Association study of WFS1 rs10010131 and type 2 diabetes microvascular complication in a Chinese population

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Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211

Second episode: When he was 59 y/o, his GAD antibody became positive after the start of 6 months of SGLT2 inhibitor treatment. In addition, Serum amylase was elevated together with rise of CA19-9, elastase-I, lipase, tripsin and IgG4. The reassessment of the radiological diagnosis has not identified pancreatic mass as a manifestation of focal pancreatitis. Because of high IgG4, he was tentatively diagnosed as having had autoimmune pancreatitis (AIP). Discrepancy: Interestingly, during the first episode, glycemic control got abruptly worse according to the elevation of GAD antibody titer. GAD antibody titer and HbA1c elevation had seemingly close relationship. In contrast, during the second episode, glycemic control was stable, seemingly having no relationship between GAD antibody titer and HbA1c level. While the difference of two times episodes was apparent, true aetiology was unknown. In conclusion, this is the first case report of mitochondrial diabetes, in which GAD antibodies were detected once positive and soon after became negative two times in life. The aetiology and pathophysiology are not fully elucidated.

PB-08 Evaluation of the web-based nutritional management program for pregnant women with diabetes mellitus Jin-Hee LEE1, Sun-Young LIM1, Hyun-Jung YOO1, Hun-Sung KIM1,2, Yoon-Hee CHOI2, Jae-Hyoung CHO1,2, Kun-Ho YOON1,2 *. 1Catholic Institute of U-Healthcare, The Catholic University of Korea, 2Department of Endocrinoloty and Metabolism, College of Medicine, The Catholic University of Korea, Korea Objective: This study aimed to evaluate the effectiveness of the web-based nutritional management program by applying to pregnant women with gestational diabetes (GDM) and type 2 diabetes mellitus (T2DM). Methods: From June 2008 to May 2010, 96 pregnant women with GDM and T2DM were included. At entrance they were instructed to record their dietary intake using the 24-hour recall method and then received nutritional education by dietitian. Since then, they had received well designed management by the web-based program for 4 weeks. Weekly nutritional intake status was assessed using data they recorded meal diary in the web-based program. Repeated measures ANOVA were performed to compare the change of intake level. Results: At entrance, mean weeks of gestation and energy intakes were 26.4, 12.3 weeks and 1590.7, 1620.6 kcal in the GDM and T2DM group, respectively and carbohydrate intakes compared with total calorie were highly presented in both group. After applying the web-based program for 4 weeks, the percentages of total energy from carbohydrate were decreased significantly (from 57.2% to 50.2% in GDM and from 63.7% to 51.6% in T2DM group) with increasing protein and fat intakes close to recommended levels. Also, weight management especially in the overweight/obese subjects was improved. Conclusion: This study showed that an effective management of nutrition intake and weight control for pregnant women with GDM and T2DM will be available by using the web-based nutritional management program and it is expected to influence positively for decrease of the maternal and fetal complications. PB-09 Study of frailty prevalence and status of elder diabetic patients in a primary care clinic Yuan-Ching LIU1,2, Neng-Chun YU2, Shu-Hua FENG2, Lan-Fen LIN2, Chia-Hui CHENG2, Mei CHANG YEH1 *. 1 Department of Nursing, College of Medicine, National Taiwan University, Taipei, 2Neng-Chun Diabetes Clinic, Yilan County, Taiwan

Background: Frailty is characterized by multi-system decline and vulnerability to adverse health outcomes. Elder diabetic patients were considered to have high risk of frailty. The goal of this study was to analyze the frailty prevalence and status of those elder diabetic patients. Methods: This pilot study was conducted in a local diabetes clinic located at Yilan County, Taiwan. A total of 181 patients aged 65 years or older were selected by randomly systematic sampling from August to December in 2015. Frailty was measured by the Chinese version of Tilburg Frailty Indicator (TFI) including 15 items. When total score was 5 or greater, they were determined to have frailty. Other baseline characteristics were evaluated by Activities of Daily Living (ADLs) scales, instrumental ADL scale, Taiwan Geriatric Depression Scale, Mini-Mental State Examination, demographic datum, and clinical parameters. Results: 181 elder diabetic patients were included in this study. Participants’ average age was 74.3 ± 5.8 years old, and the mean DM duration was 15.0 ± 9.2 years. 58.0% were male. The average A1C and BMI were 7.1 ± 1.1% and 25.3 ± 3.9 kg/m2, respectively. Hypertension (66.3%), hyperlipidemia (72.9%), diabetic nephropathy (56.4%), retinopathy (16.0%), neuropathy (4.4%), and stroke (3.9%) were reported. The average disease number of those patients was 2.7 ± 1.5. Those patients used 3.2 ± 1.7 types of medicine. The self-reported frequency of fall and hypoglycemia of those patients were 0.6 ± 1.2 and 1.7 ± 5.2 in the past year, respectively. The frailty prevalence rate for all participants was 32.0%, for male was 27.6% and for female was 38.2%. The age-specific frailty prevalence rates were 22.9%, 40.8%, and 55.6%, for 65–74.9, 75–84.9, and ≥85 y/o respectively and significantly different among age groups (χ2 = 8.63, p = 0.013). Compared to patients without frailty, patients with frailty had significantly higher percentage of stroke and fall, worse physical function, higher depressive level, and worse cognitive impairment. Conclusions: The frailty prevalence was determined to be 32.0% by TFI in a local primary care clinic. The prevalence increased with age. Patients with frailty had higher percentage of stroke and fall. They also had worse physical function, higher depressive level, and worse cognitive impairment than those patients with no frailty. More patients will be involved to verify related factors of causing frailty of elder diabetic patients in future studies. PB-10 Association study of WFS1 rs10010131 and type 2 diabetes microvascular complication in a Chinese population Yeping HUANG1,5, Rong ZHANG1–5, Cheng HU1–5 *, Weiping JIA1–5. 1Shanghai Diabetes Institute, 2Shanghai Key Laboratory of Diabetes Mellitus, 3Shanghai Clinical Center for Diabetes, 4Shanghai Key Clinic Center for Metabolic Diseases, 5 Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China Objective: Genome-wide association studies found WFS1 rs10010131 was associated with type 2 diabetes by affecting beta cell function. Diabetic nephropathy (DN) and diabetic retinopathy (DR) are both the common microvascular complications. Besides poor blood glucose control and long duration of the disease, genetic factors do predispose to diabetic nephropathy and retinopathy. The aim of the study is to investigate the association of WFS1 rs10010131 and diabetic nephropathy and diabetic retinopathy in the Chinese population. Methods: The study was conducted in two stages. In the first stage, 1251 individuals with type 2 diabetes were recruited and stratified into 4 groups: 313 with diabetic retinopathy but without diabetic nephropathy, 419 with nephropathy but without retinopathy, 281 with both retinopathy and nephropathy, and 238 with diabetes of ≥10 years duration but without microvascular complications. In the second stage,

Poster Presentations / Diabetes Research and Clinical Practice 120S1 (2016) S65–S211

594 individuals with diabetes were recruited, including 201 with diabetic retinopathy and 393 with diabetes of ≥5 years duration but without retinopathy. GCKR rs780094 genotyping was conducted with Sequenom. The diagnose and grading of diabetic retinopathy were according to fundus examination. 24-hour urinary albumin excretion rate and estimated glomerular filtration rate were used to evaluate diabetic nephropathy. Results: In the first stage, rs10010131 was significantly associated with diabetic retinopathy (OR = 1.629, 95% CI 1.019–2.606, P = 0.0416) after adjusting for duration of diabetes, HbA1c, blood pressure and body mass index. However, rs10010131 did not show association with Diabetic nephropathy (OR = 0.991, 95% CI 0.619–1.586, P = 0.970). In the second stage, no significant association of rs10010131 and DR was observed (OR = 0.837, 95% CI 0.408–1.716, P = 0.627). The metaanalysis showed that rs10010131 was not significantly associated with DR (OR = 1.334, 95% CI 0.901–1.977, P = 0.150). Conclusion: WFS1 rs10010131 was not associated with diabetic nephropathy and diabetic retinopathy in the Chinese individuals with type 2 diabetes. PB-11 In type 2 diabetes, smoking cessation is associated with deterioration in glycemic control and this is unrelated to weight gain Takako KIKUCHI1*, Kenichiro ENOOKU2, Akifumi KUSHIYAMA1, Yoko YOSHIDA1, Sayaka WAKABAYASHI1, Yasuhiko IWAMOTO1. 1The Institute for Adult Diseases, Asahi Life Foundation, 2University of Tokyo, Japan Background/aims: Diabetes mellitus (DM) are closely associated with the development of cardiovascular diseases. Smoking represents one of the most important preventable risk factors for the development of atherosclerosis. In patients with DM, smoking works synergistically in increasing the risk of cardiovascular events and death. There are some studies suggesting that diabetes control deteriorates temporarily during the first year after smoking quitting. The aims of this study were to examine whether or not quitting smoking was associated with altered diabetes control, and whether or not this association was mediated by weight change. Patients and methods: From May 2010 to October 2014, we recruited 131 patients on medication for DM and in hope to use Varenicline for smoking cessation at the Institute for Adult Diseases, Asahi Life Foundation. Physical examinations and blood samples were taken on the day of starting administration, and every two weeks thereafter. Varenicline were administered for three months. All patients gave informed written consent. We investigated the association between a quit event, smoking abstinence duration, change in HbA1c, and the mediating effect of weight change. Results: 97 (74.0%) quit smoking and remained abstinent for at least 1 year. The majority (89.7%) was male and the median body mass index (BMI) was 24.2 kg/m2 (IQR 21.8–26.9). BMI and HbA1c level showed a significant increase during smoking cessation. But this increase in HbA1c was not mediated by weight change. The changes in HbA1c during smoking cessation were not correlated with the changes in BMI, and HbA1c level increased in 75.0% of patients who decreased BMI during smoking cessation. In patients who were treated with insulin, HbA1c level increased higher than in those who were treated with oral drugs only. Patients who increased BMI during smoking cessation gained significantly more weight within the first year after quitting than those who decreased BMI during smoking cessation. Spearman’s rank correlation revealed that the white blood cell count and neutrophil to lymphocyte ratio (NLR) significantly improved immediately after smoking cessation. High-density

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lipoprotein cholesterol levels increased after smoking cessation, although BMI also significantly increased. Conclusions: In type 2 diabetes, smoking cessation is associated with deterioration in glycemic control and this is unrelated to weight gain, although smoking cessation significantly and immediately decreased systemic inflammation and increased serum HDL cholesterol level in diabetic patients. PB-12 New findings of genetic determinants of sulfonylurea efficacy from next-generation sequencing in sulfonylurea sensitive patients Qian REN1, Xueyao HAN1, Siqian GONG1, Yumin MA1, Linong JI1*. 1Peking University People’s Hospital, China Background: The genetic determinants for sulfonylureas efficacy has not been well understood until now. Methods: This pharmacogenetic study was divided into three stages. In the First stage, we screened a total of 747 patients with type 2 diabetes enrolled from the Xiaoke Pills Clinical Trial to select patients with extreme phenotype. We regarded “very sensitive to sulfonylurea” as an extreme phenotype, including two conditions (1) sulfonylurea treatment best responders: HbA1c level was decreased by more than 1%, and body weight increased by more than 5% during the first three months of follow up. (2) hypoglycemia occurred so frequently that the dose of glybeclamide was 1.25 mg/d during the whole follow up period as initial dose or the patient lost follow up because of hypoglycemia. In the second stage, next-generation sequencing was performed in patients with extreme phenotype. Variants with prediction of harmful were selected and validated by first-generation sequencing and re-sequenced them in subjects with normal glucose metabolism. In the third stage, we did case-control study in 340 patients treated with glybenclamide to investigate if the selected variants could really influence sulfonylurea efficacy. Results: We selected 32 “sulfonylurea very sensitive patients’. After next-generation sequencing, we selected 48 variants (39 genes), which seem to be harmful in prediction. Then 26 variants were successfully validated by first-generation sequencing and were re-sequenced in 20 normal glucose metabolism subjects to compare genotype between patients and controls. The genotypes were similar between patients and normal glucose metabolism subjects, except rs56743379. Rs56743379 was an insert/delete mutation in exon 5 of DMKN gene. So we did case-control study in 340 patients treated with glybenclamide to investigate the association between rs56743379 and sulfonylurea efficacy. There were 35 (10.3%) homozygous with insert mutation (Ins group), 50 (14.7%) homozygous with delete mutation (Del group). And because there were 58 SNPs downstream to the rs56743379, including 3 SNPs hit on the same contig position of rs56743379. So we regarded 255 (75%) subjects as heterozygous with varying degrees of insert/delete mutation (Hetero group). There were no significant difference between genotypes and treatment failure of glybenclamide (OR = 1.488, 95%CI 0.937– 2.361, P = 0.092). However, Logistic regression analysis showed that rs56743379 were significantly associated with proportion of patients with FPG < 7 mmol/L after adjustment of age and sex (OR = 0.630, 95% CI 0.405–0.979, P = 0.040). Conclusions: Rs56743379 in DMKN gene may be associated with sulfonylurea efficacy. Further pharmacogenetic and functional studies are needed to confirm this observation. PB-14 Impact of diabetes and Intercellular adhesion molecule-1 genetic polymorphism on coronary artery disease susceptibility in Taiwan Chihung CHOU1,2 *, Kwo-Chang UENG3,4, Shun-Fa YANG1,5, Po-Hui WANG1,4,6. 1Institute of Medicine, Chung Shan Medical University, Taichung, 2Division of Cardiology, Department of Internal