Oral Presentation

OD-01

EXERCISE AND THE RISK OF PAINFUL NEUROPATHY IN PATIENTS WITH TYPE 2 DIABETES

sHen-sHu CHIang, CHIA-LIN LEE, SHI-YI LIN, SHEU-JANE LIU, JUN-SING WANG, YEN-MIN SONG, I-TE LEE, CHIA-PO FU, WAYNE HUEY-HERNG SHEU

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

Introduction: Diabetic neuropathy is one of the most common complications in the patients with type 2 diabetes mellitus (T2DM). Currently, there are no specific therapy that could improve the neuropathy except glycemic control. In recent years, few studies revealed that moderate intensity aerobic exercise could play a valuable role to slow down the progression of diabetic peripheral neuropathy. The aim of our study was to analysis the relationship between diabetic painful neuropathy (DPN) and exercise.

Method: This cross-sectional study totally enrolled 2359 outpatients with type 2 diabetes who had completed the Douleur Neuropathique en 4 Questions (DN4) questionnaire from January 2013 to October 2013. The Patients’ characteristics, including age, sex, DM duration, anti-diabetic medication, anti-hypertensive and lipid-lowering medication, medication for diabetic neuropathy, HbA1c, systolic blood pressure, body weight and height, serum creatinine level, urine albumin to creatinine ratio, and daily exercise duration were recorded. A total score of DN4 questionnaire equal or greater than 4 was defined as having DPN. Linear regression was used to evaluate the correlation between duration of exercise and DN4 score. General linear model (GLM) was used to assess the effect of exercise and risk of painful neuropathy. results: There were 179 patients with DPN, in whom 83 were men (46.4%), mean age 69.6±12.5 years old, BMI 25.5±4.1 kg/m2, diabetes duration 13.3±9.3 years, mean DN4 score 4.49±0.75, HbA1c 7.8±1.7%, insulin users 22.9%. It was found that longer daily exercise duration was associated with a lower mean DN4 score. The mean DN4 score was 0.74, 0.62, and 0.45 in the subjects with no exercise, daily exerciseduration ≦ 30 minutes, and daily exercise duration longer than 30 minutes, respectively (P for trend <0.001.) After adjusting the sex, age, diabetes duration, neuropathy medication usage, insulin user, oral anti-diabetics drugs, systolic blood pressure, body mass index, glycated hemoglobin, low-density lipoprotein, and estimated GFR, the risk of painful neuropathy was 3.38 times in the no exercise group(95% CI 1.54-9.79)in comparison with the group with daily exercise duration more than 30 minutes.

Conclusion: The risk of painful neuropathy is markedly increased in the diabetic patients without exercise habits.

OD-02

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

1Yu-CHeng CHen, 2SHI-DOU LIN, 3PO-YEN KO

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital Yunlin Branch, Yunlin, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Cardiology, Department of Medicine, China Medical University Hospital, Taichung, Taiwan

aims: Our aims of this study were to investigate the prevalence of diabetes mellitus (DM) among patients with newly-diagnosed tuberculosis (TB) and to determine its associated risk factors in an Asian population.

Methods: The data for this study were obtained from the National Health Insurance Research Databaseand included 9831 newly-diagnosed TB individuals in the period from January 1, 2000 to December 31, 2010. The data were divided into a DM group and a non-DM group.We measured the prevalence and the associated risk factorsof DM,and amultivariate logistic regression modelwas used to estimate the adjusted odds ratios (ORs). results: During the period between 2000 and 2010, the prevalence of DM progressively increased, with an average prevalence rate of 27.9%. The patients with ages of 55-64 years had the highest risk of DM (OR=3.53), followedby those 45-54 years (OR=3.10), 65-74 years (OR=2.88), and ≥75 years (OR=2.30), compared with those under 45 years. TB patients with heart failure, ischemic heart disease, cerebral vascular disease, hypertension, dyslipidemia, chronic kidney disease, and liver disease were associated with a higher risk of DM (ORs=1.27, 1.23, 1.30, 2.32, 3.26, 1.6, and 1.68, respectively) compared to those without the variables. The average number needed to screen to find one case of newly-diagnosed DM was 30.9.

Conclusions: The prevalence of DM among TB patients in Taiwan was high and tended to increase in the past decade. Clinically, inquiring about DM history and screening routinely for those without DM history among TB patients should be carried out in Taiwan.

OD-03

HYPOGLYCEMIA IS A NOT RARE IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES AS ASSESSED BY CONTINUOUS GLUCOSE MONITORING

YIN-CHUN CHEN, YU-YAO HUANG, JUI-HUNG SUN, CHUNG-HUEI HUANG, YUTING YE, YA-HUI WU, SHIUE-HUA CHIOU, CHIa-Hung LIn

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

aims/Introduction: The objective of this study was to access hypoglycemia events among patients with poorly controlled type 2 diabetes using continuous glucose monitoring (CGM).

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

Conclusions: Hypoglycemia unawareness is not rare in poor controlled diabetes patients. Detection and avoidance hypoglycemia unawareness may be a key for control these patients.

Key words: Continuous glucose monitoring; type 2 diabetes; unawareness of hypoglycemia;

OD-04

INPATIENT GLYCEMIC CONTROL – THE EXPERIENCE IN AN ACADEMIC TEACHING HOSPITAL

sHI-dou LIn, JENG-FU KUO, SHIH-TE TU, MING-CHIA HSIEH

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital

background: Despite the awareness of the value of treating inpatient hyperglycemia and the announcement of the guidelines for managing hyperglycemia in inpatients, little is known about the glycemic control of Chinese patients during admission.

Methods: The electronic informatics system was used to retrospectively extract data on inpatient point-of-care bedside glucose (POC-BG) tests for patients admitted from April to June 2012 to a medical center in Taiwan. Mean POC-BG values and hypoglycemia and hyperglycemia rates were calculated for intensive care unit (ICU) and general ward areas. The POC-BG values in different ICU areas and patient-day-weighted mean POC-BG values in different general wards were investigated. results: A total of 3,002 patients with 70,303 POC-BG measurements were analyzed: 18,235 from the ICU and 52,068 from the general wards. Mean POC-BG was 193.2 mg/dL for the ICU and 192.7 mg/dL for the wards. Hospital hyperglycemia (>180 mg/dL) prevalence was 47.0% for the ICU and 46.4% for the wards. Hospital hypoglycemia (<70 mg/dL) prevalence was 1.9% for the ICU and 1.8% for the wards. In the ICU setting, those with lower mean POC-BG values were associated with a higher prevalence of hospital hypoglycemia. Patients in certain medical wards maintained a higher patient-day-weighted mean POC-BG level than the others during the first admission week.

Conclusions: Hospital hyperglycemia is common, and POC-BG levels vary in different inpatient care settings. This information may facilitate the creation of a process for the development of an inpatient hyperglycemic program and improved glucose management in the hospital.

OD-05

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

1CHang-Hsun HsIeH,

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

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan; 3Taitung Hospital, DOH. Taiwan. 4Division of Endocrinology and Metabolism, Cardinal Tien Hospital, New Taipei City, Taiwan

background: Glucokinase (GCK) plays an important role in the glucose regulation and interplayed by a glucokinase regulatory protein (GKRP) to maintain glucse concentration. The glucokinase regulator gene (GCKR) encodes for the GKRP and previous GWA studies showed that common genetic variants of the GCKR gene are associated with features of the metabolic syndrome (MetS). However, most of the studies have been explored in Westeran population and limited data in adolescent population of Asian. The study explores the genetic association of common genetic variant of GCKR gene with metabolic traits in Taiwan adolescent population.

Methods: After multistage sampling, we enrolled 962 adolescents (468 boys and 494 girls). IDF criteria were applied to define MetS. Subjects had 3 or more of the following cardiometabolic abnormalities that occur in MetS: high blood pressure (BP), high fasting plasma glucose (FPG), triglyceride (TG), low high-density lipoprotein cholesterol (HDL-C), and obesity (by waist circumstance, WC; and body mass index, BMI). The characteristics of the MetS and its components associated with different alleles and genotypes of the GCKR rs780094 SNP were compared. results: The boys had higher adiposity (including BMI and WC), SBP, FPG and lower HDL-C concentrations than girls and no difference was observed in DBP and TG levels. The girls had higher prevalence of CC genotypes than boys (p=0.017). Both genders did have similar allele frequencies in MetS and its components except boys with T-allele had higher prevalence of low HDL-C than C-allele (p=0.037). When gender is not considered, C-carried genotypes had lower prevalence rate of high WC and low HDL-C than non-C carried genotypes. The higher prevalence rate of low HDL-C and Mets were observed in T-carried genotype than non-T carried genotype. After adjusting age and pubertal stage, the odds ratio for low HDL-C prevalence rate in TT genotype was 2.10 (95% CI: 1.08–4.07) when compared with CC genotype in boy adolescents.

Conclusions: The GCKR rs780094 polymorphism is associated with low HDL-C levels in boys of Taiwanese adolescents.

OD-06

THE ASSOCIATION BETWEEN BODY MASS INDEX AND ALL-CAUSE MORTALITY IN PATIENTS WITH TYPE 2 DIABETES: A 5.5-YEAR PROPECTIVE ANALYSIS

Jeng-Fu Kuo, SHIH-TE TU, SHI-DOU LIN, YUNG-SHENG CHANG, YU-FANG CHENG, MING-CHIA HSIEH

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

background: Ample data have illustrated a phenomenon of obesity paradox in patients with cardiovascular disease, which means that obesity patients have a better prognosis. However, studies on the association between obesity and mortality among Asian patients are limited, especially in patients with type 2 diabetes (T2DM). We investigate the association between body mass index (BMI) and allcause mortality in Taiwanese patients with T2DM in order to define the optimal body weight for health

Materials and methods: A longitudinal cohort study of 2161 patients with T2DM and a mean follow up period of 66.7±7.5 months. Using Cox regression models, BMI was related to the risk of allcause mortality after adjusting all confounding factors. results: A J-shaped association between BMI and all-cause mortality was observed among all the participants. Those in the BMI categories of less than 22.5 had a significantly elevated all-cause mortality as compared with participants with a BMI of 22.5 to 25.0, [BMI of 17.5~20.0, HR: 1.989 (p<0.0001); BMI of 20.0~22.5, HR: 1.286 (p=0.02)], as did those in the BMI categories of more than 30.0 comparing with participants with a BMI of 22.5 to 25.0 [BMI of 30.0~32.5, HR: 1.67 (p <0.0001); BMI of 32.5~35.0, HR: 2.632 (p<0.0001)]. This J-shaped association remained when we examined data by sex, age and smoking.

Conclusions: Our study demonstrate a J-shaped relationship between all-cause mortality and BMI in patients with T2DM in Taiwan. As the knowledge of obesity increases, further study in other populations is needed in proof of our theory.

OD-07

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

1CHung-Ze wu,

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

1Division of Endocrinology and Metabolism, 3Division of Nephrology,Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University; 2Taitung Hospital; 4School of Pharmacy, National Defense Medical Center; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Xindian; 6Division of Nephrology, Department of Internal Medicine, Tri-service General Hospital, National Defense Medical Center

background: Aspects of metabolic syndrome are associated with insulin resistance, and these patients are prone to atherosclerosis and cardiovascular disease. Fibrinolytic proteins participate in the process of atherosclerosis and intravascular thrombosis. The relationship between fibrinolytic proteins and metabolic syndrome has partly suggested in adult people. In the present study, we investigated the role of urokinase plasminogen activator (uPA), soluble receptors of uPA (suPAR) and plasminogen activator inhibitor-1 (PAI-1) in metabolic syndrome components, insulin resistance and secretion in school children.

Methods: We enrolled 387 children (184 boys and 203 girls), mean age of 10.3±1.5 years, from elementary schools in Taipei. The children were divided into normal, overweight and obese groups according to the body mass index (BMI) percentile. All subjects received measurement of body anthropometry, blood pressure, fasting plasma glucose (FPG), total cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The levels of uPA, suPAR, and PAI-1 were measured by enzyme-linked immunosorbent assay (ELISA). Insulin secretion and resistance were assessed by homeostatic model assessment-β (HOMA-β) and -insulin resistance (HOMA-IR). results: In boys, the obese group had higher levels of suPAR and PAI-1 than the normal group. On the other hand, the obese group in girls had higher levels of uPA, suPAR and PAI-1 than the normal group. For associations of fibrinolytic proteins and metabolic syndrome components in boys, PAI-1 is positively associated with BMI percentile (r=0.205), TG (r=0.217), HOMA-β (r=0.228) and HOMAIR (r=0.167), and negatively associated with HDL (r=-0.188). In girls, uPA is positively related to HOMA-β (r=0.161); suPAR is associated with BMI percentile(r=0.18), body fat (r=0.191) and hsCRP (r=0.169); PAI-1 is associated with BMI percentile (r=0.146), body fat (r=0.17), SBP (r=0.151), DBP (r=0.139), TG (r=0.152), and HOMA-β (r=0.158). After adjusting for age and BMI percentile in girls, uPA was still significantly positively related to HOMA-β; suPAR is positively associated with hsCRP; PAI-1 is positively associated with DBP.

Conclusion: Changes in fibrinolytic proteins are associated with metabolic components and insulin secretion varying according to genders in children. This biochemical mechanism needs further exploration in future study.

OD-08

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

1HuI-MIn HsIeH, 2,3,5SHYI-JANG SHIN, 4HERNG-CHIA CHIU

1Department of Public Health; 2School of Medicine; 3Center of Lipid and Glycomedicine Research; 4Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University; 5Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital

research objective: To investigate the effectiveness of diabetes pay-for-performance program in Taiwan to reduce risk of diabetes related complications. The major outcome of interest was to compare the probability of incidence for high-severe and low-severe diabetes complications between P4P and non-P4P patients during the following-up period. Diabetes-related complications such as cerebrovascular diseases, cardiovascular disease, and peripheral vascular diseases were measured.

Method: We conducted a longitudinal observational cohort study design using a nationwide diabetes P4P database and the National Health Insurance (NHI) administrative claims database in Taiwan for a 2007 to 2012 period. We included diabetes patients if he or she had primarily diabetes diagnosis (ICD-9-CM codes with 250.xx or A-code 181) in at least two outpatient visits or at least one inpatient hospitalization for each year during 2007 and 2008. Using the P4P database, we identified newly enrolled P4P patients as study P4P cohorts during the patient identification period and defined the date for each P4P patient as the date that they were first enrolled in the P4P program as index date. We then identified non-P4P diabetes patients as comparison groups if those patients were not found to be enrolled in the P4P program during the above-stated time period. To avoid potential confounding by selection bias and confounding factors, we used propensity score matching approach (PSM) to determine comparison groups. We defined incidence of a diabetes complication as the first event of that specific complication after following-up. In addition, we calculated total person-years for each patient. To compare between groups, we followed each P4P and non-P4P patient until the end of study date on December 31st, 2012. Any patient was censored if he or she dropped out of the insurance program, were diagnosed for a specific diabetes complication or had died. Complication incidence rates per 1,000 person-years for each complication were calculated.

Principal Findings: Before matching, we included 34,710 P4P patients and 341,312 non-P4P diabetes patients. After PSM for 1 to 1 matching, however, the two groups were found to be similar. Diabetes complication incidence rates per 1,000 person-years were greater among P4P patients than non-P4P patients generally. However, when further looking at low and high level of severity, P4P patients tended to have non-significant difference of incidence rate in low-severe complications but smaller incidence rate in highsevere complications. For low-severe complications, for example, the HR for diabetes PVD was 1.179 (95%CI=1.107, 1.255). For high-severe complications, the HR for stroke was 0.782 (95%CI=0.747, 0.819) (p<0.001); and HR for myocardial infarction was 0.821 (95%CI=0.739, 0.911) (p<0.001).

Conclusions: Compared with those do not enroll in the P4P program, enrolled P4P patients had similar risks of low-severe complications, while they had lower risks to develop high-severe complications. There is limited evidence on whether paying for quality of care results in improved outcomes, in terms of reduced complications. Our empirical findings provided evidences for the potential long-term benefit of pay-for-performance programs.

OD-09

DETECTING MUTATIONS IN NEONATAL DIABETES AND TYPE 1B DIABETES USING EXOME SEQUENCING

1,11,12,13Yann-JInn Lee,

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

1Department of Pediatric Endocrinology, MacKay Children’s Hospital; 2Department of Pediatrics, Chang Gung Memorial Hospital; 3Department of College of Medicine, Chang Gung University; 4Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management; 5Department of Endocrinology and Metabolism, Sijhih Cathay General Hospital; 6Department of Pediatrics, MacKay Memorial Hospital HsinChu Branch; 7Department of Pediatrics, MacKay Memorial Hospital Taitung Branch; 8Department of Pediatrics, Changhua Christian Hospital; 9Department of Pediatrics, Hsinchu Cathay General Hospital; 10Department of Pediatrics, St. Martin De Porres Hospital; 11Institute of Biomedical Sciences, MacKay Medical College; 12Department of Medical Research, MacKay Memorial Hospital Tamsui District; 13Department of School of Medicine, Taipei Medical University

aim: We hypothesized that the mutations in neonatal diabetes and type 1B diabetes are genetically heterogeneous and able to be detected by exome sequencing.

research design and Methods:

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

Conclusion: Our preliminary results show that exome sequencing is robust to detect mutations in patients with NDM or T1BD of heterogeneous genetic etiologies. Patients may benefit from the knowing their underlying mutations.

OD-10

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

1CHIen-HsIng Lee, 2YI-SHING SHIEH, 1CHANG-HSUN HSIEH, 1YI-JEN HUNG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Oral Diagnosis, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

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

O-01

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

1Jun-sIng wang, 1CHIA-LIN LEE, 2WEN-JANE LEE, 1I-TE LEE, 1SHIH-YI LIN, 3WEN-LIENG LEE, 3KAE-WOEI LIANG, 1WAYNE H-H SHEU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; 3Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan.

background: Fibroblast growth factor 19 (FGF-19) has been emerged as an important hormone in regulating glucose homeostasis. We investigated factors associated with FGF-19 increment after oral glucose loading (OGL) in patients undergoing coronary angiography.

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

Conclusions: FGF-19 increment after OGL was positively associated with age and negatively associated with AGR in patients undergoing coronary angiography.

O-02

THE CONCOMITANT ASSOCIATION OF THYROID DISORDERS AND MYASTHENIA GRAVIS

1YU-PEI LIN, 1CHEN-LING HUANG, 2PHUNG-ANH NGUYEN, 3WEN-SHAN JIAN, 1,4,5CHung-HueI Hsu

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 2Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 3School of Health Care Administration, Taipei Medical University, Taipei, Taiwan; 4Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 5School of Medicine, College of Medicine, Taipei Medical University

background: Myasthenia gravis (MG) is a neuromuscular disease caused by autoimmunity, which affect the neuromuscular junction, blocking synaptic neurotransmissions and resulting in clinically symptomatic muscle weakness. The association of MG with Graves’ disease (GD), an autoimmune thyroid disease (AITD) occasionally presenting with ocular myopathy and exophthalmos, was firstly reported by Rennie in 1908.In this study, we assessed the association of MG with thyroid disorders through a large population cohort study, and evaluated the co-occurrence rate of these 2 diseases and the strength of association.

Materials and Methods: We collected the claims records of 10.8 million males and 10.6 million females from Taiwan’s National Health Insurance program for the January 2000–December 2002 period. We identified all patients with MG and thyroid disorders by referring to the International Classification of Disease, Clinical Modification, Ninth Revision [ICD-9-CM] codes. Thyroid disorders were further divided into morphological, functional, coexisting functional and morphological. The association of MG with thyroid disorders occurred only in the same person within the 3-year study period. The Q value was used to measure the strength of disease–disease associations. results: We obtained 7965 MG and 520628 thyroid disorder records for analysis. The association rate of MG and diffuse toxic goiter was highest, followed by nontoxic nodular goiter, simple goiter, chronic lymphocytic thyroiditis, thyroid cancer, and toxic nodular goiter. Female and older patients have a higher rate than their male and younger counterparts, respectively. Functional abnormalities revealed a high rate of thyrotoxicosis and hypothyroidism in both sexes. We found the strongest association in males with chronic thyroiditis, toxic diffuse goiter, thyrotoxicosis, acquired hypothyroidism, thyroid cancer, and simple goiter. Intermediate association was observed in female with toxic diffuse goiter, in male with toxic and nontoxic nodular/multinodular goiters, in female with thyrotoxicosis, thyroid cancer and acquired hypothyroidism. Weak association was found in female with toxic nodular/multinodular goiter, chronic lymphocytic thyroiditis, simple goiter, non-toxic nodular/multinodular goiter.

Conclusion: We identified the association of MG with all types of thyroid disorders, and observed a high association rate in female autoimmune thyroid disorders and in older, whereas males have a higher strength of association. Coexisting autoimmunity and genetic predisposition may play major roles in pathogenesis.

O-03

HIGH GLUCOSE CAUSES RENAL INJURY VIA GLYCOSYLATION OF RBP4 RECEPTOR SIGNALING

1ZHao-Hong CHen, 2KUN-DER LIN, 2MEI-YUEH LEE, 3TUSEY-JIUAN HSIEH, 2,3PIJUNG HSIAO, 2,3SHYI-JANG SHIN

1Graduate Institute of Medicine, 2Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 3Center of Lipid and Glycomedicine Research, Kaohsiung Medical University.Kaohsiung, Taiwan

background: An increase of retinol-binding protein 4(RBP4) concentration has been demonstrated in subjects with type 2 diabetes. RBP4 can induce insulin resistance by activating JAK/STAT5. We also found that free RBP4 can cause apoptosis through the reduction of RBP4 binding activity with STRA6(stimulated by retinoic acid 6), in turn JAK2/STAT5/JNK/p38MAPK pathway in renal cells. We hypothesized that high glucose might cause kidney injury via O-link N- acetylglucosamine(O-GlcNAcosylation) modification of STRA6, RBP4 activity with STRA6, CRBP1 and RARα signaling.

Method: The expression of STRA6, CRBP1, RARα, NOX4, Cnx, UGGT1, OST, OGT, caspase, collagen 1 and fibronectin were measured by Western blot analysis and O-GlcNAcosylation of STRA6, RBP4 binding with STRA6 was detected by immunoprecipitation method in high glucosecultured HEK cells and the kidneys of STZ-induced diabetic mice. Immunofluorescent method was done to detect O- GlcNAcosylation of STRA6, RBP4 binding with STRA6, and RNA silencing of NOX4, Cnx, UGGT1, OST and OGT were done to investigate the role of STRA6 O-GlcNAcosylation on high glucose-induced apoptosis and fibrosis. Transfection of CRBP1 gene were performed to investigate whether the reversal of CRBP 1 and RARα can reduce apoptosis and fibrosis, or affect O-GlcNAcosylation modification. result: The expression of STRA6, NOX4, Cnx, UGGT1, OST, OGT, caspase, collagen 1, fibronectin and apoptotic cell number increased, while CRBP1 and RARα decreased in high glucosecultured HEK cells and diabetic mice. Immunoprecitated and immunofluorecsent experiments showed an increase of STRA6 O- GlcNAcosylation, and decreased activity of RBP4 with STRA6 after high glucose stimulation. RNA silencing of NOX4, Cnx, UGGT1, OST and OGT can reverse above changes. Transfection of CRBP1 gene can reverses the increased STRA6 O-GlcNAcosylation, the decreased binding activity of RBP4 with STRA6, the decrease of RARα, and these increases of NOX4, Cnx, UGGT1, OST, OGT, collagen 1, fibronectin, caspase activity, and apoptotic cell number. Conclusion: High glucose can cause kidney damage via activating O-GlcNAcosylation of STRA6, reducing RBP4 binding with STRA6, and decreasing CRBP1, RARα and finally enhancing apoptosis and fibrosis in diabetic mice. These results indicate that the activation of STRA6 O-GlcNAcosylation with reduced RBP4 binding with STRA6, the decreased expression of CRBP1, RARα is one novel molecular mechanism of diabetic nephropathy.

O-04

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

1danIeL Hueng-Yuan sHen,

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

1Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.; 2Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, R.O.C.

background: Serum thyroglobulin (Tg) is a useful marker for surveillance of follicular-derived thyroid cancer after operation and radioiodine ablation therapy. However, it might be interfered by the presence of serum thyroglobulin antibodies (TA), resulting either under- or overestimation of Tg level. TA positivity occurring to more than 25% of thyroid cancer patients and its prevalence is greater than general population. In this study we intend to investigate the clinico-pathological features as well as serum Tg level in this subset of patients with positive TA.

Method and Material: In 2013 we had consecutively 322 patients undergoing I-131 diagnostic/ therapeutic scans and 10 of them were excluded because of TA data not available. Thus 312 thyroid cancer patient charts were retrospectively examined regarding with serum TA and Tg level, pathological report (tumor size, local invasion, nodal involvement) and clinical course (recurrence, metastasis). results: There were 63/312 (20.2%) of patients with detectable serum TA. It ranged from 4.18 to >1000 IU/ml (98.0+/- 172.7 IU/mL; normal reference <4.11 IU/ml). F:M = 50:13 and 58/63 (92%) were papillary type. 8/63 (12.7%) of TA-positive patient had documented Hashimoto’s thyroiditis and 2/63 (3.2%) had Graves’ disease. Although the correlation between TA concentration and tumor size was insignificant (R2=0.057), the cervical nodal involvement (33/63=52.4%) and extrathyroid extension (15/63=23.8%) were more frequently seen in the TA-positive group. Recurrence (9/63=14.3%) and distant metastases (7/63=11.1%) were noted and the incidence rate seemed not to differ greatly form the average. The serum Tg level in TA-positive patients ranged from <0.2 to 32320 ng/ml. Fifty-two (82.5%) of them had Tg <0.2 ng/ml. Interestingly, six (85.7%) out of those seven TApositive patients with distant metastases had detectable Tg>0.2 ng/ml and most of them showed Tg above 20 ng/mL.

Conclusions: TA positivity is commonly seen in thyroid cancer patients. Co-existing Hashimoto’s thyroiditis or Graves’ disease can be one etiology. The impact of TA positivity on disease severity seems not significant while the observed higher frequency of extra-thyroid extension and cervical nodal involvement requires further study. Despite that TA positivity can cause unreliable serum Tg measurement, our preliminary results indicate the serum Tg might be detectable, albeit with great variation, in presence of distant metastases.

O-05

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

1CHIn-CHang CHen, 2YUNG-PEI HSU, 3CHING-FAI KWOK, 1YAN-JIE LIN, 3KUANG-CHUNG SHIH, 1,2,3,4LOW-TONE HO

1Institute of Physiology, National Yang-Ming University, Taiwan, ROC; 2 Department of Medical Research, Taipei Veterans General Hospital, Taiwan, ROC; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, ROC; 4School of Medicine, National Yang-Ming University, Taiwan, ROC

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

O-06

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

1,2Kuo-CHIn Huang,

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

1Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taiwan, R.O.C.; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taiwan, R.O.C.; 3Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taiwan, R.O.C

Introduction: Thyroid nodule is a common thyroid disease. Most thyroid nodules are benign, but about 5% of thyroid nodules are malignancy. Generally, we followed up patients’ nodular goiter by thyroid ultrasonography and fine needle aspiration cytology in clinical practice. But it was difficult to distinguish from follicular adenoma and follicular carcinoma by cytology only. We conducted a retrospective study to evaluate if thyroid ultrasonography is helpful to distinguish follicular carcinoma from follicular adenoma.

Patient and Method: Patients who received thyroidectomy from Jan, 2001 to Dec 2013 in China Medical University Hospital that pathological report were follicular adenoma or follicular carcinoma were enrolled in this study. We compared patients’ age, sex, TSH, free T4, thyroglobulin, nodular size (including width, tall, and tall to width ratio), nodular margin and echoic density between the groups of follicular carcinoma and follicular adenoma. TSH was graded in 4 groups by <0.1, 0.1 to <0.34, 0.34 to 5.6, and >5.6 IU/L. Thyroglobulin was divided in the four grades based on Quartiles. Patients who were positive of anti-thyroglobulin antibody were excluded in this variable. Nodular margin and echoic density were divided into four grades (0, 1, 2, 3), which higher grade mean more irregularity and lower echoic density. Differences between the follicular carcinoma and follicular adenoma groups were compared by Student t-test for continuous variables and by χ2 test for categorical variables. Multivariate logistic regression model to determine the odds ratios (ORs) and 95% confidence intervals (CIs) of variables which p value were <0.2. For ORs, p-values < 0.05 were considered statistically significant. result: A total of 104 patients, who were 68 patients of follicular carcinoma and 36 patients of follicular adenoma, were enrolled in this study. Fifty sex patients of follicular carcinoma and total of follicular adenoma had received the examination of thyroid sonography before operation. Patients with follicular carcinoma were older, and their thyroid nodules’ margins were more irregularity. There were no difference in sex, TSH, Free T4, thyroglobulin, tumor size and echoic intensity. Multivariate logistic regression model showed statistic significant of nodular margin after adjust age, sex, nodular density, and tall. The odds ratio of grade 2 and grade 3 of modular margin were 4.8 folds and 38 folds compared with grade 0.

Conclusion: Regularity of nodular margin detected by thyroid sonography would be a criteria to differentiate follicular carcinoma and follicular adenoma. Irregular nodular margin predicted increase risk of malignancy.

O-07

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

1,4K-d LIn, 2,3,4P-J HSIAO, 4M-Y LEE, 2,3,4S-J SHIN

1Graduate Institute of Medicine, 2School of Medicine, College of Medicine, 3Center of Lipid and Glycomedicine Research, Kaohsiung Medical University, 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C.

Introduction: Parkinson’s disease (PD) is an age-related neurodegenerative disease, characterized by muscle rigidity, slowing of physical movement, behavioral abnormalities and autonomic impairment. All of which have a dramatic impact on quality of life in these elderly patients. The incidence of PD was reported higher in type 2 diabetic patients by NHRI database in Taiwan.

The pathophysiology about diabetes and PD is variable, including suppression of central dopamine levels, inflammation, oxidative stress and cerebrovascular diseases. A number of the hypothesized pathogenesis of PD may be related to blood cholesterol. Statin has effects on lowering blood cholesterol level and anti-inflammatory effects especially in type 2 diabetic patients. We study the effects of statin use on PD incidence in type 2 diabetic patients by using NHRI database.

Materials and Methods: A random sample of one million subjects covered by the NHI in 2005 was used. Incidence rate and relative risk of PD (ICD-9-CM 332.0) in type 2 diabetic patients (ICD-9CM 250.xx) were evaluated to investigate the risk factors including age, sex, statin use, hypertension, stroke and ischemic heart disease. results: There are 58601 type 2 diabetic patients enrolled in our study. Statin use rate was lower in older patients (14.28% in patients older then 70 y/o v.s. 59.22% in patients between 40~60 y/o) and higher in female patients (53.53% v.s. 46.47%). The incidence rate of PD increased from 139.25 to 1022.35 per 100,000 person-years as the age increased from 40 y/o to older than 70 y/o. The crude hazards ratio was 4.67(4.11~5.29) in age 61~70 y/o group and 7.53(6.66~8.52) in age >70 y/o group referenced by the group of age 40~60 y/o. The multivariate adjusted relative risk increased with age. The relative risk was 3.78(3.31~4.32) in age 61~70 group and 5.13(4.47~5.89) in age >70 group referenced by age 40~60 group.

The PD incidence rate was lower in statin users v.s. non-statin users. The crude HR of statin users was 0.53(0.48~0.57) and the multiple-adjusted relative risk is 0.71(0.64~0.79) referenced by non-statin users. The PD incidence rate was inverse correlated with statin dose duration day(DDD) in type 2 diabetic patients. The trend test for the relative risk of statin DDD with incidence of PD is significant (P<0.0001, X2=51.8515).

Conclusion: Type 2 diabetic patients had higher risk of developing Parkinson’s disease. Statin use in type 2 diabetic patients protects them from having PD. The dose respond relative risk was invert correlated with incidence of PD in type 2 diabetic patients.

O-08

RESPONSE OF DIFFERENT DEGREE PEDIATRIC GROWTH HOROME DEFICIENCY DURING REPLACEMENT THERAPY

gao bIng-ru, 1,2CHEN PIN-FAN, 1LIAN WEI-CHENG, 1YAN SHIH-TANG, 1CHEN

TING-CHANG

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

aim: Pediatric growth horomone (GH) deficiency is one the the correctable cause of grwoth failure and can be cured by GH repalcement therapy. The indication of GH repalcement has been varified from GH level <10 ng/ml to <7ng/ml during GH provocative tests by National Health Insurance in Taiwan in Dec. 2011. We try to invesgate the responsiveness of two different groups of growth hormone deficiency according to the changes of GH levels in NHI criteria.

Method: From year 2005 to 2013, 17 patients who diagnosed as growth horome deficiceny and received replacement therapy in Dalin Tzuchi General Hoispital were enrolled in this study. One patients were excluded. Of the remaining patients, we devided into group 1 ( GH <7 ng/ml) and group 2 (7-10 ng/ml) according to the GH value during endocrine provocative tests. The annual growth velosity and body weight change during replacment therapy were recorded and compared. In addition, the basic chemobiochemsty tests was also recorded and analysed. results: A total 16 patients, aged 9.6±2.1 (mean±SD) years old were devided into group 1 (n=12) and group 2 (n=4) with mean follow-up period 3.0 ±1.4 years. The anunal growth velosity (adjusted mean±SEM) in group 1 v.s group 2 was 8.7±2.0 cm v.s 8.9±1.4cm (p=0.750); 6.6±0.7 cm v.s 8.0±1.3cm (p=0.005) and 6.0±2.6 cm v.s 6.5±1.7cm (p=0.259) in the first, second, or third year, respectively.

Conclusion: Patients with higher degree of GH provocative tests have better response to GH therapy in the second year after GH replacement. There is a need of placebo-control group to strengthen this finding.

O-09

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

1PeI-wen wang, 2YEN-HSIANG CHANG, 1I-CHIN HUANG, 1CHING-JUNG HSIEH

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

background: Most cases of differentiated thyroid cancer (DTC) are curable with the use of surgery and radioactive iodine (RAI) ablation. However, when RAI becomes ineffective against DTC, ten-year survival is <10%. RAI-resistance is believed to be progressive tumoral de-differentiation over time and loss the ability of iodine uptake, organification and retention. The aim of this study was to evaluate the prevalence and clinical characteristics of patients who developed RAI resistance in Kaohsiung CGMH.

Materials and Methods: Two cohort of DTC patients were analyzied: (1) a prospective study of 222 patients who had received 131I whole body scan (WBS) in the year of 2006 and (2) a retrospective review of 126 patients with distant metastasis and long term follow-up (9.6 ± 5.2 yr). RAI-refractory DTC was defined: (1) tumors did not take 131I at initial treatment or lost the ability during follow-up (2) disease progression despite significant uptake of 131I (3) 131I uptake retained in some lesions but not in others, and (4) persistent disease after the administration of a cumulative activity of 600 mCi. results: In the prospective year 2006 131I WBS cohort, 44 patients were observed to have RAIrefractory disease in 2014, including 12 patients diagnosed before 2006, 5 in 2006 and 27 after 2006. The prevalence and incidence in year 2006 were 7.7% (17/222) and 2.4% (2/210) respectively. During the follow-up of 8 years, 15.2% (32/210) developed RAI resistance. RAI refractory cancer was more frequently observed in patients with older age, large tumor burden, and lesions detected by18F-FDG.

In the retrospective metastasis cohort, 131I avidity was more frequently observed in patients with younger age, whose primary tumors without local invasion, and whose metastases detected at the first 131I ablation. For papillary thyroid cancer patients, 84.8% showed 131I avidity, while 29.3% obtained disease remission with undetectable Tg. For follicular thyroid cancer patients, 90.6% showed 131I avidity, while 15.6% obtained disease remission. Patients whose diseases went into remission had a lower mean cumulative dose of 131I than those who did not (297±195mCi vs. 618±381mCi).

Conclusion: There are about 15% patients with DTC developed RAI-refractory disease in our series. Risk factors include old age, invasive tumor behavior, and metastases detected by 18F-FDG. These patients need more careful evaluation and choice.

O-10

LOW-DENSITY LIPOPROTEIN CHOLESTEROL ESTIMATION WITH VARIOUS FORMULAE

CHIng-Yun Hu, CHIA-LIN LEE, CHIA-PO FU, JUN-SING WANG, I-TE LEE, YENMIN SONG, SHI-YI LIN, WAYNE HUEY-HERNG SHEU

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

background: The Friedewald formula (FF) is the most often used formula for estimation of lowdensity lipoprotein cholesterol (LDL-C) in clinical trial and clinical practice. A simple new formula (NF) to estimate LDL-C had been recently developed by us and showed to have better accuracy than FF in subjects with total cholesterol (TC) levels between 100 and 299 mg/dL. This study was aimed to compare various published LDL-C estimation formulae with ours in a Chinese population.

Methods: This is a cross-sectional study in outpatients who had full lipid profiles report at a medical center in central Taiwan from January 2004 to October 2014. All subjects had measurements of TC, triglyceride, high-density lipoprotein cholesterol, and directly-measured LDL-C in the same blood sample. Patients with TG level greater than 400 mg/dL were excluded. The mean differences of estimated and directly-measured LDL-C were compared between different formulae. results: A total of 32, 753 subjects were included for analysis and the directly-measured LDL-C levels were 116±39mg/dL. The NF by us yield estimated LDL-C, which was equal to 0.75×TC–25. The mean estimated LDL-C levels were 104±42mg/dL, 114±35mg/dL, 109±41mg/dL, 97±40mg/ dL, 113±37mg/dL, 105±36mg/dL, 100±34mg/dLby using FF, NF, DeLong formula, Hattori formula, Chen formula and Cordova formula respectively, and mean differences with measured LDL-C were 12.1 ± 19.1mg/dL (p<0.001), 1.3±19.2mg/dL (p<0.001), 7.1±15.3mg/dL (p<0.001), 18.6±18.6mg/ dL (p<0.001), 3.1± 11.9mg/dL (p<0.001), 10.4±12.1mg/dL (p<0.001), 15.2±19.8mg/dL (p<0.001). In subjects with type 2 diabetes mellitus, the mean difference were 13.0±22.1 (p<0.001), 0.7±21.4 (p<0.001), 7.7±18.0 (p<0.001), 19.2±21.4 (p<0.001), 3.3±14.1 (p<0.001), 9.9±14.3 (p<0.001), 13.0±21.7mg/dL (p<0.001). In subjectswithouttype 2 diabetes mellitus, the mean difference were 11.1± 15.4 (p<0.001), 1.9±17.9 (p<0.001), 6.5±11.8 (p<0.001), 18.0±15.2 (p<0.001), 2.8±9.2 (p<0.001), 10.9±9.4 (p<0.001), 17.4±17.4 mg/dL (p<0.001).

Conclusion: The NF had better performance than other formulae and was not affected by the diabetes mellitus diagnosis. Further study should be validated in different population.

OE-01

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

1,4Yan-JIe LIn,

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

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

objective: Endothelin-1 (ET-1) is the most potent vasoconstrictor by binding to endothelin type A receptor (ETAR) in vascular smooth muscle cells (VSMCs). Angiotensin II (Ang II) and Ang II type one receptor (AT1R) react together as transient constrictor of VSMCs. The synergistic effect of ET-1 and Ang II on blood pressure has been observed in rats; however, the underlying mechanism remains unclear. We hypothesize that Ang II leads to enhancing ET-1-induced vasoconstriction through the activation of ETAR on VSMCs.

Methods: The ET-1-induced vasoconstriction, 125I-ET-1 binding, and mRNA and protein of endothelin receptors were explored in the isolated endothelium-denuded aortae and A-10 VSMCs. results: Ang II pretreatment enhanced ET-1-induced vasoconstriction and ET-1 binding to the aorta. Ang II enhanced mRNA and protein of ETAR, but not ETBR, in aorta and increased ET-1 binding, mainly to ETAR on A-10 VSMCs. Moreover, Ang II-enhanced ET-1 binding and ETAR expression were blunted reduced by AT1R antagonism or by PKC- or ERK-inhibitor individually.

Conclusion: Ang II enhances ET-1-induced vasoconstriction by upregulating ETAR expression and ET-1/ETAR binding, which may be because of the AngII receptor/PKC/ERK signaling. These findings suggest the synergistic response of Ang II and ET-1 on the pathogenic development of hypertension.

OE-02

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

1,2JuI-Hung CHen, 3DEE PEI, 1YI-JEN HUNG, 1CHANG-HSUN HSIEH, 4YEN-LIN CHEN

1Division of Endocrinology and Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Internal Medicine, Tri-Service General Hospital Songshan Branch, National Defense Medical Center, Taipei, Taiwan; 3Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; 4Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

background: Although uric acid (UA) is not a traditional criteria for Metabolic syndrome (MetS), many studies had identified a positive association between UA and MetS in different age and ethnic population. However, the association between UA and MetS is not fully elucidated in the very aged population.

Methods: We selected subjects aged 65 and older undergoing routine health checkups in Taiwan. After excluding subjects with taking medications known to influence components of MetS or UA, a total of 18,906 Chinese elderly were eligible for analysis. Modified Adult Treatment Panel III criteria were used to define MetS. All the participants were further divided into nine groups with gender specification according to the age (the young-old : 65 to 74, the old-old : 75 to 84 and the oldest-old : 85 and over) and UA level. UA level is assigned from lowest to highest tertile with UA Gr1:<5.7 mg/ dl, UA Gr2:5.7~6.7 mg/dl and UA Gr3:>6.7 mg/dl in male and Gr1:<4.9 mg/dl, UA Gr2:4.9~5.9 mg/ dl and UA Gr3:>5.9 mg/dl in female. A cross-sectional study was first performed to determine the correlation between UA and MetS. A longitudinal study then excluded subjects with MetS at baseline to explore the risk of MetS among different UA level of 3 aged populations. results: Based on the demographic data, we found a graded positive association between UA and MetS components but alleviated with aging. Higher UA level have higher odds ratio (OR) of having MetS but the condition also eased up with aging (OR: 1.383 and 2.030 in male and 1.596 and 3.021 in female in UA Gr2 and UA Gr3 in the young-old group and OR: 2.303 in female in UA Gr2 and 1.922 in male and 2.690 in female in UA Gr3 in the old-old group with UA Gr1 as reference group). In the second part, the Kaplan–Meier plot showed that higher levels of UA would have higher risk of developing MetS in the young-old group of both genders (p<0.01 when UA Gr 3 compared with UA Gr1 and UA Gr 2, respectively). In addition, the Cox regression model further confirmed the results (UA Gr3 HR: 1.898 in male and HR: 1.832 in female).

Conclusions: In conclusion, the preset study revealed that higher UA level in the young-old group in Chinese elderly had higher risk for developing MetS and being regard as an adjuvant tool for early awareness of MetS. However, the condition weakened with age greater than 75 years old.

OE-03

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

1CHIa-HuI CHang, 1SHI-WEN KUO, 2YAO-CHOU TSAI, 3VIN-CENT WU, 1YA-HUI HU

1Division of Endocrine and Metabolism, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Taiwan; 2 Division of Urology, Department of Surgery, Taipei Tzu Chi Hospital, The Buddhist Medical Foundation, Taiwan; 3 Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital.

Purpose: A few recent studies show possible predictors or critical prognostic factors affecting complete hypertension cure after adrenalectomy for primary aldosteronism (PA) including BMI, preoperative plasma aldosterone concentration (PAC), duration of hypertension, preoperative response to spironolactone, genotype, tumor size, etc. In this study, we demonstrated the clinical outcome after unilateral adrenalectomy in PA. We try to identify critical predictors for hypertension cure by statistical analysis.

Methods: We reviewed the medical record of our patient group of 17 people who had been clinically confirmed (by ARB suppression test) to have PA and had undergone unilateral adrenalectomy between 2010 and 2014. The postoperative patients were divided into three groups based on blood pressure control namely cure group (anti-hypertension drugs all deactivated), improvement group (anti-hypertension drugs have reduced or have lower blood pressure in the same dosage), nonimprovement group (anti-hypertension drugs can’t be reduced). We analyzed the differences in BMI, PAC, potassium level, etc. in these three groups. Statistical analysis was performed using one-way ANOVA. Statistical significance was defined as a P value of <0.05. result: There were 10 males and 7 females, with a mean age 54.6±9.4 years. There were 10 males and 7 females, with a mean age 54.6±9.4 years. There were 1 heart failure (5.8%), 5 CVA (29%), 3 CKD (17.6%), 7 DM (41.4%) and 16 hypokalemia (94.1%) in our population of 17 patients before operation. After operation, almost the patients who suffered from hypokalemia have been cured, but most of DM patients show no improvement. No any postoperative adrenal insuffiency was noted. The number of left side lesion was about 2.5 times of right side lesion (12:5). BMI show significant differences (P=0.029). Preoperative PAC show boderline differences (P=0.054) in these three groups but potassium level does not (P=0.307).

Conclusion: We suggest that BMI and preoperative PAC can be critical predictors rather than potassium level for hypertension cure in primary aldosteronism but more PA population will be needed. There is no evidence of association between DM and PA in our database.

OE-04

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

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

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan, R.O.C. 2Department of Pathology, Chang Gung Memorial Hospital, Taiwan, R.O.C. 3Department of General Surgery, Chang Gung Memorial Hospital, Taiwan, R.O.C.

objective: Follicular variant of papillary thyroid carcinoma (FVPTC) is the most common subtype of papillary thyroid carcinoma. The previous study reveals its clinical behavior is a mixed type of classic papillary thyroid carcinoma (C-PTC) and follicular thyroid carcinoma (FTC). Locoreginal extension was lower in FVPTC than C-PTC; however, distant metastasis rate of FVPTC is higher than C-PTC. Unlike experiencing an indolent clinical course in most FVPTC cases, patients with distant metastasis have a worse prognosis. The aim of this study is to evaluate risk factors of distant metastasis in FVPTC post-operatively.

Method: A retrospective review of total 359 patients with final pathological diagnosis of FVPTC treated in Chang Gung Memorial Hospital from January 2000 to January 2014 was performed. After excluding patients who had inadequate pathology specimen and did not attend regular follow-up for more than one year, 346 patients were finally included in this study. The following data were extracted from admission records for analysis: age, gender, primary tumor size, ultrasonographic findings, FNAC results, operative methods, histopathology, TNM staging, one-month post-operative serum Tg levels, causes of death, and survival status. Univariate and multivariate statistical analysis were performed to determine the significance of various factors. Statistical significance was set at a p value of 0.05 or below. result: Of 346 patients with FVPTC, 19 (5.5%) patients had lymph node metastasis ; 32 (9.2%) patients had distant metastasis. Among the distant metastasis group, 25 (78.1%) patients were diagnosed initially and 7 (21.9%) patients were recurrent with distant metastasis during followup period. Two positive and one negative risk factors were predictive for distant metastasis by multivariable analysis: angiolymphatic invasion (odds ratio (OR) 3.069 , 95% confidence interval 1.004 to 9.384), extrathyroidal extension (OR 3.256, 1.04 to 10.194) and encapsulation (OR 0.384, 0.162 to 0.912).

Conclusion: The presence of angiolymphatic invasion, extrathyroidal extension and encapsulation were associated with distant metastasis in FVPTC in this study. Post-operative investigation for distant metastases may be warranted in the presence of these two positive risk factors in FVPTC.

OE-05

ASSOCIATION OF MEAN ARTERIAL PRESSURE AND MORTALITY IN DIABETES PATIENTS WITH NORMAL ANKLE-BRACHIAL INDEX

Yu-Hsuan LI, I-TE LEE, SHI-YI LIN, WAYNE HUEY-HERNG SHEU

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

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

Conclusions: Our findings showed that in the subjects with normal value of ABI, mean arterial pressure, but not UT, was associated with an increased risk of all cause mortality in the subjects with normal value of ABI.

OE-06

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

1ang-Tse Lee,

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

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

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

Conclusion: Higher serum total bilirubin concentration was associated with lower risk of CKD, regardless of other conventional CKD risk factors.

OE-07

SERUM STIMULATED THYROGLOBULIN LEVELS AT THE TIME OF 131I ABLATION THERAPY IS A GOOD PROGNOSTIC MARKER TO PREDICT LONG-TERM STRUCTURAL PERSISTENT DISEASE IN WELL-DIFFERENTIATED THYROID CARCINOMA

Feng-CHIH sHen, CHING-JUNG HSIEH, I-CHIN HUANG, PEI-WEN WANG

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

Introduction: This study was conducted to identify the prognostic factors for the prediction of long term disease status in patients with differentiated thyroid carcinoma (DTC) who received 131I ablation therapy after total thyroidectomy. We also want to access the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (sTg) at the first 131I ablation for the prediction of prognosis.

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

Conclusions: stimulated serum thyroglobulin at the first 131I ablation and old age are good predictors of structural persistent disease for long-term prognosis.

OE-08

ELASTOGRAPHY OF THYROID ULTRASONOGRAPHY PREDICT RECURRENCE OF GRAVES’ DISEASE

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

1Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taiwan, R.O.C; 2Department of Integration of Traditional Chinese and Western Medicine, China Medical University Hospital, Taiwan, R.O.C.; 3School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taiwan, R.O.C.

Purpose: To retrospectively evaluate efficacy of elastography of thyroid ultrasound predict recurrence of Graves’ dis after antithyroid agents management.

Patients and Methods: Patients who received antithyroid agents for a period till to stable of clinical condition with lower dosage of antithyroid agents from Jan, 2003 to June 2014 in China Medical University Hospital. Total enrolled 102 subjects and divided to recurrent group and nonrecurrent group. Each group compared age, sex, TSH, free T4, TRH receptor Ab and picture of elastography in thyroid ultrasound. Statistics was Chi-square test, dependent test. P-values < 0.05 were considered statistically significant. results: A total of 102 patients, who were divided into 25 patients in recurrent group and 77 patients in non-recurrent group. No evidence differentiation of age , sex, free T4, TSH, TSH receptor antibody, Acoustic Radiation Force Impulse (ARFI) in thyroid US were noticed between two groups. All p-values were over 0.05.

Basic data in recurrent and non-recurrent group.

Conclusions: No evidence data can support elastography of thyroid ultrasound or other items could predict recurrence of Graves’ disease after hold antithyroid agents.

OE-09

AMIODARONE - ASSOCIATED THYROID DYSFUNCTION

1HsIao-LIen CHen, 2PAI-LIEN CHEN, 1HUAN-WEN CHEN, 3PEI-LING CHAN

1Division of endocrinology and Metabolism, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.; 2Division of endocrinology and Metabolism, Department of Internal medicine, Luo Dong Saint Mary’s Hospital ,Taiwan, R.O.C.; 3Department of Nursing, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.

objective: To determine the incidence of amiodarone-induced thyroid dysfunction in patients with amiodarone treatment. research design and methods: We performed a retrospective review charts among patients from 2011/7/11 to 2012/12/31 who had been prescribed amiodarone for six consecutive months were identified through the computer based information integrated system. Patients treated with amiodarone for six months and at least one time check thyroid function test after amiodarone were included. Baseline characteristics, laboratoratory parameters were evaluated. results: A totalof 144 patients were studied (mean age, 76+10 years (range, 51-90 year) were studied. Of the 144 patients, 51% (n=73) developed thyroid dysfunction:10%( n=14) became hyperthyroid and 40% (n=59) hypothyroid.Female sex more significant for thyroid dysfunction 45% than euthyroid 32 %.

Conclusions: Amiodarone can cause hypothyroidism, or hyperthyroidism. During the first several months of treatment, there is often a transient period of mild hypothyroidism. A few patients remain hypothyroid, and fewer develop hyperthyroidism. Because there is no set time course for the development of thyroid abnormalities, it is important to evaluate and monitor thyroid function after starting amiodarone therapy.

OE-10

EPIMEDIUM EXTRACTS INDUCED C2C12 PROLIFERATION AND HYPERTROPHY

1YI-an LIn, 2MEI-CHICH HSU, 3SZU-TAH CHEN

1National Taiwan Sport University; 2 Kaohsiung Medical University; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital

backgroud: Epimedium is commonly used as an aphrodisiac agent to improve sexual dysfunction in traditional Chinese medicine. Icariin, a natural flavonoid glucoside isolated from Epimedium extracts (EE), has been proved to exhibit an anabolic effect on in vivo as well as in vitro studies. Even so, the anabolic effect of EE on skeletal muscle has not been thoroughly investigated.

Purpose: This study is to determine the effects of EE on the proliferation and differentiation of C2C12 cells, a well-established mice myoblast cell line.

Methods: After exposure to EE for 72 hours, proliferation of the cells was determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. For myotube development, EE was applied 3 days after differentiation media has been given. Myotube diameter was measured by computer-aided software before and after EE treatment. Western blots were used to assess the amounts of total and phosphorylated Akt and p70S6K proteins critical in the insulin-like growth factor-1 (IGF1) signaling pathway. results: EE treatment enhanced myoblast proliferation at 24 hour under the range of 10 to 100 ug/ml. In addition, EE significantly facilitated myotube growth by increasing its diameter. Both Akt and p70S6K were significantly phosphorylated after EE stimulation, and this response could be abolished by phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitors.

Conclusion: By using C2C12 cells, we found EE potentially facilitate myoblast proliferation and myotube hypertrophy. Our results suggest that PI3K/Akt and mTOR/p70S6K signaling pathway may play an important role in the EE-induced anabolic effect.