MDI) in type 1 diabetes (T1D).

However, there are still patients, especially children at school, only choosing twice daily regimen because of the difficulty in multiple injections. Insulin analogs have accounted for 93.2% of the total insulin use. The proportion of insulin prescriptions is gradually shifting from human insulin to insulin analogue, and there is a consistent trend regardless of the T1D duration.

Pre-mixed insulin prescriptions are mainly used for a small number of adult T1D patients over the age of 20, and the proportion has shown a downward trend year by year, which is gradually consistent with Western countries, and shifts to the direction of MDI. From the perspective of all age groups, only 64.5% of patients with type 1 diabetes use MDI. Compared with advanced western countries, the proportion of patients with T1D who use intensive insulin therapy (including MDI and insulin pump) is still insufficient and must be promoted.

The acute hyperglycemic and hypoglycemic complications are decreased slowly in recent years.

The prevalence of chronic micro- and macro-vascular complications is also going down although the risk is increased after 10 years of diagnosis. The reimbursement of SMBG test strips and insulin analogue is account for the improvement of diabetic control. In conclusion, the quality of T1D control is improving but more advanced help in new treatment paradigm shift in the near future is needed.

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SD1-3

UTILIZATION OF MEDICAL RESOURCE AND QUALITY OF CARE IN PATIENTS WITH TYPE 1 DIABETES IN TAIWAN 1

JUN-SING WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

The incidence of type 1 diabetes is continuously increasing worldwide in recent decades. Patients with diabetes are at risks of chronic micro- and macro-vascular complications. Treatments for these complications lead to huge burden for medical cost, especially for inpatient care. The medical cost for patients with diabetes was more than double the amount for patients without diabetes in the United States, among which 25% was for inpatients care. The prevalence of patients with type 1 diabetes in Taiwan was lower than that in the United States. Moreover, we did not have data on medical resource utilization for patients with type 1 diabetes in Taiwan. Here, we reported findings regarding the utilization of medical resource using data from National Health Insurance Research Database.

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Abstract SD2-2

UPDATE OF DKD IN TAIWAN FOCUS ON DKD TREATMENT GUIDELINE. SHU-HENG HUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

It has been near 6 years since the National Institutes of Health published the guideline for " Clinical diagnosis and treatment of chronic kidney disease in Taiwan " in 2015. In these chronic kidney disease patients, diabetic kidney disease(DKD) accounts for a major part of this population. Prevention and treatment of diabetic kidney disease is an indispensable part of Taiwan. In the past few years, many studies have published grant advances in the medical treatment of DKD, including sodiumglucose cotransporter-2 inhibitors(SGLT2i) and glucagon-like peptide 1 agonists (GLP-1 agonist).

Successive reports are showing that the use of these drugs has a clear effect on the control of diabetes, cardiovascular disease, and DKD. Diabetes Association of the R.O.C. had published " 2019 Taiwan Clinical Practice Guideline for Diabetic Kidney Disease", based on the epidemiology, prevalence, definition, and risk factors of diabetic kidney disease. Diabetes Association has made an integrated overview, according to the evidence of clinical trials in the last few years. The guideline also integrated nutrition and daily activity. Besides, recent studies have also shown that DKD can also be affected by other specific diseases. Thus, the guideline also explored specific groups like individuals with hepatitis C, renal urinary tract disease, obesity, end-stage of renal disease, and older adult.

At present, there are more and more researches on DKD like DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) and FIDELIO-DKD (Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes). Diabetic Association expected to revise the latest DKD guidelines this year based on the latest level of evidence and immediate rolling updates. This section will share the main content of the upcoming changes.

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DIABETIC KIDNEY DISEASE AND ESRD IN TAIWAN SHANG-JYH HWANG, M.D. Nephrology Division, Department of Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan. Taiwan Society of Nephrology.

The persistent high incidence and prevalence of dialysis ESRD is still a big issue in Taiwan.

However, the trends of incidence and prevalence become flatten after age standardization, which indicates a significant contribution of elderly dialysis population to the growth of ESRD. Similar trend is also noted in both the incidence and prevalence in DM. Diabetes still has a 45-47% contribution to incident ESRD population in these years. Aged, diabetes, acute kidney injury, and/or AKI on CKD are the most common encountered situations in CKD care before entering dialysis, Diabetes with multisystemic comorbidities is the most difficult clinical situation to be cared, especially combined with cardiovascular comorbidity and complication.

Diabetes is known to be associated with CKD and CVD independently. It not only causes the morbidity and mortality of the affected persons, but also develops lots of complications in diabetic patients. Subsequently, the major target organ damages result in organ failure, especially in kidney and heart, and thus ESRD and EFrHF become major issue in clinical care. Dialysis diabetic patients even further develop multiple complications in various system, which constitute the major part of medical expenditures and burdens.

Taiwan has launched series of projects for prevention of DM, kidney diseases and care of DM/ CKD patients in the past 20 years, including Diabetes Integrated Care in 2000, Program, Pre-ESRD care project for stage 3b-5 patients in 2007 and Early CKD project for stage 1-3a in 2011. All projects provided patient education and multi-disciplinary care management, which were reimbursed by NHI. Recently, there is a project to include the CVD patients under planning. Definitely, a well collaboration of care among different specialists and professionals is the essential factor for successful care. With the discovery of ACEI/ARB and recent new DM treatment drugs of SGLT2 inhibitors. Effectiveness has been proved in many prestigious clinical trials. Their roles in control of sugar, prevention of early DKD, reduce incidence of HF, and improvement of long hard outcomes are confirmed.

We expect a new era of treatment not only in diabetes but also in kidney and heart field.

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NOVEL INSIGHTS INTO THE THERAPEUTIC POTENTIAL OF THERMOGENIC FAT YU-HUA TSENG, PH.D. Joslin Diabetes Center, Harvard Medical School, MA, USA

We are amid a global epidemic of obesity and metabolic syndrome. Crucial to these pathologies is adipose tissue. However, not all adipose tissue is linked to storing energy. Instead, there are functionally distinct types of adipose tissue. White adipose tissue is the primary site of triglyceride storehouse, whereas thermogenic fat, which consists of classical brown and inducible beige/brite adipocytes, concentrates on thermogenic energy expenditure. The identification of active brown adipose tissue (BAT) in adult human subjects over a decade ago has ignited interest in this thermogenic tissue as a potential target for developing anti-diabetic and anti-obesogenic therapies. The primary physiologic function of BAT is to convert nutrients into physical heat. A key pathway for generating heat in BAT is by uncoupling oxidative phosphorylation through uncoupling protein 1 (UCP1).

Numerous recent studies have shown that, in addition to its role as a thermogenic organ, BAT secretes several factors (i.e., the ‘batokines’) that regulate whole-body metabolism. In this talk, I will discuss our recent efforts in exploring new therapeutic pathways by harnessing the power of thermogenic fat and the impacts on energy metabolism.

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SD3-2

METAINFLAMMATION OF ADIPOCYTES AND BEYOND 1,2

W-S YANG, 1Y-T CHEN, 2F-R YANG, 3C-I HSIEH, 4H-C NIEN, 5T-W KAO, 1P-C CHOU, 2 Y-C CHI, 6P-J YANG 1

Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan. Departments of 2Internal Medicine, 4Family Medicine, and 6Surgery, National Taiwan University Hospital, Taiwan.

3 Departments of Internal Medicine, Chang Gung Memorial Hospital, Taiwan. 5Departments of Family Medicine, Tri-Service General Hospital, Taiwan.

OBJECTIVE To investigate the genetic factors related to metainflammation in adipocytes and their biological and clinical implications METHODS Reduction of adiponectin gene expression was adopted as a biomarker of insulin resistance in adipocytes. Metainflammation has been considered as an important factor for insulin resistance. We treated mouse 3T3-L1 adipocytes with IL-1β to mimic metainflammation in adipocytes.

The mRNA from 3T3-L1 cells treated with or without IL-1βwas sent for cDNA microarray study.

Genes with significant up or down-regulation were further investigated in human studies. We also studied relevant issues of MFLD and myosteatosis in humans or cells.

RESULTS We found that indeed adiponectin gene expression was reduced by IL-1β treatment.

Several genes from the microarray assays were chosen for human studies. We found that RNase-L, S14, and LBP were related to metabolic syndrome, MFLD or inflammation. LRG1 was demonstrated to inflammation and cardiovascular disorders. We also showed that increased adiposity may reduce muscle function at human and cellular level.

CONCLUSION This genomic approach is a sensible way to relate metainflammation of adipocytes to many aspects of human metabolic disorders and their compliations.

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Abstract SD3-3

THE ROLE OF METFORMIN AND ORGANIC CATION TRANSPORTER 2 IN MANAGEMENT OF RENAL CELL CARCINOMA 1

Y-F DU, 2C-Y HU, 3H-T WU, 1H-Y OU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 2Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.

OBJECTIVE This study explores the association the pathophysiological role of metformin and organic cation transporter 2 (OCT2) expression in management of renal cell carcinoma.

METHOD We used lentiviral vectors to overexpress OCT2 in 786-O RCC cells (786-O-OCT2).

The percentage of surviving cells were calculated after treatment with metformin, compared with control and cells lack of OCT2 expression (786-O). We also implanted 786-O cells or 786-O-OCT2 cells subcutaneously into the right flanks of two groups of mice. When tumors grow up to 50 mm3, we treated both groups of mice with metformin 50 mg/kg/day for 20 days. The volume of the tumors was calculated, and the weight of the excised tumor was measured after sacrificing the mice.

RESULT The cell viability of OCT2-overexpressed 786-O RCC cells treated with metformin was significantly decreased compared with cells without OCT2 expression. Under metformin treatment, the tumor size in OCT2-overexpressed 786-O xenograft is smaller than GFP-control.

CONCLUSION Metformin exerted better anti-cancer activity in OCT2-overexpressed RCC cells.

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SD4-1

UPDATE OF GENETIC, BASIC, AND TRANSLATIONAL RESEARCHES OF TYPE 2 DIABETES AND OBESITY YI-CHENG CHANG1,2,3 1

Division of Endocrinology and Metabolism, National Taiwan University Hospital Graduate Institute of Medical Genomics and Proteomics, National Taiwan University 3 Institute of Biomedical Sciences, Academia Sinica 2

Recent advance of genomics have shaped the genetic architecture of type 2 diabetes and obesity.

Most of the genes associated with type 2 diabetes are related to pancreatic beta-cell function and most genes associated with obesity is related to neuronal control and immune function. Recent advance in appetite control, thermogenesis control, gut microbiota, metabolomic signature, and the role of immune cells in metabolism will be presented. In addition, some promising preclinical anti-diabesity therapy will be introduced.

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Abstract SD4-2

LIFESTYLE AND MEDICAL INTERVENTION OF DIABESITY 1

K-C HUANG

1

Department of Family Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

Obesity is highly associated with type 2 diabetes mellitus (T2DM), therefore diabesity indicates the coexistence of diabetes and obesity. Adequate weight reduction can prevent T2DM incidence in high risk subjects and improve the blood glucose control among those with diabetsity. Lifestyle modification, restricted balanced diet and increased physical activity, remains as the mainstream in the management of diabesity. Anti-obesity medications may be considered if lifestyle modification does not work. In Taiwan, only Xenical and Saxenda are two available anti-obesity drugs. Furthermore, weight neutral or reducing anti-diabetic medications should be considered as the first line of blood glucose lowering drugs for patients with diabesity. Bariatric surgery is indicated if the patient fail after lifestyle modification and pharmacotherapy. In the future, long acting or oral form GLP-1 agonists or other gut hormones will be on the market to assist patients with diabesity to control their body weight as well as blood glucose.

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SURGICAL INTERVENTION FOR DIABESITY: A STORY OF 5% WEI-JEI LEE, MD&PHD Professor of Surg, Min-Sheng General Hospital, National Taiwan University, Taiwan

Diabesity, obesity and associated type 2 diabetes mellitus (T2DM), is becoming a serious medical issue worldwide. Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients. Today, bariatric surgery is played as metabolic surgery for the treatment of diabesity. Because Asian people are more sensitive to diabesity and tend to have an earlier onset T2D than Caucasian, Asian surgeons had more experience in using metabolic surgery to treat diabesity. The status and future of metabolic surgery for Asia diabesity depends on the 5% of medical statistics. 1) 5% of Taiwan National Health Budget: According to the report of Taiwan National Health Insurance Department, they spend 10% (55 billion Taiwan dollars) of their annual budget for hemodialysis of patients with end stage renal disease (ESRD). Half of the cause of ESRD in Taiwan is due to T2DM. Among them, most of them had their T2DM develop before age 40, so called young onset disease. Metabolic surgery plays a very important role in this group of patients and might prevent them from going into ESRD, and markedly reduce the dollars in treating them.

2) 5% of the whole T2D population in Taiwan: According to the data of Taiwan Diabesity

Study (TDS), 5% of the whole T2DM population in Taiwan are possible candidate for metabolic surgery. However, metabolic surgery provided a better glycemic control, improving peripheral neuropathy and increasing renal function than patients received only medical treatment. Therefore, patients with high risk of T2DM complication and high response rate to metabolic surgery, such as young onset diabesity, should be the patients of priority to receive metabolic surgery.

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THE PARADIGM OF CGM AND CSII BASED ON ADVANCED A.I. TECHNOLOGY FOR THE ARTIFICIAL PANCREAS ROBERT A. VIGERSKY, M.D. Chief Medical Officer, Medtronic Diabetes and Professor of Medicine of the Uniformed Services University of the Health Sciences

There have been major advances in automated insulin deliver systems over the past 10 years.

The most recent iterations are the Medtronic MiniMedTM 780G and the Tandem Control-IQ which provide automated basal insulin delivery and automated correction boluses for persons with type 1 diabetes. However, these systems remain “hybrid” closed loop (HCL) systems because of the need for persons with diabetes (PWD) to interact with the system for the multiple insulin-dosing decisions surrounding their meals, exercise and other predictable activities. Thus, HCL’s fall short of being true artificial pancreas systems (APS). To become a true APS, artificial intelligence (AI) and machine learning (ML) must be incorporated into current algorithms to reduce or eliminate the need to rely on accurate carbohydrate counting and appropriately timed insulin administration. Using geolocation data from a smartphone, ML can assist an APS by predicting the content of an upcoming meal based on past behavior and help safely initiate the appropriate amount of insulin in advance of the meal.

The amount of the insulin dose can be confirmed by a smart watch that contains an AI-derived hand gesture algorithm thereby informing the APS algorithm about when a meal is initiated, how long the meal lasts, and the likely quantity of the food being eaten. Accelerometers and heart rate monitors can identify the amount and intensity of exercise to further inform the system about the appropriate amount of insulin to be delivered. Integrating these data with glucose trends permits more timely and precise insulin delivery. By iteratively updating an automated insulin delivery algorithm, glycemic control can not only be maximized in a truly personalized way that few HCPs or PWD could otherwise achieve.

AI- and ML-driven algorithms are putting us on the cusp a fully closed-loop artificial pancreas.

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SD5-2

THE ADVANCE OF A.I. FROM RETINA TO WHOLE BODY IN FUTURE HEALTH INDUSTRY YIH-SHIOU HWANG, MD, PHD Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou and Taipei.

Background: Retinal imaging has been applied for detecting eye diseases and cardiovascular risks using deep learning–based methods. However, a deep learning–based method using retinal images for detecting other systemic diseases has not yet been well studied.

Aim: Our works aimed to develop and evaluate a deep learning model for detecting other systemic disease using retinal fundus images.

Methods: This retrospective study enrolled patients who underwent renal function tests with color fundus images captured at any time between January 1, 2001, and August 31, 2019. A deep learning model was constructed. Model performance was evaluated with respect to the receiver operating characteristic curve and area under the curve (AUC).

Conclusions: The deep learning model can be used to enable the detection of some systemic diseases.

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POST -PANDEMIC ERA-DIGITALIZATION FLIPS HEALTH EDUCATION OF DIABETES SHI-YU CHEN Tri-Service General Hospital, Taipei, Taiwan RN, CDE

In the early 1980, continuous blood glucose monitor and insulin pump completely changed the paradigm of diabetes self-management. Diabetes management emphasis on preventive, predictive, personalized and involvement of patient and their families’ participatory which is the core of treatment decision-making (4P medical care). With high-tech wearable products providing instant and accurate blood glucose readings, the trends of blood glucose fluctuation combined with the use of precise model to calculate the demand for insulin dose and basal insulin delivery in a segmented manner. In the literature review, the use of high-tech products such as continuous blood glucose monitors are relatively good in terms of physical and psychological risks to the future. Somehow, there is still people quit using it after trying. At present, most of the research on the use of these high-tech products including continuous blood glucose monitors are for system development, refinement, and scientific proof of accuracy, safety and effectiveness. Fewer studies considering patients' thoughts or expected responses to these high-tech systems, and even underestimate the central role played by psychosocial factors in diabetes management. The purpose of the course is to further investigate the post-pandemic era-digitalization flips health education of diabetes, the patient adoption, utilization and continuance to use the complex process of successful implementation of continuous blood glucose monitoring, and the insight into the human factors of high-tech management of diabetes, reminding the basic literacy and ability of diabetes professionals to improve.

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SD6-1

THE PERSPECTIVE OF ISLET TRANSPLANTATION ON THE TREATMENT OF TYPE 1 DIABETES J-H JUANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taiwan, R.O.C.

For patients with type 1 diabetes, isolation of islets from a deceased donor pancreas with intrahepatic transplantation of allogeneic islets can ameliorate problematic hypoglycemia, stabilize glycemic lability, and maintain on-target glycemic control, consequently with improved quality of life. Recent progress in techniques for islet isolation, islet culture, and peritransplant management of the islet transplant recipient has resulted in substantial improvements in metabolic and safety outcomes for patients. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction (IBMIR), potent host auto- and alloimmune responses, and β cell toxicity from immunosuppressive agents. Protective strategies are being tested to circumvent several of these events including exploration of alternative transplantation sites, alternative islet cell sources, co-transplantation with mesenchymal stem cells or exploration of novel immune protective agents.

Extrahepatic sites have included the renal subcapsular space, striated muscle, pancreas, omentum, eye chamber, and testis. Thus far, all attempts have remained elusive to be superior to the intraportal site.

Current work has focused on two potential sources for islets, namely xenogeneic islets and stem cell-derived islets. Pig islets provide an attractive source. The opportunity to genetically manipulate the pig genome initially with knock-out constructions for decay accelerating factor, and Gal epitopes, and more recently the potential to humanize the pig genome using CRISP-Cas9 technologies, offers great potential. Human embryonic stem cell (hESC) and induced pluripotent stem cells (iPSC) are being intensively investigated for their ability to differentiate into insulin producing cells. Two clinical trials utilize hESC-derived pancreatic endoderm cells contained in a macroencapsulation device. Ongoing research is determining the utility of generating patients’ own β cells with the iPS approach.

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ENGINEERING OF MICROCAPSULES FOR OVERCOMING BARRIERS FOR ISLET TRANSPLANTATION. KUN-HO YOON M.D. Professor, Department of Endocrinology & Metabolism, The Catholic university Medical college, Seoul,

Korea One of the strategies for overcoming lifelong immunosuppression after islet transplantation is the incorporation of encapsulation technology, which can provide a physical immune barrier by keeping out high molecular weight immune system components, while still allowing low molecular weight oxygen, insulin and nutrients to pass through. Encapsulated islet transplantation approaches that have been studied so far include macroencapsulation, microencapsulation, conformal coating and nanoencapsulation. Among these methods, microencapsulation technology already translated into clinical practice. However, we still need to overcome the barriers such as incomplete function as an immune barrier, fibrosis on the surface and hypoxic damage on the encapsulated islets. To overcome these problems, our group has been developed surface coating capsules with various immunosuppresants to suppressed surface fibrosis. We also try to incorporate the perfluorodecalin to improve oxygen delivery to encapsulated islets and observed reduction of islet death in hypoxic environments in vivo and in vitro. With immune isolation with microencapsulation of the islets, we could incorporate the wide and genetically modified pig islets into the microcapsules and transplanted in small and large animals including dogs and monkeys. In this talk, I will present our recent results of pig islet transplantation on monkeys.

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CURRENT PROGRESS IN STEM CELL THERAPY FOR DIABETES MELLITUS 1

CHIA-NING SHEN, PH.D.; 1EDWARD PO-FAN CHU, PH.D.; 2CHIA-HUNG LIN, M.D., PH.D.; 1I-FEN CHENG, PH.D; 1CANDY HSIN-HUA CHO, PH.D.; TZU-CHIEN KUO, M.SC.; 1 FANG-PEI CHANG, PH.D.; 3I-TE LEE, M.D., PH.D.; 3WAYNE H-H SHEU, M.D., PH.D. 1

Genomics Research Center, Academia Sinica, 115 Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Islet transplantation is a potential way to sustainably control blood sugar levels of patients with Type 1 diabetes mellitus (T1DM). However, the shortage of donor islets and poor islet graft survival limit the potential use of islet transplantation to treat T1DM patients. Recent research progress had demonstrated that stem cells hold potentials to be used for the treatment of DM patients. For example, both induced pluripotent stem cells and mesenchymal stem cells have been used to generate insulinproducing cells for the purpose of treating T1DM. In addition, we recently demonstrate beta-like cells derived from hepatocyte reprogramming could not only ameliorate autoimmune diabetes but can also significantly suppress autoreactive T cells. The findings raise the possibility of developing cell therapeutic strategies for autoimmune diabetes utilizing reprogramming approaches. Indeed, deficits of β-cell functional mass are now recognized as hallmarks for both T2DM as well as type 1 diabetes. Therefore, it is important to preserve β-cell functional mass in the management of diabetes.

Development of strategies that can either induce β-cell regeneration or increase β-cell functional mass would be important for both types of diabetes. Induced pluripotent stem cells (iPSCs) generated from patients’ cells have been utilized for studying disease mechanisms and validating drug response. To derive diabetic patient-specific induced pluripotent stem cells (iPSCs) for purpose of modeling diseases causes and for evaluating therapeutic efficacy, we have then established methodologies to generate iPSCs from PBMCs of patients with T1DM and T2DM. To identify novel insulin secretagogues and/ or discover novel therapeutic target that can promote β-cell differentiation, we developed a reliable method that allows high-throughput identification of compounds that would enable to enhance betacell differentiation based on combining a calcium flux indicator together with insulin-luciferase fusion protein. We used the platform to assess a number of drugs that target various pathways to enhance β-cell differentiation. For example, we discovered that the use of IBMX as agent to increases Ca2+ influx through voltage-dependent Ca2+ channels could largely enhance the efficiency of iPSCs to differentiate into beta-cells. Importantly, we also utilized iPSCs to dissect mechanism involved in development of diabetic retinopathy. Based on establishment of protocols to differentiate of T2DM patients’ iPSCs into retinal pigment epithelial (RPE) cells and endothelial cells, we determined the 64

Abstract role of miRNAs in pathogenesis of diabetic retinopathy and identified RPE cells derived from iPSCs of DM-PDR patients had lower levels of phagocytic activity in high glucose condition. The findings possibly unravel the clues to the risk of DM patients to develop diabetic retinopathy. Hopefully, our findings would lead to developing novel cellular therapeutics for DM patients soon.

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CAN WE RELY ON NUTRITION SCIENCE FOR DIABETES AND CARDIOVASCULAR DISEASE? PEY RONG CHEN Dietetic Department of National Taiwan University Hospital, Taiwan, R.O.C.

Due to factors such as the collection method of dietary intake, experimental design, selection and number of subjects on nutrition research, the degree of reliability of the research results will vary.

Exploring the relationship between diet and disease, including cohort or retrospective studies. Such studies involve the completeness and accuracy of dietary intake, the length of collection time, the frequency of collection during the research period, consideration of seasonal factors, etc.; collection of dietary information Tools also have very important influencing factors, such as food weighing, food records, and dietary recall; subjects self-reported or interviews by trained interviewers, etc. The collection of dietary data is the most challenging part of nutrition research. For the complex content of human diets and time-consuming and labor-intensive issues, various dietary questionnaires have been developed to study the relationship between dietary habits and diseases, such as the Mediterranean diet.

Nutritional intervention research, the outcome is easily affected by whether other diet component is properly controlled, and the research results are also easily questioned. The collection of outcome parameters and the verification of results are also a university question. This also includes that with the advancement of medical research, the pathogenic mechanism and risk factors also keep pace with the times. For example, the risk of cardiovascular disease in the past has been based on total cholesterol, then, shift to LDL, LDL/HDL, and inflammatory markers, but now it may depends on the intestinal microbiota.

Nutrition-related research on DM or CVD should focus on individualized considerations when applied to the clinical fields; if the multiple situation of the case is not carefully evaluated, such as medication, exercise, work and life style, nutrigenomics or metabolomics, the results will be limited.

The nutritional treatment of chronic diseases should be refined towards a new model as precision nutrition.

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INTERMITTENT FASTING IN PATIENTS WITH DIABETES MELLITUS W-L CHUANG Department of Endocrinology, Lukang Christian Hospital, Taiwan, R.O.C.

Although more and more drugs developed to help patient to control blood glucose, nutrition therapy is still a popular method and issue in the News, internet discussion, and Youtube videos.

Intermittent fasting is one of recent popular diet approaches for treating or preventing diabetes mellitus. But is intermittent fasting effective for treating or preventing diabetes mellitus and is it safe ?

Is there sufficient evidence to support this diet approach?

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SD7-3

PARADIGM SHIFTS IN NUTRITION THERAPY FOR TYPE 2 DIABETES 楊宜瑱 中山附設醫院 內分泌新陳代謝科

Nutrition therapy is the initial treatment for diabetes. However, recommended nutrition therapies tend to be largely based on consensus among experts rather than on scientific evidence. The principles of nutrition therapy have been inherited from the pioneers of diabetes research, but they lack current updates reflecting advances in nutrition science. Nutrition science is a constantly advancing field, just like other fields of science, and the accepted knowledge base changes over time. This session will review the evolution history of nutrition therapy for diabetes and then the future directions will be discussed. .

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ACCUMULATED CV DATA FROM SGLT2I OUTCOME TRIALS SHIH-HSIEN SUNG Attending Physician, Division of Cardiology, Taipei Veterans General Hospital, Taiwan Associate Professor, National Yang-Ming University

Cardiovascular (CV) diseases are the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (DM). Therefore, there has been an increasing endorsement from diabetic associations across the globe for the use of anti-diabetic drugs, which not only provide not only glycemic control but also have cardioprotective effects. Recent clinical trials have shown that sodium glucose co-transport 2 inhibitors (SGLT2i) have dramatic beneficial cardiovascular outcomes, independent of glycemic control. These include a reduced incidence of cardiovascular death, heart failure hospitalization, deterioration of renal function in people with and without diabetes, and those with and without prevalent heart failure or chronic kidney disease. The actual mechanisms responsible for these beneficial effects are not completely clear. Several potential mechanisms have been proposed to explain the cardioprotective and renal protective effects of SGLT2 inhibition, which include diuresis/natriuresis, blood pressure reduction, erythropoiesis, resume of tubuloglomerular feedback, improved cardiac energy metabolism, inflammation reduction, inhibition of the sympathetic nervous system, prevention of adverse cardiac remodeling, prevention of ischemia/reperfusion injury, inhibition of the Na+/H+-exchanger, inhibition of SGLT1, reduction in hyperuricemia, increasing autophagy and lysosomal degradation, decreasing epicardial fat mass, increasing erythropoietin levels, increasing circulating pro-vascular progenitor cells, decreasing oxidative stress, and improving vascular function.

Although the published trials have enrolled type 2 DM patients with varied baseline characteristics in terms of age, BMI, sex, glomerular filtration rate, or history of existing renal diseases, the SGLT2i were found generally to be beneficial by significantly reducing all-cause mortality, CV death, and risk of major CV events. Therefore, the clinical application of SGLT2i might be critical for specific populations and specific purposes. We have to understand the subtle differences between the SGLT2i to maximize the clinical benefits to our patients.

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ACCUMULATED CARDIOVASCULAR DATA FROM GLP-1 RECEPTOR AGONIST CARDIOVASCULAR SAFETY TRIALS 1

H-Y LI,

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital.

GLP-1 receptor agonists are incretin mimetic drugs that act on the GLP-1 receptor. It can stimulate pancreatic beta-cells to secrete insulin, inhibit pancreatic alpha cells for glucagon secretion, decrease appetite, and enhance satiety. Therefore, it is effective in lowering hyperglycemia and reducing body weight. In recent years, many cardiovascular safety studies have been published, such as The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial for liraglutide, The Harmony Outcome trial for albiglutide, The Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial for dulaglutide, The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial for lixisenatide, The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial for one-weekly exenatide, The Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6) for semaglutide, and the Peptide Innovation for Early Diabetes Treatment (PIONEER) 6 for oral semaglutide. Among these trials, liraglutide, albiglutide, dulaglutide, and semaglutide have been shown to reduce cardiovascular events in subjects with type 2 diabetes significantly. In this talk, data from these cardiovascular safety trials will be reviewed.

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OPTIMIZING DELIVERY OF GUIDELINE-BASED CARE IN PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE JENNIFER B. GREEN, MD Department of Medicine, Division of Endocrinology and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA

Cardiovascular and kidney disease are common causes of premature death and disability for patients with type 2 diabetes mellitus (T2DM). Many agents in the SGLT2 inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP-1RA) classes have demonstrated cardiovascular risk reduction and kidney function benefits which appear additive to traditional risk reduction strategies and also largely independent of the medications’ glucose lowering effects. Care guidelines from cardiovascular, kidney, and diabetes care societies have changed dramatically in response to this information; however, these beneficial medications are significantly underutilized in patients at high risk for adverse cardio-renal complications. There are numerous barriers to the adoption of evidence‐based therapies, including patient, clinician, and system‐level obstacles. Lack of clinician familiarity, inconsistencies in society guidelines, clinical inertia, cost considerations, and fragmentation of care all contribute to this evidence‐to‐practice gap. Primary care physicians, cardiologists and nephrologists will need to play key roles in the implementation of effective care strategies; fortunately, highly practical care pathways have been developed to facilitate appropriate use of SGLT2i and GLP-1RA medications in those clinical settings.

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RISK FACTOR CONTROL IN DIABETIC PATIENTS WITH CARDIOVASCULAR AND KIDNEY DISEASES - TAIWAN DIABETES REGISTRY STUDY 1

S-Y LIN, 2WAYNE H-H SHEU

on behalf of Taiwan Diabetes Registry Study

Objectives: We aimed to examine the achievement of guideline-recommended targets and medication use in diabetic patients enrolled from October 2015 to August 2018 in Taiwan Diabetes Registry.

Results: Among all 1201 participants (52.8% males), they had a mean age 65.7 ±11.7 years, and disease duration 15.2 ±7.7 years. The prevalence of cardiovascular diseases (CVD), including coronary artery disease, stroke, and peripheral arterial disease, was 11.5%, and 48.7 % for diabetic kidney disease (DKD), as defined by estimated glomerular filtration rates (eGFR) <60 ml/min/1.73 m2 or spot urine albumin to creatinine ratio (UACR) ≥30 mg/g. Among the patients with CVD, the control rates for glycated hemoglobin (HbA1c)<7% were 26.1%, 63.8% for blood pressure (BP)<140/90mmHg (35.5% for BP <130/80mmHg), and 73.2% for TC <160 mg/dL or LDL-C <100 mg/dL. In participants with DKD, the control rates were 31.2% for HbA1c <7%, 34.6% (BP <140/90mmHg), 62.6% (<130/80mmHg), and TC <160 mg/dL or LDL-C <100 mg/dL was 69.7%. In participants with CVD, all three risk factor control rates were 7.3% (BP <130/80 mmHg), and 13.8% (BP <140/90 mmHg), and in those with DKD, the control rates of all three risk factors were 10.3 % (BP <130/80 mmHg), and 16.3% (BP <140/90 mmHg). For those with CVD, the use of statin was 48.6%, and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) were prescribed in 43.9 % of patients with DKD. Conclusion: In the TDR, suboptimal proportions of patients achieved composite targets. Care quality of diabetic patients remained to be improved.

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FACTORS ASSOCIATED WITH QUALITY OF LIFE AMONG PATIENTS WITH DIABETES: THE TAIWAN DIABETES REGISTRY STUDY 1

YI-JING SHEEN, 1SHIH-YI LIN, 2WAYNE H-H SHEU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.

OBJECTIVE A higher risk of depression and anxiety have been observed among T2DM patients. Disease severity, physical condition, economic factors, medication use, and psychosocial well-being could be factors that play a role in the complex interaction between T2DM and quality of life. Despite a growing appreciation for the quality of life and psychosocial well-being, there are limited studies exploring these complex issues among patients with diabetes in Taiwan. In the present study, we aimed to investigate factors associated with quality of life and measures depression in patients with diabetes using data from the Taiwan Diabetes Registry Study.

METHODS Study source: Taiwanese Diabetes Registry (TDR), a web-based platform, was launched in 2015. A total of 14 medical centers, 44 regional, local hospitals, and 37 general practice clinics participated in the TDR. Data were collected from 2015 Oct to 2018 Aug. The study subjects comprise groups including those who ever participated in “quality control study by Taiwan Association of Diabetes Educators” in 2006 and 2011 (group 1); newly diagnosed type 2 diabetes within 6 months (group 2). Outcome measurement: Quality of life was evaluated by the EuroQol- 5 Dimension (EQ5D), patients will be divided into two groups EQ-5D <1 vs. EQ-5D =1. The severity of depression was evaluated by the PHQ-9 (Patient Health Questionnaire: a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders).

RESULTS Proportions of patients with poor quality of life evaluated by EQ-5D were 38% and 31% in group 1 and group 2, respectively. Multiple logistic regression analyses revealed independent risk factors of poor quality of life of group 1 patients were: aged, female, abnormal PHQ-9; among patients in group 2, independent risk factors were aged, female, abnormal PHQ-9, and those who under insulin treatment for glycemic control. The proportions of depression detected by PHQ-9 rates were 23% and 20% among patients in group 1 and group 2, respectively. Multiple logistic regression analyses revealed that in group 1, independent risk factors of depression were: young, female, higher fasting glucose value; independent risk factors of group 2 were young, female, eGFR< 30, and ever experienced hypoglycemia events. In addition, there was a significant correlation between EQ-5D and PHQ-9 among both patients in group 1 and group 2 (AUC of ROC were 0.72 and 0.71 in group 1 and group 2, respectively).

CONCLUSIONS Type 2 diabetic patients with depressive situations also had a lower diabetes73

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specific quality of life. Aged patients were associated with poor quality of life; however, young patients have a higher depression risk. Insulin injection is an independent risk factor of poor quality of life among newly diagnosed type 2 diabetes, however, it seems didn’t affect patients with a long duration of diabetes significantly. Monitoring for depression is needed while patients with poor quality of life among patients with type 2 diabetes. Awareness of depression in young female patients is also important.

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TREATMENT GOAL ACHIEVEMENT AND ASSOCIATION WITH 10YEAR AND 30-YEAR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISKS IN PATIENTS WITH TYPE 1 DIABETES MELLITUS IN TAIWAN 1

HSUAN-WEI LIN, 2TSUNG-HUI WU, 2CHII-MIN HWU

1

Department of Internal Medicine, Taipei Veterans General Hospital Hsinchu Branch, Hsinchu County, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

OBJECTIVE This study evaluated the status of attainment of treatment goals in patients with type 1 diabetes mellitus (T1D) in Taiwan and its association with 10-year and longer-term (30-year) risks for atherosclerotic cardiovascular disease (ASCVD).

METHODS Between 1 October 2015 and 31 August 2018, 1083 patients with T1D enrolled in the Taiwan Diabetes Registry were analyzed. The 10-year and 30-year ASCVD risk estimates were calculated respectively for patients aged 40-79 years with Pooled Cohort Equations and for those aged 20-59 years with the prediction algorithms based on the Framingham Offspring cohort. Multiple linear regression was used to examine the associations between ASCVD risk estimates and potential risk factors that were not included in risk calculations.

RESULTS The estimated 10-year ASCVD risk decreased with greater achievement of treatment goals (from none to all three goals: geometric mean [95% confidence interval] 4.6% [3.19-6.64], 3.39% [2.76-4.16], 2.09% [1.67-2.61], and 1.68% [1.11-2.55]). Similar declines in estimated 30year ASCVD risks with goal attainment were found. In addition, the waist circumference showed a significant association with 10-year ASCVD risk independently of other potential risk factors in multivariable regression analysis (β coefficient 0.24; P=0.002).

CONCLUSION Attainment of two or more treatment goals is associated with lower shortterm and longer-term estimated ASCVD risks in patients with T1D compared to those with lesser goal achievement.

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SD9-4

THE EPIDEMIOLOGIC INVESTIGATION AND RISK FACTOR ANALYSIS OF DIABETIC KIDNEY DISEASE AMONG TYPE 1 DIABETES PATIENTS IN TAIWAN 1

TJ CHANG, 2YB LIN, 3LM CHUANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C

OBJECTIVE To identify risk factors of diabetic kidney disease (DKD) in type 1 DM patients.

METHODS We conducted a cross-sectional study by obtaining questionnaires from type 1 DM patients who has registered in Taiwan Diabetes Registry Study from 2015 to 2018. The definition of DKD is based on clinical guideline for diabetic management in chronic kidney disease (KDIGO 2020).

Student’s t-test and Chi-square test were used to compare the difference of various parameters between patients with and without DKD. Pearson correlation was used to identify the association of various continuous variables with eGFR. Logistic regression was applied to identify DKD risk factors, and multivariable linear regression was conducted to identify the factors associated with eGFR. RESULTS A total of 1086 type 1 DM patients were enrolled in our study, and 459 (42.3%) were defined as DKD, with median age 32 years (interquartile range, 22 to 41 y/o) and female predominant (57.3%). The type 1 DM patients with DKD had higher BMI, higher SBP & DBP, higher waist and HbA1C, longer disease duration, lower education level, higher percentage with family history of DM & hypertension, higher percentage with diabetes retinopathy, inpatient history within 3 years, and higher percentage of using ACEI/ARB. According to logistic regression model, lower education level, family history of DM, higher DBP, diabetes retinopathy and use of ARB were independent risk factors associated with DKD. According to multiple regression model, age, sex, use of ARB, education level, HbA1c, diabetes retinopathy, inpatient history within 3 years, and SBP were independently associated with eGFR. We also found only 3.1% and 10.3% T1DM patients with DKD receiving ACEI or ARB, respectively.

CONCLUSION In the Taiwan type 1 diabetes cohort, the presence of diabetic retinopathy, lower level of education and higher blood pressure were independently associated to with both DKD and lower eGFR. The administration of ACEI or ARB will be strongly recommended in patients with DKD to fulfill the standard of care in DKD patients.

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NEW DEVELOPMENTS IN REPRODUCTION AND GENETICS MING CHEN, MD, PHD Departments of Research, Genomic Medicine, and Ob/Gyn, Changhua Christian Hospital, Taiwan

In the past decade, the clinical practice as well as research in the field of reproductive genetics has evolved rapidly, from the classic cytogenetics and Sanger-sequencing based technologies that had prevailed since 1980 to recent advances; prenatal diagnostic techniques have become less invasive, and the adoption of preimplantation genetic testing (PGT) has also improved, largely due to the advances of newer instrumentation and technology such as multiplex fluorescence in situ hybridization (mFISH), digital PCR, microfluidics, chromosome microarray, next generation sequencing (NGS), and the optimization of bioinformatics. Reproductive genetics has become an important pillar in this NGS-dominant era. However, on many occasions such paradigm shifts in the practice of reproductive genetics have been pushed forward initially by the demand of patients, which is often before reliable randomized controlled trials are available. The ability to sequence the entire fetal genome noninvasively from the maternal blood in a timely, efficient, and affordable way has long been sought and is considered the “Holy Grail” of prenatal diagnosis.

Meanwhile, the attitudes of clinical practitioners are also evolving. It is now considered ethical by PGT-M (formerly known as preimplantation genetic diagnosis; “M” denotes monogenic diseases) to avoid the transmission of the monogenic inherited disorders from generation to generation; for PGT-A (formerly known as preimplantation genetic screening; “A” denotes aneuploidy) practitioners have divided opinions, wavering between full endorsement as a routine practice and total refusal. The rapid evolution of reproductive genetics also changed the practice and even training of subspecialties such as maternal fetal medicine (MFM) and in vitro fertilization (IVF) within the scope of obstetrics and gynecology. (Quoted from the Call for Papers of the Research Topic: “Emerging New Tests and Their Impact Upon the Practice of Reproductive Genetics”, published by Frontiers in Genetics, edited by Ming Chen, Kwok-Yin Leung, Antoni Borrell, Mark I Evans).

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SE1-2

UPDATE ON PREMATURE OVARIAN INSUFFICIENCY JENG-FU KUO 彰化基督教醫院內分泌新陳代謝科主治醫師

Premature ovarian insufficiency (POI), cessation of menstruation before the age of 40, is a condition of hypergonadotropic hypogonadism with early exhaustion of ovarian follicles.

These patients undergo normal puberty and a variable period of cyclic menstruation followed by oligomenorrhea or amenorrhea with hot flashes and urogenital atrophy.

The cause of POI is largely unknown. POI usually manifests as an isolated autoimmune disease, but can be related to hypothyroidism, diabetes mellitus, hypoadrenalism, hypoparathyroidism, autoimmune polyendocrine syndrome, or systemic lupus erythematosus. Hypothyroidism, adrenal insufficiency and diabetes mellitus are the most common endocrine disorders associated with POI. Two genetic syndromes associated with POI are gonadal dysgenesis with primarily mosaic X-chromosome defects and FMR1 (fragile X mental retardation 1) gene permutation. A chromosomal analysis is recommended for the POI patients younger than 30 years of age because of the increased risk of a gonadal tumor correlated with the presence of a Y chromosome. These malignant tumors originate from germ cells and include gonadoblastomas, dysgerminomas, yolk sac tumors, and choriocarcinoma.

Periodic endocrine testing for glucose intolerance, adrenal or parathyroid function, and autoimmune disease (e.g., SLE) should be considered according to clinical presentation. Treatment of POI should be targeted toward its specific cause. In most cases, a specific cause cannot be identified if karyotypic abnormalities are not present. Early menopause has been associated with increased cardiovascular mortality and stroke, bone fracture, colorectal cancer risk and lower overall quality of life. Hormone therapy, which uses combined estrogen and progestin or low-dose oral contraception, is central to managing these women.

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THE NEW ERA IN REPRODUCTIVE MEDICINE HUANG, SHANG-YU, M.D. Attending Physician, Chang Gung Memorial Hospital, Linkou Branch Assistant Professor, Chang Gung University

The number of couples seeking IVF treatment has increased significantly. According to statistics from the National Health Administration in 2018, the number of IVF treatment cycles in Taiwan has reached 39,840 cycles per year, which has almost doubled compared to the 17,393 cycles in 2013.

At the same time, more than one-third of the treatment cycle is for women over 40 years old. The difficulty that elderly women face in receiving IVF treatment is much higher than that of young people.

With an average pregnancy rate of only 21%, how to help elderly women get pregnant smoothly through artificial reproductive technology is a topic that needs to be dealt urgently in contemporary times. In the process of IVF treatment, it is often necessary to inject a large number of gonadotropins for good ovulation stimulation. However, it can also cause medical complications such as ovarian hyperstimulation. A large number of injections will also increase the patient's physical burden.

Therefore, the treatment of IVF has also tended to be customized in recent years. By predicting the patient's ovarian response, appropriate doses of injections are given to achieve the most appropriate treatment, which avoids over-stimulation and makes the overall treatment experience much friendly.

In addition, we also began to explore the reasons for repeated implantation failures which including immune imbalance, endocrine system imbalance, shifting of implantation windows, and deficit in human microbiota. The advancement of germ cell freezing technology has also allowed cancer patients to preserve their fertility. The freezing technology also allows women who postpone her marriage or women with early ovarian aging tendency to preserve fertility. In this talk, we will introduce new developments and new concepts in the field of artificial reproductive medicine. We hope that more professionals in related fields can contribute their efforts in the field of artificial reproductive medicine and unlock more unknown answers.

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CLINICAL IMPLICATION OF RADIOFREQUENCY ABLATION IN LOCALLY RECURRENT THYROID CANCER WEI-CHE LIN, MD, PHD Department of Radiology, Kaohsiung Chang Gung Memorial Hospital. Taiwan

PTC is the most common subtype of thyroid cancer. However, postoperative recurrence occurs in up to 20% and 59% of patients with low- and high-risk papillary thyroid cancer, respectively.

Reoperation followed by radioactive iodine therapy and thyroid hormone therapy are the gold standard treatments for recurrence. However, reoperation can be difficult to perform because of distortion of the normal tissue planes and severe fibrosis caused by scar tissue formation in the surgical bed, which leads to a high risk of complications. RFA is recently reported on the possibility as nonsurgical therapeutic options for locoregional recurrent control even for tumors invading the airway in the longer-term period. In this talk, we will review the current evidence of RFA in cancer locoregional control, technique apply during the procedure and preliminary treatment result in KCGMH.

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NOVEL TARGETED THERAPIES FOR THE TREATMENT OF ADAVNCED THYROID CANCERS DHY SHEN, YF CHEN, Y LEE, CH KAO Department of Nuclear Medicine & Multi-disciplinary team of thyroid cancer management, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.

Advanced thyroid cancers such as radioiodine-refractory thyroid cancer (RR-DTC) and anaplastic thyroid cancer (ATC) usually lose the capacity of iodide uptake due to dysfunction of sodium iodide symporter (NIS). Genetic alterations driven mitogen-activated protein kinase (MAPK) pathway is recognized as the key event lead to oncogenesis as well as NIS dysfunction, thus leading to RAIrefractoriness of advanced thyroid cancers as well as aggressiveness of such tumors. Since a couple of years ago, two multi-tyrosine kinase inhibitors (i.e. sorafenib and lenvatinib), mainly through anti-VEGF activity, have been approved as systemic therapies of RR-DTC. Through recent studies, some more specific mutated gene-directed targeted therapies are recommended for advanced thyroid cancers. For example, inhibitors for neurotrophic receptor kinase (NTRK) fusion (e.g. larotrectinib and entrectinib) are suggested for advanced thyroid cancers harboring NTRK fusion. Similarly, RET and bRAF inhibition is suggested for advanced thyroid cancers with RET fusion-positive and mutated bRAF, respectively. For the later setting, bRAF inhibitors can be used in conjunction with MEK inhibitors in RR-DTC reverse RAI-refractoriness, i.e. serving as “re-differentiation” therapy, by which NIS function can be restored in order to render RAI treatment effective to achieve tumoricidal effects.

In very recently, the use of larotrectinib, a NTRK fusion inhibitor has also been reported to enhance RAI avidity of RR-DTC. Whether combination of these mutated gene-directed target therapies and RAI treatment can augment RAI effectiveness warrants for further clinical investigation.

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NAVIGATION ASSISTED ENDOSCOPIC ORBITAL DECOMPRESSION FOR THYROID ORBITOPATHY CHENG-HSIEN CHANG Department of Ophthalmology, Kaohsiung Medical University, Kaohsiung, Taiwan

OBJECTIVE Surgical decompression of the orbit is a recognized management of thyroid orbitopathy (TO) for severe proptosis, optic neuropathy not responding to medical management, uncontrollable raised IOP, or aesthetic restoration. Endoscopic decompression of thyroid orbitopathy assisted with navigation image guide system is a relative safe when compared to traditional orbital decompression.

MATERIALS AND METHODS Patients with vision loss due to orbital compression by enlargement of extraocular muscles were initially treated with pulse therapy with methylprednisolone.

Those patients who responded poorly to the medical treatment were immediately advised for orbital decompression. Our procedure is decompression of medial wall using transnasal endoscopic approach assisted with navigation system. Lamina papyracea was removed as close as possible to the orbital apex, aiming mainly on salvation of compromised optic nerve.

RESULTS Reduction of proptosis was from 2 to 3 mm. No complications were encountered in our procedures. Patients have no new onset postoperative diplopia. Stereotactic setup added less than 10 min to preparation time. Patients with newly onset of visual loss had a better recovery than those with long-term visual loss. Postoperative recovery is quick and smooth with short period of admission.

Patients are routinely discharged one day after the surgery.

CONCLUSIONS Navigation assisted endoscopic decompression of orbital medial orbital wall is an effective and safe procedure to save visual compromise.

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STATISTICAL CHALLENGES OF PRECISION MEDICINE: INTEGRATIVE ANALYSIS OF LONGITUDINAL HEALTH RECORDS DATA S-H CHANG Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan, R.O.C.

OBJECTIVE The analysis of longitudinal cohort data is important to gain knowledge for understanding the evolution of disease and advancing the prevention and treatment of disease over time in precision medicine research. Electronic health records (EHR) data are a longitudinal collection of the digital records of patients’ health information and become a key data resource in precision medicine. Some potential statistical challenges are needed to be addressed in analysis of longitudinal data by extracting and linking EHR data with other types of data.

METHODS In precision medicine research, multiple repeated measurements and a single or multiple time-to-event outcomes are often encountered. For example, in the longitudinal studies of chronic diseases, patients are at risk for multiple events, such as recurrences and death. In EHR data, recurrent events, comorbid conditions, and biological markers are examined at intermittently clinical visits, which are dictated by physicians or patients. Therefore, visit times are likely to be related to patient’s health status. The traditional methods for analyzing a single or multiple time-to-event outcomes need to assume that the visiting process and multiple outcomes are mutually independent and the repeated measurements are missing completely at random. These assumptions for EHR data are unlikely to hold and may lead to biased inferences. The need of integrating EHR data with other types of data (for example, genomic data) is driven by precision medicine research. A variety of existing joint modelling methods have proposed to tackle these challenges and to address scientific questions.

CONCLUSIONS EHR data have become an important resource in precision medicine.

Integrative analysis of longitudinal EHR and biomedical databases provides key insights into identifying dynamic risk factors and revealing new biomarkers in the long-term course of disease.

Such data integration also presents a number of analytic challenges. Existing statistical methods and tools are available to analyze the need of such integrated data.

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SE3-2

APPLICATION OF ANCILLARY DIAGNOSTIC TECHNIQUES IN THE DIAGNOSIS OF THYROID NODULE 陳瑜忻 國泰綜合醫院細胞學科主任暨內分泌新陳代謝科主治醫師

In general practice, ambiguous diagnostic impression would happen in routinely stained or a lesion would be identified with several diagnostic possibilities. Ancillary diagnostic techniques are utilized to confirm or support the ambiguous diagnoses or diagnostic possibilities. These tests range from simple histochemical stains to immunochemistry, electron microscopy, tissue cultures, flow cytometry, and image analysis.

Most of the thyroid lesions are relative easy to interpret. But, there are certain thyroid lesions continue to cause difficulties because the interpretation of the criteria for various lesions has turned out to be very subjective. These difficulties cause controversies in the diagnoses and patient management.

The diagnostic difficulties involve not only in cytopathology but also in histopathology. In our practice, the diagnoses of thyroid lesion affect the management decisions and the extent of surgical procedures.

The inability to make a precise diagnosis of a follicular lesion has led to ancillary diagnostic techniques. These new techniques would offer more information about the biologic behavior and prognosis of the disease and have change in patient management. The ancillary diagnostic techniques applicable to thyroid lesions include histochemical and immunocytohistochemical stains, flow cytometry, image analysis and more recently, molecular testing.

This is a brief description about the application of these ancillary tests in the diagnosis of thyroid disease.

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MARKER TO PREDICT THE PROGNOSIS OF PATIENTS WITH THYROID CANCER DH SU Far Eastern Polyclinics

In clinical practice, the records of patients with chronic diseases is a form of the follow- data.

At each patient’s visit, the physician will collect the signs or event information to understand the level of the patient's future risk of complications or death. According to the level of these risks, physicians need to take some appropriate actions to prevent or delay the occurrence of complications or death. So, how to quantify such risks is a clinically important issue.

Markers could predict the patients’ prognosis. The possible markers of thyroid carcinoma include the patients’ basic characteristics, lab data, imaging studies, events and pathological reports. The important events for patients with thyroid carcinoma are locoreginal recurrences and distant metastases. Their pathological characteristics are tumor size, surgical margin involved, lymph node metastases, extrathyroidal extension, capsular involved and so on.

To predict the prognosis of patients with thyroid carcinoma, the patients’ basic characteristics, such as age and sex, are important. In addition, lab data, imaging studies and pathological report are also important prognostic factors. During follow-up, the messages of thyroglobulin, sonographic finding, locoreginal recurrences and distant metastases are important predictor of their death.

Cox’s model is a very common regression model in the survival analysis and takes the advantage of long-term data with chronological features. Time-dependent Cox’s model was used to clearly construct the correlation between basic covariate, marker process and the termination event without the assumptions of the specific distributions of these variates.

The purpose of this lecture is to use the dynamic messages of marker and the patients’ basic characteristics to predict the patients’ survival.

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SE3-4

THE UTILITY OF BIOMARKERS IN THE TREATMENT OF THYROID CANCERS SHU-FU LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City 23652, Taiwan

Anaplastic thyroid cancer (ATC) is a rare disease with a dismal median survival of only 3 to 5 months using conventional treatment. Recently, the US Food and Drug Administration approved a BRAF inhibitor (dabrafenib) plus a MEK inhibitor (trametinib) for locally advanced, metastatic ATC with BRAFV600E mutation after a clinical trial showed a high response rate, durable responses and improved overall survival.

Papillary thyroid cancer (PTC) accounts for more than 85% of patients with thyroid carcinoma.

Most patients with PTC survive for more than 10 years after diagnosis following standard treatment with surgery, radioactive iodine (RAI) and thyroid hormone therapy. However, a small proportion of patients who develop metastatic RAI-refractory PTC have the mean life expectancy of 3-5 years and the 10-year survival rate is only 10%. Chromosomal fusion events involving the carboxy-terminal kinase domain of NTRK and upstream amino-terminal partners have been demonstrated in various cancers and are implicated in up to 1% of all solid tumors. Larotrectinib, a potent and selective smallmolecule inhibitor of NTRK protein has demonstrated potent and durable antitumor activity in solid tumors with NTRK fusions, including PTC in a phase 1–2 trial.

Medullary thyroid cancer (MTC) originates from parafollicular C cells and accounts for 3-5% of all thyroid cancers. The clinical course of MTC can be indolent for years. However, aggressive MTC is associated with a high mortality rate. About 70% of MTC harbors mutant RET. Selpercatinib has demonstrated durable therapeutic efficacy in patients with RET-mutated MTC in a phase 1–2 trial.

In conclusion, these genetic alterations are pivotal biomarkers for thyroid cancer management.

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Abstract SE4-1

UPDATE IN THE TREATMENT OF 2ND HYPERPARATHYROIDISM IN DIALYSIS PATIENTS JIN-BOR CHEN Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.

Secondary hyperparathyroidism is a common event in chronic kidney disease(CKD) and dialysis patients. The pathogenesis is complex and consequently to deleterious outcomes in CKD population.

Treatment measurements include medical option and surgical parathyroidectomy and ablation therapy. The outcomes of parathyroidectomy and ablation therapy relating to all-cause mortality and cardiovascular mortality remain to be validated by large-scale population study. Regarding medical therapy, several drug categories have been recommended by Clinical Practice Guidelines including Taiwan Guideline in 2015. These drugs include phosphate-binder, vitamin-D analogs and calcimimetics. In this presentation, the content will cover the relevant field including background of pathogenesis, clinical outcomes esp. experience in Kaohsiung Chang Gung Memorial Hospital in Taiwan, briefing clinical practice guidelines, potential monitoring biomarkers and therapeutic measures.

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SE4-2

NEW TREATMENT FOR OSTEOPOROSIS IN TAIWAN J-S H Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

Osteoporosis is a growing major public health problem in many countries, as well as in Taiwan.

It’s the most common metabolic bone disorder, characterized by a decrease in bone mass and deterioration in skeletal microarchitecture, which lead to increased fragility and susceptibility to fractures, with an impact on quality and quantity of life that crosses medical, social, and economic lines.

The prevention and treatment of osteoporosis was changed significantly in recent years, osteoporosis can be stratified according to high-risk and very-high-risk features, which includes prior fractures. Stratification of the patient drives the choice of the initial agent as well as the duration of therapy. Several therapeutic options are available for the treatment or prevention of osteoporosis, and many drugs were proved to be as efficacious and safe in Asian population. These agents are alendronate, ibandronate, zoledronate, raloxifene, denosumab, and teriparatide. They increase BMD, improve bone strength, and reduce fracture risk.

Recently, the FDA approved romosozumab is a new class of osteoporosis treatment, a monoclonal antibody directed against sclerostin. Sclerostin binds with the Wnt receptor and inhibits the differentiation of precursor cells into mature bone-forming osteoblasts. Blocking sclerostin binding to osteoblasts allows osteoblast activity to increase. Bone turnover markers suggest an early anabolic effect, bone density increases are dramatic, and biopsies indicate an anabolic effect through both modeling and remodeling. In the two clinical trials, patients received either subcutaneous romosozumab 210 mg monthly or placebo for 12 months; then, received denosumab, and in the other trial, patients received monthly romosozumab or oral alendronate for 12 months; then, received alendronate. Both trials showed significant reductions in radio-graphic and clinical vertebral fractures at 12 months and 24 months.

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LONG TERM DRUG TREATMENT FOR OSTEOPOROSIS IN TAIWAN – A PERSONAL PERSPECTIVE K-S TSAI Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

There is a high prevalence rate of osteoporosis in the elderly Taiwanese. Physicians often need to see patients at around 65 year of age while they will live into their nighties. Since osteoporosis will progress with aging, we need to treat them long term. With the introduction of the anabolic drugs for osteoporosis, the patients would have more favorable effects. However, these drugs are allowed to be used for less than 2 years. Thus, anti-resorptives will be the main treatment in the 20 to 30 years of treatment periods. Embarrassingly, the 2 main side effects of long term anti-resorptive therapy, osteonecrosis of jaw bones, and atypical femoral fracture are common in Taiwan. As a results, high fracture risk patients are afraid and reluctant to use these drugs, and the physicians are having difficulties to draw a safe and effective long term treatment plan for the patients. We may wait for new drugs which do not have these problems, but globally there seems to be no new drug in the pipelines of the major pharmaceutical companies. Under the circumstances, it is reasonable to try to clarify the acceptable pathways to treat osteoporotic patient with different levels of fracture risks with the currently available drugs.

For patients with low or moderate fracture risk, raloxifene or half or one quarter dose of oral bisphosphonate may be the easy and cost benefit pathway. Patients should be followed with BMD measurement 2 to 3 years. If BMD could not hold, patients may use a larger dose of bisphosphonate or use denosumab. For patients with moderate to high fracture risks, regular dose of bisphosphonate for less than 4 to 5 years, or denosumab for up to 12 years may be used. More than 4 years of bisphosphonate use is associated with a 1% cumulated rate of osteonecrosis of jaw bones. Denosumab is the most potent antiresorptive currently. Its use are also associated with osteonecrosis of jaw bones.

While effective, stopping using it without the coverage of other drugs is well known to cause a rapid rebound of bone loss and may cause multiple vertebral fractures. For patients with multiple fractures and very high fracture risks, the effects of using anabolics before long term antiresorptives are well documented. The duration of anabolic treatment may be somewhat shortened if cost is a concern, but any anabolic treatment should be followed by a certain period of antiresortive drug use, otherwise the BMD gained will be loss very fast.

Vitamin D and calcium supplement to replete the patients is mandatory, Non-drug management including fall prevention, exercise programs, and case management team are all very important. For a good compliance, discussion with the patients and family, and shared decision making are also required. These measures should be prepared for a successful, safe long term treatment program of the osteoporotic patients.

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SE5-1

PRECISION THERAPY IN ACROMEGALY INDUCED BY PITUITARY ADENOMA 1

N-C YEH

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

Acromegaly presents with a range of symptoms and comorbidities caused by chronic and progressive growth hormone and IGF-1 (insulin-like growth factor 1) elevations, such as hypersecretion, sleep apnea, diabetes mellitus or cardiovascular disease. Without complete biochemical control, there are a poorer outcome. Although pharmacological treatments got improvement compared with decades ago. A lot of patients still get stuck in unsuccessfully biochemical control. Assessment of current and novel predictors of responsiveness to distinct therapy can lead to precisely categorizing patients, allowing reduction of morbidity and mortality as¬sociated with acromegaly.

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CONTEMPORARY SURGICAL MANAGEMENT OF ACROMEGALY ABEL PO-HAO HUANG National Taiwan University Hospital

Growth hormone (GH) hypersecretion from a pituitary adenoma results in acromegaly, an endocrinological disorder with multiple systemic manifestations that presents several unique challenges in terms of perioperative management and long term outcomes. Current guidelines provide stringent criteria for determining biochemical remission, necessitating an aggressive approach to management. Despite the development of several non-surgical therapies, transsphenoidal surgery, the endoscopic approach in particular, remains the primary line of treatment for rapid normalization of GH and Insulin-like growth factor with a low incidence of perioperative morbidity. Tumor size and invasiveness are important factors predicting surgical outcomes with better rates of postoperative remission seen in smaller and non-invasive tumors. Postoperative remission rates reported in literature with the 2020 consensus criteria vary from 30 to 85% probably reflecting varying prevalence rates of invasive tumors. Thus, a significant proportion of patients fail to achieve remission after surgery for whom treatment options for residual disease must be carefully considered. This review article discusses the surgical management of acromegaly and provides a summary of contemporary outcomes and current treatment controversies.

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LOWER-DOSE GAMMA KNIFE RADIOSURGERY FOR ACROMEGALY CHENG-CHIA LEE, MD, PHD 台北榮民總醫院神經醫學中心神經外科、國立陽明大學醫學系助理教授

Despite the extensive literature on the radiosurgical outcomes for acromegaly, conclusions drawn from analyses of these series have been limited by the heterogeneity in patient selection, radiosurgical techniques, follow-up lengths, and biochemical remission criteria. The reported biochemical remission rates vary widely, ranging from 17% to 65% at 3 to 4 years following stereotactic radiosurgery (SRS).

The reported positive predictors of remission include high radiation dose, small tumor volume, and low initial serum growth hormone (GH) and insulin-like growth factor (IGF)-1 levels.

In this presentation, I will report our work in Taipei Veterans General Hospital. We have investigated the endocrine outcomes of patients with acromegaly who underwent Gamma Knife radiosurgery (GKRS). The goal of this presentation is to evaluate the efficacy and safety of GKRS and improve the co-work in treatment of acromegaly patients. .

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Abstract SE6-1

MANAGEMENT OF PROLACTINOMAS DURING PREGNANCY 1

C-H LIN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Biomedical Park Hospital, HsinChu branch, National Taiwan University Hospital, Taiwan, R.O.C.

Hyperprolactinemia results in suppression of gonadotropin-releasing hormone (GNRH) followed by decrease of pulse amplitude and frequency of luteinizing hormone (LH). Therefore, patients with hyperprolactinemia often suffer from menstrual disorders and infertility. Prolactinomas are the most common cause of pathological hyperprolactinemia. In patients with macroprolactinoma, visual disturbance, headache and additional hypopituitarism could also be presented as a result of mass effects. The gold-standard treatment is dopamine agonist (DA), which can improve hypogonadism, infertility, hyperprolactinemia, and tumor shrinkage in most cases. However, DA exposure was reported to be associated with preterm birth and fetal malformations in the literature. In contrast, the elevated estrogen level during pregnancy stimulates lactotroph hyperplasia, increases prolactin level, and possibly causes enlargement of prolactinoma or compressive symptoms from tumor growth. The dilemma of DA use during pregnancy is sometimes troublesome for clinicians in making clinical decisions. Based on current evidence and guidelines, DA should be discontinued as soon as pregnancy is confirmed in patients with microprolactinomas and intrasellar macroprolactinomas. In invasive or extensive macroprolactinomas, maintenance of DA should be considered concerning the risks of tumor growth. Bromocriptine is the more favored DA because of its shorter half-life and larger experience of use during pregnancy as compared with cabergoline. Periodical follow-up and evaluation are mandatory to decide further strategy of management. If medical treatment fails, neurosurgery is indicated if compressive symptoms is present and tumor growth is confirmed by sellar MRI.

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THYROID DISEASE AND IODINE INTAKE IN PREGNANCY CHUN-JUI HUANG, MD, PHD Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.

Pregnancy has a huge impact on the thyroid. Placental human chorionic gonadotropin stimulates thyroid hormone production and leads to suppressed maternal thyrotropin concentrations. The concentration of the thyroxine-binding globulin (TBG) is also increased in pregnancy causing total T4 and total T3 levels to be elevated. This makes normal thyroid function reference values different in the pregnant and non-pregnant population. Trimester specific thyroid function ranges are needed in each region and these values differ largely among ethnicities and iodine status. More iodine is lost from the urine as a result of increased glomerular filtration rate in pregnancy. The fetus is totally dependent on maternal supply of iodine during pregnancy. Therefore, the pregnant women have been considered the vulnerable groups for iodine deficiency and the world health organization (WHO) recommended that their daily iodine intake to be higher (250 μg) than the usual recommended amount (150 μg) for non-pregnant adults. Both hyper- or hypothyroidism results in unfavorable pregnancy outcome, including miscarriage, perinatal death, gestational hypertension, and low birth weight, etc. Subclinical hyperthyroidism with suppressed TSH levels is the result of physiological changes in pregnancy and is not associated with adverse pregnancy outcome On the contrary, subclinical hypothyroidism which is usually tolerable in non-pregnancy conditions has been shown to be associated with increased risk of miscarriage, pre-term labor, gestational hypertension, and low birth weight. Even thyroid peroxidase antibody positivity with or without subclinical hypothyroidism increases the risk of pregnancy complications. Correct diagnosis and prompt treatment of thyroid dysfunction in pregnancy is of crucial importance and could only be achieved using a reliable gestation specific reference standard.

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Abstract SE6-3

PHEOCHROMOCYTOMA IN PREGNANCY 1

YI-HSUAN LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan City, Taiwan, ROC

Pheochromocytoma in pregnancy is a rare condition. The reported incidence of 1 in every 54,000 pregnancies. It untreated, fetal and maternal mortality reaches approximately 40% to 50%. Owing to earlier recognition of the disease and the subsequent initiation of proper treatment, the overall maternal mortality associated with pheochromocytoma has progressively decreased from 48% before 1969 to 4% during the 1990s, and further drops to 2% when the diagnosis is made antepartum. However, fetal outcomes still remain poor, with a fetal mortality rate of 11% . It has been decreased from 55% in 1969 to current 7% if diagnosed antenatally.

The fetus is not exposed to maternal circulating levels of catecholamines due to the high placental expression of catechol O-methyltransferase and monoamine oxidase. The placental exposure to maternal hypertension and to high catecholamines levels, however, can cause constriction of the maternal uterine circulation, inducing uteroplacental insufficiency. Pregnant woman with pheochromocytoma sometimes can be asymptomatic. In a majority of cases, however, symptoms of pheochromocytoma in pregnant patients are similar to those detected in nonpregnant patients.

Hypertension is the most common symptom, and other includes headache, palpitation, sweating, chest pain, dyspnea, vomiting, hyperglycemia, arrhythmia, Heart failure with pulmonary edema, postural hypotension, syncope, unexplained shock, intrauterine fetal death, fetal hypoxia, spontaneous abortion and fetal growth restriction.

Diagnosis usually is made in prenatal period in 73% of cases, during the second trimester in 32%, and during the third trimester in 42%. Therefore, in 27% of cases the diagnosis was missed and the tumor is diagnosed as a result of an acute complication. The clinical suspicion of PCC must be confirmed by increased catecholamines or their metabolites levels. The most sensitive test currently available is represented by plasmatic and urinary metanephrines. Catecholamine metabolism is unaltered during healthy pregnancy, and in patients with preeclampsia plasma catecholamine levels are only slightly increased.32 Possible interferences must be considered if patients are using a-methyldopa or labetalol, which can determinate false-positive results. Imaging based on ionizing radiation exposure is contraindicated in pregnancy for the possible negative effects on fetal outcome. In pregnant women, ultrasound and MRI are the imaging techniques more used to localize a tumor. Metaiodobenzylguanidine scinti scan is not considered safe for the fetus because of radioactive exposure.

After diagnosis and during follow-up, genetic consultation should be considered, because diseaserelated mutations can be found in approximately 30% of cases of pheochromocytoma diagnosed during 95

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pregnancy, an incidence similar to that detected in nonpregnant population.

Surgery represents the definitive treatment of pheochromocytoma in pregnancy. The time of surgery depends on gestational age, location of tumor, and maternal and fetal response to the medical treatment. It generally is recommended to remove the tumor in the second trimester (after the completion of the organogenesis). On the contrary, if the diagnosis is performed in the third trimester, it is recommended to plan the adrenalectomy after delivery. The adrenalectomy should be planned at least 10 days to 14 days after starting medical treatment. Preoperative medical treatment with α -adrenergic receptor blockade must be started for at least 10 days to 14 days before surgery. β -Adrenergic receptor blockers can be added to the treatment to contrast tachyarrhythmias and the possible a-adrenergic receptor blockade–associated reflex tachycardia. It’s should be Started after some days of appropriate α -adrenergic blockade. For pregnant women with pheochromocytoma in situ, there is no consensus about the preferred modality of delivery.

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Abstract SE7-1

NEW PROGRESS IN THE DIAGNOSIS AND TREATMENT OF PRIMARY BILATERAL MACRONOCULAR HYPERPLASIA 1

J-Y LU, 2T-S HUANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2 Department of Internal Medicine, MacKay Memorial Hospital, Taiwan, R.O.C.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a rare cause of endogenous Cushing’s syndrome (CS) with diverse clinical presentations. Hypersecretion of cortisol caused by PBMAH is adrenocorticotropin (ACTH) independent; however, local secretion of ACTH in adrenal glands also affects the excessive production of cortisol through paracrine or autocrine mechanisms. The clinical presentations of PBMAH range from rare but severe overproduction of cortisol and adrenal enlargement to relatively asymptomatic or only mildly symptomatic cases, combined with less significant adrenal structural alteration. The signal transduction pathways include activation of cAMP/PKA, no matter through direct alteration of downstream signaling pathways, or the aberrant expression of G-protein-coupled receptor (GPCR), thus affecting the synthesis and secretion of cortisol and the proliferation of adrenocortical cells. The most common genetic defect is the germline mutation of Armadillo repeat containing 5 (ARMC5). The diagnosis of PBMAH includes imaging assessment, and the characteristics of hormonal secretion. Imaging assessment needs to evaluate and confirm the structure of every single adrenal lesions. Hormonal secretion should contain evaluation of primary aldosteronism, pheochromocytoma, and CS, including 1mg dexamethasone suppression of ACTH followed by morning cortisol testing, to ensure the endogenous over secretion of cortisol independent of ACTH, the midnight salivary cortisol and the 24-hour urinary free cortisol excretion. The concomitant examination of cortisol and ACTH can help confirm the hypercortisolism independent of ACTH secretion. Comparing with other forms of CS, such as adrenal adenoma or pituitary adenoma, PBMAH pertains the clinical feature of relatively inefficient steroidogenesis.

The most suitable management of PBMAH remains controversial. In patients receiving bilateral adrenalectomy, life-long steroid supplement and the potential risk for adrenal crisis should be considered. Thus, bilateral adrenalectomy is only indicated in more severe form of CS. Otherwise, in selected patients, unilateral adrenalectomy is already enough to help control the clinical manifestations of PBMAH and prevent the complications related to hypercortisolism. Some patients with identifiable aberrant receptors can be treated with medications inhibiting the signal transduction of related pathways.

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UPDATE IN ADRENAL INCIDENTALOMA – INVESTIGATION AND MANAGEMENT T-W LEE Division of Endocrinology and Metabolism, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C.

An adrenal incidentaloma is a common endocrine diagnosis because of the widespread use of thoracic and abdominal imaging. A multidisciplinary approach is required to assess the hormonal status and malignant potential of an adrenal incidentaloma for effective management. The majority of adrenal incidentalomas are benign and nonfunctional. Measurement of precontrast Hounsfield units on computed tomography scan is an imaging study of choice to diagnose the etiology of an adrenal incidentaloma. All patients with adrenal incidentalomas should undergo careful evaluation to exclude cortisol and catecholamines excess. Aldosteronism should be excluded in patients with adrenal incidentaloma and concomitant hypertension or unexplained hypokalemia. Follow-up imaging studies and biological investigations are not necessary in patients who have a typical benign and hormonally inactive adrenal adenoma at initial evaluation unless new comorbidities appear. The application of novel adrenal imaging and urine steroid metabolomics will improve early detection and patient stratification in the future.

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Abstract SE7-3

ADVANCES IN ADRENAL DISEASE:S STEROID PROFILING IN ADRENAL DISEASES 1

MING-HSIEN WU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital (built and operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

OBJECTIVE Liquid chromatography–tandem mass spectrometry (LC–MS/MS) is an analytical chemistry technique used to analyze biochemical, organic, and inorganic compounds. Due to multiple hormones secretion in adrenal cortex, LC-MS can be used to reinforce the diagnosis of variable adrenocortical diseases by analyzing steroid profiling in urine or serum.

MATERIAL AND METHODS LC–MS/MS panels for the study of the adrenal secretion usually included pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione and testosterone. There existed different proportions of these hybrid steroids in adrenocortical diseases including primary aldosterone, hypercortisolism, adrenal insufficiency, adrenocortical carcinoma and disorders of sex development.

RESULTS In primary aldosterone, 18-oxocortisol was elevated in patients with aldosteroneproducing adenoma (APA) versus bilateral hyperplasia (BAH); correspondingly cortisol, corticosterone and Dehydroepiandrosterone level were lower in APA than BAH. In hypercortisolism, patients with adrenal cause had the lowest concentrations of androgens, whereas those with ectopic and pituitary cause showed the lowest concentrations of aldosterone. In adrenal insufficiency (AI), aldosterone level was significantly lower in primary PI than secondary AI. In adrenocortical carcinoma (ACC), 11-deoxycortisol and 17-hydroxypregnenolone were confirmed invariably higher in plasma of ACC versus non-ACC patients. In disorders of sex development (DSD), different genes encoded different enzymes in adrenal steroidogenesis pathway.

Thus, each mutation of these genes exited special steroid profiling.

CONCLUSIONS In the future, the measurement of a large panel of steroids by LC–MS/ MS may provide outstanding improvement in the diagnosis and subtypes discrimination of various adrenocortical diseases.

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EVALUATION AND MANAGEMENT OF CHILDREN WITH SHORT STATURE SHIH-YAO LIU Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

As the rapid improvement of worldwide economical and nutritional supply, human beings are indeed getting higher than before. On the other hand, the growth and development of each child have been more emphasized by the parents as well. A variety of height-promoting therapies are advocated in recent years; however, a number of those are not well-documented in evidence-based medicine and some children may enter certain unnecessary treatment courses before receiving appropriate evaluation.

Definitions and evaluations of short stature and growth retardation have been documented for decades. The diagnosis of growth hormone deficiency (GHD) remains a clinical one, where one synthesizes auxologic, anatomic, and laboratory data to arrive at a diagnosis. The measurement of serum insulin-like growth factor I (IGF-I) is an important component in the evaluation of a child with growth failure. With appropriate clinical settings for GH stimulation tests, the activity of GH-IGF-I axis can be assessed to confirm the diagnosis. Furthermore, the evolving understanding of growth plate physiology has led to an increasing focus on genetic testing and innovative therapies for extremely short children.

The use of recombinant human growth hormone in treating children with GHD has been proved to be a safe and effective management. Novel treatment approaches, including use of long-acting GH formulations as well as new GH secretagogues have prompted expert consideration. In this section, A brief overview of evaluation and management for short children will be addressed.

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Abstract SE8-2

DIAGNOSIS AND MANAGEMENT OF PRECOCOUS PUBERTY 1,2

W-H TING

1

Department of Paediatric Endocrinology, MacKay Children’s Hospital, Taipei, Taiwan. 2Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.; 3MacKay Junior college of Medicine Nursing and Management, New Taipei City, Taiwan

Puberty is the transition stage between children and adult. Normal puberty onset vary greatly between individuals, and usually occur between 8-13 years in girls and 9-14 in boys. Therefore, precocious puberty is defined by the onset of secondary sexual characteristics before the age of 8 years in females and 9 years in males. Depending on the primary source of the hormonal production, precocious puberty may be classified as central (gonadotropin dependent) precocious puberty (CPP) or peripheral (gonadotropin independent) precocious puberty.

The impact of precocious puberty on children’s health include: 1. Pathological cause of precocious puberty.

2. Early and rapid progression of precocious puberty result in compromised adult height.

3. Psychological stress (including immature skills for self-management of menstruations).

Therefore, pediatricians should be familiar with the normal puberty onset mechanism, evaluation of precocious puberty, differentiation diagnosis, the possible CNS lesions in CPP patients (especially in boys), and the benefits and risk of Gonadotropin-releasing hormone analogs in treating CPP children. Besides, some normal pubertal variants, like premature thelarche, premature pubarche, and gynecomastia, are also frequent complaint in outpatient clinics, and should be differentiated from precocious puberty.

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DELAYED PUBERTY YI-CHING TUNG Division of Pediatric Endocrinology, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

Delayed puberty is defined as the absence of breast development at 13 years in girls or lack of testicular development above 3mL at 14 years in boys. The commonest cause is constitutional delay of growth and puberty (CDGP), which is considered as benign variant and these patients usually have strong family history of delayed puberty. This represents the normal spectrum of late pubertal timing. Pubertal timing is determined by complex interactions between genetic and epigenetic factors.

The environmental factors, such as nutrition and endocrine disrupting chemicals, may mediate the activation of hypothalamic-pituitary-gonadal (HPG) axis via epigenetic mechanism.

Permanent hypogonadism includes hypogonadotropic hypogonadism (HH) and hypergonadotropic hypogonadism, both can be congenital or acquired. Congenital HH, or isolated HH (IHH), is rare and caused by the failure of GnRH neuron migration or deficiency in the production, secretion and action of GnRH. Congenital HH is classified as Kallmann syndrome (KS) with anosmia or normosmic IHH (nIHH). Sixty of IHH patients could find the genetic etiology by whole exome sequencing (WES). CHD7, FGFR1, and ANOS1 were the common causative genes. Functional HH is usually seen in patients with chronic inflammatory disease, anorexia nervosa or in athletics with intensive training. Hypergonadotropic hypogonadism is due to primary gonadal failure, such as chromosomal abnormality or gonadal dysgenesis. Radiation or chemotherapy frequently causes acquired HH or hypergonadotropic hypogonadism, depending on the agents, dosages or site of radiation exposure.

Most children with CDCP may experience a period of retarded growth, compared with their peers. Psychological support is the choice of therapy. For those with extreme end of puberty delay and being bullied, low dose hormone induction therapy may be considered. Patients with permanent hypogonadism should start hormone replacement therapy (HRT) at appropriate time. HRT could be increased the dosage gradually to adult levels two to three years later, mimicking the normal process of puberty.

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Abstract WE

THYROID CYTOLOGY 1

I-S JAN, 2T-C CHEN

1

Department of Laboratory Medicine, National Taiwan University Hospital, 2Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Taiwan, R.O.C.

Thyroid cytology workshop is focus on the morphological interpretation of common thyroid disease diagnosed by fine-needle aspiration (FNA) cytology of the thyroid. Clinical history, laboratory data, thyroid echo images and thyroid FNA pictures of 10 selected cases will be presented by the endocrinologist and cytologist.

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LS1

NEW APPROACHES FOR CHRONIC KIDNEY DISEASE IN TYPE 2 DIABETES MANAGEMENT RALPH DEFRONZO Diabetic kidney disease is the leading cause of kidney failure worldwide; in the USA, it accounts for over 50% of individuals entering dialysis or transplant programmes. Unlike other complications of diabetes, the prevalence of diabetic kidney disease has failed to decline over the past 30 years. Hyperglycaemia is the primary aetiological factor responsible for the development of diabetic kidney disease. Once hyperglycaemia becomes established, multiple pathophysiological disturbances, including hypertension, altered tubuloglomerular feedback, renal hypoxia, lipotoxicity, podocyte injury, inflammation, mitochondrial dysfunction, impaired autophagy and increased activity of the sodium–hydrogen exchanger, contribute to progressive glomerular sclerosis and the decline in glomerular filtration rate. The quantitative contribution of each of these abnormalities to the progression of diabetic kidney disease, as well as their role in type 1 and type 2 diabetes mellitus, remains to be determined. Sodium–glucose co-transporter 2 (SGLT2) inhibitors have a beneficial impact on many of these pathophysiological abnormalities; however, as several pathophysiological disturbances contribute to the onset and progression of diabetic kidney disease, multiple agents used in combination will likely be required to slow the progression of disease effectively.

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Abstract LS2

COMPREHENSIVE REVIEW ON RENAL SAFETY DATA FOR TRULICITY ON PATIENTS WITH TYPE 2 DIABETES 張宏猷 由於新型的血糖藥物發展快速，有越來越多血糖藥物可供選擇。其中，部分新型的血糖藥 物由於在 CVOT 取得了降低心血管事件風險結果，讓 ADA 的建議也從 2018 年開始，現在除 了控制血糖外，也將心血管事件預防的考量納入其中。當中有一部份提到，若病患有 ASCVD 風險，可考慮優先使用 GLP-1 RA。Trulicity 為台灣第一個一週一次的 GLP-1 RA 藥物，在 2018 年 REWIND 發表後，也同時拿到 ADA/EASD 在 primary 與 Secondary prevention 的認可， 隨後，台灣也於 2020 年拿到此適應症。在 REWIND 發表後的兩年間，Trulicity 陸陸續續發表 了許多其他次分析，其中也包含了對於腎功能的結果，此次演講將以腎病變當出發點，探究 Trulicity 是否能為糖尿病患合併腎病變的過程帶來幫忙。

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SEE ASIA - SITAGLIPTIN AND ERTUGLIFLOZIN EFFICACY IN ASIAN T2DM PATIENTS 王治元教授 臺大醫院新陳代謝科

Current guidelines recommend that a single agent be added to treatment in patients with inadequate glycemic control with metformin monotherapy. Although some patients achieve glycemic control with dual therapy, many, especially those starting at higher HbA1c levels, may not. Further, patients who achieve glycemic control with dual therapy may experience progressive deterioration of glycemic control. In some cases, it may be appropriate to consider addition of a combination of two anti-hyperglycemic agents (AHAs) with complementary mechanisms of action, favorable safety profiles and without pharmacokinetic interaction, such as a sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors.2 This may provide a more robust and sustained antihyperglycemic effect, resulting in more patients achieving and maintaining glycemic goals, and could become a useful alternative to the single stepwise antihyperglycemic approach. Ertugliflozin is an inhibitor of SGLT2, with high selectivity relative to SGLT1, Ertugliflozin as monotherapy or as add-on to metformin or metformin and sitagliptin improved glycemic control and reduced body weight, with a safety profile consistent with that of other SGLT2 inhibitors. Sitagliptin is a DPP-4 inhibitor indicated for treatment of type 2 diabetes. Sitagliptin as monotherapy, or as part of dual or triple therapy for patients with type 2 diabetes, provides clinically meaningful reductions in blood glucose. The primary objective was to determine whether coadministration of ertugliflozin with sitagliptin provides better glycemic benefit for patients with type 2 diabetes who were inadequately controlled with metformin.

An updated data of VERTIS-CV adds additional understanding of Ertugliflozin on HF & Renal understanding.

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Abstract LS4

NEW ERA OF CONVENIENT INSULIN REGIMENS: THE FIRST 2-IN-1 INSULIN CO-FORMULATION IDEGASP 王俊興 台灣第二型糖尿病患者接受胰島素治療時，多以基礎胰島素作為起始。然而國內研究顯 示，僅約一成患者在接受基礎胰島素 24 周後達到 HbA1c 的目標 (J Diabetes Investing 2016; 7:881-888)。而亞洲地區因人種以及飲食習慣以米食為主的關係，餐後血糖對高血糖的貢獻度 較西方人高，顯示餐後血糖的控制於亞洲族群更顯重要。因此，預混胰島素為目前常用來控制 餐後血糖的選項之一，預混型胰島素在一支筆針同時包含速效及中長效胰島素，可同時有效控 制及餐後血糖，並提供簡單方便的治療方式，減少病人須學習多種注射藥物的障礙。同時，目 前也將有新形態的可溶性雙胰島素問世，IDegAsp 為第一個能夠將兩種不同胰島素類似物混合 於同一筆針的可溶性雙胰島素，成分包含超長效胰島素 Insulin Degludec 及速效胰島素 Insuln Aspart，藥水呈透明澄清，病患使用前不須重新搖振均勻。此外，IDegAsp 可做為胰島素起始 以及強化的選擇，能減少低血糖發生風險，同時有效控制空腹及餐後血糖，並使用改良式注射 器幫助病患方便有效的控制血糖。

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LS5

糖尿病之血脂異常治療 葉乃誠醫師 奇美 新陳代謝科

糖尿病腎病變 (Diabetic Kidney Disease, DKD) 是導致末期腎病變 (End Stage Renal Disease, ESRD) 最主要的原因，也是世界各國都非常重視的公衛議題，因它為個人和整體社會經濟都帶 來嚴重的負面影響。過去幾十年來在糖尿病腎病變的領域有許多觀念的變革與藥物的發展，因 此重新認識糖尿病腎病變乃為此演講的重點。 糖尿病合併腎病變的病人，心血管風險甚至逼近有發生過心肌梗塞的病人，所以如何藉由 三高控制將風險降低是重要的議題，降血糖藥物上除了 SGLT-2 血糖藥證明了對於心臟及腎臟 的好處外，血脂控制上在最新 ADA,ESC 的治療指引中，也將 LDL 的目標從 100 下修 70，針 對降血脂藥物的選擇也偏向更高強度的 statin，或加上 Ezetimibe 或 PCSK9i 來達到目標。 Atorvastatin 不需要根據腎功能調整劑量，且不會影響腎功能或造成蛋白尿等問題，對於糖 尿病合併有腎病變的病人是降脂達標的選擇之一。

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Abstract LS5

糖尿病周邊神經病變之診斷與治療 董欣醫師 台中榮總神經內科

神經病變是糖尿病最常見的慢性併發症，亦為造成糖尿病患者殘障及產生多樣不適症狀的 主要原因之一。其盛行率可由初期診斷糖尿病時的 7.5% 至 25 年後的 50-60%。一般而言，糖 尿病病期超過十年以上，約有四分之一的第二型糖尿病患者出現糖尿病多發性神經病變。 糖尿病神經病變因為受影響的神經不同 , 在臨床上表現的很多樣性。大致上分為以侵犯「感 覺 - 運動 - 自律神經混合型」的對稱性多發性神經病變 ( 約占 70-75%) 及局部性神經病變 ( 約 佔 25-30 %)。 糖尿病神經病變之分類 一、多發性神經病變 二、自主神經病變 三、局部性神經病變或單一神經病變 糖尿病神經病變的治療目標在於：預防疾病形成 ( 良好的血糖控制 )、早期診斷、改善症 狀、避免次發性合併症及輔導病患自我照顧。重點在於良好的病患教育，幫助病患了解疾病可 能造成的症狀以及清楚認識良好控制血糖的重要性，將血糖控制在正常範圍內，有助於延緩或 預防周邊神經病變及其他併發症的發生（例如視網膜病變、腎臟病變等）。適當的足部護理及 物理與藥物治療等等。藥物治療治療的藥品包括抗憂鬱藥、抗癲癇藥 ( 如 Lyrica)、辣椒素軟膏、 Lidocaine 貼布、alpha-lipoic acid 和經皮神經電刺激。其中 Lyrica 是經由抑制興奮性神經傳遞物 質的釋放，從而降低神經疼痛的症狀。 起始劑量應從 150 mg / 天 (75 mg bid) 開始，最高建議劑量是 300 mg / 天，劑量越高止痛 效果越佳，疼痛改善了，睡眠品質也會提升 !

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nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS6

OPTIMIZE T2D TREATMENT STRATEGY TO MAXIMIZE PERSISTENCE OF OAD PROF. ALICE CHENG 近年來，小於 40 歲的年輕糖尿病患者逐漸增加，且隨著平均餘命的增加，整體的糖尿病 治療年限大幅上升，而許多患者甚至確診 8 年即已使用到三線口服藥品加上胰島素注射才能 控制糖尿病，尤其亞洲族群糖尿病患者本身 beta-cell function 更是只有西方人的一半，該如何 選擇加藥的種類、用藥時機，才能最大化每一線藥品的治療年限、延緩患者施打胰島素的時 間，而針對 beta cell function，或許臨床上無法定期監測，但是否可以由試驗證據，應用至臨 床實踐中。

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Abstract LS7

IMPORTANCE OF EARLY INSULINIZATION AND HOW TOUJEO HELPS 范綱志 Type 2 diabetes occurs when the body’s pancreas does not produce sufficient insulin and/or cells respond poorly to insulin and take in less glucose. Current guidelines recommend diet and lifestyle modification with or without oral diabetic agents (OADs) as the first step in treating Type 2 diabetes.

However, to only rely on OADs for treatment will result in beta cells being overworked, gradually losing the cells’ ability to produce insulin to support the patient’s needs, thereby necessitating the initiation of insulin.

The invention of insulin injectables aims to supplement the body’s need for insulin and to slow the progression of the disease. Research has shown the benefits of early use of insulin to reduce HbA1c levels and to reduce the risk of comorbidities associated with increased HbA1c levels. In addition, with the advancement of once daily second-generation basal insulin, patients today can achieve glycemic control while reducing the risk of hypoglycemia. This helps to lower potential resistance to injectables and makes it safe for patients to embark on this treatment.

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nd Annual Meeting of March 27-28, 2021 The Endocrine Society and The Diabetes Association of the R.O.C. (Taiwan)

LS8

CURRENT CONCEPT OF LIPID LOWERING THERAPY 李貽恒 Statin reduces low-density lipoprotein cholesterol and improves clinical outcomes in high risk patients. In general, statin is a safe and well-tolerated medication. However, varieties of adverse effects are reported in some patients and may interfere long-term drug compliance. Statin-associated muscle events and liver function change account for most of these adverse effects. Patients are regarded as statin intolerance if they need to discontinue statin therapy due to these adverse effects. To date, there is no universal standard definition of statin intolerance. But a pragmatic definition of statin intolerance is essential and helpful for clinicians in daily practice. In this article, after expert consensus meetings and literature review, criteria were recommended to identify patients with statin intolerance in Taiwan.

The purpose of this statement is to help health care professionals in Taiwan to diagnose and manage individuals who develop muscular and hepatic side effects after statin therapy.

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Abstract LS9

VERIFY THE ROLE OF EARLY COMBINATION : FOCUS ON BETA CELL PRESERVATION 翁瑄甫 英國前瞻性糖尿病研究 UKPDS 和 ADOPT 研究表明，儘管經過治療，但由於 β 細胞功能 的逐步下降，血糖控制仍隨時間而惡化。這些數據突顯了第 2 型糖尿病（T2DM）的治療中保 存 β 細胞功能的重要性。 2020 年 Diabetes care Guideline 基於 VERIFY study 發表後建議在新診斷第二型糖尿病患可 建議病患積極使用 Metformin 合併 Vildagliptin， Metformin 治療失敗後才合併 Vildagliptin 可延 緩病患疾病進程，並降低第一次及第二次治療失敗風險，VERIFY Study 是一雙盲、隨機分配 的臨床試驗，主要針對新生糖尿病 A1C 介於 6.5% 至 7.5% 的病患，探討早期合併 metformin 及 Vildagliptin 與階梯式使用 Metformin 治療失敗後合併 vildagliptin 在治療上的差異。 以 incretin 為基礎的療法可改善 T2DM 患者的 β 細胞功能。許多的研究發現 Vildagliptin 治療使得 β cell 與 T2DM duration 之間呈負相關。 與此，VERIFY study 中支持早期合併治療 Metformin 及 Vildagliptin 顯示早期合併治療得 以保存第二型糖尿病病患的 β- 細胞功能，支持早期合併治療延遲第二型糖尿病自然疾病進程， 使得疾病進程得以改善。

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LS10

EVOLUTION OF T2D CARE, MOVE FROM CONVENTIONAL TO COMPREHENSIVE THERAPY 蔡世澤 根據統計，多數第二型糖尿病人合併有心腎共病，而血糖與心腎互相影響並且息息相關。 2020 年底 ADA 發表 2021 新的治療指引，也指出針對心血管高風險族群除了血糖的控制之外， 提早做器官保護也一樣重要，而對於非屬於這些族群的糖尿病患者，應同時考量到藥物的療 效、減少患者對副作用的負擔及提升服藥順從性。因此，糖尿病治療必須思考長期治療策略， 讓病患在控制血糖的進程中，兼顧共病管理、降糖療效、以及順服性，以達到最大化的臨床 效益。

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Abstract LS11

ADVANCED IN INJECTABLE THERAPY: ADDRESSING THE NEED FOR INTENSIFICATION AND HOW WE MAKE IT SIMPLER LEIGH PERREAULT The global burden of type 2 diabetes is increasing worldwide, although the the benefits of early, aggressive glycemic control are clearly established, treatment remains suboptimal. Many patients fail to achieve long-term glycemic control, approximately 50% of patients with type 2 diabetes mellitus (T2DM) do not achieve glycemic targets and require treatment intensification.

Many studies have shown that delayed treatment intervention of diabetes is associated with increased risk of complications. Now a day, several studies demonstrate that early intensification is associated with a larger reduction in A1c across all baseline A1c categories, and may decrease the risks of CV events in T2D patients.

Patients with A1c>9% usually required injectable therapy for intensification. Traditional intensified strategies with prandial insulin can cause hypoglycemic episodes, weight gain and burden of multiple daily injections. Adding glucagon-like peptide-1 receptor agonists, such as the short-acting lixisenatide, are able to control postprandial excursions, without weight gain, and with a low risk of hypoglycemic events. iGlarLixi (Soliqua®) is a titratable, co-administration of BI/GLP-1RA in a single once-daily injection. This so-called fixed-ratio combination (FRC) agent can exploits the complementary mechanisms of action, with greater reduction in HbA1c, improving convenience of mitigating GI symptoms due to gradual dose increment.

In this talk, Dr. Perreault will lead the audience to explore the journey of iGlarLixi clinical program and let us know why iGlarLixi can make T2D treatment simpler from her clinical experience.

Overall, the efficacy, safety, and convenient once-daily administration schedule of iGlarLixi make it a valuable treatment option for patients with T2DM requiring treatment intensification.

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LS12

ADVANCING DIABETES CARE WITH GLP-1 RECEPTOR AGONISTS 杜思德醫師 Glucagon-like peptide 1 is a hormone of the incretin system, responsible for a variety of glucose regulating effects, including the secretion of glucose-dependent insulin and inhibition of glucagon release. This effect can be impaired for type 2 diabetes patients (T2D). Using GLP-1 receptor agonist (GLP-1RA) to solve this defect is an effective therapy for T2D, and has accumulated more than ten years of clinical experience. This presentation reviews the evidence of subcutaneous GLP-1RA and its role in the treatment of T2D. Clinical trials and real world evidence of subcutaneous GLP-1RA have shown that these drugs have a good glycated hemoglobin (HbA1c) lowering effect , an inherently low potential for hypoglycemia, and reduce body weight. Cardiovascular outcome trials have established cardiovascular safety and have shown that human-based GLP-1RA can reduce the risk of major adverse cardiovascular events (MACE) in patients with established or higher CV risks.

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Abstract LS13

PREVENTING HYPOGLYCEMIA BY USING TECHNOLOGY IN DIABETES SELF-MANAGEMENT 林慶齡 The international standard ISO (International Organization for Standardization) 15197 defines various requirements for SMBG systems, concerning safety and reliability, analytical performance (e.g. system accuracy), information supplied by the manufacturer and performance in the hand of layusers. The currently applicable version of the standard is ISO 15197:2013, its predecessor was ISO 15197:2003.

Regarding system accuracy, ISO 15197:2013 describes the following minimum criteria: Criterion A: At least 95% of a system’s measurement results shall fall within ±15 mg/dl of the comparison measurement results at blood glucose (BG) concentrations <100 mg/dl and within ±15% at BG concentrations ≥100 mg/dl. Criterion B: At least 99% of individual measurement results shall fall within Consensus Error Grid zones A and B. Criterion A is also applicable for user performance evaluation.

A number of accuracy evaluation studies performed in recent years have reported that not all available SMBG systems show sufficient measurement quality to comply with ISO 15197 requirements. However, there are qualitative differences even among SMBG systems that comply with ISO 15197 requirements. Simulation studies show that higher accuracy leads to clinical benefit.

User performance evaluation studies showed that SMBG systems showing high accuracy when used by trained professionals do not necessarily also showed high accuracy in the hands of lay-users. This underlines the importance of patient education and training, not only to avoid meter-independent factors like contamination of hands, but also to highlight meter-specific details. A reliable and accurate SMBG system is an important aspect in optimizing insulin-dependent patients’ therapies.

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LS14

RELENTLESS PROTECTION OF PROLIA (DENOSUMAB) IN ENDOCRINOLOGY 廖國盟 • 骨質疏鬆症（osteoporosis）是一種因骨量減少或骨密度降低而使骨骼微細結構發生破壞的慢 性疾病，惡化的結果將導致骨骼脆弱，並使骨折的危險性明顯增高。 • 對於具有高骨鬆性骨折風險或已發生骨鬆性骨折的患者而言，僅提供非藥物治療是不足的， 應要積極使用抗骨鬆藥物治療。 • Prolia（保骼麗），注射針劑，屬細胞核 kB 受體活化因子抑制劑（RANKL Inhibitor），每 6 個月皮下注射一次，使用方便，對蝕骨細胞的抑制效果比雙磷酸鹽類的藥物更強。 • 積極治療骨質疏鬆症，預防突如其來的脆弱性骨折。

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Abstract LS15

PRECISION MEDICINE IN THYROID CANCER- UPDATED NTRK FUSION - TKI USE IN RAI-REFRACTORY DTC AND ATC 諶鴻遠 NTRK gene fusion 的 RR-DTC 和 ATC • NCCN guidelines 中建議，對於晚期、進行性 (progressive) 的甲狀腺癌，或有危及生命的疾病 時，可以讓病患接受基因檢測，以確認是否有 NTRK、RET 等基因融合 (gene fusion)，並了 解其腫瘤突變負荷量 (tumor mutational burden, TMB)。對於 NTRK gene fusion 呈陽性的病患， 可以給予 Larotrectinib 或 entrectinib；如果有 RET fusion，可給予 selpercatinib；如果 TMB≥ 10 mut/Mb，可給予免疫治療藥物；而沒有做基因檢測的狀況下，對於進行性及 / 或有症狀 的疾病，則可考慮使用 lenvatinib 或 sorafenib2。對於 ATC 的病患，則建議在一開始就盡快做 基因檢測 2。 • Larotrectinib 治療：合併第一期的試驗和第二期的 NAVIGATE 研究來看，共有 28 位帶有 NTRK 基因融合的局部晚期或轉移性甲狀腺癌病患，其中 ATC、濾泡型甲狀腺癌 (follicular thyroid cancer, FTC) 和 甲 狀 腺 乳 突 癌 (papillary thyroid cancer, PTC) 病 患 分 別 佔 25%、7% 和 68%4。結果顯示，ATC 病患接受 Larotrectinib 治療反應有些兩極，總體反應率 (overall response rate, ORR) 為 29%。而 Larotrectinib 對於中樞神經系統 (central nervous system) 轉移 的病患治療也有效 ( 圖三 )；在整體病患中，治療持續時間 (duration of treatment) 最長可達 45.4 個月以上，反應持續時間 (duration of response) 在第 12 個月還有 95%，而第 12 個月的 無惡化存活期 (progression-free survival, PFS) 和整體存活期 (overall survival, OS) 比率分別為 81% 和 92%4。安全性表現的部分，則是幾乎沒有第 3 和第 4 級的不良反應 4。 • 對於晚期甲狀腺癌，Larotrectinib 可以加強 (enhance) 放射碘吸收的能力：發表在 N Engl J Med 中的一項案例報告中提到，一位 64 歲的女性患有 PTC 達 34 年，且有肺部轉移。陸續 接受碘 -131、lenvatinib 治療後仍復發，且有一些較嚴重的不良反應。予以基因檢測後顯示 為 NTRK3 gene fusion，因此給予 larotrectinib 100 mg BID，治療後病患的狀況即控制下來。 此外，在接受 larotrectinib 治療前，病患的影像檢查顯示除了胃和腸子之外，沒有放射碘吸 收的情形，然而，在 larotrectinib 治療後則發現，肺部變成有放射碘吸收的情況 5。 Reference 1. Zaballos MA, et al. J Endocrinol. 2017; 235(2): R43-R61.

2. NCCN guidelines: Thyroid cancer. 2020 version 2.

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3. Suzuki K, et al. Cancers (Basel). 2019; 11(9): 1290.

4. Cabanillas ME, et al. Poster presented at ESMO Virtual Congress 2020, September 19–21, 2020.

Abstract 1916P. 5. Groussin L, et al. N Engl J Med. 2020; 383(17): 1686-1687.

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Abstract OD1

GLYCATED HEMOGLOBIN VARIABILITY, MEAN HBA1C AND HEART FAILURE IN PATIENTS WITH TYPE 2 DIABETES 1

YOU-TING LIN, 1WEI-LUN HUANG, 2HUNG-PIN WU, 1CHWEN-TZUEI CHANG, 1 CHING-CHU CHEN 1

Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan; 2Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, Taiwan

Aim: To evaluate the association of HbA1c variability and mean HbA1c with heart failure (HF) in patients with type 2 diabetes mellitus (T2DM).

Materials and Methods: Using Diabetes Share Care Program data, patients with T2DM had at least three HbA1c measurements within 12-24 months were included. The cutoffs of mean HbA1c (HbA1c-Mean) were set at <7%, 7-7.9%, and ≥8%. The associated risk of HbA1c-Mean, HbA1c variability (tertiles of HbA1c-SD and HbA1c-adjSD), and HF during 2008-2018 were estimated by using a Cox proportional hazards model.

Results: A total of 3824 patients were included, of whom 315 patients developed HF during the 11.72 years observation period. The associated risk of HF increased with cutoffs of HbA1c-Mean and tertiles of HbA1c variability. In mutually adjusted models, HbA1c-Mean showed a consistent doseresponse association with HF, while the association of HbA1c variability with HF disappeared. Among patients with HbA1c-Mean < 7%, the associated risk of HF in patients with HbA1c variability in tertile 3 was comparable to patients with HbA1c-Mean ≥8%.

Conclusions: Mean HbA1c was an independent predictor of HF and not explained by HbA1c variability. In addition to absolute HbA1c level, targeting on stability of HbA1c in patients with well glycemic control was also important for the development of HF in patients with T2DM.

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OD02

THE ASSOCIATIONS BETWEEN NEGATIVE EMOTION, AUTONOMIC ACTIVATION, AND GLYCEMIC CONTROL IN TYPE 2 DIABETES 1

KUN-DER LIN, 2I-MEI LIN, 1I-TING LIN, 3SHU-HENG HUANG, 2HUI-JING JI

1

Division of Endocrinology and Metabolism, Kaohsiung Medical University Chung-Ho Memorial Hospital Department of Psychology, Kaohsiung Medical University 3 Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital 2

Background: Depression decreased autonomic activation in physical illness and mental disorder.

The heart rate variability (HRV) was an index of autonomic activation. This study explored the associations between negative emotion, autonomic activation, and glycemic control in patients with Type 2 diabetes.

Methods: A total of 222 patients with Type 2 diabetes were recruited in the outpatient center.

The mean age was 62.61 ± 9.98 years with 127 (57.20%) male and 95 (42.80%) females. The Patient Health Questionnaire 9 (PHQ9) and General Anxiety Disorder 7 (GAD7) were used to screening depression and anxiety. A 5-min electrocardiography was measured and transformed into HRV indices.

The fasting sugar, hemoglobin A1C (HbA1c), and lipid profiles (cholesterol, triglyceride, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) were collected for three years from the medical record.

Results: After controlling age, body mass index, lipid profiles, and length of diabetes diagnosis, the positive correlations were found between depression and LF/HF ratio of HRV (r = .145, p = .048).

After controlling the demographic data and lipid profiles, the logistic regression showed that higher depression and lower HRV (standard deviation of NN intervals) had poor glycemic control for three years (HbA1c ≥ 7%). The multivariate analysis showed that high sympathetic group (LF/HF ratio ≥ 2.5) had higher cholesterol, LDL, and HbA1c than those low sympathetic group (LF/HF ratio < 2.5) (F

圖三、Larotrectinib 於 NTRK gene fusion 甲狀腺癌的治療反應

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Abstract = 13.14, p < .001, ŋ2 = .070; F = 13.03, p < .001, ŋ2 = .070; F = 5.04, p = .026, ŋ2 = .028).

Conclusions: Depression was related to higher sympathetic activation, and higher sympathetic also related to poor lipid profiles and glycemic control in patients with Type 2 diabetes. Depression and low HRV can also predict poor glycemic control for three years in patients with Type 2 diabetes.

Therefore, measures of depression and autonomic activation are needed in the future.

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OD03

MITOCHONDRIAL HAPLOGROUPS HAVE A BETTER CORRELATION TO INSULIN REQUIREMENT THAN NUCLEAR GENETIC VARIANTS FOR TYPE 2 DIABETES MELLITUS IN TAIWANESE INDIVIDUALS 1

FENG-CHIH SHEN, 1SHAO-WEN WENG, 2MENG-HAN TSAI, 3YU-JIH SU, 1 JUNG-FU CHEN, 4YEN-HSIANG CHANG, 2CHIA-WEI LIOU, 2TSU-KUNG LIN, 5 JIIN-HAUR CHUANG, 1PEI-WEN WANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3 Division of Rheumatology, Allergy, and Immunology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4 Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Objective Identifying the diabetes-susceptible genetic variants will help to provide the personalized therapy for type 2 diabetes. Previous studies have reported a genetic risk score (GRS) calculated according to the number of nuclear DNA (nDNA) risk alleles may predict the future requirement of insulin therapy. Although mitochondrial dysfunction has close association with insulin resistance (IR), there are few studies investigate whether genetic variants of mitochondrial DNA (mtDNA) will affect the clinical features of type 2 diabetes.

Research Design and Methods We determined mitochondrial haplogroups using mtDNA whole genome next generation sequencing and 18 single nucleotide polymorphisms (SNPs) in nDNA susceptibility loci of 15 genes in 604 Taiwanese individuals with type 2 diabetes. A genetic risk score (GRS) of nDNA was calculated by summation of the number of risk alleles. We assessed the association between mtDNA haplogroup and the clinical features of type 2 diabetes by logistic regression analysis. The results were compared with the GRS subgroups for the risk of insulin requirement.

Results Mitochondrial haplogroups modulate the clinical features of type 2 diabetes, in which patients harboring haplogroup D4, as compared to those harboring non-D4 haplotypes were less prone to require insulin treatment, after correction for age, sex and diabetes duration. However, there was no association between clinical features and GRS calculated from nuclear genetic variants.

Conclusions Mitochondrial haplogroups, but not GRS constructed by nuclear genetic variants, have a better association with the insulin requirement. Our results highlight the role of mitochondria in the management of common metabolic diseases.

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PROGNOSTIC MODEL FOR CKD REGRESSION AND PROGRESSION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1,2

CHIEN-HSING LEE, 2YAU-JIUNN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2 Lee's Endocrinologic Clinic, Pingtung, 90000, Taiwan

Background: To investigate the validation of a risk prediction model that has published recently in the prediction of development, progression, and regression of the renal function changes in patients with type 2 diabetes mellitus (T2DM).

Methods: T2DM patients who constitutively managed for at least 12 months were included.

Participants were categorized into stable, progression, or regression groups according to their change in estimated glomerular filtration rate and urinary albumin/creatinine ratio. Baseline clinical characters and biochemical data were applied to the model.

Results: 8367 T2DM patients were enrolled in this study and followed-up for a mean of 8.2 years. The score obtained at the baseline of the prediction model was significantly associated with the baseline renal function status. The progression group had the highest score and the regression group had the lowest score. In addition, when patients without clinical evidence of kidney disease, the baseline score we also found to be associated with the newly developed kidney damage.

Conclusions: Our data indicated that the prediction score is a useful clinical tool in evaluating the renal changes of patients with T2DM in clinical practice.

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OD05

HYPOGLYCEMIA AND HEART RATE VARIABILITY: SYNCHRONOUS DETECTION BY HOLTER AND CONTINUOUS GLUCOSE MONITORS. CHIA-JUNG HSU, FENG-HSUAN LIU, SHU-FU LIN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

Background: Hypoglycemia is a notorious diabetic side effect leading to unwanted major vascular events and sudden cardiac death due to change in autonomic cardiac function. Previous studies have reported electrocardiographic (ECG) abnormalities such as QT interval prolongation in patients with hypoglycemia. The aim of this study was to document ECG and heart rate variability (HRV) changes during hypoglycemia, and to explore risk factors that may also affect ECG changes in poor controlled diabetic patients.

Methods: Seventeen participants including twelve poor controlled type 2 diabetes, four type 1 diabetes and one suspected nesidioblastosis were enrolled in this study. There were eleven females and six males, aged from 37 to 77 (mean 50.3 ± 12.0) years old, with self-reported duration of diabetes from 6 to 33 (mean 20.8 ± 8.7) years. The mean HbA1c was 8.3 ± 1.4 % on the time of the examination. We used Holter monitor (VitalSigns) and continuous glucose monitor (Medtronic) to record ECG waveform, heart rate variability and glucose level with synchronization of time for a duration of seven days.

Results: Three of the seventeen participants did not experience hypoglycemia (≤ 70 mg/dL). The other participants who experienced hypoglycemia revealed, as a whole, a trend of correlation between blood glucose, corrected QT Interval (QTc), heart rate (HR) and low frequency/ high frequency (LF/ HF) ratio. When the participants experienced hypoglycemia were sub-divided into response and nonresponse groups according to the appearance of QTc prolongation, significant negative correlations were found between the length of QTc interval as well as LF/HF ratio and glucose levels in the response group. In contrast, no significant correlation was found between glucose levels and QTc length as well as LF/HF ratio in the non-response group. It was also interestingly to find that the nonresponse group of participants are mostly type 1 diabetic patient.

Conclusions: We found that the appearance of QTc prolongation and LF/HF ratio elevation during hypoglycemia was quite different in our patients with poor sugar control, and the cause of the heterogenecity may be due to individual difference of autonomic dysfunction, glycemic variability and/or mean absolute glucose change per unit time.

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INFORMATION SYSTEM INITIATED ACTIVE CONSULTATION FOR IN-PATIENTS WITH HYPERGLYCEMIA COULD IMPROVE MEDICAL CARE QUALITY 1,2 1

CHING JUNG HSIEH

寶建醫療社團法人寶建醫院內科部、2 美和科技大學 護理學系

Background Many studies have shown that hyperglycemia correlates with mortality and morbidity in patients in hospital. Well glycemic control could decrease healthcare resource utilisation including length of stay (LOS) in hospital, hospital mortality, and 30-day readmission rate in critically and non-critically ill patients regardless of the presence or absence of diabetes. In our previous study, we also found high glucose variability increases 30-day readmission rates in patients with type 2 diabetes hospitalized in department of surgery. In another our ten-years’ study, early short-term intensive multidisciplinary diabetes care could decrease coronary artery disease and nephropathy progression. In this study, we want to investigate whether proactive and intensive intervention with multidisciplinary diabetes care for in-hospital patients could reduce healthcare resource utilisation and glucose variability.

Methods We used our automatic information systems to inform doctor of Endocrine &Metabolism to make immediately recommendation for in-hospital patients with first sequential 2 times of blood glucose levels more than 250 mg/dL measured after admission, then initiated multidisciplinary diabetes care. In charged attending could decide receiving autonomic consultation or not. The patients not receiving proactive multidisciplinary diabetes care were as control group.

Outcome measure included average and standard deviation (SD) of blood glucose and health care cost during admission, glycated hemoglobin (HbA1c), lipid profile and urine albumin/ creatinine ratio(UACR), changes of medication for DM after discharge 3-6 month , LOS, readmission within 30 days, and mortality rate. Discharge diagnosis, in-charged subspecialist and number of ED/office visits were also recorded.

Results There are 505 patients who had received active consultation system had lower readmission rate within 30 days after discharge (3.4% vs 6.8%), health care cost (23,3253 ± 10,5325 NTD vs. 26,7462 ± 10,4228 NTD, p < 0.001), mortality rate (2.2% vs.3.4%) and LOS (7.0 ± 1.8 days vs 9.0 ± 1.6 days, p = 0.010) than 610 patients as control. Comparing to control group, the study group also had lower HbA1c (7.7 ± 2.2% vs. 8.5 ± 2.3% p = 0.015) after discharge and less blood glucose fluctuation during admission (75.7 ± 20.5 mg/dL vs. 99.1 ± 26.5 mg/dL, p = 0.088). The SD of blood glucose level was apparent correlated with HbA1c after discharge and health care cost. There were no group differences in in-charged subspecialist, number of ED/office visits, medication amount for DM,

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lipid profile, UACR and discharge diagnosis.

Conclusion Intensive early intervention by active consultation system and multidisciplinary diabetes care may decrease blood glucose fluctuation, healthcare resource utilisation including decrease the LOS, hospital mortality, total cost of care and 30-day readmission rate.

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CHANGE OF REAL-TIME ULTRASOUND STRAIN ELASTOGRAPHY IN PATIENTS WITH GRAVES’ DISEASE. KUN-YO LAI, FENG-HSUAN LIU, SHU-FU LIN, SZU-TAH CHEN Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou,Taiwan

Objective: The purpose of this study is to detect the change of tissue stiffness of patients with Graves’ disease (GD) before and after treatment with real-time ultrasound strain elastography (SE) technique.

Methods: A total of 67 subjects (54 women and 13 men) with Graves’ disease, aged from 16 to 68 (42.73 ± 11.74) y/o were enrolled for strain elastography examination. They were divided into hyperthyroid (n = 39) and euthyroid (n = 28) groups in this study. Two measurements of elastic modulus values, i.e. liver fibrosis index (LFI) and strain ratio, were performed in the cross-sectional view, strain ratio was obtained by comparing with the ipsilateral sternocleidomastoid muscle.

Thyroid function tests including T4, TSH, and TSH receptor antibody (TRAB) were detected in all patients. Independent sample t-test, logistic regression, Pearson’s correlation and receiver operating characteristic (ROC) curve were applied for statistical analysis.

Results: The elastic modulus value of LFI in hyperthyroid and euthyroid groups ranged from -1.0 to 2.06 (mean 0.49 ± 0.77) and -0.72 to 3.23 (mean 1.05 ± 1.14), p < 0.05, respectively. Patients with higher LFI showed lower risk of hyperthyroidism (OR: 0.53, 95% CI, 0.31-0.92); in contrast, patients with lower LFI showed higher risk of euthyroidism (OR: 1.87; 95% CI: 1.08-3.24). LFI was also found to be negatively correlated with T4 (r = -0.26), TRAB(r = -0.28) and hyperthyroidism (r = -0.28) in GD, all p < 0.05. The area under the curve of ROC (AUC ROC) of euthyroidism evaluated by LFI was 0.63, with the best discrimination point of value of 0.85 (sensitivity 57.1% and specificity 69.2%). In addition, TRAB displayed positive correlation with T4 (r = 0.40, p < 0.001) and hyperthyroidism (r = 0.40, p < 0.001); age showed positive correlation with LFI (r = 0.39, p < 0.01) and strain ratio (r = 0.31, p < 0.05). No correlation was found between strain ratio and T4, TSH or thyroid function status.

Conclusion: LFI of strain elastography correlates with thyroid function status in GD patients. In addition, TRAB and age could influence thyroid stiffness of GD.

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OE02

STABILITY OF THYROID STIMULATING HORMONE RECEPTOR ANTIBODY IN THE STORED SERUM SAMPLES 1

TA-CHI CHEN, 1I-TE LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan

Background As the measurement of serum thyroid stimulating hormone receptor antibody (TRAb) and thyroid stimulating immunoglobulin (TSI) becoming the standard of care for diagnosis of Graves’ disease, sensitivity and specificity of every test kit also became a research issue. However, before validating those results, we must make sure that the samples we used could reveal consistent result during every test---after all, the difference between each kit was so small, and a minor sample factor could result in different conclusion. This study aimed to discover the impact of sample storage on subsequent test results.

Methods Patient group: Those who came to outpatient clinic of Taichung Veterans General Hospital with thyroid disease. All the patients signed informed consent for additional sample collection during regular blood draw, for the need of further research on thyroid diseases.

According to storage record, all the serum samples were stored in the refrigerator under -70’C in the lab. There was no additional thawing and freezing processes on collected samples before this study.

All the samples tested on the same day for twice with Roche e602 anti-TSHR( the TRAB kit) and twice with Siemens IMMULITE 2000 Xpi(the TSI kit). TSH(thyroid stimulating hormone) and free T4(tetraiodothyronine) level was acquired at the time of blood draw with Siemens IMMULITE i 2000XPi. Results From 2012/3/20 to 2018/11/22, serum sample of 88 patients were collected. All the samples were tested on 2019/7/12 for this study. Among all the patients there were 15 male, 73 female, aged 21 to 68 years old with median age 39 years old.

According to the patients’ serum level of TSH and free T4, 16 had hypothyroidism, 38 had hyperthyroidism and 34 were under euthyroid status. The test result of TRAB had a very high correlation with TSI (Pearson correlation 0.37, P value < 0.0001). The Mean absolute deviation between 2 TSI tests was not associated with storage time (Pearson correlation 0.16, P value 0.145), but the Mean absolute deviation between 2 TRAB tests was highly associated with storage time (Pearson correlation 0.54, P value <0.0001).

Conclusions The level of TSI may decrease over time even if it was stored under -70’C condition. The decay of TRAB may affect the result and the confidence interval of each test may have to change according to storage time of samples, if retrospective study was to perform.

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Abstract OE03

THE DIAGNOSTIC UTILITY OF LIQUID-BASED CYTOLOGY FOLLOWING INADEQUATE RESULT OF CONVENTIONAL SMEAR IN FINE NEEDLE ASPIRATION OF THYROID NODULES. 1

LAY SAN LIM, 1CHEN-KAI CHOU

1

Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Background: Thyroid fine-needle aspiration (FNA) is a cost-effective and safe diagnostic tool for evaluation of thyroid lesions. Traditionally, conventional smear (CS) method with modified Romanowsky stain or Papanicolaou stain has been widely used for cytologic preparation of thyroid despite its limitations as blood-obscuring background, poor cellularity and personal smearing skill.

Liquid-based cytology (LBC) has been introduced and applied widely in recent years. This study aimed to evaluate the diagnostic utility of LBC following inadequate result of CS in thyroid FNA. Methods: From September 2019 till October 2020, 210 LBC were collected. Among these 210 LBC cases, 159 cases had previous CS data. Cytomorphological features were categorized using the Bethesda system for reporting thyroid cytopathology (BSRTC). 59 of 159 CS were categorized as BSRTC I had repeated thyroid FNA using LBC and the rate of adequacy were assessed. 32 cases of 210 LBC underwent surgical resection and correlation with the histology diagnosis was done.

Results: Among CS with BSRTC I, adequacy of sampling increased 49% by repeat FNA using LBC method. Two of previous CS with BSRTC I cases were classified as BSRTC V after repeat FNA with LBC. One case received surgical resection and the pathology report turned out papillary thyroid cancer (PTC). LBC has 69% NPV (9/13, 2 cases of incidental findings of papillary thyroid microcarcinoma, 1 case of follicular carcinoma and 1 case of PTC, follicular variant) for cases diagnosed as benign (BSRTC II). For group of suspicious for malignancy (BSRTC V), LBC has 100% PPV. Conclusions: LBC represent as alternative or additional method to CS of thyroid FNA, especially in CS group with the diagnosis of BSRTC I to obtain informative results. More data and further studies are needed.

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OE04

THE IMPACT OF DISTANT METASTASIS ON PROGNOSIS IN PATIENTS WITH FOLLICULAR THYROID CARCINOMA 1,2

MING-HSIEN WU, 1,2YI-YIN LEE, 1,2YU-LING LU, 1,2SHU-FU LIN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital (built and operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan

Background: Follicular thyroid carcinoma (FTC) is the second most common of the thyroid carcinoma and accounts for approximately 10–15% of all thyroid cancers. Patients with FTC usually have favorable prognosis. However, the outcome in patients with metastatic FTC is considered to be poor. We investigated the impact of distant metastasis at presentation or during follow-up on outcomes in patients with FTC. Methods: Patients with FTC diagnosed between December 1976 and May 2020 were analyzed using a prospectively maintained database of patients with thyroid cancer. A total of 190 patients, including 29 had metastatic FTC at initial presentation (Group A), 14 had metastatic disease during follow-up (Group B), and 147 without metastatic disease thorough the clinical course (Group C) were assessed. Data on basal demographic characteristics, tumor staging, laboratory tests and type of surgical treatment were collected. Statistical analyses used in this study were descriptive statistics, Kaplan-Meier survival curves and Cox proportional hazards regression.

Results: Among three groups, Group A was the oldest (66.1 ± 8.9 years), followed by Group B (59.7 ± 8,7 years) and Group C (42.7 ± 17.3 years). Group A had highest post-surgery thyroglobulin (Tg) level and the most advanced cancer staging as compared with the other two groups. The overall cancer-specific survival was 8.4 years in Group A, 21.7 years in Group B, and no mortality occurred in Group C during a mean follow-up of 7.6 years. Univariate analysis demonstrated older age (> 55 years), metastatic disease, higher accumulated 131I dose (> 100 mCi), higher post-surgery Tg (≥ 30 ng/mL) and advanced TNM classification (stage III and IV) were associated with poorer cancerspecific survival. Multivariate analysis reveals metastasis and advanced TNM classification (stage III and IV) were associated with shorter cancer-specific survival.

Conclusions: Our data indicate patients with metastatic FTC at presentation had poor prognosis.

However, the patients developing metastatic PTC during follow-up usually harbored favorable overall survival.

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Abstract OE05

THERAPEUTIC OUTCOMES USING TARGETED THERAPY IN PATIENTS WITH ANAPLASTIC THYROID CANCER 1,2

YI-YIN LEE, 1,2MING-HSIEN WU, 1,2YU-LING LU, 3YU-TUNG HUANG, 1,2SHU-FU LIN

1

Division of Endocrinology and Metabolism, New Taipei Municipal TuCheng Hospital (Built and operated

by Chang Gung Medical Foundation), New Taipei City, Taiwan; 2 Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Taoyuan, Taiwan; for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Background: Anaplastic thyroid carcinoma (ATC) is a rare but fatal disease, with median survival of 3-6 months. Multimodality treatment, including surgery, chemotherapy and radiotherapy provides limited therapeutic benefits. Recently, US FDA approved a BRAF inhibitor (dabrafenib) plus a MEK inhibitor (trametinib) for locally advanced, metastatic ATC with BRAFV600E mutation.

Lenvatinib and sorafenib have demonstrated activity against ATC in clinical trials.

Methods: Patients with ATC were analyzed using a prospectively maintained database of patients with thyroid cancer registered at a medical center between January 2000 and November 2020. Subjects were classified into three groups according to treatment modalities: best supportive care (Group 1), conventional treatment (Group 2) and targeted therapy (Group 3). Baseline characteristics, tumor staging, BRAF mutation status, and comorbidities were assessed. Survival were analyzed using Kaplan-Meier method.

Results: A total of 38 patients were identified, including 9 in Group 1, 23 in Group 2, and 6 in Group 3. Most patients were female (60.5%) and the median age was 74.4 years. Most patients had stage IVC disease (65.8%), followed by stage IVB (21.1%) and stage IVA (13.2%). Five patients had concurrent papillary thyroid cancer. The most common comorbidities were hypertension (48.6%), followed by diabetes (21.2%), coronary heart disease (8.1%), cerebrovascular accident (8.1%), and the other malignancy (8.1%). Twenty patients (52.6%) received surgery and 23 patients (62.2%) received radiotherapy. Targeted therapies used were dabrafenib plus trametinib (n = 3), lenvatinib (n = 1), and sorafenib (n = 2). Six-month and 12-month survival rates were 10% and 0% in Group 1, 30.4% and 13% in Group 2, and 100% and 75% in Group 3. Targeted therapy significantly improved survival compared with either best supportive care or conventional treatment (P < 0.05 for both comparison).

Conclusions: Patient with ATC had dismal outcomes either treated with best supportive care or conventional therapy. However, targeted therapy improved survival in this papulation.

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OE06

CLINICAL EXPERIENCE WITH RECOMBINANT HUMAN THYROTROPHIN (RHTSH) IN DIFFERENTIATED THYROID CANCER FROM A MEDICAL CENTER IN SOUTH TAIWAN JIA-RUEI TSI, CHEN-KAI CHOU Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

INTRODUCTION: The use of recombinant human thyroid-stimulating hormone (rhTSH), which is known to be efficient in remnant ablation. The objective of the current study was to assess the impact of age and cancer stage influence on cancer treatment response with use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC).

METHOD: From 2013 to 2019, total of 1421 DTC cases received radioiodine ablation in Kaohsiung Chang Gung Memorial Hospital were included in this study. We analyzed sequential follow up treatment response defined by America Thyroid Association guideline in the DTC patients who use of rhTSH and levothyroxine withdrawal (THW) after thyroid remnant ablation.

RESULT: Among 1421 received radioiodine ablation cases, 1089 of them were female and 334 of them are males. All subjects were classified as rhTSH group (N = 396) and THW (N = 1027). No obvious treatment response difference was noted between rhTSH group (30.2%) versus THW group (27.9%). Furthermore, no significant treatment response differences between different age and cancer stage group (P > 0.05, respectively).

CONCLUSION: In conclusion, treatment response by either rhTSH or THW are comparable for DTC patients, even in different cancer stage or age based on current study observations.

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Abstract PD01

ASSOCIATION OF PREGNANCY OUTCOMES IN WOMEN WITH TYPE 2 DIABETES TREATED WITH METFORMIN VERSUS INSULIN WHEN BECOMING PREGNANT 1,2,3

SHU-FU LIN, 3,4,5,6SHANG-HUNG CHANG, 3,7,8CHANG-FU KUO, 5WAN-TING LIN, 8 MENG-JIUN CHIOU, 5YU-TUNG HUANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan,Taiwan; 5Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Linkou, No.15, Wunhua 1st Rd., Gueishan Dist, Taoyuan City 333, Taiwan; 6Graduate Institute of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan; 7Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 8Center for Artificial Intelligence in Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Background: Metformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment.

Methods: The cohort of this population-based study includes women of age 20–44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes.

Results: A total of 1166 pregnancies were identified in the insulin group (n = 222), the switching group (n = 318) and the metformin group (n = 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth ( 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40–0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27–0.94) and similar risk for the other outcomes as compared with the insulin group.

Conclusions: Metformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.

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PD02

MATERNAL PLASMA LIPIDS DURING PREGNANCY, PLACENTAL GROWTH FACTORS, AND EXCESS FETAL GROWTH: A PROSPECTIVE COHORT STUDY 1

KUAN-YU CHEN, 2SHIN-YU LIN, 2CHIEN-NAN LEE, 3HUNG-TSUNG WU, 4,5 CHING-HUA KUO, 5HAN-CHUN KUO, 5CHIA-CHI CHUANG, 6CHUN-HENG KUO, 7 SZU-CHI CHEN, 8KANG-CHIH FAN, 2MING-WEI LIN, 9CHI-TAI FANG, 10HUNG-YUAN LI 1

Department of Internal Medicine, ANSN Clinic, Hsin-Chu, Taiwan; 2Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan; 3Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; 4School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; 5The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; 6Department of Internal Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University; 7Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei City Hospital, Ren-Ai branch, Taipei, Taiwan; 8Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Taiwan ; 9Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 10Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Background: Intra-uterine environment, not limited to maternal glucose availability, has a great influence on excess fetal growth. Both maternal lipids during pregnancy and placental growth factors contribute significantly. However, how these factors interact to result in increased risk of delivering large-for-gestational-age (LGA) newborns remains unclear. In this study, we investigated the interplay between maternal plasma triglyceride (TG) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA, and studied the effect of different fatty acids (FAs) on placental IGF-1 secretion.

Methods: This cohort study included pregnant women with singleton and term pregnancy and without diabetes nor hypertensive disorders in pregnancy. Maternal fasting plasma TG and FFAs were measured in the second trimester. Cord blood growth factors including IGF-1, IGF-2, and IGF binding protein-1 and -3 were measured. A human trophoblast cell line, 3A-Sub-E, was used to evaluate the effect of different FAs on placental IGF-1 secretion.

Results: We recruited 598 pregnant women-newborn pairs, including 43 LGA newborns.

Maternal plasma TG and cord blood IGF-1 concentrations were higher in the LGA group and were associated with birth weight z-score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) nor lenoleic acid (LA), were associated with cord blood IGF-1 concentrations.

In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced the expression and secretion of IGF-1.

Conclusions: Certain FAs can induce placental IGF-1 secretion, which is a novel pathophysiology linking maternal plasma lipids and LGA. 136

Abstract PD03

ASSOCIATION STUDY BETWEEN THE STAPHYLOCOCCUS AUREUS STRAINS AND CLINICAL OUTCOMES IN DIABETIC FOOT ULCER 1

JUI-HSIANG LI, 2YI-SHENG CHEN, 2YUN-SHIEN LEE, 2{HUI-CHUNG WU

1

Division of Endocrinology and Metabolism, Tao-Yuan General Hospital; 2 Department of Biotechnology, Ming Chuan University

Diabetic foot ulcer (DFU) is one of the most common chronic complications of diabetic patients. Patients often need recurrent hospitalizations or even amputation if the wound heals poorly and continues to deteriorate. Therefore, foot infections in patients with diabetic must be diagnosed and treated appropriately. Studies have pointed out that the microbial flora may affect the healing of diabetic foot ulcers. However, reports of the impact of specific microorganisms on the wound healing of diabetic foot ulcers remains scarce. In addition, the relationship between the microflora of the wound and the occurrence of diabetes complications is still unclear. Many literature points out that Staphylococcus is the most common bacteria observed in DFU. A study “Strain- and SpeciesLevel Variation in the Microbiome of Diabetic Wounds Is Associated with Clinical Outcomes and Therapeutic Efficacy” (Cell Host Microbe. 2019 8;25[5]:641-655.e5.) revealed the strainlevel variation of Staphylococcus aureus. Using Metagenomic shotgun sequencing to analyze the longitudinal samples of 100 patients, findings suggest that the DFU microbiota may be a marker for clinical outcomes and response to therapeutic interventions. Our study collected samples from 11 patient specimens in Taoyuan Hospital and determined the microflora of the wounds. The result shows that the bacterial test in the hospital laboratory are consistent to the results of the traditional bacterial culture method for detecting Staphylococcus aureus. Importantly, comparing the odds ratio of patients having Staphylococcus aureus and hospitalization for more than one week and patients without Staphylococcus aureus and hospitalization for less than one week, the Odd Ratio is up to 7.5 (p value = 0.20). In addition, by the traditional bacterial culture method, a potential novel species of Streptococcus was identified and the most similar species were Streptococcus mitis NCTC 12261.

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PD04

THE EFFECT OF SGLT2 INHIBITOR ON CEREBROVASCULAR EVENTS: A META-ANALYSIS 1

WEN-HSUAN TSAI, 1SHIH-MING CHUANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (ROC)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown impressive effect in reducing major vascular events in several randomized controlled trials (RCTs). The purpose of this study was to perform a meta-analysis to evaluate the effect of SGLT2 inhibitor on the risk of stroke and its subtypes.

Methods: All data from prospective randomized placebo-controlled trials up to 27 May 2020 involving SGLT2 inhibitor which reported stroke events as primary endpoints or safety in subjects with type 2 diabetes were meta-analysed Results: Five eligible randomized placebo-controlled trials (EMPA-REG, CANVAS, DECLARE, CREDENCE and VERTIS CV) involving 46969 participants were included. Pooled analysis of RCTs showed no significant effect of SGLT2 inhibitors on total stroke [risk ration (RR) 0.97; 95% confidence interval (CI) 0.87–1.08, P = 0.614]. The subgroup analysis indicated that the effect of SGLT2 inhibitor had no significant effect against fatal stroke (RR = 0.87, 95% CI 0.61-1.26, P = 0.472), non-fatal stroke (RR = 0.96 95% CI 0.88-1.10, P = 0.750), ischemic stroke (RR = 0.99, 95% CI 0.88-1.12, P = 0.949) or transient ischemic attack (RR: 0.94, 95% CI: 0.80–1.12; P = 0.506). When only hemorrhagic stroke was included, SGLT2 inhibitor was associated with a significant reduction by 50 % compared with placebo (RR = 0.50, 95% CI 0.30–0.83, P = 0.007).

Conclusions: The meta-analysis support SGLT2 inhibitors have neutral effect on risk of stroke and its subtypes, and possible potential protective effects against hemorrhagic stroke despite small number events.

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Abstract PD05

CONTINUOUS GLUCOSE MONITORING (CGM) AND 5-HOUR ORAL GLUCOSE TOLERANCE TEST IN A RARE CASE WITH INSULINOMA 1

CHI-EN YEN, 1SHU-YI WANG, 1SHI-DOU LIN, 1SHANG-REN HSU, 1SHIH-TE TU

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Taiwan, R.O.C

Insulinoma is a rare pancreatic islet cell tumor that cause high endogenous insulin secretion resulting in episodes of hypoglycemia. We report here the case of an 64-year-old female with a past history of hypertension, hyperlipidemia and diagnosed with diabetesmellitus. She was presented to our clinic, due to frequent hypoglycemic episodes ever with loss of consciousness. Hypoglycemic episodes frequently attack around 10:00 am. These symptoms resolve promptly following glucose administration. Elevated C-peptide level in the presence of hypoglycemia. Abdominal sonography showed cystic lesion 1.4 cm over pancreatic head. Abdominal computed tomography scan revealed a 1.5 cm enhancing nodule in pancreatic neck. Pancreatic insulinoma was highly suspected. Continuous glucose monitoring showed downward glucose excursion after breakfast, with hypoglycemia before lunch. 72 hours fasting test was arranged, but the data is not complete, due to the patient feels hypoglycemia symptoms without hypoglycemia. A 5-hour Oral 75 gm Glucose Tolerance Test (5-hour OGTT) showed hypoglycemia episode noted after glucose intake around 3 ~ 3.5 hours. The patient underwent successful resection of the tumor, and his symptoms showed complete resolution.

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PD06

GLP-1 RECEPTOR AGONIST MODULATES BILE ACID METABOLISM TO ATTENUATE HIGH FAT DIET-INDUCED HEPATIC STEATOSIS 1

HE-JIUN JIANG, 2TIEN-CHOU SOONG, 1YU-HSI KAO, 1PI-JUNG HSIAO

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital Department of Weight Loss and Health Management Center, E-DA Dachang Hospital

2

Aim: Glucagon-like peptide 1 receptor analogues (GLP-1 RAs) are currently approved as a class effect to improve hepatic steatosis even absence of GLP-1 receptor on hepatocytes. GLP1RA significantly delays the intestinal motility and transit time, which may affect the enterohepatic circulation of the bile acids homeostasis. Therefore, modification of the enterohepatic circulation and hepatic BA pools was speculated for the hepatoprotective effect of GLP-1RAs. Materials and Methods: A mice model of high fat diet (HFD) induced hepatic steatosis was designed to test the changes of hepatic histology, lipogenesis (FASN, ACC, SREBP-1) and inflammasome (NLRP3, pNFκB), hepatic bile acids pool and bile acid signaling (FXR, TGR5). The effect to add on Bydureon (extended-released exenatide, 500 g/kg/wk) treatment for 16 weeks was compared with groups of chow diet and HFD. The bile acid analysis was conducted by ultra-highperformance liquid chromatography coupled with triple quadrupole Mass Spectrometer (UPLC/ TQMS).

Results: HFD significantly induced weight gain, hepatic steatosis, insulin resistance, increased lipogenesis and inflammation and altered hepatic BA pool. The total hepatic BA pool was 5438.21 ± 438.75 nM in groups of chow, significantly decreased to 4029.46 ± 198.76 nM by HFD but markedly raised to 6491.47 ± 810.47 nM by add on Bydureon. The hepatic BAs as ligands of the FXR/ TGR5 receptors displayed significant changes by HFD, while both of FXR/TGR5 agonists or FXR antagonists were significantly raised by Bydureon treatment. Hepatic expression of the FXR/TGR5 was downregulated by HFD with relevant to enhanced lipogenesis and inflammasome. But, Bydureon treatment significantly reversed all these changes.

Conclusions: HFD resulted in an altered BA homeostasis. GLP-1RA treatment could modulate hepatic BA homeostasis and improve hepatic steatosis and inflammation, which may be mediated by the FXR/ TGR5 signaling.

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Abstract PD07

INFLUENCE OF WEIGHT LOSS ON BLOOD SUGAR CONTROL AND TREATMENT SATISFACTION FROM THE USE OF GLP-1 RA CHEN-JUNG SHEN, CHIEH-TING YEH 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, An Nan Hospital, China Medical University,Tainan, Taiwan, R.O.C.; 2Nursing Department, An Nan Hospital, China Medical University,Tainan, Taiwan, R.O.C.

Background: Less than 35% of diabetic patients reach the standard for HbA1c; most of the cases fail to reach the standard after using a variety of oral drugs. At this time, consider the use of injectable drug treatment, which is one of the effective methods to control blood sugar. However, most patients are reluctant to receive injection therapy because they are worried about side effects and medication inconvenience. Compared with insulin, GLP-1 RA effectively controls blood sugar without causing weight gain, and the risk of hypoglycemia is relatively low. Besides, GLP-1 RA may reduce body weight and motivate the patient to receive medication more aggressively.

Method: Included cases: The following conditions must be met: 1. Type 2 diabetes cases tracked in the outpatient clinic, 2. Have received oral hypoglycemic drugs, but blood sugar control is still reach target, need to receive injection treatment, 3. Have not received insulin treatment, 4. After diabetic education, the patient is willing to receive the treatment of GLP-1 RA injection. In addition to the original diabetes medication, the professional team added GLP-1 RA injection therapy to the admitted patients, plus intervention to improve their lifestyle, and cooperated with health education tools (digital health education manual, blood glucose pull board, diabetes personal dialogue and viewing Picture talk) to improve the compliance of the case, improve the blood sugar control of the case, strengthen weight management, and improve the quality of life It is planned to execute the itinerary from March 1, 2018 to September 30, 2018, a total of seven months. During the acceptance period, each case was fully observed for three months.

Results: A total of 50 people have been included in this project, and the project results are as follows • The average HbA1c of all cases dropped from 8.37% to 6.99%, an improvement of 1.38%.

• The average weight of all cases dropped from 82.17 kg to 76.84 kg, and the weight loss ratio: -5.33%.

• Changes in fasting blood glucose in the first 2-4 weeks of all cases: 130.68 mg/dL • The average score of patients’ satisfaction with treatment is 26.72 (out of 30) Conclusion: With the intervention of professional health education, the diabetes team enhances the individual’s understanding of GLP1-RA injection therapy, which can enhance the individual’s compliance with the treatment. With appropriate drug adjustments, the lifestyle improves, which can significantly improve blood sugar control and reduce blood pressure. Blood sugar occurs, reducing weight and improving quality of life.

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PD08

PYOGENIC LIVER ABSCESS RISK IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS: A NATIONWIDE, POPULATION-BASED COHORT STUDY IN TAIWAN 1

TZU-YUAN WANG, 2HSIN-HUNG CHEN, 1MING-CHIA HSIEH, 1CHING-CHU CHEN, 1 CHWEN-TZUEI CHANG, 1RONG-HSING CHEN, 1CHUN-WEI HO, 1WEI-LUM HUANG, 1 YI-CHIN HUNG, 1TUEI-YU TSENG, 1JIA-YIN GUO, 1YOU-TING LIN 1

Intelligent Diabetes Metabolism and Exercise Center, Department of Internal Medicine, China Medical University Hospital, Taichung,Taiwan, ROC; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan.ROC.

Background: Pyogenic liver abscess (PLA) is a serious infectious and life-threatening disease with a low but gradually increasing annual incidence rate. To date, no comprehensive epidemiological study exists for PLA risk in patients with newly diagnosed type 2 DM worldwide. The aim of this study is to explore newly diagnosed type 2 DM and PLA risk in Taiwan.

Methods: We extracted a DM and comparison cohorts from the Longitudinal Health Insurance Database and compared PLA risks between them. In the DM cohort, patients newly diagnosed as having type 2 DM (ICD-9-CM 250) from 2000 to 2009 were enrolled. We used date of initial DM diagnosis as the index date. In the comparison, individuals without a history of DM were randomly 1:4 frequency-matched with the DM cohort, the matching was based on the age of cohort entry (per 5 years) and sex. The index date for the comparison cohort was a randomly assigned date, in the same year as that of the index date of their DM cohort patients.

Results: A total of 44728 patients with DM and 178912 patients without DM were enrolled.

In DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10000 personyears) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10000 person-years).The DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in DM cohort was the highest in those younger, men and patients in the first 2 years after diagnosis of type 2 DM. In the DM cohort, the most common PLA causative agent was Klebsiella pneumoniae. In addition, PLA risk was high in DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with type 2 DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in DM cohort.

Conclusions: In paitents with newly diagnosed type 2 DM, PLA risk was high and acarbose demonstrated beneficial effect of reducing PLA risk.

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Abstract PD09

GCK-MODY DIAGNOSED BEFORE 4 YEARS OF AGE: A STUDY ON TWO FAMILIES 1,2,3,4,5

YANN-JINN LEE, 1,4,6WEI-HSIN TING, 1,4,6CHI-YU HUANG, 7,8FU-SUNG LO, 9 CHAO-HSU LIN, 10YI-LEI WU, 2CHIUNG-LING LIN 1

Pediatric Endocrinology, MacKay Children's Hospital; 2Medical Research, MacKay Memorial Hospital Tamsui District; 3Pediatrics, School of Medicine, College of Medicine, Taipei Medical University; 4Medicine, Mackay Medical College; 5Institute of Biomedical Sciences, Mackay Medical College; 6MacKay Junior College of Medicine, Nursing, and Management; 7Pediatrics, Chang Gung Memorial Hospital; 8College of Medicine, Chang Gung University; 9Pediatrics, Mackay Memorial Hospital HsinChu Branch; 10Pediatric Endocrinology and Metabolism, Chuanghua Christian Children's Hospital

Introduction Maturity onset diabetes of the young (MODY) is caused by single gene mutations, resulting in defects in the development, proliferation/regeneration, and/or function of β cells. Strict criteria for the diagnosis of MODY include diabetes in at least 3 genera¬tions with autosomal dominant transmission and diagnosis before age 25 yr in at least 1 affected subject. We reports 2 children younger than 4 years with hyperglycemia and mutations of the GCK gene, which are transmitted from their parents.

Case reports Patient 1 1 1/12 year-old boy had fasting hyperglycemia accidentally found. His Glucose was 110 mg/dl and HbA1c 6.2%. His mother also had fasting hyperglycemia and gestational diabetes.

Molecular analysis on the GCK gene was performed by using PCR and sequencing. The variations detected are listed below. The specimen from the client is heterozygous for mutation c.556C>T, p.Arg186Ter which is pathogenic.

The analysis showed that Mother has the variant but her parents did not have. De novo mutations in the GCK gene have been described in literature. Paternity and maternity were confirmed using HLA-B locus genotyping (Table 1, Figure 3).

Table 1. GCK and HLA-B genotypes in patient 1 and his family Patient ID GCK allele GCK other allele HLA-B allele HLA-B other allele 6873 c.556C>T No mutation 6873F No mutation No mutation 6873M c.556C>T No mutation 46:01 81:01/02 143

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6873MF No mutation No mutation 15:01 81:01/02 6873MM No mutation No mutation 38:02 46:01 F, Father; M, Mother; MF, Mother's father; MM, Mother's mother Figure 1. Mutation c.556C > T, p.Arg186Ter in the GCK gene. The mutation causes a truncated protein of 185 amino acids.

Patient 2 A 3.9-year-old boy was found to have hyperglycemia during a laboratory work-up when he had acute bronchiolitis. His father has diabetes mellitus. A pathogenic variant was detected in GCK (Table 2, Figure 2). He inherited the variant from his father.

Table 2. Patient 2 Patient ID GCK allele GCK other allele 7108 c.505A > G No mutation 7108F c.505A > G No mutation 7108M No mutation No mutation 7108S1 No mutation No mutation F, Father; M, Mother; S1, sister Figure 2. Mutation c.505A > G, p.Lys169Glu in the GCK gene. The mutation leads to GCKMODY. Clinical Management Because GCK-MODY needs no treatment of hypoglycemic agents, healthy daily life is emphasized to avoid obesity and deranged metabolism.

Conclusions Children with mutations in GCK were instructed to avoid unnecessary treatment with hypoglycemia agents.

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Abstract PD10

THE EFFECT OF SGLT-2 INHIBITOR ON DIABETIC NEPHROPATHY AND WEIGHT CONTROL 1

CHEN-JUNG SHEN, 2CHIEH-TING YEH

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, An Nan Hospital, China Medical University,Tainan, Taiwan, R.O.C.; 2Nursing Department, An Nan Hospital, China Medical University,Tainan, Taiwan, R.O.C.; Nursing Department

Background: According to the annual report of kidney disease in Taiwan, there are about 78,000 dialysis patients in Taiwan, among which diabetes patients account for 49.3%. With the increasing prevalence of diabetes, the number of patients with diabetic nephropathy (DKD) has also increased year by year. However, more than 60% of diabetics in Taiwan still fail to meet the standard of glycosylated hemoglobin (HbA1c) (7%), of which 15% of diabetics will develop nephropathy, 39.7% of diabetics have albuminuria, and Taiwan’s acute chronic kidney disease patients More than 40% are caused by diabetes. In addition, 32% of diabetics have cardiovascular disease, and 15% of diabetics have heart failure. There are many treatment options for diabetes, including oral, injection, and lifestyle changes. However, some patients still do not respond well to treatment. SGLT2 inhibitors can improve blood sugar control, as well as kidney protection and weight loss. However, clinical original research data on the effectiveness of indigenous SGLT-2 inhibitors is relatively lacking in Taiwan. This project is expected to evaluate the effectiveness of SGLT-2 inhibitors for blood glucose, renal function, and weight control in patients with diabetes and nephropathy.

Methods: 1. or people with type 2 diabetes who have not been treated with SGLT-2 inhibitors, their eGFR > 45ml/min/1.73m2, and combined with the following two: (1) HbA1c > 7%, (2) UACR > 30mg /g, give SGLT-2 inhibitor treatment to track the overall HbA1c improvement, weight loss rate, and urine protein (UACR) decline rate of the accepted cases.

2. The acceptance period is 3 months (February 1, 2020 to April 30, 2020), and the observation period is 3 months (May 1, 2020 to July 31, 2020) 3. Exclusion conditions: cases receiving diuretic treatment during the observation period.

Results: A total of 60 people were admitted in this study. After treatment with SGLT2 inhibitors, the overall improvement of the case: the overall average HbA1c decreased from 9.11% to 8.30%, an improvement of 0.805%. The average weight was reduced from 73.82kg to 72.42kg, with an average loss of 1.39kg.

The average UACR decreased from 481.69mg/g to 278.86mg/g, and the average rate of decrease was 19.7%.

Conclusions: SGLT2 inhibitors are a new class of anti-diabetic drugs. This study shows that 145

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SGLT2 inhibitors can significantly improve HbA1c, reduce body weight, and reduce UACR. For patients with diabetes and nephropathy, SGLT-2 inhibitors may be a good choice. However, the overall improvement of diabetes comorbidities may require more clinical treatment data to support it.

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Abstract PD11

ASSOCIATION OF BODY MASS INDEX WITH ALL-CAUSE MORTALITY IN THE ELDERLY POPULATION OF TAIWAN: A PROSPECTIVE COHORT STUDY 1

YU-KAI LIN, 2,3CHUN-CHIEH WANG, 4,5,6YUNG-FENG YEN, 7LI-JUNG CHEN, 8 PO-WEN KU, 4CHU-CHIEH CHEN, 7,9,10YUN-JU LAI 1

Department of Health and Welfare, College of City Management, University of Taipei, Taiwan; 2Division of Chest Medicine, Department of Internal Medicine, Puli branch of Taichung Veterans General Hospital, Taichung, Taiwan; 3Central Taiwan University of Science and Technology Department of Eldercare, Taichung, Taiwan; 4 Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan; 5Section of Infectious Diseases, Taipei City Hospital, Taipei City Government, Taipei, Taiwan; 6Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 7Department of Exercise Health Science, National Taiwan University of Sport, Taichung, Taiwan; 8Graduate Institute of Sports and Health, National Changhua University of Education, Changhua, Taiwan; 9School of Medicine, National Yang-Ming University, Taipei, Taiwan; 10Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli Branch of Taichung Veterans General Hospital, Nantou, Taiwan

Background: The nutritional status of the elderly is different from that of young people. Body composition changes as people age, for example, fat mass increases, muscle mass decreases, and body fat distribution is changed. We aimed to investigate the association of body mass index (BMI) with cause-specific mortality in elderly population.

Methods: The data of annual health examination for the older citizens (≥ 65 years old) from 2006 to 2011 in Taipei City Hospital were used. Information on baseline demographics, lifestyle behaviors, medical and drug usage were collected by a self-administered questionnaire. Cause-specific mortality was ascertained from the National Registration of Death. Individuals were followed-up until death or December 31, 2012, whichever was earlier. Univariable and multivariable Cox proportional hazard analyses were applied to investigate the association between BMI and all-cause mortality.

Results: Among 81,221 older people included in the analysis, 42,602 (52.45%) were men. The mean age was 73.85 ± 6.32 years. Among the 81,221 participants, 3,398 (4.18%) were underweight, 36,476 (44.91%) were normal weight, 25,708 (31.65%) were overweight, and 15,639 (19.25%) were obese. Those in the BMI category 27 ≤ BMI < 28 kg/m2 had the lowest all-cause mortality risk. The BMI of lowest cause-specific mortality was between 27 kg/m2 and 28 kg/m2 in infection mortality, between 28 kg/m2 and 29 kg/m2 in circulation mortality, between 29 kg/m2 and 30 kg/m2 in respiratory mortality, between 31 kg/m2 and 32 kg/m2 in cancer mortality.

Conclusions: The current study found J-shaped relation between BMI and cause-specific mortality in elderly population of Taiwan.

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PD12

A SIMPLE TREATMENT FOR AN EFFECTIVE OUTCOME: USE OF IGLARLIXI TOGETHER WITH REAL-TIME CONTINUOUS GLUCOSE MONITORING TO ACHIEVE BLOOD GLUCOSE STABILITY IN NEWLY DIAGNOSED TYPE 2 DM 1

CHUN-HSING LIN, 1CHENG-PIN CHENG , 1YA-CHUN LI, 1MAN-NI LU, 1 TING-YU CHEN, 1,2,3CHUN-JUI HUANG 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 3 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Background: iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar -100) and the GLP-1 RA lixisenatide, is robustly used to improve glycemic control of patients with T2DM. Its effectiveness has been demonstrated in a wide variety of clinical settings, including patients inadequately controlled with basal insulin or oral anti-diabetic agents. However, there is less experience in using iGlarLixi in people newly diagnosed with T2DM and concomitantly applying realtime continuous glucose monitoring (RT-CGM).

Methods: Three patients with newly diagnosed type 2 DM and HbA1c >9.0% were selected in Taipei Veterans General Hospital to initially receive insulin glargine 300 U/mL combined with oral agents and further shifted to iGlarLixi to simplify regimen and reduce glucose fluctuation. During titration phase I, insulin glargine 300 U/mL was initiated along with metformin and mitiglinide. The insulin dosage was titrated to reach a fasting blood glucose (FBG) of 150 mg/dl and RT-CGM was introduced for the following 7 days. In titration phase II, insulin was substituted with iGlarLixi and the dosage was titrated to reach FBG around 130 mg/dl. RT-CGM was applied for another 7 days thereafter. To prevent hypoglycemia in phase II, mitiglinide was either discontinued or the dosage was reduced. In both phases, patients maintained a detailed dietary record and shared the information with diabetes educator through Health2Sync.

Results: The first case was a 32 year-old male who experienced very high post-prandial blood glucose around 250-350 mg/dl in phase I. After introducing iGlarLixi, the percentage of time in range (TIR, 70-180 mg/dl) improved from 22% to 89% without any blood glucose level exceeding 250 mg/ dl. The second and third case were 60 year-old female and 55 year-old male whose TIR did not differ significantly between the two phases (case 2: 80% v.s. 78%, case 3: 97% v.s. 98%). However, the 2% of blood glucose above 250 mg/dl disappeared in case 2 and hypoglycemia improved in case 3 under the use of iGlarLixi along with dietary modifications. The overall reduction of HbA1c in three months were 2.0%, 6.1%, and 4.6% respectively (HbA1c: 9.2% to 7.2%, 13.3% to 7.2%, and 12.5% to 7.9%).

Patient’s response to direct glucose readings were rapid and the dietary adjustments were rewarding.

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Abstract Conclusions: The use of iGlarLixi in patients with newly diagnosed T2DM not only simplified treatment regimen but also improved glucose stability. Both iGlarLixi and RT-CGM were able to enhance patients’ compliance and treatment outcome.

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PD13

THE EFFECTIVENESS OF PAY-FOR-PERFORMANCE PROGRAM ON DIABETES CARE FOR OUTPATIENTS IN A PSYCHIATRIC REGIONAL HOSPITAL IN MIDDLE TAIWAN. 1,2

CHIN-CHOU YANG, 2SHIAO-CHI WU, 2MING-CHEN GUO, 2WEI-CHENG TSAI

1

Department of Psychiatry, Division of General Medicine, TsaoTun Psychiatric Center, Ministry of Health and Welfare, Taiwan; 2Institute of Health and Welfare Policy, National Yang-Ming University

Background: Diabetes is a common health issue in the world. The prevalence of diabetes in patients with mental illnesses, such as schizophrenia, bipolar disorder, and anxiety disorder, are higher than general population(Grigolon et al., 2019; Mamakou et al., 2018), including Taiwan (Chien et al., 2010; Chien et al., 2009). The coincidence of mental disorders and diabetes mellitus has adverse effects on diabetes control (Abrahamian et al., 2019).

Good diabetes control has already been proved efficacious to prevent many acute and chronic diabetic complications (Turner, 1998). Pay-for-performance(P4P) program of diabetes care (or Diabetes Shared Care Program), which was initiated in 2001 by the Ministry of Health and Welfare in Taiwan, helps patients with diabetes to achieve better glycemic control (Wang et al., 2014). This care model has demonstrated successful outcomes in the P4P participants with type 2 diabetes (Hao et al., 2011). However, there were no endocrinologist hired by any psychiatric hospital in Taiwan before 2019, and P4P program of diabetes has never been adopted in these psychiatric hospitals.

Nearly everyone in Taiwan is covered with National Health Insurance, including those with mental disability. Up to 2017, according to the National Statistic Report of Ministry of Health and Welfare in Taiwan, there were about 1,167,000 people certified mental disability. Some of them were living in community. However, for some patients who have severe mental illness, they may reside in chronic wards of psychiatric hospitals for a long period of time. Psychiatric hospitals also have outpatient departments providing services for patients with mental illness. Beside treatment for mental illness, patients may also receive treatment for diabetes from psychiatrist in the same time.

In 2019, P4P program of diabetes care was implemented in a regional psychiatric hospital in middle Taiwan, which was also the only psychiatric hospital hired a full-time endocrinologist in Taiwan. This regional psychiatric hospital had about total 1,200 hospital beds, including emergency department, intensive care unit, 6 acute and 16 chronic wards, and 4 nursing homes. The objective of this study is to examine the effectiveness of P4P program of diabetes for outpatients, assess the quality of care and outcome of psychiatric patients with diabetes, and share the feasibility and experiences of building a diabetes care system in a regional psychiatric hospital in middle Taiwan.

Methods: Our study utilized a retrospective cohort design to examine the effect of P4P program of diabetes care for psychiatric patients with diabetes. The intervention took place in the outpatient 150

Abstract department of a regional psychiatric hospital in middle Taiwan. The program was applied since Jan 2019. The staff members of P4P program worked as a coordinated multidisciplinary team, which consisted of a full-time endocrinologist, diabetes nurses, and dieticians. According to the rules of P4P program, the care team was required to provide regular evaluations for the enrolled patients, including biochemical tests, educational programs, and management plans. Because all hospitals participating the P4P program were required to submit data to receive P4P follow-up payments, our database is undoubtedly reliable.

The study selection process is illustrated in Figure 1. In the 1st quarter of 2019, there were total 129 psychiatric patients with diabetes participated in P4P program of diabetes care. According to the rule of P4P program, HbA1c should be tested every 3 months. Individualized health education was also provided every 3 months. Those who loss follow-up for more than twice during 2019 were excluded from our study. We collected HbA1c data of the 4th quarter in 2018 as baseline, while P4P program was not applied yet. HbA1c data of every quarter in 2019 was collected as dependent variable. The basic characteristics of our patient, including sex, age, body mass index (BMI), and comorbidities (hypertension and hyperlipidemia) were recorded as covariance. Generalized estimating equations (GEE) with SPSS 26 was used for statistical analysis. The study was approved by the institutional review board of Tsaotun psychiatric center for medical ethics.

Results: There were total 129 patients enrolled in our study. 53.5% of them was male, and 46.5% was female. The mean HbA1c level of female patients were significantly higher than HbA1c level of male patients. The prevalence of hypertension and hyperlipidemia was slightly higher (without significance) among male patients. The results of statistical analysis were demonstrated in Table-2.

The HbA1c level increased slightly in the first quarter (p>0.05), and then decreased gradually since the second quarter. The HbA1c level got significant improvement in the third quarter (P<0.05), and the effectiveness of P4P persisted to the fourth quarter. The mean HbA1c level of male patients seems got more improvement than female patients after P4P intervention. Patients with hyperlipidemia also got more improvement than those without hyperlipidemia.

Conclusions: The implementation of P4P program of diabetes care is a novel way to deliver diabetes care services for patients with mental illness, and it should be actively promoted.

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PD14

CEMIP-HBC DNA VACCINE INHIBITS KIDNEY FIBROSIS IN HIGH FAT DIET MICE THROUGH INTERFERING WNT/Β-CATENIN SIGNALING 1

PI-CHEN LIN, 2YI-CHEUNG WONG, 1KUN-DER LIN, 2GUAN-MING KE, 2,3 CHAO-HUNG CHEN 1

Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University; 23 Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology; 3 General Research Service Center, National Pingtung University of Science and Technology

Background: Obesity is a common risk for cardiovascular diseases and type 2 diabetes, which both result in developing chronic kidney disease (CKD). berration of wnt/β-catenin signaling is associated with obesity, dyslipidemia, diabetes and nephropathy.The hyaluronan-binding protein (CEMIP) is identified to mediate hyaluronan degradation and participate in migration and tumorigenesis. In addtion, CEMIP involves fibrosis, proliferation and migration of atherosclerosis.

This study intended to design CEMIP-HBc (human hepatitis virus B core portein) DNA vaccines for nephropathy in obesity, through diminishing Wnt1/β-catenin pathway.

Methods: In an 8-week experiment, plasmid-encoding CEMIP and HBc was vaccinated high fat diet(HFD) mice in the first 4 weeks, and then vaccination was stopped for at least 4 weeks.At the end point, mice were sacrificed for analysis of the CEMIP/Wnt1/β-catenin pathway and fibrogenesis in kidneys.

Results: Anti-CEMIP antibody was successfully produced in the CEMIP-HBc vaccinated group, while Wnt1/β-catenin signaling and fibrosis was consistently lower in this group.

Conclusions: This study revealed that application of CEMIP-HBc DNA vaccine efficiently repressed expressions of Wnt1/β-catenin/ECM pathway in kidney tissue of HFD mice.Based on these outcomes, CEMIP/ Wnt1/β-catenin pathway is considered as novel therapeutic target of nephropathy.

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Abstract PD15

THE EFFECTS OF DIPEPTIDYL PEPTIDASE 4 INHIBITORS ON RENAL OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

WAN-CHIA HSU, 1JUNG-FU CHEN, 2CHUN-SHENG LIN, 1CHIH-MIN CHANG

1

Department of Endocrinology and Metabolism, Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.; Kaohsiung Chang Gung Memorial Hospital, Taiwan, R.O.C.

2

Background: Many prior clinical trials confirmed glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have benefits on renal outcomes in patients with type 2 diabetes mellitus (DM). This study evaluated whether dipeptidyl-peptidase 4 (DPP-4) inhibitors, an anti-hyperglycemic drug to increase GLP-1 serum concentration, also have benefits on renal function as GLP-1 RAs. Methods: We conducted this retrospective cohort study by using the Chang Gung Research Database, which is an electronic medical record derived from Chang Gung Memorial Hospital.

In this retrospective cohort study, patients aged ≥ 18 years diagnosed with type 2 DM treated with anti-hyperglycemic agents between January 1, 2008 and December 31, 2011 were enrolled.

We compared the time to first occurrence of eGFR decline of ≥ 30% from baseline between patients treated with DPP-4 inhibitors and with other anti-hyperglycemic drugs except for DPP-4 inhibitors for 5 years. Subgroups stratified by baseline chronic kidney disease (CKD) stage and other risks factors for eGFR decline were also analyzed.

Results: A total of 12073 eligible patients, 7525 in DPP-4 inhibitors users group and 4548 in non-DPP-4 inhibitors group, were identified. 1101 DPP-4 inhibitors users and matched non-DPP-4 inhibitors users were finally analyzed after propensity score matching with 1:1 ratio. The incidence of eGFR decline of ≥ 30% from baseline was 10.08% in DPP-4 inhibitors group comparing with 16.17% in non-DPP-4 inhibitors group with significant difference (p < 0.001).

The mean time to event is significant longer in patients using DPP-4 inhibitors (2.84 ± 1.60 years vs. 1.96 ± 1.30 years, p < 0.001). The cumulative incidence of eGFR decline ≥ 30% is lower in DPP4 inhibitors users (log-rank test, p = 0.001), and regardless of baseline CKD stage, DPP-4 inhibitors users have lower incidence rate of eGFR decline ≥ 30%. Patients who are younger than 65 years old (HR 0.36, 95% CI: 0.25 - 0.53, p for interaction < 0.001), with better baseline eGFR (p for interaction = 0.001), without preexisting hyperlipidemia (HR 0.31, 95% CI: 0.22 - 0.45, p for interaction < 0.001), and without prior statin use (HR 0.29, 95%CI: 0.21 - 0.41, p for interaction = 0.028) have more reduced risks of declined renal function.

Conclusions: There are significant lower risks in patients with normal or mildly impaired baseline renal function, having risks reduction of 69% for eGFR ≥ 90 mL/min/1.73m2 and 59% for ≥ 60 to < 90 mL/min/1.73m2, respectively.

In conclusion, our study demonstrated that adult patients diagnosed of type 2 diabetes receiving 153

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DPP-4 inhibitors with or without other anti-hyperglycemia agents have lower risks of eGFR decline, comparing to patients under other types of anti-hyperglycemia agents except for DPP-4 inhibitors.

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Abstract PD16

OXIDATIVE LDL ACTIVATES INTERACTION OF SARS-COV2 SPIKE PROTEIN AND TMPRSS4 RESULTED IN LIVER INJURY 1

PI-CHEN LIN, 2YI-CHEUNG WONG, 2CUI-YAN WANG, 1KUN-DER LIN, 2 GAUN-MING KE, 2,3CHAO-HUNG CHEN 1

Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung Medical University; 2,3Graduate Institute of Animal Vaccine Technology, College of Veterinary Medicine, National Pingtung University of Science and Technology; 3 General Research Service Center, National Pingtung University of Science and Technology

Background: In 2019, SARS-CoV-2 first spread and caused severe pneumonia and high fatality rate.In particular, clinical studies have found that a considerable proportion of SARS-CoV-2 infected persons have severe acute respiratory diseases with liver damages. However, SARS-CoV-2 receptors, ACE2 in the liver were significantly lower than that in the lungs or gastrointestinal tract.

Transmembrane Protease, Serine 4, TMPRSS4 has been considered as SARS-CoV-2 co-receptors for infecting human cells. Clinical studies have also found that a high proportion of COVID-19 patients with dyslipidemia or metabolic syndrome will develop severe illnesses such as liver failure. Therefore, investigating the capable mechanism of high negative charge LDL in assisting the SARS-CoV-2 virus to infect the liver has considerable research value in the therapy on COVID-19 combined with acute liver damages.

Methods: This study is based on SARS-CoV-2 epidemic prevention work and laboratory safety considerations, and uses pseudovirus which carries SARS-CoV-2 spike protein (S-protein) to simulate SARS-CoV-2 infection in oxLDL-cultured control siRNA or TMPRSS4 siRNA-transfected human hepatic cells . Furthermore, SARS-CoV-2 pseudovirus was injected to chow or high fat diet (HFD) mice. At end of experiments, livers and cultured hepatic cells were harvested for analysis.

Results: Under SARS-CoV-2 pseudovirus infection, hepatic TMPRSS4 highly expressed in HFD mice compared with chow mice. Proximal ligation assay shows high expression of S-proteinTMPRSS4 complexes in HFD mice. Immnuoprecipitation showed S-protein significantly expressed on serum LDL of HFD mice. TUNEL assay demonstrated more increase of apoptotic cells on liver of HFD than chow mice with SARS-CoV-2 pseudovirus infection. In vitro, oxLDL-cultured hepatic cells significantly presented S-protein-TMPRSS4 complexes and apoptosis compared with normal LDLcultured hepatic cells. However, these oxLDL effects were repressed by TMPRSS4 siRNA. Conclusions: This first study first elucidated that possibility of dyslipidemia or metabolic syndrome contributes COVID-19 combined with acute liver injury is through high negative charge LDL participating interaction of SARS-CoV-2 S-protein and TMPRSS4.

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PD17

CIRCULATING LEVELS OF SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR 2 ARE ASSOCIATED WITH PROGRESSIVE DIABETIC KIDNEY DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1,2

LIANG-YU LIN, 1,2TSUNG-HUI WU, 3LI-HSIN CHANG, 1,2CHII-MIN HWU, 1,2 HARN-SHEN CHEN 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Department of Medicine, Yeezen General Hospital, Taoyuan, Taiwan

Background: Chronic low-grade inflammation is considered one of the major mechanisms for the progression of diabetic kidney disease. We investigated the prognostic value of circulating soluble tumor necrosis factor receptor 2 (sTNFR2) for early nephropathy in patients with type 2 diabetes.

Materials and methods: A total of 346 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 were followed up for a median of 4 years. Renal outcomes were defined as a composite of either or both a >30% decline in the eGFR and/or albuminuria stage progression determined with consecutive tests.

Results: Sixty-nine patients developed renal composite events. Serum concentrations of sTNFR2 were strongly associated with the risk of renal function decline and progressive changes in albuminuria.

Through a receiver operating characteristic curve analysis, a serum sTNFR2 level of 1.608 ng/mL was adopted as the discriminator value for predicting renal outcomes (area under the curve 0.61, 95% confidence interval 0.54-0.68, p = 0.005), yielding a sensitivity of 73.9% and a specificity of 48.7%.

The association of sTNFR2 levels ≥1.608 ng/mL to renal outcomes was significant after adjusting for relevant variables (hazard ratio 1.95, 95% confidence interval 1.01-3.74, p = 0.046) and remained consistent across subgroups stratified by age, sex, systolic blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system blockers.

Conclusions: Higher circulating levels of sTNFR2 are independently associated with an eGFR decline and progressive albuminuria in patients with type 2 diabetes.

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Abstract PD18

NON-ISLET CELL TUMOR HYPOGLYCEMIA SECONDARY TO A GIANT BREAST TUMOR: A CASE REPORT AND REVIEW OF LITERATURE 1

YU-LIN YANG, 1CHUN-TA HUANG, 2CHI-YUAN TZEN, 1CHUN-CHUAN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 2Department of Pathology, MacKay Memorial Hospital, Taiwan, R.O.C.

Case presentation: A 41-year-old non-diabetic woman was brought to emergency department for unconsciousness before dinner. Severe hypoglycemia (serum glucose 21 mg/dL) was documented and her symptoms had full recovery with no neurologic deficit after the correction of hypoglycemia.

Lab results and brain image were unremarkable but physical exam revealed a huge right breast tumor, which she ignored intentionally for years. Refractory hypoglycemia (35 mg/dL) occurred during hospitalization despite continuous hypertonic glucose infusion. Diagnostic studies including 72-hour prolonged fasting tests were performed. Low serum C-peptide and insulin level were detected during hypoglycemia with serum glucose increased by more than 25 mg/dL after glucagon injection. Insulin antibody was negative and we carefully excluded adrenal insufficiency and hypopituitarism. The above findings are suggestive of non-islet cell tumor hypoglycemia (NICTH). Her hypoglycemia improved after steroid use and she was free of hypoglycemia after complete resection of the right breast tumor.

Final pathology of right breast tumor was compatible with a phyllodes tumor.

Conclusion: Although NICTH due to IGF-2 overproduction is a rare phenomenon, mainly observed in case of mesenchymatous tumor, it should be considered in presence of severe hypoglycemia with plump mass and without hyperinsulinism.

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PD19

WAIST CIRCUMFERENCE IS A DETERMINANT FOR MUSCLE QUALITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS 1

YI-LUN CHIANG, 2TING-CHUNG CHEN, 3HSUAN WU, 4TING-GRU LIN, 2 JING-YA PENG, 3SHIOW-CHWEN TSAI, 2CHIAO-NAN CHEN, 5CHII-MIN HWU 1

Division of Endocrinology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Departent of Physical Therapy and Assistive Technology, National Yang-Ming University, Taipei, Taiwan; 3Institute of Sports science, University of Taipei, Taipei, Taiwan; 4Departent of Nursing, National Taipei university of Nursing and Health Science, Taipei, Taiwan; 5Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Muscle damage has recently been recognized as a complication of type 2 diabetes mellitus (T2DM), and impaired muscle function adversely affects physical activities, quality of life and mortality. Waist circumference (WC) is related with visceral fat and insulin resistance. The present study aimed to evaluate the relationship of muscle quality and WC in patients withT2DM. Methods: We recruited 145 patients with T2DM aged ≥ 50 years. Subjects divided into three groups based on WC. Total muscle mass, grip strength, knee extension strength and ankle dorsiflexion and plantarflexion strength were assessed.

Results: 145 subjects were subdivided into three groups according to the tertiles of WC. These subjects with a wider WC tended to be more obese, had more muscle mass, higher level of fasting plasma glucose and little muscle quality.

Muscle quality of bilateral arms was correlated with age, gender, WC and estimated Glomerular filtration rate (eGFR). Muscle quality of lower limbs was correlated with age, WC and eGFR. After multivariant analyses, WC was the only factor which still showed significant to muscle quality of four limbs.

Conclusions: Independent from muscle mass, WC is a good determinant for muscle quality in T2DM subjects.

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Abstract PD20

SARC-CALF AND OTHER RISK FACTORS IN PREDICTION OF SARCOPENIA IN ELDERLY WITH TYPE 2 DIABETES 1

BO-CHUN CHEN, 1HUI-I YU, 1TSAI-SUNG TAI, 1FANG-PING KUNG, 2SHU-FEN SHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital; 2Diabetic Center

Background: Diabetes patients have higher prevalence of sarcopenia. Sarcopenia is often associated with frailty and had poor prognosis. Recently SARC-F questionnaire is recommended as a tool for screening sarcopenia. However, it has low sensitivity. Though adding calf circumference measurement can increase sensitivity, we want to know combine with SARC-F and calf size, if adding clinical risk factors will increase prediction of sarcopenia in type 2 diabetes.

Methods: We enrolled 166 type 2 DM patients from 201912 to 202003, who were older than 50 years of age, and received diabetes education at least twice in our META OPD. We excluded patients with previous stroke history, carpal tunnel syndrome, severe hip or knee osteoarthritis, dysarthria, dysphagia, use of a walker, physical disability that affects hand grip or walking. SARC-F questionnaire was asked and calf circumference was measured by DM educator. Appendicular skeletal muscle mass was measured by bioelectrical impedance analysis (BIA) and handgrip strength was evaluated.

Definition of sarcopenia was diagnosed if appendicular muscle mass/height 2 < 7kg/m2 in men and < 5.4 kg/m2 in women. Hand grip strength < 26kg in men and < 18kg in women. Patients’ working status, health behaviors, body composition, and serum biomarkers were collected for analysis.

Results: There were 56 patients have sarcopenia according to muscle mass and muscle strength measurement. 35 (62.5%) patients were female. Sarcopenia patients were older (mean age 68 y/o vs 64 y/o). They have significantly lower BMI and blood pressure, waist circumference, triglyceride, liver enzyme (ALT) but higher HDL-C. There were no differences in diet pattern and health behavior or working condition. For prediction of sarcopenia, we found in receiver operating characteristics (ROC) analysis, SARC-CalF alone showed AUC is 0.76, p< 0.005, sensitivity 0.436, specificity 0.86.

If we added gender, age, A1C, HDL-C, TG, GPT, exercise, BMI can increase AUC value to 0.825, sensitivity is 0.655 and specificity is 0.86. The sensitivity is still not good. Further risk factors or biomarkers survey might be needed.

Conclusions: In elderly type 2 diabetic patients, adding clinical risk factors such as age, BMI, exercise behaviors, glycemic control, lipid profile, liver profile with SARC-CalF might increase sensitivity in prediction of sarcopenia. Further validation is still needed.

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PD21

EUGLYCEMIC KETOACIDOSIS IN PATIENT TREATED WITH SGLT-2 INHIBITOR 1

CHE-YU LIU, 1HUI-I YU, 1RU-LAI HUANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Ditmanson Medical Foundation Chia-yi Christian Hospital

Euglycemic diabetic ketoacidosis was ever reported in diabetic patient who treated with SGLT-2 inhibitor. It may occur in several conditions such as patient took SGLT-2 inhibitor without adequate hydration, reduced or discontinued insulin therapy, underwent prolonged fasting or ate low carbohydrate diet. These conditions were often accompanied with metabolic acidosis.

We presented this patient who developed euglycemic ketoacidosis after the tooth extraction surgery. The patient was a 33-year-old man and was admitted for face cellulitis. He took SGLT2 inhibitor for diabetic treatment before. The glycemic control was not well and the recent HbA1c revealed 10.1%.

This time, he suffered from focal infection over face after tooth extraction surgery recently. After the surgery, the amount of oral intake reduced, however, he took SGLT-2 inhibitor as usual. During the hospital course, he still had poor oral intake. Initially, we discontinued the medicine (SGLT-2 inhibitor), but found severe metabolic acidosis 2 days after admission (pH 7.069, HCO3 4.1 mmol/L) with euglycemic status (196 mg/dl) and increased serum ketone. We gave intravenous fluid hydration, insulin therapy, started enteral feeding and the ketoacidosis improved gradually.

Our report demonstrates a rare but important side effect of SGLT-2 inhibitor (the euglycemic diabetic ketoacidosis). Hold SGLT-2 inhibitor temporarily is important to reduce euglycemic ketoacidosis risk, especially before surgery or during acute illness.

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Abstract PD22

HYPERLIPIDEMIA ASSOCIATED WITH LORLATINIB, IMPROVED AFTER ALIROCUMAB USED: A CASE REPORT 1

FANG-YU CHEN, 1TSUNG-HUI WU, 1HUI-LING LIN, 1,2TANG-YI LIAO, 1,3CHII-MIN HWU 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 3 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Background: Lorlatinib is a highly potent, brain-penetrant, third generation ALK/ROS1 tyrosine kinase inhibitor (TKI) and has potency against most known resistance mutations developed during treatment with crizotinib and second-generation ALK TKIs. Hyperlipidemia was the most common adverse event reported with Lorlatinib and most patients need at least one lipid-lowering agent within three weeks of the first Lorlatinib dose. Usually, treatment with statins was first considered at the first sign of elevated cholesterol and/or triglyceride levels.

Methods: We report a case of successfully improved lipid profile under Alirocumab treatment in a lung cancer patient with Lorlatinib related hyperlipidemia. .

Results: This 58- year-old male patient with lung adenocarcinoma of left upper lobe, stage IV, was receiving TKI treatment due to tumor tissue pathology yield anaplastic lymphoma kinase (ALK) mutation positive. Hyperlipidemia developed soon after Lorlatinib taken and a statin was given as treatment. However, the treatment showed ineffective and Ezetimibe was added with laboratory data revealed partial improvement. Acute onset right sided weakness with slurred speech for hours developed during lung cancer related admission 16 months after starting Lorlatinib treatment. Brain MRI showed small early subacute infarct in left corona radiata. Due to hyperlipidemia complicated by subacute ischemic stroke despite Rosuvastatin and Ezetimibe used, we applied Alirocumab for reducing the risk of recurrent atherosclerotic cardiovascular disease event. After agreed by National Health Insurance Committee, Alirocumab 75mg was given every two weeks while Rosuvastatin and Ezetimibe kept given. Lipid profiles showed dramatic improvement after we added Alirocumab in antihyperlipidemic treatment.

Conclusions: Proprotein convertase subtilisin/kexin type 9 inhibitors may be effective in secondary prevention of atherosclerotic cardiovascular disease in hyperlipidemia patients receiving Lorlatinib treatment if statins and ezetimibe is ineffective.

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PD23

DIABETES SECONDARY TO ACROMEGALY, AND ACROMEGALY SECONDARY TO DIABETES: BIDIRECTIONAL ANALYSES USING A NATIONAL COHORT 1

YUAN-HORNG YAN, 2I-JU TSAI, 1SHIH-TING TSENG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, 2Department of Medical Research, Kuang Tien General Hospital, Taichung, Taiwan, R.O.C.; 2Department of Medical Research, Kuang Tien General Hospital, Taichung, Taiwan, R.O.C.

Background: Diabetes mellitus (DM) is a known complication of acromegaly. However, diagnosis of acromegaly in patients with coexisting DM is difficult. The objective of this study is to evaluate the associations between DM and acromegaly using bidirectional analyses in a national cohort.

Methods: This is a retrospective cohort study using Taiwan's National Health Insurance Research Database. We conducted bidirectional analyses in this study. Analysis 1 consisted of 181,573 patients with newly diagnosed DM in 2005-2017 and 181,573 randomly selected normal controls frequencymatched by index year, age and sex. Analysis 2 compared 280 patients with newly diagnosed acromegaly in 2005-2017 and 1,120 randomly selected normal controls frequency-matched by index year, age and sex. At the end of 2017, analysis 1 measured the risk of developing acromegaly and analysis 2 measured the risk of developing DM. Results: In analysis 1, patients with coexisting DM had significantly higher risk of acromegaly compared with normal controls, with an adjusted HR of 4.09 (95% CI = 2.27-7.37). The risk of acromegaly in coexisting DM patients regardless of age or sex stratification was higher than in the normal controls. In analysis 2, patients with acromegaly had significantly higher risk of developing DM within 1-year follow-up (adjusted HR = 2.47 with 95% CI = 1.17-5.20).

Conclusions: Acromegaly was significantly associated with DM bidirectionally.

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Abstract PD24

RETROPERITONEAL SOLITARY FIBROUS TUMOR PRESENTED WITH HYPOGLYCEMIA: A CASE REPORT 1

YI-CHING TSAI, 1CHING-CHUNG CHANG, 1CHING-CHU CHEN, 1 CHWEN-TZUEI CHANG, 1MING-JIA XIE, 1RONG-HSHING CHEN, 1TZU-YUAN WANG, 1 JUN-WEI HE, 1WEI-LUN HUANG 1

Division of Endocrinology and Metabolism, Intelligent Diabetes Metabolism and Exercise Center, Department of Medicine, China Medical University Hospital, Taichung, Taiwan

Background: Non-diabetic hypoglycemia is a rare condition. It may result from drugs, critical illness, hormone deficiency, non-islet cell tumors, endogenous hyperinsulinemia or exogenous hyperinsulinemia. Among non-islet cell tumors induced hypoglycemia, mesenchymal tumors and hepatocellular origin tumors are most commonly described. Here, we present a case of retroperitoneal fibrous tumor presented with hypoglycemia.

Case report: A 51 year-old woman without significant medical history presented to Emergency Department due to traffic accident resulting from conscious loss. Hypoglycemia (plasma glucose 30mg/dl) with c-peptide 0.104 ng/ml (reference range: 0.9-7.1 ng/ml) was detected. The patient also mentioned a palpable abdominal mass for 4 months. Abdominal CT scan showed a 10cm x 8cm welldefined enhancing mass over left proximal ureter with left hydronephrosis. Laboratory data showed insulin level 0.07mU/L (reference range: 1.9-23 IU/mL), insulin-like growth factor-1 15.3ng/mL (reference range: 55-248 ng/mL), normal reference range of HbA1c, cortisol, ACTH, aldosterone, renin, β-HCG and tumor markers including SCC, CA-199, CA125. Urine cytology showed negative for high grade urothelial carcinoma. She received left retroperitoneal tumor excision and left nephrectomy. Pathology disclosed a retroperitoneal fibrous tumor involving left renal vein. After then, hypoglycemia resolved, and insulin and c-peptide levels returned to normal range.

Discussion: olitary fibrous tumor associated with non-islet cell tumor hypoglycemia is called Doege–Potter syndrome which was first described in 1930. It is a rare mesenchymal tumor. It may present with slowly growing mass or paraneoplastic syndrome. Most solitary fibrous tumors (up to 80%) are benign but some have aggressive behaviors. The solitary fibrous tumor may overproduce big IGF2, an unprocessed high-molecular-weight that has insulin-like activity. As a result, It increases glucose utilization and induces hypoglycemia. Surgical resection of tumor is the first priority of management.

Conclusion: Non-diabetic hypoglycemia may be a paraneoplastic syndrome related with nonislet cell tumor.

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PD25

SGLT-2 INHIBITOR TREATMENT FOR ALPELISIB (PI3K INHIBITOR) INDUCED SEVERE HPERGLYCEMIA 1,3

TANG-YI LIAO, 1HARN-SHEN CHEN, 2CHUN-YU LIU, 1FANG-YU CHEN, 1 HUI-LING LIN, 1TSUNG-HUI WU 1

Division of Endocrinology and Metabolism, Department of Medicine Taipei Veterans General Hospital, Taipei, Taiwan; 2Division of Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan

This 80-year-old woman with medical history of hypertension, and invasive ductal carcinoma of right breast with lymph node metastasis(pT2N1Mx). In 2009, she received modified radical mastectomy and chemotherapy with FEC(5-FU+epirubicin+cyclophosphamide). During 2010~2015, she received chemotherapy of Taxotere and hormone therapy. In 2018, invasive ductal carcinoma of left breast(triple negative breast cancer) was diagnosd, and she received wide excision and sentinel lymph node biopsy. After the surgery, she received oral navelbine, aromasin (aromatase inhibitor), and afinitor (mTOR inhibitor) treatment. However, progressive disease was noted (CEA and CA-153 continued elevating, and new chest lesions at CT finding). On 2020/07, gene survey revealed PIK3CA mutation (E545K), then she started to received the compassionate treatment of alpelisib 300mg QD (PI3K inhibitor).

Few days after alpelisib treatment, obviously elevated glycemic condition was noted(selfmonitoring of blood glucose more than 500 mg/dL). Then the patient was admitted for blood glucose control. During the hospitalization, oral antidiabetic drugs were administered as metformin and acarbose. Multiple dose insulin injection with insulin aspart and insulin glargine was also applied. The insulin dosage was up-titrated to 2 units/kg/day one week after admission; however, hyperglycemia was still noted (blood glucose more than 350 mg/dL). Due to the obvious adverse effect, Alpelisib was held for four days, and then hyperglycemia resolved gradually and insulin dosage was tapered to 0.3 units/kg/day. After the glycemic condition became relatively stable, alpelisib was resumed with lower dosage (200mg QD). In the following days, hyperglycemia attacked again, and insulin dosage was up-titrated to 1.6 units/kg/days. Due to difficulty control of glycemia by insulin, SGLT-2 inhibitor (empagliflozin 25mg QD) was added. Then hyperglycemia improved dramatically and insulin dosage was tapered rapidly.

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Abstract PD26

THE BENEFICIAL EFFECTS OF VITAMIN E SUPPLEMENT ON METABOLIC SYNDROME COMPONENTS IN HEALTHY POPULATION 1,2

KUO-HSIN WU, 3,4DEE PEI, 1,2FENG-JU CHANG, 1,2JIUNN-DIANN

Background: Vitamin E, well known as an antioxidant agent, is proved to reduce inflammation and oxidative damage. Some clinical investigations indicated vitamin E deficiency is associated with increased risk of cardiovascular events. We explored the change of metabolic syndrome components in subjects with or without vitamin E supplement for two years.

Methods: Subjects receiving routine annual health examinations were divided to with or without vitamin E supplement according to questionnaire. Demographic data, anthropometry and metabolic syndrome components were collected respectively with interval of two years. Finally, the variations of metabolic syndrome components in two years were analyzed in age- and sex-match individuals between two groups.

Results: There were 699 healthy subjects enrolled this study. Subjects with vitamin E supplement had lower waist circumference (WC), fasting plasma glucose (FPG), systolic blood pressure (SBP), uric acid (UA) and higher high density lipoprotein cholesterol (HDL-C). After sex- and agematch, subjects with vitamin E supplement had lower WC, body mass index (BMI), body fat (BF), FPG, triglyceride (TG), UA, and higher HDL-C. Two years later, half of heath subjects continued supplement of vitamin E. However, metabolic syndrome components between continuing and noncontinuing group showed no significant difference.

Conclusions: Subjects with vitamin E supplement had less risk of obesity, hyperglycemia, and dyslipidemia. However, the beneficial effects of vitamin E supplement showed no significant difference after discontinue vitamin E.

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PD27

WHITE BLOOD CELL COUNT AND METABOLIC SYNDROME COMPONENTS IN HEALTHY SUBJECTS WITH PROPOLIS 1,2

FENG-JU CHANG, 1,2KUO-HSIN WU, 3,4DEE PEI, 1,2JIUNN-DIANN

Background: Several studies showed propolis has beneficial effects on anti-inflammation and anti-oxidative damage. Propolis is a widespread health food applied on anti-aged and promoting immunity. We explored the effects of white blood cell count and metabolic syndrome components in subjects with or without supplement of propolis.

Methods: Subjects receiving routine annual health examinations were divided to with or without propolis supplement according to questionnaire. Demographic data, anthropometry and metabolic syndrome components were collected. Finally, the metabolic syndrome components and white blood cell count were analyzed in age- and sex-match individuals.

Results: There were 134 healthy subjects enrolled this study after sex- and age-match pair.

Subjects with propolis supplement had lower waist circumference, fasting plasma glucose, systolic blood pressure, diastolic blood pressure and higher high density lipoprotein cholesterol. However, white blood cell count between subjects with and without propolis supplement showed no significant difference.

Conclusions: Subjects with propolis supplement had lower waist circumference, blood pressure and fasting glucose, and higher high density lipoprotein cholesterol. However, white blood cell count showed no significant difference between subjects with and without propolis supplement.

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Abstract PD28

A SHORT SLEEP DURATION IS ASSOCIATED WITH INCREASED RISK OF PRE-DIABETES: A COMMUNITY-BASED COHORT STUDY IN TAIWAN 1

I-RUEI YU, 2SHIH-TE TU, 2SHU-YI WANG, 3MAO-SHIN LIN, 3SHYANG-RONG SHIH, 4 CYUE-HUEI HUA, 4YENH-CHEN HSEIN, 3HUNG-YUAN LI 1

Department of Family Medicine, Changhua Christian Hospital, Changhua, Taiwan.; 2 Division of Endocrinology and Metabolism Changhua Christian Hospital, Changhua, Taiwan.; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.; 4 Division of Clinical Pathology National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Taiwan.

Background: Sleep duration is reported to be associated with increased risk of pre-diabetes and diabetes in the literature. However, the relationship remains unexplored in Taiwan. In this study, we investigated the relationship between sleep duration, pre-diabetes, and diabetes in Taiwan.

Methods: In this community-based study, 2084 subjects were enrolled in 2006-2019. Prediabetes and diabetes were diagnosed by the results of oral glucose tolerance tests and hemoglobin A1c, or if anti-diabetic agents were used. Sleep duration was acquired by a questionnaire.

Results: Subjects slept < 6 hours had a higher risk of pre-diabetes (odds ratio (OR) 2.03, p < 0.001) and diabetes (OR 1.64, p = 0.04), compared with subjects who slept 6-7.5 hours. However, the OR of diabetes became insignificant after adjusted for age (OR 0.80, p = 0.416), although the OR of pre-diabetes remained significantly elevated (OR 1.49, p = 0.024). The results were similar after further adjustment for age, body mass index, plasma high-density lipoprotein cholesterol, plasma triglyceride, gender, and homeostasis model assessment 2 insulin resistance index (OR for pre-diabetes in subjects slept < 6 hours 1.52, p = 0.021, compared with subjects who slept 6-7.5 hours). There was no significant difference in the risk of pre-diabetes and diabetes in subjects who slept ≥ 7.5 hours, compared with subjects who slept 6-7.5 hours.

Conclusion: Subjects who slept < 6 hours had an increased risk of pre-diabetes, compared with subjects who slept 6-7.5 hours.

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PD29

EMPAGLIFLOZIN AND LIRAGLUTIDE DIFFERENTIALLY MODULATE CARDIAC METABOLISM IN DIABETIC CARDIOMYOPATHY 1

NGUYEN NGOC TRANG, 2,3CHENG-CHIH CHUNG, 4,5TING-WEI LEE, 2,6 WAN-LI CHENG, 2,6YU-HSUN KAO, 4,5,7TING-I LEE, 2YI-JEN CHEN 1

International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University; 2Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University; 3Division of Cardiology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; 6Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University; 7Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) are antihyperglycemic agents with cardioprotective properties against diabetic cardiomyopathy (DCM). However, the distinctive mechanisms underlying GLP-1RAs and SGLT2is in DCM are not fully elucidated. The purpose of this study was to investigate the impacts of GLP1RAs and or SGLT2is on myocardial energy metabolism, cardiac function, and apoptosis signaling in DCM. Materials and Methods: Biochemistry and echocardiograms were studied before and after treatment with empagliflozin (10 mg/kg/day, oral gavage), and/or liraglutide (200 μg/kg every 12 h, subcutaneously) for 4 weeks in male Wistar rats with streptozotocin (65 mg/kg intraperitoneally)induced diabetes. Cardiac fibrosis, apoptosis, and protein expressions of metabolic and inflammatory signaling molecules were evaluated by histopathology and Western blotting in ventricular cardiomyocytes of different groups.

Results: Empagliflozin and liraglutide normalized myocardial dysfunction in diabetic rats.

Upregulation of phosphorylated-acetyl-CoA-carboxylase, carnitine palmitoyl transferase 1β, cluster of differentiation 36, and peroxisome proliferator-activated receptor gamma coactivator, and downregulation of phosphorylated adenosine monophosphate-activated protein kinase α2, glucose transporter 4, phosphorylated protein kinase B, and phosphoinositide 3-kinase protein levels in diabetic cardiomyocytes were restored by treatment with empagliflozin or liraglutide. Nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3, interleukin-1β, tumor necrosis factor-α, and cleaved caspase-1 were significantly downregulated in empagliflozin-treated and liraglutide-treated diabetic rats. Both empagliflozin-treated and liraglutide-treated diabetic rats exhibited attenuated myocardial fibrosis and apoptosis.

Conclusion: Empagliflozin modulated fatty acid and glucose metabolism, while liraglutide regulated inflammation and apoptosis in DCM. The better effects of combined treatment with GLP1RAs and SGLT2 is may lead to a potential strategy targeting DCM. 168

Abstract PD30

A CASE REPORT OF 31-YEAR-OLD WOMAN, PRESENTING AS NEWLY DIAGNOSED TYPE 2 DIABETES MELLITUS COMBINED WITH MYELITIS 1

YU YI LIN, 2YU-HUA LAI, 3KAI-CHEN WANG

1

Division of general medicine, Department of Internal Medicine, Cheng Hsin Hospital, Taiwan, R.O.C Division of neurology, Department of Internal Medicine, Cheng Hsin Hospital, Taiwan, R.O.C

2,3

Introduction: Diabetes neuropathy is the most prevalent complications of diabetes, initial presenting as limbs numbness. However other neuropathy or myelopathy may be accompanied in diabetic patient. Case Report:We present a case of 31-year-old Taiwanese single woman visited to endocrine outpatient clinic for progressive severe bilateral legs numbness with weakness, unsteady gait, recurrent falling down episodes for 2 months and apparent body weight loss of 4 kg (80 to 76 kg) within one month. Initial work up showed newly diagnosed type 2 diabetes mellitus with poor glycemic control (HbA1c 13.6%, fasting c-peptide 2.74 ng/mL, no ketoacidosis ). She was admitted for intensive insulin therapy. After admission, her limbs numbness and weakness got worse rapidly and which was not compatible with usual diabetic neuropathy. Neurologist was consulted and neurological examination revealed sensory impairment below the umbilical region with left upgoing planter reflex and lower legs muscle power of 3-4 over both sides. Myelopathy was highly suspected. NCV and EMG limbs revealed normal result. Spine MRI disclosed long spinal cord lesions. T3-6 myelopathy with paraparesis and hypoesthesia was impressed . Autoimmune studies including ANA, ds-DNA, STS, SSA/SSB and CPK, myoglobin, folic acid, vitamin B12 level were within normal limit. AntiAQP4 Ab was also negative. After exclusion of possible infection and tumor by lumbar puncture, high dose steriod pulse therapy was administered urgently under the diagnosis of myelitis. Rehabilitation was arranged together. Steriod dose were tapered when her weakness got improved. During the follow up, another attack of myelitis recurred and also responding to steroid pulse therapy as well. Recurrent myelitis with long term immunosuppressant and low dose steroid were needed under intensive blood glucose control. Due to person reason, she was transferred to southern Taiwan hospital for further rehabilitation program. Conclusion: Clinicians caring for patients with diabetes should be keep in mind possibility of myelopathy in addition to diabetic neuropathy. Proper neurological examination and clinical awareness is very important to avoid delayed diagnosis and management.

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PE01

ECTOPIC ADRENOCORTICAL CARCINOMA IN THE OVARY: A CASE REPORT 1

WEN-HSUAN TSAI, 2TZE-CHIEN CHEN, 3SHUEN-HAN DAI, 1YI-HONG ZENG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan (ROC); 2 Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan (ROC); 3 Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan (ROC)

Adrenocortical carcinoma (ACC) is a rare malignancy with an incidence of 0.7–2.0 cases/ million habitants/year. Ectopic adrenal adenomas are uncommon and ectopic ACCs are rarely seen.

We presented a 59-year-old woman who suffered from abdominal fullness for 6 months and increased abdominal circumstance. A huge pelvic tumor was noted. She received debulking operation. Initial diagnosis was ovarian neuroendocrine carcinoma with omentum, lymph nodes, lung and peritoneum metastasis. Pathology report revealed local tumor necrosis and prominent lympho-vascular invasion.

The Ki-67 proliferation labeling index is very high > 50%. Immunohistochemically, tumor cells are focally positive for CD56, synaptophysin but also focally positive for calretinin. She received 3 cycles of etoposide, cisplatin and bevacizumab. 2 months later, pathologist confirmed diagnosis of ectopic ACC by positivity for synaptophysin, alpha-inhibin, TFE-3, calretinin (focal), and CD56 (focal), and high Ki-67-labeling proliferating index (> 80%). Non-functioning tumor was diagnosed according to hormone profile. She received mitotane 6 months after operation but died of cachexia 3 months later.

There was limited knowledge of the incidence and prognosis of ectopic ACC. Diagnosing ACC from ectopic organ can be tricky and comprehensive IHC may shed light on the correct diagnosis.

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Abstract PE02

WEE1 INHIBITION BY ADVOSERTIB FOR ANAPLASTIC THYROID CANCER THERAPY 123

YU-LING LU, 123SHU-FU LIN, 4YU-TUNG HUANG, 5TING-CHAO CHOU, 6 RICHARD J. WONG 1

Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan; Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Chang Gung University, Taoyuan, Taiwan; 4Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 6Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 2

Background: Wee1 is a kinase that regulates the G2/M progression by inhibition of CDK1, which is critical for ensuring DNA damage repair before initiation of mitotic entry. Targeting Wee1 may be a potential strategy in the treatment of anaplastic thyroid cancer, a rare but lethal disease.

Methods: The therapeutic efficacy of Adavosertib, a Wee1 inhibitor for treatment of ATC was evaluated in vitro and in vivo. The expression of cleaved PARP was assessed using Western blot. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were evaluated by flow cytometry and fluorometric assay. Mice bearing flank ATC were treated with either adavosertib, dabrafenib plus trametinib, or combination of adavosertib with dabrafenib plus trametinib.

Results: Adavosertib inhibited cell growth in three anaplastic thyroid cancer cell lines in a dose-dependent manner. Cell cycle analysis revealed cells were accumulated in the G2/M phase.

Adavosertib induced caspase-3 activity and led to apoptosis. Adavosertib monotherapy did not significantly retard the growth of anaplastic thyroid cancer tumors in two xenograft models. However, the combination of adavosertib with dabrafenib plus trametinib significantly inhibited tumor growth compared with placebo treatment in two anaplastic thyroid cancer xenograft models with BRAFV600E mutation.

Conclusions: Our findings suggest adavosertib holds the promise for the treatment of patients with anaplastic thyroid cancer.

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PE03

LOW DOSE OF LENVATINIB TREATMENT FOR PATIENTS OF RADIOIODINE-REFRACTORY DIFFERENTIATED THYROID CARCINOMA: A REAL-WORLD EXPERIENCE 1

HE-JIUN JIANG, 2YEN-HSIANG CHANGE, 3YEN-HAO CHEN, 3YEN-YANG CHEN, 2 PEI-WEN WANG, 1PI-JUNG HSIAO 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Dachang Hospital; Department of Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital; 3Department of HematologyOncology, Kaohsiung Chang-Gung Memorial Hospital 2

Background: Lenvatinib treatment of 24 mg/day for radioiodine-refractory differentiated thyroid carcinoma (RRDTC) patients was almost intolerable, with high rates of dose reduction, interruption and discontinuation. Balancing treatment safety, disease risks and appropriate dose remains challenging. A real-world experience of low dose of lenvatinib treatment was assessed from two medical centers of South Taiwan.

Methods: A total of 65 RRDTC patients treated with lenvatinib were retrospectively reviewed from Oct. 2015 to Mar. 2020. The median follow-up period was 48 months. Drug tolerability, treatment efficacy and clinical outcomes were analyzed.

Results: Lenvatinib was initiated and maintained with a median dose of 10 mg/day at 10 mg/ day in the first 3 months. The disease control rate reached 89.2%, including 24.6% partial response and 64.6% stable disease. Disease progression occurred in 10.8% of patients and increased to 40.0% at the end of follow-up. Eventually, the low dose treatment achieved a median progression-free survival (PFS) of 26.1 month (95% CI: 17.1-NA) with overall survival (OS) not reached yet (24.1~NA).

Overall, the 48-month PFS rate was 35.6% (95% CI: 18.5-68.4) and 48-month OS was 54.3% (95% CI: 41.2-71.7). The dose was tolerable with a dose reduction rate of 44.6%, dose interruption rate of 40.0% and fewer high-graded adverse events. The drug discontinuation rate was only 3.1%. Low dose lenvatinib treatment appeared beneficial for patients with less bone metastasis or structural progression.

Conclusions: Assessing treatment intensity, safety and efficacy, low dose lenvatinib treatment was well tolerated by patients with RRDTC and the therapy displayed acceptable drug efficacy and competitive outcomes.

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Abstract PE04

DETERMINATION OF IODINE CONTENT IN MILK AND EGGS 1

FAN-FEN WANG, 2CHYI-HUEY BAI, 3KAM-TSUN TANG, 4YI-LIN LIU, 4 CHEN-CHANG YANG, 3CHUN-JUI HUANG, 1SHEAU-FANG PAN 1

Division of Endocrinology and Metabolism, Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan; 2Department of Public Health, College of Public Health, Taipei Medical University, Taipei, Taiwan; 3Division of Endocrinology and Metabolism, Taipei Veterans General Hospital, Taipei, Taiwan; 4 Department of Clinical Toxicology & Occupational Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Iodine is essential for the production of thyroid hormones and is acquired through the diet. Dairy products and eggs are primary source of iodine in many countries. However, a survey of iodine content of dairy products and eggs had not been conducted in Taiwan.

Methods: The current study is a sub-study of the Nutrition Survey of Pregnant Women in Taiwan 2017-2019, evaluating dietary iodine sources. Iodine levels of 10 brands of liquid milk, 7 brands of milk made from milk powder, and 10 brands of yogurt were measured by inductively coupled plasma mass spectrometry. Iodine content of the yolk of boiled eggs was measured by thermal cycler digestion microplate method.

Results: All liquid milk samples had at least 43.8 μg iodine/250ml, ranging from 43.8-68.2 μg (median: 49.4 μg). The median iodine levels in milk made from milk powder was lower (11.8 μg iodine/250ml, range: 8.6-80.5 μg). The median iodine concentration of yogurt was 15.2 μg iodine/250ml, but the iodine level of one brand of yogurt reached to 152.7 μg/250ml. The 6 brands of eggs contained a median 19 μg/yolk of iodine (range 12.2-40.5 μg).

Conclusions: Iodine is contained in dietary food in Taiwan as in many other countries, but in varying concentrations, especially in yogurt. However, iodine content is not reported on most food labels. We suggest the iodine content of liquid milk, milk powders, and yogurt should be included in the ingredient and nutrient lists on package labels.

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PE05

POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME INDUCED BY ABIRATERONE IN A PATIENT WITH METASTATIC PROSTATE CANCER: A CASE REPORT 1

KUAN-YU LIN, 2HAO-CHIA HSU, 1CHUN HSIEN LIN, 3KUAN-HUA CHEN, 2 JEN-JEN SU, 1SHYANG-RONG SHIH 1

Division of Endocrine and Metabolism National Taiwan University Hospital; 2 Department of Neurology, National Taiwan University Hospital; 3 Division of Endocrine and Metabolism E-Da Hospital

Background: The selective CYP17 inhibitor, abiraterone, blocks androgen biosynthesis, and is approved for treating metastatic prostate cancer in combination with prednisolone. Treatment with abiraterone alone is associated with symptoms and signs of mineralocorticoid excess, including high blood pressure and hypokalemia.

Posterior reversible encephalopathy syndrome (PRES) is an acute neurotoxic syndrome presented with reversible subcortical vasogenic brain edema, and usually resulted from rapid blood pressure ascension. Here, we report the first case of abiraterone-induced refractory hypertension and PRES. Case presentation: An 82-year-old man, diagnosed with metastatic prostate cancer in January 2020, underwent palliative transurethral prostatectomy in May 2020. Due to biochemical progression under androgen deprivation therapy with leuprolide and bicalutamide, abiraterone acetate was initiated alone in June 2020. The patient developed severe headaches and hypertension one month later and was sent to the emergency department owing to deteriorating consciousness. Emergent brain magnetic resonance imaging (MRI) revealed bilateral posterior cerebral focal edema, and initial laboratory data revealed hypokalemia. He was admitted to the intensive care unit, but his symptoms responded poorly to multiple antihypertensive agents. Assessment of secondary hypertension revealed elevated serum levels of adrenocorticotropic hormone (ACTH) and aldosterone, and reduced levels of cortisol, progesterone and testosterone. Under the impression of medication related secondary hypertension, abiraterone was discontinued owing to abiraterone-induced adrenal insufficiency and mineralocorticoid excess. Glucocorticoid supplementation with prednisolone 7.5 milligrams daily was initiated. His symptoms soon improved, and the anti-hypertensives and potassium supplementation were discontinued. His consiousness was clear and oriented during the remaining admission period.

Conclusions: In conclusion, abiraterone induces secondary hypertension, and should be combined with corticosteroids for treatment. If not, adequate monitoring of blood pressure and electrolytes are necessary.

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Abstract PE06

FOLLICULAR THYROID CARCINOMA PRESENTING AS A GROWING SCALP MASS: A CASE REPORT 1

TSUNG-HUI WU, 1FANG-YU CHEN, 1HUI-LING LIN, 2CHUN-FENG WU, 1,2 TANG-YI LIAO, 1,3,4CHIN-SUNG KUO 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 3Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan; 4Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

Background: Metastasis of follicular thyroid carcinoma to the skull is rare, and the prognosis is poor in these patients. Total thyroidectomy and removal of metastatic lesions remain the first treatment, and radioactive iodine therapy should be performed postoperatively. Tyrosine kinase inhibitor therapy could be considered in patients with radioactive iodine-refractory metastatic follicular thyroid carcinoma.

Methods: We report a case of follicular thyroid carcinoma with skull metastasis as the presenting symptom.

Results: The 46-year-old female patient presented to our endocrine clinic due to a growing bulging mass at posterior scalp for 1 year. She underwent right thyroid lobectomy 10 years ago and left thyroid lobectomy 3 years ago for multinodular goiter. Thyroid nodules were diagnosed as follicular adenomas based on the second operation. However, histopathological examination of the biopsy taken from the scalp lesion showed metastatic follicular thyroid carcinoma. The serial image studies revealed prominent tumor mass at left thyroid fossa with cervical lymphadenopathy and distant metastases to brain, skull, nasal tip, bilateral lungs, liver, right kidney with invasion to right renal vein and inferior vena cava, left adrenal gland, and bone. She received craniotomy, total thyroidectomy with lymph node dissection, and right radical nephrectomy combined with left adrenalectomy, inferior vena cava thrombectomy, and partial hepatectomy sequentially. She had radioactive iodine therapies for 2 times after surgeries. As metastatic tumors became radioactive iodine-refractory, she received lenvatinib to control the metastatic disease.

Conclusions: The possibility of skull metastasis from follicular thyroid carcinoma should be considered in patients with metastatic skull tumors.

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PE07

A NOVEL MUTATION OF THE AVPR2 GENE CAUSING NEPHROGENIC DIABETES INSIPIDUS: A CASE REPORT AND REVIEW OF LITERATURE 1

YU-LIN YANG, 1YI-HONG ZENG, 2PEI-CHEN WU, 1CHUN-CHUAN LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.

Background: Congenital nephrogenic diabetes insipidus (cNDI) is a rare disease characterized by a malfunctioning renal response to the antidiuretic hormone arginine vasopressin (AVP).

Approximately 90% of all patients with cNDI have X-linked inherited disease caused by variants in the arginine vasopressin receptor 2 (AVPR2) gene. Our objective is to report a small deletion in the AVPR2 gene causing cNDI in a 29-year-old man, presenting with chronic polyuria, polydipsia, recurrent urinary tract infection, bilateral severe hydroureter, bilateral pelviectasis, detrusor muscle areflexia, and an atonic bladder.

Case description: The patient was diagnosed with NDI based on the clinical phenotype, the water deprivation test and the inadequate response to 1-desamino-8-Darginine vasopressin (DDAVP) administration. Sequencing analysis of the AVPR2 gene revealed a novel mutation of c.328delG, p.Ala110fs and his mother was also the carrier of AVPR2 gene c.328delG.

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Abstract PE08

THE INCREASING RISK OF PAPILLARY THYROID MICROCARCINOMA: A SINGLE-CENTER EXPERIENCE LI-CHING LI, KORNELIUS EDY, SHIH-CHANG LO, CHIEN-NING HUANG, YI-SUN YANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, R.O.C.

Background: Thyroid cancer incidence has surged globally, the most common type is Papillary thyroid carcinoma (PTC), accounting for 70-90%. Papillary thyroid micro-carcinoma (PTMC) was defined by PTC tumor size with less than 1 cm in diameter. This study aimed to evaluate the prevalence of PTMC in Chung-Shan Medical University Hospital (CSMUH).

Methods and Results: Between 2016 and 2019, we retrospectively analysed 287 thyroid cancer patients in CSMUH. We found that PTMC patients were primarily diagnosed incidentally after a thyroid operation. Only eight cases were discovered by ultrasound-guided fine-needle aspiration cytology before surgery. 225 patients (78.3%) of all thyroid cancers were diagnosed as PTC. Among PTC patients, 75 patients (33.3%) were diagnosed as PTMC and 32 patients (14.2%) had combined PTMC and PTC tumor size with more than 1 cm in diameter. The Prevalence of PTC among thyroid cancer patients in CSMUH increased from 70.4% in 2016 to 80.3% in 2019, while that of PTMC also increased from 29.5% in 2016 to 39.2% in 2019. Patients with papillary subtype contained a higher proportion of females (75%). In the age-specific prevalence of PTC, males (peak 60-69 years) were generally older than the females (peak 40-49 years). In contrast, PTMC cases were mostly diagnosed at a younger age in males (peak 40-49 years) than females (peak 50-59 years).

Conclusions: PTMC stands the common subtype of PTC in thyroid malignancy that increasing numbers in recent years. In prevalence, although females were found to be younger in PTC, males were younger than females in PTMC.

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PE09

SEVERE OSTEOPOROSIS WITH HYPOPHOSPHATEMIA PRESENTATION: A CASE REPORT CHING-MEI HSU, KORNELIUS EDY, SHIH-CHANG LO, CHIEN-NING HUANG, YI-SUN YANG Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.

Background: Hypophosphatemia appears most often in acutely or critically ill individuals. In order to delineate among the causes of hypophosphatemia in the setting of metabolic bone diseases, it is important to obtain a thorough history, physical examination and laboratory analysis.

Methods: We reported a case of hypophosphatemia with laboratory data and imaging studies including X-ray and lumbar spine magnetic resonance imaging.

Results: A 65-year-old male presented for evaluation of fragility fracture in the setting of hypophosphatemia. At age of 60, he was given a diagnosis of cervical radiculopathy, severe osteoporosis, Parkinsonism and was placed on therapy of Madopar and analgesic agents. In the past five years, he had worsened decrease in body height at a rate of 1 centimeter per every three months.

He was a vegetarian for 27 year and heavy smoker. On physical examination, the patient had a height of 141cm and a weight of 33kg. Laboratory data showed low serum phosphorus (1.6mg/dl), mild low serum creatinine(0.57mg/dl), high alkaline phosphatase (256 IU/L), normal intact parathyroid hormone(66.6pg/mL), normal morning cortisol(12.649μg/dL), normal TSH (1.238 uIU/ml)and normal free T4(1.435 ng/dl). Subsequent evaluation showed low 25-OH Vitamin D (24 ng/mL) and low 24 hour urine phosphorus (381.58mg/day).

Conclusion: Hypophosphatemia in the setting of complex bone disorders needs a careful evaluation. In clinical practice, we should evaluate all men diagnosed with osteoporosis carefully for secondary causes of bone loss.

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Abstract PE10

VALIDATION OF A NEW METHOD FOR DETERMINING URINARY IODINE BY INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY 1,2

LIN-HSUAN LEE, 1CHENG-PIN CHENG, 3YI-LIN LIU, 3WEI-LAN CHU, 1,4,5 CHUN-JUI HUANG, 3,4,5CHEN-CHANG YANG, 1,6FAN-FEN WANG 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National YangMing University, Taipei, Taiwan; 3 Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6 Department of Medicine, Yangming Branch, Taipei City Hospital, Taipei, Taiwan

Background: Urinary iodine concentration (UIC) has been traditionally determined by a modified microplate method utilizing the Sandell-Kolthoff (S-K) reaction in Taiwan. However, the S-K method consumes more time and produces toxic wastes from arsenic trioxide. The study aimed to develop and validate a new method for determining UIC by inductively coupled plasma mass spectrometry (ICP-MS).

Methods: Samples and iodate calibrators were diluted 100 times into aqueous solution containing triton X-100, 0.5% ammonia solution and tellurium (128Te) as an internal standard. Digestion was not necessary before analysis. A total of 183 excess urine samples covering a wide range of iodine concentrations were measured by both methods. Passing-Bablok regression and Bland–Altman plots were used to compare values across methods.

Results: The limit of detection by ICP-MS was 1 μg/L. For UIC values above 200 μg/L, the total coefficients of variation (CVs) were below 10%. Pearson correlation coefficient was 0.997, suggesting a high level of agreement between the two methods. The y-intercept for Passing-Bablok regression was 3.12 and the slope was 0.99. A small but neglectable mean difference of -0.8 μg/L was detected on Bland–Altman plots.

Conclusions: A simple, rapid, and accurate ICP-MS method has been validated for measuring UIC in Taiwan.

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PE11

PATIENT ADHERENCE TO LOW IODINE DIET FOR PREPARATION OF RADIOACTIVE IODINE ABLATION THERAPY 1,2

LIN-HSUAN LEE, 1CHENG-PIN CHENG, 3SHAN-FAN YAO, 1,5,6CHUN-JUI HUANG, 4,5,6 CHEN-CHANG YANG, 3WEN-SHENG HUANG 1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; 3 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 4 Division of Clinical Toxicology & Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 5 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Background: The degree of total body iodine depletion was considered to be related to the efficacy of radioiodine ablation therapy (RAIT) and was traditionally evaluated by random urinary iodine concentration (UIC) on the last day of low iodine diet (LID). However, changes in daily urinary iodine excretion varies greatly and one measurement could not truly reflect patient adherence to LID. The study aimed to determine patient adherence to LID and the possible dietary sources of iodine causing violation of LID. Methods: Patients with papillary thyroid carcinoma scheduled for RAIT were recruited in Taipei Veterans General Hospital from March to October of 2020. Random spot urine samples were collected daily during the two weeks’ period of LID and a simple food frequency questionnaire (FFQ) was completed on the day of RAIT. The cut-off of urinary iodine/creatinine (I/Cr) ratio was set at 100 μg/ gCr. Violation of LID was defined as a mean UIC of three consecutive days above 100 μg/gCr since day 4 of LID. Results: A total of 43 patients participated in the study and 58.1% (n = 25) of them stringently followed LID. Among the 41.9% (n = 18) who violated LID, three patients took iodine-containing nutritional supplement and seven patients did not avoid iodized salt. If only one measurement of urinary I/Cr ratio < 100 μg/gCr on the last day was used as the criteria to determine the degree of total body iodine depletion, 66.7% (n = 12) of the patients who violated LID would be misclassified as having good adherence to LID. Conclusions: Despite years of experience in implementing LID in Taiwan, patient adherence remains suboptimal.

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Abstract PE12

ECTOPIC CERVICAL THYMOMA-A CASE REPORT AND REVIEW 1

ZI-JIAN LIN, 2SHU-YI WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan

Thymomas are epithelial tumors of the thymic gland that usually arise in the anterior superior mediastinum. These tumors are rare neoplasms comprising less than 1% of adult cancers. Ectopic thymomas are thought to arise from aberrant thymic tissue displaced during embryologic development and are extremely rare, accounting for only up to 4% of all thymomas. This report described a 40-year-old woman who had a right-sided highly suspicious thyroid nodule, size: 3.9x 2.31x2.11 cm, by ultrasound with AmCAD-UT at health exam, without clinical symptoms including palpitation, dyspnea, hand tremor, or other immune disorders. Thyroid function was within normal range. Three times of fine-needle aspiration biopsies revealed negative for malignant cell. The histopathological diagnosis of the specimen after unilateral thyroid surgery was ectopic cervical thyroidal thymoma.

Immunohistochemical stain reveals CK(+), TTF-1(-), INSM1(-), p63 diffuse(+), PAX8(+), GLUT1 diffuse(+), CD117 focal(+) and BCL2(+) for tumor cells. CD5(+) and Tdt focal(+) in scattered lymphocytes are seen. Radiotherapy has been shown to be an effective treatment, and it has a favorable prognosis. This case presented highlight an unusual tumor entity that can be clinically confused for common lesions affecting the thyroid gland.

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PE13

DETERMINATION OF IODINE CONCENTRATION OF SOY SAUCE IN TAIWAN 1

CHENG-PIN CHENG, 1,2LIN-HSUAN LEE, 1,3,4CHUN-JUI HUANG, 5WEN-SHENG HUANG

1

Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2 Institute of Food Safety and Health Risk Assessment, School of Pharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; 3 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 4 Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5 Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan;

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Because soybean and most soybean products contain iodine, patients with thyroid carcinoma preparing for radioiodine ablation were educated not to ingest soy sauce during the two weeks’ period on a low iodine diet. The aim of the study was to determine the iodine contents of common domestic soy sauces.

Methods: Twenty-six different brands of soy sauce were diluted with distilled water with a dilution factor of fifty. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated five times for determination of mean and standard deviation (SD).

Results: Among the twenty-six surveyed soy sauce, only three brands of soy sauce contained iodine. The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.4 ± 0.4, 5.1 ± 0.4, 11.1 ± 1.0 mg/L respectively. The other twenty-three soy sauces were iodine-free. Two of the three iodine-containing soy sauce were supplied with kelp extract for additional umami, which were the major sources of iodine.

Conclusions: Most soy sauces were iodine-free and may be allowed on a low iodine diet.

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Abstract PE14

A NEWBORN WITH CONGENITAL GOITER AND HYPOTHYROIDISM FROM A MOTHER WITH THYROTOXICOSIS: A CASE REPORT AND REVIEW OF LITERATURE 1

YU-LIN YANG, 1CHUN-TA HUANG, 2WEI-HSIN TING, 3YI-YUNG CHEN, 1 CHUN-CHUAN LEE 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 2Division of pediatric endocrinology and diabetes, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.; 3Division of High Risk Pregnancy, Department of Obstetrics and Gynecology, MacKay Memorial Hospital, Taipei 10449, Taiwan, R.O.C.

Background: Fetal goiter is a rare condition that affects one out of 30,000 pregnancies in iodinesufficient areas, usually in association with maternal Graves’ disease. Large goiters that obstruct fetal swallowing may lead to polyhydramnios and subsequent gastrointestinal dysgenesis, placing the pregnancy at risk of pre-term birth. Hyperextended neck caused by goiter and inadequate head flexion during labor increase the risk of neonatal respiratory distress as well as difficulties in intubation.

Both neonatal hypothyroidism secondary to over-treatment of a thyrotoxicotic mother and neonatal hyperthyroidism due to transplacental passage of maternal auto-antibodies are possible etiologies.

Nonetheless, it is not always easy to distinguish one from the other. Fetal ultrasound examination allows recognition of the goiter’s size but is unreliable to establish correct diagnosis. Maternal thyroid function and several fetal physiological parameters can provide important clues. Prompt adjustment of maternal anti-thyroid drugs and multidisciplinary team are crucial to avoid peri-partum complications.

Case presentation: A 34-year-old woman with underlying Graves’ disease, treated with PTU (250mg/day), had normal to slightly decreased level of free-T4 level and elevated TSHR-Ab level during the third trimester of pregnancy. She was admitted to our hospital at 37+5 weeks of gestation for elective caesarean-section owing to fetal goiter (thyromegaly) detected under pre-natal sonography.

The infant presented with temporary symptoms of hypothyroidism that cured after thyroxine replacement.

Conclusions: The recommended perinatal management of Graves’ disease is to adjust free T4 within a range from the upper limit of normal to a slightly elevated level in order to maintain the thyroid function of the fetus.

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PE15

LOCAL AND SYSTEMIC TREATMENTS IN A CASE OF METASTATIC DIFFERENTIATED THYROID CANCER WITH MULTIPLE TIMES OF RECURRENCE: A CASE REPORT AND REVIEW OF LITERATURE 1

YVONNE CHIEW, 1CHEN-KAI CHOU

1

Division of Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.

Background: Various local and systemic treatments are available for metastatic differentiated thyroid cancer. Cryotherapy, radiotherapy frequency ablation (RFA) and target therapy were relatively uncommon comparing to metastatic surgery and radioactive iodine therapy (RAI). We present a case of metastatic differentiated thyroid cancer with multiple times of recurrence who underwent various treatment for metastatic lesions including RAI, surgery resection of metastatic nodules, RFA, cryotherapy, radiotherapy, and target therapy.

Case presentation: This is a 44-year-old woman diagnosed with right papillary thyroid cancer in 2017. She received total thyroidectomy in February of 2017 with initial staging of pT3Nx, followed by radioactive iodine(I-131) therapy (RAI, dose: 150mCi) in May of 2017 at other hospital. Cervical lymph node dissection was done in December of 2017, followed by RAI administration (100mCi, no uptake, accumulated dose: 250mCi) in March 2018 for thyroid cancer recurrence, stage pT4aN1b. As persistent high thyroglobulin level (Tg: 27ng/mL) was detected, she came to our hospital for second opinion. She suffered from multiple times of thyroid tumor recurrence and metastasis over neck, lung, and mediastinum area. She received total 3 times of RFA for metastatic nodules over neck, thyroid bed, paratracheal region and isthmus region in year 2018 and 2019. Wedge resection for lung metastasis and resection for mediastinum tumor were performed in year 2018 and 2019. In 2020, newly found pulmonary nodules over right lower lung and progressive increase in the size of soft tissue mass over sternal area with sternal bone destruction were detected by chest CT and PET. Cryotherapy was arranged for sternal tumor in April of 2020. She started target therapy with Lenvatinib 10mg per day since April 2020 and increased to 20mg per day since July 2020, her urine protein in April 2020 was negative. She received radiotherapy for sternal mass from May 2020 to June 2020. Her Tg level from October 2017 to April 2020 ranged from 27 to 423 ng/mL. Her image study showed tumor regression and her Tg level was decreasing (Tg level in October 2020: 10.8ng/ mL). Unfortunately, hypertension and proteinuria were noted since October 2020, antihypertensive medication was prescribed and her Lenvatinib dose was decreased to 8mg QD since then.

Conclusions: In metastatic thyroid cancer, surgery and RAI remain as the standard curative therapy. Unresectable regional and distant metastasis can be managed by local therapy such as cryotherapy, RFA and radiotherapy. Kinase inhibitor therapy can be offered in RAI refractory DTC 184

Abstract patients with rapidly progressive, metastatic cancer despite local treatments. The treatment should be patient-tailored, by weighing the risks and benefits, and put into consideration of life quality besides the risks of injury and death.

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PE16

DIFFERENTIATED THYROID CANCER WITH BONE METASTASISTHREE CASES REPORT AND LITERATURE REVIEW 1

YU-YEN TSAI, 1SHU-YI WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua City, Changhua County, Taiwan

In patients with differentiated thyroid cancer (DTC), bone metastasis (BM) is the second most common site of distant metastasis, usually associated with low survival rates. Diagnosis of DTC with BM is established by correlating clinical suspicion with imaging. The management of DTC with BM is challenging with regard to its heterogeneous courses, thus imaging is essential to detect, localize, and assess the lesions and should be used in conjunction with clinical evidence. This article includes 3 elderly female patients of DTC with BM, who initially presented with low back pain or abnormal soft tissue mass and was reported to be caused by bone metastasis according to imaging such as CT or MRI. Biopsies of the metastatic tumor in these patients all suggested a thyroid origin tumor.

Specimen was obtained via bilateral total thyroidectomy, confirming the histopathological diagnosis of follicular carcinoma in two and papillary carcinoma in one of these cases. One of the patients with follicular carcinoma had undergone radiotherapy, radioactive iodine and kinase inhibitor of sorafenib.

Subsequent whole body scans (WBS) and CT showed stable disease and decreased size of previous metastasis. The other two patients had also received radiotherapy and they will have radioactive iodine in the near future. These cases put an emphasis on accurate staging for appropriate follow-up, which allows early detection and improves treatment outcome. Furthermore, factors affecting metastatic susceptibility, such as gene expression profiles that predict the aggressive behavior of thyroid cancer cells, will be discussed, so as to provide more specific and personalized approach to achieve better disease control.

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Abstract PE17

THYROID ECTOPIA, A CASE REPORT 1

WAN-TING HUANG, 1BAO-YIN CHEN, 1YUN-SHING PENG, 1HO CHENG, 2 MING-FONG TSAI, 1YUNG-HSIANG LIN 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, CGMH, Chiayi.

Department of Nuclear Medicine, Chang Gung Memorial Hospital, Chiayi.

2

Background: Thyroid ectopia is a result of the failure of migration of the developing thyroid from the pharyngeal floor to its usual pre-tracheal region. It’s usually located along the normal path of thyroid descent. In 70% of all cases, the lingual thyroid gland is the only thyroid. It is rare for two ectopic thyroid tissue to be present simultaneously.

Case presentation: A 43 years old female presented with fatigue and weakness, was referred to our department due to hypothyroidism.(TSH:82.030 uIU/mL Free T4:0.76 ng/dL) Submental lump about 2 cm noted since childhood and a family history of thyroid disease(Her mother and younger brother) were mentioned during history taking. Physical examination revealed that the thyroid gland was not palpable. Thyroid ultrasonography confirmed the absence of thyroid gland and one isoechoic, heterogeneous solid nodule (2.36 x 2.29 x1.74cm) over the submandibular area found. Thyroid ectopia was suspected. Tc-99m thyroid scan was arranged to confirm the diagnosis. Anti-thyroid peroxidase antibody(anti-TPO ab.) was checked to survey the cause of hypothyroidism.

Results: Tc-99m thyroid scan revealed non-visualization of thyroid gland in the thyroid beds bilaterally. And, there was obvious radioactivity in the submandibular and upper mediastinum, left lower to the thyroid bed. Anti-TPO ab. revealed high titer(592.92 IU/mL). Dual thyroid ectopia with autoimmune thyroid disease related hypothyroidism was impressed. Thyroxine replacement was started. I-131 thyroid scan and SPECT/CT image fusion study will be arranged for confirmation and localization of the impressed thyroid anomaly.

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PE18

COMPLETE ANDROGEN INSENSITIVITY SYNDROME: A CASE REPORT 1

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

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

Background: Androgen insensitivity syndrome is an X-linked recessive genetic disease.

Mutations in the androgen receptor gene are 70% inherited and 30% de novo. Prevalence of complete androgen insensitivity syndrome is around 1/20400 to 1/99100. Patients present female external genitalia with a 46 XY karyotype at birth and primary amenorrhea at puberty. Normal breast development and absence of pubic hair were found due to complete androgen receptor dysfunction.

High Luteinizing hormone and testosterone level were also noted.

Methods: We reported a 16 years old female with complete androgen insensitivity syndrome who received laparoscopic orchiectomy and estrogen replacement therapy.

Results: A 16 y/o female denied any systemic disease before. Her grandmother accompanied with her to our endocrine clinic due to amenorrhea, while. she did not complain any other discomfort.

Physical examination showed normal breast development (Tanner stage IV-V) and absence pubic and axillary hair (Tanner stage I).

The patient denied any sexual experience before and the pregnancy test was negative. Luteinizing hormone (LH 44.53 mIU/mL), follicle stimulating hormone (FSH 46.3 mIU/mL) and testosterone (5.47 ng/mL) all were higher than female normal range in her age. Pelvic echo showed no uterus nor adnexa. Genetic test was done, and karyotype revealed 46 XY. Abdominal CT revealed testis at lateral aspect of bilateral pelvic cavity, so she was transferred to division of urology. Laparoscopic orchiectomy was done. After surgery, estrogen replacement therapy was given to keep her female characteristics.

Conclusions: Almost all patients with complete androgen insensitivity syndrome received gonadectomy and hormone replacement therapy after surgery, but the timing of gonadectomy is still controversial. Delay of operation is more considerable nowadays because the tumor risk of testes with complete androgen insensitivity syndrome is low before the puberty peroid.

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Abstract PE19

THERAPEUTIC INHIBITION OF POLO-LIKE KINASES IN ANAPLASTIC THYROID CANCER 1,2,3

SHU-FU LIN, 3,4CHUN-NAN YEH, 5YU-TUNG HUANG, 6,7TING-CHAO CHOU, 8 RICHARD WONG 1

Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan; Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Chang Gung University, Taoyuan, Taiwan; 4Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 6Laboratory of Preclinical Pharmacology Core, Memorial Sloan-Kettering Cancer Center; 7PD Science, Inc., 599 Mill Run, Paramus, NJ, USA; 8Head and Neck Survice, Memorial Sloan-Kettering Cancer Center 2

Background: Polo-like kinases (PLKs) are potent regulators of cell proliferation and cell survival. PLKs are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease.

Methods: The therapeutic efficacy of volasertib, a PLKs inhibitor, alone and in combination with sorafenib, for treatment of ATC was evaluated in vitro. The expression of PLKs was assessed using Western blot. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were evaluated by flow cytometry and fluorometric assay. Mice bearing flank ATC were treated with volasertib and sorafenib.

Results: Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose-dependent manner. Volasertib caused ATC cells to accumulate in G2/M phase, activated caspase-3 activity, and induced apoptosis. Combination therapy of volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single-agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals treated with either single agent or combination treatment.

Conclusions: These preclinical findings suggest that volasertib may be an effective drug in treating ATC.

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PE20

PULMONARY CRYPTOCOCCOSIS AND MULTIPLE VERTEBRAL FRACTURES AS INITIAL PRESENTATIONS OF ADRENAL CUSHING’S SYNDROME 1

KUAN-YU LIN, 2TSONG-YOW WU, 1CHIH-YUAN WANG

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2 Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

Background: Complications of untreated Cushing’s syndrome included hypertension, impaired glucose tolerance, osteoporosis and susceptibility to infections. However, literature regarding pulmonary fungal infections as initial presentations of Cushing’s syndrome were rare.

Methods: We presented a case of adrenal Cushing’s syndrome with rare initial presentations of pulmonary cryptococcosis and multiple vertebral fractures.

Results: This 57-year-old woman was diagnosed with papillary thyroid cancer and received total thyroidectomy 6 years ago before this evaluation. A right lower lobe nodule, 1 cm in diameter, was accidentally found by low dose CT 29 months ago, and was enlarged to 1.5 cm in diameter one year later. She received video-assisted thoracoscopic tumor wedge resection 14 months before this evaluation, and the pathology revealed pulmonary cryptococcosis. She received fluconazole 400 mg daily for 6 months postoperative. On the other hand, pre-operative CT revealed a 2.8 cm right adrenal nodules and T7 spine compression fracture. She had a fall episode while skiing one month earlier.

A DEXA scan performed later revealed osteoporosis, with lumbar T score of -4.5. Oral calcium and calcitriol supplement, with monthly teriparatide injection were prescribed. Additional history taking revealed that she had hypertension, hyperlipidemia and weight gain of more than 10 kilograms in recent 5 years. The patient’s vital signs were stable. She was obese, with some supraclavicular and posterior neck fat pads deposition. There were no typical Cushingoid features like moon face, purple striae or proximal myopathy. Laboratory examinations revealed increased neutrophils counts, decreased lymphocyte counts, mild hypernatremia and hypokalemia. Serum cortisol levels were within upper normal limit, but without diurnal change (8 AM 17.10 μg/dl, 4 PM 15.30 μg/dl, reference range 8 AM 3.7 - 19.4 μg/dl, 4 PM 2.9 - 17.3 < 1.8). Serum ACTH level was low. One milligrams dexamethasone suppression test failed to suppress morning cortisol level, and 24-hr urinary free cortisol was elevated. Serum aldosterone, plasma renin activity, 24-hr urinary catecholamines and VMA level were all within normal range. Under the diagnosis of adrenal Cushing’s syndrome, the patient received laparoscopic right adrenalectomy. The pathology revealed cortical adenoma. The postoperative course was uneventful. She lost 9 kilograms in 3 months after surgery. She felt well under oral cortisone supplement at a dose of 25 mg in the morning and 12.5 mg in the afternoon.

190

Abstract Conclusions: Clinical awareness of atypical presentations of Cushing’s syndrome is important.

Single-point, morning cortisol level may not accurately reflect the severity of corticosteroid excess, and further dynamic tests are warranted if high clinical suspicions. Early diagnosis and treatment of Cushing’ syndrome prevent long-term sequelae such as severe infections and osteoporosis.

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PE21

ANTERIOR NECK HEMATOMA WITH TRACHEAL COMPRESSION AFTER FINE-NEEDLE ASPIRATION CYTOLOGY OF THYROID: A RARE BUT PRECAUTIOUS COMPLICATION IN ENDOCRINE PROCEDURE 1

TSONG-YOW WU, 2KUAN-YU LIN, 2CHIH-YUAN WANG

1

Department of Internal Medicine, National Taiwan University Hospital, Taiwan, R.O.C.; 2 Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taiwan

Background: Fine needle aspiration cytology (FNAC) is usually the routine diagnostic pathway to assess lesions of the thyroid gland. The simple technique was considered to be a relatively costeffective and low risk methodology for initial differentiating benign nodular goiter from malignant one.

Methods: We presented a case of right neck progressively swelling with tracheal compression after fine-needle aspiration of thyroid.

Results: This 62 year-old man has been regularly followed up at an endocrinologist's outpatient-clinic for his acromegaly and bilateral multinodular goiter. Blood tests on 2019/08/09 showed elevation of serum thyroiglobulin (182 ng/ml). Thyroid sonography on 2019/9/03 showed enlargement of right cystic goiter (5.82 x 5.118 x 3.31 cm). Fine-needle aspiration was suggested but postponed to 2019/9/10 due to taking fish oil. He denied taking any anti-platelet or anti-coagulant. Fish oil was discontinued for one week and fine-needle aspiraiton was performed to right cystic lesion at 15:00 on 2019/9/10. Total 25 c.c dark brownish fluid was drained. After aspiration, the thyroid echo showed decreased thyroid cyst and no actvie bleeding. However, progressive pain and swelling of the right neck developed in the following hours. No dyspnea or stridor was noted. Due to above reasons, he came to our emergency department for help. Head and neck CT-scan showed a large hematoma at the anterior right lower neck, mainly from the thyroid gland, with contrast extravasation. The trachea was compressed and displaced to the left side. Trans-arterial embolization was indicated but respiratory distress in supine position developed. Therefore, endotracheal tube intubation was performed for airway protection. Trans-arterial embolization was done smoothly and he received intensive care thereafter. Fortunately, he recovered smoothly and discharged from hospital three weeks later.

Conclusions: Although FNAC is a relatively safe procedure for detecting the cytological findings of nodular goiter, the associated complications, including hemorrhage, incidental trauma around soft tissue, infection, inflammatory response still should be concerned. Pre-procedural preparation with delicate survey of probable routine medications, coagulopathy and healthy food will be pivotal, together with gentle procedure with sono-guided aspiration technique.

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Abstract PE22

FAMILIAL THYROID PAPILLARY CARCINOMA: A CASE REPORT HUI-LING LIN, TSUNG-HUI WU, TANG-YI LIAO, FANG-YU CHEN, CHII-MIN HWU Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Background: Familial papillary thyroid carcinoma (FPTC) is rare, and it is defined as the same diagnosis in three or more first-degree relatives in one family. It’s believed that FPTC is more aggressive with higher rates of recurrence, comparing to sporadic PTCs. Methods: We report a series cases of familial follicular thyroid carcinoma.

Results: The 49-year-old male accidentally found a left neck mass during a health examination in January 2012. According to the patient, he had heat intolerance for years. There were also general malaise and easy sweating at night. However, the patient denied body weight loss or palpitation. Thus he came to the other hospital for further survey, and thyroid sonography revealed a thyroid mass of 2.8 cm, whereas fine needle aspiration showed benign nature. The patient came to our hospital for regular following up then. In May 2013, aspiration cytology revealed thyroid papillary carcinoma.

Total thyroidectomy with central lymph node dissection was prescribe on 2013-07-19. Total 2 tumors, size 0.3 cm and 3.5x3x2 cm were found, pTNM stage is pT2N0Mx. Then we let the family come for further evaluation. His mother was diagnosed with micro papillary thyroid carcinoma in 2015. His 1st young brother received right lobectomy for 7cm right neck mass in 2015, pathology revealed nodular goiter with cystic degeneration. In 2020, his 2nd younger brother was also diagnosed with papillary thyroid carcinoma. Due to above description, familial papillary thyroid carcinoma is diagnosed.

Conclusions: Regular following up of first-degree relatives should be considered when papillary thyroid carcinoma is diagnosed.

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PE23

THYROTROPIN (TSH)-SECRETING PITUITARY ADENOMAS CASE REPORT AND ANALYSIS OF CLINICAL FEATURES AND TREATMENT IN A 5-YEAR CASE SERIES IN NATIONAL TAIWAN UNIVERSITY HOSPITAL 1

CHUN-HSIEN LIN, 3HSIN-YI HUANG, 2PO-HAO HUANG, 2SHIH-HUNG YANG, 1 JIN-YIN LU, 1WAN-CHEN WU 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital; 2Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital; 3Department of Pathology, National Taiwan University Hospital

Background: Thyrotropin (TSH)-secreting pituitary adenomas (TSH-omas) is a rare pituitary adenoma, accounting for 0.5-3% of all functioning pituitary adenomas. According to the 2017 WHO classification, it may be classified as thyrotroph adenoma or plurihormonal adenoma. We reported a case of thyrotroph adenoma, and presented analysis of clinical symptoms, diagnosis, treatment and prognosis in a 5-year TSH-omas case series in National Taiwan University Hospital (NTUH).

Case Report: A 68-year-old female without known systemic diseases was presented to the emergency department due to recurrent vertigo and hypertension. The neurological examination was unremarkable. However, blood tests showed high free T4 (fT4) (2.15 ng/dL) with non-suppressed thyroid stimulating hormone (TSH) (4.96 μIU/mL). She had no obvious symptoms related to thyrotoxicosis, and there was no family history of thyroid diseases. Repeated blood tests using different laboratory methods showed the same results, and central hyperthyroidism was suspected.

The pituitary MRI revealed a 1.2 cm adenoma at right pituitary gland with stalk deviation to the left side. Other pituitary hormones were all within normal limits. Thyrotropin-releasing hormone (TRH) stimulation test yielded blunted response and octreotide suppression test showed TSH was well suppressed, compatible with TSH-oma. Octreotide 100 mcg per 8 hours was administered for 7 days and endoscopic transsphenoidal adenomectomy was performed. The immunohistochemistry (IHC) stain showed strong positive of β-TSH and negative of other pituitary hormones, compatible with thyrotroph adenoma. Transient central hypothyroidism occurred within a few months after surgery, and was replaced with levothyroxine for around 6 months. There was no residual tumor in MRI, lab profile showed euthyroid state without levothyroxine replacement, the vertigo resolved and hypertension was well controlled at current 1.5-year follow up.

Method: We retrospectively enrolled cases diagnosed with TSH-omas and received surgery from 2016/1 to 2020/12 in NTUH. The diagnosis of TSH-omas included blood test showed central hyperthyroidism and the pathology confirmed thyrotroph adenoma or plurihormonal adenoma by 2017 WHO classification criteria. We analyzed these patients' clinical features, treatment, and prognosis.

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Abstract Results: A total 378 patients had pituitary tumor and underwent pituitary surgery, and the pathology of 344 patients showed pituitary adenoma. 22 of the 344 pituitary adenomas (6.4%) showed positive IHC stain of TSH. Only four cases (1.2%) fulfit the diagnosis of TSH-omas. Two of them were thyrotroph adenoma, and blood tests showed central hyperthyroidism without abnormalities in other pituitary hormones. The other two cases were plurihormonal PIT1-positive adenomas.

Laboratory data of both showed also central hyperthyroidism, but one had combined high hGH and IGF-1 level, who had obvious acromegaly features. These four patients were all women without any systemic diseases, and the age of diagnosis was 24 to 68 years old. The initial presentations were blurred vision, vertigo, dysmenorrhea, and insomnia/dizziness respectively. The thyroid function tests were fT4 1.79-3.98 ng/dL and TSH 3.57-5.32 μIU/ml. Two of them had some symptoms which may be related to hyperthyroidism, such as hypertension and menstrual irregularity, and the other two had no obvious related symptoms. Two of them also had a combination of autoimmune thyroid disease diagnosed by positive thyroid auto-antibodies and sonographic characters. TRH stimulation tests and octreotide suppression tests were performed in 3 patients. Two showed blunted TSH response to TRH and well suppressed TSH to octreotide, and one showed borderline TSH response to TRH, and partially suppressed TSH to octreotide. Three of them received octreotide therapy before operation, three patients had transient diabetes insipidus. Three patients returned to euthyroid state However, one had persistent hyperthyroidism 2 months after surgery, and underwent further evaluation recently.

Conclusions: TSH-oma is a rare functioning pituitary adenoma. Patients with TSH-oma may not always present typical thyrotoxic symptoms. For patients whose blood tests showed elevated fT4 with non-suppressed or elevated TSH, doctors should be aware of “inappropriate secretion of TSH (IST)”, and TSH-oma is one of the causes. Management of TSH-oma and primary hyperthyroidism are completely different. If TSH-oma is misdiagnosed as primary hyperthyroidism, and treated with antithyroid drugs, which may aggravate TSH-oma. The other important differential diagnosis of IST is resistance to thyroid hormone (RTH), which can be differentiated from family history, pituitary imaging, TRH stimulation test, and response test to somatostatin analogue.

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ADRENAL INCIDENTALOMA WITH AUTONOMOUS CORTISOL SECRETION AND UNCOMMON PATHOLOGICAL FINDING 1

CC KU, 1YM CHIEN, 2HM CHAO, 1CJ CHANG, 1,3,4TI LEE, 1,4TW LEE

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital; 2Department of Pathology, Wan Fang Hospital; 3Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Background: Adrenal incidentaloma may present with autonomous cortisol secretion, a state of hypercortisolism without prominent clinical features of Cushing’s syndrome, causing diabetes mellitus, hypertension, osteoporosis, and obesity.

There existed controversy in whether adopting surgical resection as an optimal therapeutic choice.

Patient's therapeutic strategy needs to be individualized based on efficacy and benefit.

Case Presentation: A 69-year-old woman has type 2 diabetes mellitus for 14 years, hypertension, and hyperlipidemia.

She was incidentally found to have a 1.5 cm tumor over left adrenal gland by abdominal noncontrast computed tomography on 2019/02/25. (Figure 1).

Hormone work-up ruled out the diagnosis of primary aldosteronism (Table 1) and pheochromocytoma (Table 2).

Physical examinations showed no clinical features of hypercortisolsim related abnormality such as moon facies, buffalo humps, purple striae, and thin skin.

1mg overnight dexamethasone suppression test (DST) showed nonsuppressible cortisol levels: 5.457pg/ml on 2019/6/21.

Repeated 1mg overnight DST, which was adopted in order to verify the biochemical authenticity of diagnosis because of discrepancy between 24 hour urine free cortisol level and 1mg overnight DST, also showed nonsuppressible cortisol levels: 4.43pg/ml on 2019/8/17. (Table 3) The patient underwent left laparoscopic adrenalectomy on 2019/12/18, a golden yellow nodule (A) and another dark brown pigmented nodule (B) were found on the left adrenal gland (Figure 2).

Pathological examination revealed macronodular hyperplasia (Figure 3).

Based on the results of biochemical studies and pathological findings, ACTH-independent macronodular hyperplasia (AIMAH) was impressed.

Post-operatively, the patient’s antidiabetic and antihypertensive drugs were reduced.

Better glycemic control with lowering AC glucose 92mg/dl, PC glucose 152mg/dl, and HbA1c 4.5% in contrast to each counterpart with 184mg/dl, 326mg/dl, 9.3% at 2019/12/7 before operation were noted.

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Abstract Discussion: Autonomous cortisol secretion accounts only 5.7% of all adrenal incidentalomas.

AIMAH commonly presents with bilateral adrenal gland enlargement and multiple adrenal nodules.

Our patients had only left adrenal gland nodule, which might be mistaken as a common unilateral adrenal adenoma.

Either bilateral adrenalectomy or pharmacological inhibition of autonomous cortisol secretion would be treatment option.

Age, degree of cortisol excess, general health, comorbidities and patient’s preference should be taken into account in patients with adrenal incidentaloma and autonomous cortisol secretion considered for adrenal surgery.

Our case suggested that adrenalectomy is beneficial in patients with autonomous cortisol secretion and associated comorbidities, such as hypertension and diabetes mellitus.

Conclusions: Adrenal surgery in patients with adrenal incidentaloma and autonomous cortisol secretion may lead to improved glycemic and blood pressure control.

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PE25

A COEXISTENCE OF TSH-SECRETING AND GH-SECRETING PITUITARY TUMOR: A CASE REPORT 1

YOU-TING LIN, 1TZU-YUAN WANG, 1MING-JIA XIE, 1CHING-CHU CHEN, 1 CHWEN-TZUEI CHANG, 1RONG-HSHING CHEN, 1JUN-WEI HO, 1JUEI-YU TSENG, 1 JIA-YIN GUO, 1YING-YU TSENG 1

Intelligent Diabetes Metabolism and Exercise Center, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Background: While full-blown forms of acromegaly due to growth hormone-secreting tumor are often easily recognizable clinically, co-secreting thyrotropin (TSH) and growth hormone (GH) pituitary adenomas are rarely reported.

Case report: A 50-year-old man with a history of hypertension, valvular heart disease and atrial fibrillation was sent to emergency room at local clinic due to traffic accident without head trauma.

After conservative treatment, he was informed further investigations is needed because of the high index of suspicion for features of acromegaly. He has had hypertension and atrial fibrillation for 5 years and regularly sees his cardiologist, which are controlled on olmesartan medoxomil 20 mg daily, furosemide 40mg daily, spirolactone 25mg daily, rivaroxaban daily, and digoxin 0.25 mg daily.

At our neurosurgery outpatient department, a hGH level of 7.011 ng/mL (<1 ng/mL), insulin-like growth factor-1 level of 607 ng/mL (48.1-209 ng/mL), free T4: 3.86 ng/dL (0.54-1.40 ng/dL). Other laboratory test results, including complete blood cell count, routine chemistries, anterior hormonal data including TSH, ACTH, cortisol, LH, FSH, testosterone, prolactin, are all normal. The initial pituitary-dedicated MRI documents a lobulated tumor measuring 26x25x23 mm in the enlarged pituitary fossa, left cavernous sinus involvement, encasement of left internal carotid artery, and mild suprasellar bulging. Cardiac echography shows a dilated aortic root and multiple moderate valvular regurgitations including aortic, tricuspid, mitral and pulmonary valve. The neurosurgeon requests an endocrine consult preoperatively. On physical examination, his height is 176 cm and weight is 94.6 kg (BMI: 30.5 kg/m2). His blood pressure is 165/82 mm Hg and pulse rate is 102 beats/min with irregular rhythm and systolic murmur grade 3, enlarged nose, macroglossia, protruding jaw, big hands and feet, and lower extremity edema. 75 gram of glucose fails to suppress the 6 time-serial hGH level by a 2-hour GH-suppression test. The thyroid stimulating immunoglobulin, antithyroid peroxidase antibody, and antithyroglobulin antibody are all below the reference range, and thyroid echography demonstrates a symmetrically enlarged thyroid. All above clinical presentations and studies are suggestive of a coexistence of TSH-secreting and GH-secreting pituitary tumor. Due to the high risk of transsphenoidal surgery under not well controlled cardiac failure, long-acting somatostatin analogue and gamma knife radiosurgery are clinically feasible alternative measure.

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Abstract Conclusion: Clinician should be able to cognizant of the clinical presentations of acromegaly and the potentially of other co-secreting hormone such as, though its rarity, the TSH, even in the absence of relevant symptoms. Control of co-secreting GH and TSH pituitary macroadenomas is possible with somatostatin analogue and gamma knife radiosurgery.

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PSUDOHYPOPARATHYROIDISM?! OR PSEUDOPSEUDOHYPOPARATHYROIDISM ??!

1

CHIA-TE WU, 1CHING-LING LIN, 1LI-CHI HUANG, 1WEI CHANG CHEN, 1 TIEN-SHANG HUANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Cathey General Hospital.

Introduction Psuedopseudohypoparathyroidism(PPHP) is an extremely rare genetic disease, unlike other forms of pseudohypoparathyroidism(PHP) usually comes with resistance to PTH, which is characterized by a constellation of clinical features collectively termed Albright hereditary osteodystrophy (AHO) but no evidence of resistance to parathyroid hormone (PTH). Here we presented with a case.

Case Report On 2018/07/17, A 15-year-old adolescent female came to our Metabolic Endocrinology outpatient clinic due to obesity(115kg) and progressive weight gain for 8 years. On examination, she had short stature (155 cm) and shortened 4th and 5th fingers bilaterally. Hand radiographs confirmed symmetric (AHO-like ) abnormalities of both hands with shortening at the right 4th metacarpal bone and left 3rd & 4th metacarpal bone. Cushingoid features with moon facies, buffalo hump, purple striae, and acanthosis nigricans on the posterior neck were noted as well. She had no ectopic calcifications on the chest radiograph, serum calcium and phosphate were normal as well as intact parathyroid hormone (i-PTH) levels (26.4pg/ml). Cushing syndrome had been ruled out after over-night and standard two days dexamethasone suppression test were repeated for 2 times.

Molecular genetic testing was performed however it showed no evidence of mutation in her GNAS gene. Based on her clinical presentation and hormonal and biochemical profile, the diagnosis of pseudopseudohypoparathyroidism was concluded.

Discussion Obesity in adolescents is a common issue due to several environmental, medical, or physiological reasons. However, when obesity combined with brachydactyly, few congenital anomalies should be kept in mind especially PHP and its varients. Diagnosis of PPHP is based on the presence of typical features of AHO (X-rays confirmed shortening of the fourth metacarpal) and exclusion of other forms of PHP (by measuring serum calcium, phosphate, and iPTH which are typically normal in PPHP). Molecular genetic testing in PHP might showed mutation in the coding sequence of GNAS gene (the maternal allele) in PHP1a; abnormal methylation at the GNAS A/B:TSS-DMR in PHP1b; mutation in the coding sequence of GNAS gene (the maternal allele)(exon 13 preferentially) in PHP1c and mutation in the coding sequence of GNAS gene (the paternal allele) in PPHP. However, the sensitivity of the molecular genetic testing is only 50-72% thus negative result should not exclude the diagnosis. For our patient, the diagnosis of PPHP is based on her typical AHO feature with negative hormonal and biochemical laboratory result.

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Abstract Pseudopseudohypoparathyroidism is not life-threatening but the quality of life can be affected in those with severe ectopic ossification. Currently, no treatment is required but genetic counseling is recommended.

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PE27

RADIOFREQUENCY ABLATION FOR LOCALLY INVASIVE PARATHYROID CARCINOMA: A CASE REPORT 1

WEI-CHANG CHEN, 1CHING-LING LIN

1

Department of Endocrinology and Metabolism, Cathy General Hospital, Taipei, Taiwan

Case presentation: A 63 years old female patient under thyroxine treatment due to left partial thyroidectomy about 45 years ago for nodular thyroid disease. In 2008, primary hyperparathyroidism was diagnosed due to severe hypercalcemia (15.4mg/dL) with chondrocalcinosis. Post-operative serum calcium return to normal range with surgical removal of a 4.45x3.01x2.59 cm parathyroid tumor from right thyroid bed. Serum i-PTH level as well as calcium elevated shortly after initial normalization postoperatively. Repeated parathyroid scan showed residual parathyroid tissue in right upper thyroid bed and thyroid echogram showed a hypoechoic lesion in upper right thyroid bed with intrusion into airway lumen through thyroid cartilage. As patient was in good general wellbeing and further radical resection may cause major function destruction, Cinacalcet was used since 2012/09 for treating hypercalcemia with dose up-titrated to 75 mg/day but hypercalcemia persisted and eventually she could not tolerate such high dose of Cinacalcet due to recurrent diarrhea therefore dose of Cinacalcet was tapper down to 50 mg/day. During this period, her DM improved as well as her low BMD and she remained free of symptoms although her serum level remained elevated around 1213 mg/dL. However, deterioration of renal function and persistent nephrocalcinosis were noted and followed larynx CT (2018/08) showed 1.6 cm bi-lobular lesion at right upmost thyroid bed and right subglottic luminal area causing mild airway obstruction. For renal function preservation, correction of persistent hypercalcemia through debulking surgery was performed through intra-laryngeal approach and the lesion was partially removed however hypercalcemia persisted. Echo-guided radiofrequency ablation (RFA) of residual tumor through transcutaneous approach was performed on 2019/05/23 and hypercalcemia resolved and level of parathyroid hormone declined as tumor volume furtherly reduced

by RFA and her renal function stabilized thereafter.

Discussion: Hypercalcemia is a common clinical problem and is mostly caused by primary hyperparathyroidism or malignancy. Severe hypercalcemia which is defined as calcium > 14 mg/dL is associated with more severe symptoms and required immediate therapy. Parathyroid carcinoma is a rare cause of primary hyperparathyroidism which accounts for 1-2% and it is commonly associated with severe hypercalcemia(65-75%). Diagnostic criteria of parathyroid carcinoma include: 1. local invasion of contiguous structures or 2. lymph node or distant metastases. Surgery is the mainstay of therapy for initial treatment, locally recurrent or metastatic disease of parathyroid carcinoma.

Medical therapy, including bisphosphonate, denosumab and Cinacalcet is used to control persisted hypercalcemia or unresectable disease. RFA is currently indicated for symptomatic benign thyroid 202

Abstract nodule and may indicate for palliative treatment for unresectable thyroid cancer but seldom use for parathyroid cancer with hypercalcemia. In this case, we use RFA to shrink the mass and normalize serum calcium level without major functional destruction and resulted in stabilization of patient’s renal function. Since unresectable parathyroid carcinoma is a rare clinical condition the indication of and effectiveness of RFA in this kind of patients remains to be an open question.

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PE28

THE ASSOCIATION BETWEEN HEMORRHOID AND GRAVES' DISEASE 1,2

HSIN -HUNG CHEN

1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan; 2 Chung Sheng clinic, Nantou, Taiwan

Background: To investigate the association between Graves’ disease (GD) and hemorrhoid Methods: Patients with at least two out-patients and one admission record of ICD-9-CM disease code 455.1-455.5 and 455.8 were defined as hemorrhoids patients in this study. Hemorrhoids patients and control patients were matched by sex, age and co-morbidities in the ratio of 1:4.The incidence of GD (ICD-9-CM code 242.0) was the primary event in this study. The Cox proportional hazard model was used to estimate the risk of GD. Univariable model was used to estimate crude hazard ratio (HR) and the multivariable model was used to estimate the adjusted HR. The cumulative incidence curves were obtained by the Kaplan-Meier method and assessed by the Log-rank test.

Results: We recruited 13,165 hemorrhoids patients and 52,660 control patients in this study.

The mean follow up time was about six years. The incidence rate of GD in patients with hemorrhoids was 1.57 per 1,000 person-years and that in the controls was 1.13 per 1,000 person-years. The risk of GD increased by 1.39 times (95% CI = 1.13, 1.71) in hemorrhoids patients compared to the control patients. Female patients with hemorrhoids had a higher risk of GD than those without hemorrhoids (adjusted HR = 1.44; 95% CI = 1.13, 1.83). People in age group 30-39 and suffered with hemorrhoids were more likely to develop Graves’ (adjusted HR = 1.73; 95% CI = 1.18, 2.55).

Conclusions: According to our analysis, the incidence rate of GD in patients with hemorrhoids was higher. Compare to non hemorrhoid group, Patients who were female and younger were the high risk group for GD in the hemorrhoid group.

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Abstract AP-1

SERUM ANGIOPOIETIN-LIKE PROTEIN 6, RISK OF TYPE 2 DIABETES, AND RESPONSE TO HYPERGLYCEMIA: A PROSPECTIVE COHORT STUDY 1,2

KANG-CHIH FAN, 3HUNG-TSUNG WU, 4JUNG-NAN WEI, 5LEE-MING CHUANG, 1 CHIH-YAO HSU, 1I-WENG YEN, 1CHIA-HUNG LIN, 5MAO-SHIN LIN, 5 SHYANG-RONG SHIH, 6SHU-HUEI WANG, 5TIEN-JYUN CHANG, AND 5HUNG-YUAN LI 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan; 2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 3Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan; 4Chia Nan University of Pharmacy and Science, Tainan, Taiwan; 5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 6Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan

Purpose Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia.

To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion.

Method This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome.

Result We recruited 1103 participants without diabetes at baseline. During the 4.22-year followup, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P < 0.05).

Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.

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AP-2

PROTHYMOSINΑ ACTIVATES TYPE I COLLAGEN TO DEVELOP A FIBROTIC PLACENTA IN GESTATIONAL DIABETES 1

WU, H-T, 2KANG, L, 3SU, Y-C, 4OU, H-Y, 5CHAN, F-Y, 6CHEN, Y-C, 7SU, B-H, 5WANG, Y-S, 6WU, C-L, 5SHIAU, A-L AND 2,8,9WU, P 1Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei, Taiwan; 2Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Otolaryngology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 6 Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8 Academic Unit of Obstetrics and Gynecology, University Hospital of North Midlands, Stoke-on-Trent, United Kingdom; 9Keele Cardiovascular Research Group, Centre for Prognosis Research, School of Medicine, Keele University, Stoke-on-Trent, United Kingdom

Purpose High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide.

GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear.

Methods A total of 141 participants with or without GDM were recruited and the blood and placentae samples were collected for a cross-sectional study. Plasma ProTα concentrations were measured by ELISA, and the expressions of ProTα placenta were determined by Western blots.The causal relationship between ProTα and GDM was then investigated in animal and cell models. ProTα transgenic mice were generated to investigate the role of ProTα in placenta. Streptozotocin-induced GDM mouse model was used to clarify the role of ProTα in the development of GDM. 3A-sub-E trophoblasts were used to clarify the possible mechanism of ProTα-induced fibrosis in placenta.

Result In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n = 39), compared with the healthy group (n = 102), and were positively correlated with Col-1 expression.

Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced 206

Abstract nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS).

Conclusion In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.

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AP-3

ABERRANT EXPRESSION OF ANDROGEN RECEPTOR ASSOCIATED WITH HIGH CANCER RISK AND EXTRATHYROIDAL EXTENSION IN PAPILLARY THYROID CARCINOMA 1

CHEN-KAI CHOU, 2SHUN-YU CHI, 2FONG-FU CHOU, 3SHUN-CHEN HUANG, 1 JIA-HE WANG, 1CHUEH-CHEN CHEN AND 4,5HONG-YO KANG 1

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang GungMemorial Hospital, Chang Gung University College of Medicine; 2 Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine; 3 Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine; 4 Graduate Institute of Clinical Medical Sciences, Chang Gung University; 5 Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine

Purpose Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (AR) gene expression on the clinical features and progression of PTC. Method The levels of AR mRNA and protein in frozen, formalin-fixed, parafin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between AR expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the efects of AR on the regulation of cell migration, and key epithelial– mesenchymal transition (EMT) markers.

Result AR mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in AR mRNA expression diminished during PTC tumorigenesis, as AR mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women.

AR mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of AR in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of N-cadherin, Snail1, Snail2, Vimentin, and TWIST1 and up-regulating E-cadherin gene expression.

Conclusion These results suggest that suppression of the androgen–AR axis may lead to aggressive tumor behavior in patients with PTC.

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Abstract AP-4

HLA-DQ GENOTYPE AND BIOCHEMICAL CHARACTERIZATION OF ANTI-TRANSGLUTAMINASE 2 ANTIBODIES IN PATIENTS WITH TYPE 1 DIABETES MELLITUS IN TAIWAN 1,2,4,6,10

LEE YJ, 2,3,4TING WH, 1YANG YW, 5LIN CJ, 1,7HSIEH YT, 2,3,4HUANG CY, 8.9LO FS, 6 CHU CC, 6LIN CL, 6LIN WS, 1LAI TS 1

Institute of Biomedical Sciences, Mackay Medical College, New Taipei; 2 Department of Medicine, Mackay Medical College, New Taipei; 3 MacKay Junior College of Medicine, Nursing, and Management, Taipei; 4 Department of Pediatric Endocrinology, MacKay Children's Hospital, Taipei; 5 Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; 6 Department of Medical Research, MacKay Memorial Hospital Tamsui District, New Taipei; 7 Department of Clinical Laboratory, MacKay Memorial Hospital, Taipei; 8 College of Medicine, Chang Gung University, Taoyuan; 9 Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan; 10 Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, ROC

Purpose Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown.

Method We screened 532 Taiwanese T1DM patients for CD biomarkers including anti-tissue transglutaminase (TGM2), anti-gliadin and anti-neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. Results 3.76% of Taiwanese patients had TGM2-Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2-Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti-gliadin or anti-neoepitope Abs coexisted with ~3/4 of TGM2-Abs positive patients that were likely due to gluten-ingestion, while the cause of TGM2-Abs production for other ~1/4 of patients was unknown.

Purified anti-TGM2 IgA (TGA) and anti-TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2’s transamidation activity by up to 80% but TGG had no effects.

Epitope mapping of all TGM2-Abs positive sera demonstrated that TGM2-Abs had heterogeneity in specificities.

Conclusion This is the first study on Taiwanese Han T1DM patients and demonstrated the differences between our patients and Caucasian ones in HLA genotypes and properties of anti-TGM2-Abs.

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BP-1

EFFICACY OF INVESTIGATIONAL DULAGLUTIDE DOSES OVERALL AND BY BASELINE HBA1C AND BMI: EXPLORATORY SUBGROUP ANALYSIS OF THE AWARD-11 TRIAL 1

ENZO BONORA, 2JUAN FRIAS, 3LUIS NEVAREZ RUIZ, 4ZHUOXIN YU, 4 ZVONKO MILICEVIC, 4RALEIGH MALIK, 4ANGELYN BETHEL, 4DAVID COX, 5 THOMAS LEW (NON-AUTHOR PRESENTER) 1

University of Verona, Verona, Italy; 2National Research Institute, California, USA; 3Hospital Angeles Chihuahua, Chihuahua, Mexico; 4Eli Lilly and Company, Indianapolis, Indiana, USA; 5Eli Lilly and Company, Taipei, Taiwan, R.O.C

Background and aims: Dulaglutide (DU) is approved at doses of 0.75 and 1.5 mg for type 2 diabetes (T2D). The AWARD-11 trial assessed whether higher DU doses (3 mg and 4.5 mg) provide further improvements over the 1.5 mg dose in glucose and body weight (BW) in patients with T2D inadequately controlled with metformin monotherapy. Exploratory prespecified subgroup analyses assessed the effect of DU on HbA1c and BW reduction by baseline HbA1c (< 8.5% or ≥ 8.5%) and BMI (< or ≥ median [34.2 kg/m2]).

Materials and methods: Patients were randomized (1:1:1) to once-weekly DU 1.5 mg (n = 612), DU 3 mg (n = 616), and DU 4.5 mg (n = 614). All patients initiated once-weekly DU 0.75 mg for 4 weeks, followed by step-wise dose escalation every 4 wks to the randomized dose. The primary objective was change in HbA1c from baseline at 36 wks. Secondary objectives included change in BW and % of pts achieving HbA1c < 7% at 36 wks.

Results: At baseline patients had a mean age of 57.1 yrs, HbA1c of 8.6%, and BW of 95.7 kg.

At the 36-wk primary endpoint, both the DU 3 mg and 4.5 mg doses were superior to the DU 1.5 mg dose for HbA1c change (1.5 mg, -1.5%; 3 mg, -1.7% [p = 0.003]; 4.5 mg, -1.9% [p < 0.001]), % of patients achieving HbA1c < 7% (1.5 mg, 57%; 3.0 mg, 65% [p = 0.006]; 4.5 mg, 71% [p < 0.001]) and BW (1.5 mg, -3.1 kg; 3 mg, -4.0 kg [p = 0.001]; 4.5 mg, -4.7 kg [p < 0.001]). Treatment group differences in HbA1c change favored the higher doses vs the 1.5-mg dose in each HbA1c subgroup, with dose-related HbA1c improvements being larger in the higher baseline HbA1c subgroup. BW reduction was dose related in each baseline HbA1c subgroup but was larger among patients with lower baseline HbA1c. Treatment effects on HbA1c were similar between baseline BMI subgroups. Absolute BW reduction was larger across dose groups in the higher baseline BMI subgroup, but treatment group differences were similar between subgroups. Common adverse events were similar between HbA1c and BMI subgroups.

Conclusions: In patients with T2D and inadequate glycemic control on metformin, escalation from DU 1.5 mg to DU 3 mg or DU 4.5 mg once-weekly provided clinically relevant, dose-related 210

Abstract improvements in HbA1c and BW overall and in subgroups of baseline HbA1c and BMI. Consistent with results from other GLP-1 agonists, dose-related improvements in HbA1c were larger among patients with higher baseline HbA1c, whereas dose-related BW reduction was larger among patients with lower baseline HbA1c.

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BP-2

PREFERENCES AND HEALTH STATE UTILITIES ASSOCIATED WITH ROUTES OF ADMINISTRATION FOR ORAL SEMAGLUTIDE, INJECTABLE SEMAGLUTIDE AND DULAGLUTIDE 1

KRISTINA BOYE, 2KATELYN CUTTS, 2KATIE STEWART, 3KIRSI NORRBACKA, 4 LUIS-EMILIO GARCÍA-PÉREZ, 2LOUIS MATZA, 5THOMAS LEW (NON-AUTHOR PRESENTER) 1

Eli Lilly and Company, Indianapolis, IN, USA; 2Patient-Centered Research, Evidera, Bethesda, MD, USA; 3Eli Lilly Finland, Helsinki, Finland; 4Lilly S.A., Alcobendas, Spain; 5Eli Lilly and Company, Taipei, Taiwan, R.O.C

OBJECTIVE: Previous studies have examined health state utilities (which are preference weightings for use in cost-effectiveness analyses) associated with injectable GLP-1 receptor agonists for treatment of type 2 diabetes (T2D). An oral formulation of semaglutide (sema) has recently become available. This study estimates health state utilities representing preferences associated with routes of administration for daily oral sema and two weekly injectable GLP-1 receptor agonists.

METHODS: Participants with T2D in the UK valued four health state vignettes (drafted based on drug labels and device instructions for use) in time trade-off interviews to estimate preference-based utility scores. The vignettes had identical descriptions of T2D, but differed in treatment process: (1) daily simple oral treatment (tablets without specific administration requirements), (2) daily oral sema (tablet with administration requirements per product label), (3) weekly dulaglutide (dula) injection, (4) weekly sema injection.

RESULTS: Interviews were completed by 201 participants (52.7% male; mean age = 58.7).

Preferences among routes of administration varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral sema, 0.878 for dula injection, and 0.859 for sema injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences among the four utility scores (p < 0.01), except the comparison between oral sema and dula which was not significant (p = 0.49).

CONCLUSIONS: While some participants preferred daily oral treatment, others preferred one of the weekly injections. Results suggest that patient preferences for routes of administration cannot be compared using only the simplest descriptions (e.g., “oral” vs. “injectable”). The details of treatment administration and treatment frequency have an impact on preference and should be considered.

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Abstract BP-3

CONVERSATIONS AND REACTIONS AROUND SEVERE HYPOGLYCEMIA (CRASH): SURVEY RESPONSE OF PEOPLE AGED 65+ WITH TYPE 1 DIABETES OR INSULIN-TREATED TYPE 2 DIABETES AND CAREGIVER 1

FRANK SNOEK, 2ERIK SPAEPEN, 3DONALD M BUSHNELL, 2CHRISTOPHER J CHILD, 3 ZANETA BALANTAC, 2BETH D MITCHELL, 4MARK PEYROT, 5THOMAS LEW (NONAUTHOR PRESENTER) 1

Amsterdam University Medical Centers, Amsterdam, The Netherlands, 2Eli Lilly and Company, Indianapolis, United States, 3Evidera, Bethesda, United States, 4Loyola University, Baltimore, United States, 5Eli Lilly and Company, Taiwan, R.O.C

Background and aims: The CRASH online survey examined the experience and treatment of a severe hypoglycemic event (SHE) in people with type 1 diabetes (T1DM) or insulin-treated type 2 diabetes (T2DM) or their caregivers (CGs).

Materials and methods: Eligible participants experienced ≥ 1 SHE in the last 3 years with insulin treatment at the time of event. Reported here are results from people with diabetes (PWD) aged ≥ 65 years and CGs of PWD ≥ 65 years old from Canada, Germany, Spain, UK, and USA. Results: Because the majority of the responses were similar between T1D PWD (N = 74) and CGs (N = 95) and also between T2D PWD (N = 104) and CGs (N = 231), results were combined for PWD and CGs and are reported as ‘T1DM’ (PWD and CGs) and ‘T2DM’ (PWD and CGs), respectively. During the last SHE, reported glucagon use was low for T1DM (9.5%) and T2DM (7.5%); primary reason reported was no prescription available or filled (T1DM 24.3%, T2DM 29.3%).

Of those who ever discussed SHE at their healthcare provider (HCP) visit (T1DM 138, T2DM 243), less than half (T1DM 41.3%, T2DM 34.2%) reported discussion of SHE at every HCP visit. No discussion of the most recent SHE occurred for 34.3% (T1DM) and 31.0% (T2DM). During the most recent SHE many felt unprepared (T1DM 35.5%, T2DM 47.2%), scared (T1DM 60.9%, T2DM 64.2%), and helpless (T1DM 39.1%, T2DM 51.3%). After the last SHE, changes were reported to insulin regimens, meal plans, carrying sugar/sweets, checking blood glucose more often or using continuous glucose monitors, and increasing access to glucagon.

Conclusions: Clinical guidelines recommending discussion of hypoglycemia at each HCP visit for PWD at risk for SHE are not being met and should occur, and CGs should be included in preparedness strategies.

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BP-4

EFFECT OF DULAGLUTIDE OF KIDNEY FUNCTION-RELATED OUTCOME IN TYPE 2 DIABETES: POST HOC ANALYSIS FROM REWIND TRIAL 1

JONATHAN SHAW, 2FADY T. BOTROS, 2RALEIGH ELIZABETH MALIK, 2CHARLES MESSAN ATISSO, 3HELEN COLHOUN, 4HERTZEL GERSTEIN, 5THOMAS LEW (NONAUTHOR PRESENTER) 1

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia; 2Eli Lilly and Company, Indianapolis, IN, USA; University of Edinburgh, Edinburgh, Scotland, UK; 4Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada; 5Eli Lilly and Company, Taipei, Taiwan, R.O.C 3

Background and Aims: In participants with type 2 diabetes (T2D) in the REWIND trial, dulaglutide (DU) use for a median follow-up of 5.4 years was associated with a reduction in the composite renal outcome, defined as first occurrence of new macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR) of ≥ 30%, or chronic renal replacement therapy.

Objective: To evaluate the effect of dulaglutide on renal outcomes related to kidney function that are typically used in renal outcomes studies, defined as the composite endpoint of sustained eGFR decline ≥ 40%, end-stage renal disease (ESRD), or all-cause death.

Materials and Methods: Participants with T2D and cardiovascular (CV) disease or CV risk factors were randomized (1:1) to DU 1.5 mg once-weekly or placebo. This post hoc analysis used Cox proportional hazards modeling for time-to-first-event to determine the risk of renal outcomes. Two additional sensitivity analyses were conducted by replacing the “all-cause death” component initially with “CV or renal death” component, or “renal death only” component.

Results: At baseline, treatment groups had similar eGFR (mean ± SD: DU = 77.2 ± 22.7; placebo = 76.6 ± 22.8). The incidence rate of the composite endpoints was significantly lower for the DU group compared with placebo with 17% risk reduction when including all-cause death, 18% risk reduction when including CV or renal death, and 28% risk reduction when only including renal death This effect was mainly driven by the significantly lower proportion of participants with sustained eGFR decline ≥ 40% in the dulaglutide group compared to placebo.

Conclusion: Treatment with DU 1.5 mg was associated with a 17% risk reduction in kidney function-related outcomes, suggesting potential delay in progression of diabetic kidney disease in patients with T2D and established CV and CV risk factors.

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Abstract BP-5

EMPAGLIFLOZIN FACILITATES SUSTAINED INSULIN DOSE REDUCTIONS IN PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE: THE EMPA-REG OUTCOME TRIAL 1

M VADUGANATHAN, 2N SATTAR, 3D FITCHETT, 4AP OFSTAD, 5,6M BRUECKMANN, 5 J GEORGE, 3S VERMA, 7M MATTHEUS, 8C WANNER, 9SE INZUCCHI, 10B ZINMAN, 11 J BUTLER 1

Brigham and Women’s Hospital, Harvard Medical School, Boston, USA; 2University of Glasgow, Glasgow, United Kingdom; 3St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; 4Boehringer Ingelheim KS, Asker, Norway; 5Boehringer Ingelheim International Pharma GmbH, Ingelheim, Germany; 6 University of Heidelberg, Mannheim, Germany; 7Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 8University Hospital Würzburg, Würzburg, Germany; 9Yale University School of Medicine, YaleNew Haven Hospital, New Haven, CT, USA; 10Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada; 11University of Mississippi, Jackson, MS, USA

Background: Many patients with T2D require insulin therapy and reducing insulin requirements is attractive to both patients and practitioners. Limited data are available regarding the effects of SGLT-2 inhibitor initiation on background insulin doses.

Methods: In EMPA-REG OUTCOME, 7,020 patients were treated with empagliflozin (EMPA) 10, 25mg, or placebo (PBO). This analysis focuses on the 3,387 (48%) patients treated with insulin at baseline.

After the first 12 weeks, changes in background antihyperglycemic therapy were permitted. We assessed treatment effects of pooled EMPA arms vs. PBO on time to sustained total daily insulin dose reduction from baseline by 10%, 20%, and 30% for at least 2 consecutive study visits by Cox regression adjusting for baseline risk factors. Dose reductions were considered appropriate if they were accompanied by no subsequent change (defined as < 0.2% increase) or a decrease in subsequent HbA1c.

Results: EMPA significantly increased the proportion of patients achieving sustained and appropriate (without increases in HbA1c) insulin dose reductions by > 20% from baseline compared with PBO after accounting for key covariates (adj. HR 1.87 [95% CI: 1.39-2.51]; P < 0.0001). Similarly, consistent benefits were observed when considering sustained insulin dose reductions of > 10% from baseline in EMPA vs. PBO (14.0% vs. 7.5%; adj. HR 1.91 [95% CI: 1.50-2.43]; P < 0.0001) or > 30% from baseline (5.6% vs. 3.3%; adj.

HR 1.68 [95% CI: 1.17-2.43]; P = 0.0055).

Conclusions: Among insulin-treated patients with T2D and CVD, EMPA facilitates meaningful, sustained, and appropriate reductions in insulin requirements.

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BP-6

EFFECT OF EMPAGLIFLOZIN ON CARDIORENAL OUTCOMES AND MORTALITY ACROSS BMI CATEGORIES: SUBGROUP ANALYSIS OF THE EMPA-REG OUTCOME TRIAL WITH A FOCUS ON ASIAN PATIENTS 1

Q JI, 2L JI, 3Y MU, 4J ZHAO, 5B ZINMAN, 6C WANNER, 7JT GEORGE, 8I ZWIENER, 9 K UEKI, 10K YOKOTE, 11W OGAWA, 12OE JOHANSEN 1

Department of Endocrinology, Shaanxi Aerospace Hospital, Xi'an, China; 2Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China; 3Department of Endocrinology, Chinese PLA General Hospital, Beijing, China; 4Shandong Provincial Hospital, Shandong University, Jinan, China; 5LunenfeldTanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; 6Department of Medicine, Wuerzburg University Clinic, Wuerzburg, Germany; 7Boehringer Ingelheim International GmbH, Ingelheim, Germany; 8Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany; 9Department of Molecular Diabetic Medicine, Diabetes Research Center, National Center for Global Health and Medicine, Tokyo, Japan; 10Department of Endocrinology, Hematology, and Gerontology, Chiba University Graduate School of Medicine, Chiba, Japan; 11Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 12Boehringer Ingelheim Norway KS, Asker, Norway

Background and aims: Epidemiology studies show a J- or U-shaped relationship between body-mass index (BMI) and mortality where individuals at the lower end of the BMI distribution, as well as those who are overweight/obese, have increased risk of mortality. Although obesity characteristics differ between Caucasian and Asian populations, such a relationship is observed in both populations. We explored the association between differing BMI at baseline, according to World Health Organization categories (< 25, 25 to < 30, ≥ 30 kg/m2), and mortality and cardiorenal outcomes with empagliflozin (EMPA), a sodium-glucose co-transporter-2 inhibitor, in the EMPAREG OUTCOME trial.

Materials and methods: In EMPA-REG OUTCOME, patients with type 2 diabetes (T2D) and prior cardiovascular (CV) disease were treated with EMPA or placebo (PBO) (median followup: 3.1 years). We used Cox regression to analyse post hoc the effects of EMPA vs PBO on all-cause mortality, the composite of CV death (excluding fatal stroke) or hospitalisation for heart failure (HHF), and incident or worsening nephropathy across baseline BMI categories (< 25, 25 to < 30, ≥ 30 kg/m2) overall and in patients of Asian race.

Results: Of the 7020 patients overall, 934 (13.3%) had BMI < 25 kg/m2 and 3621 (51.6%) had BMI ≥ 30 kg/m2; a total of 1517 (21.6%) were of Asian race. EMPA reduced all-cause mortality, CV death/HHF, and incident/worsening nephropathy in patients across BMI categories, with benefits being consistent between those with BMI < 25 kg/m2, 25 to < 30 kg/m2 and ≥ 30 kg/m2. The cardiorenal protective effects of EMPA were similar in Asians.

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Abstract Conclusion: This subgroup analysis of EMPA-REG OUTCOME, in which 934 patients had BMI < 25 kg/m2 and 1517 were Asian, suggests that the beneficial cardiorenal effects of EMPA are not affected by BMI, either overall or in Asian patients specifically.

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