OD：Oral presentation-Diabetes (1-6

OD-1 CARDIOVASCULAR EFFECTIVENESS AND SAFETY OF EMPAGLIFLOZIN IN ROUTINE CARE IN EAST ASIA: RESULTS FROM THE EMPRISE STUDY

1WAYNE H-H SHEU, 2ELISE CHIA-HUI TAN, 3YUTAKA SEINO, 4DAE JUNG KIM, 5DAISUKE YABE, 4KYOUNG HWA HA, 6WEI-YU LEI, 7WOOK-JIN CHUNG, 8ATSUTAKA YASUI, 9RIHO KLEMENT, 10MOE KYAW, 10KIMBERLY G. BRODOVICZ

1Division of Endocrinology and Metabolism, Taichung Veterans General Hospital, Taichung, Taiwan; 2National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan, and Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan; 3Kansai Electric Power Medical Research Institute, Kobe, Japan; 4Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea; 5Kansai Electric Power Medical Research Institute, Kobe, Japan, and Department of Diabetes and Endocrinology, Gifu University Graduate School of Medicine, Gifu, Japan; 6Boehringer Ingelheim Taiwan Ltd., Taipei, Taiwan; 7Department of Cardiovascular Medicine, Gachon University Gil Medical Center, Incheon, Korea; 8Nippon Boehringer Ingelheim Co. Ltd., Tokyo, Japan; 9EPID Research, Tartu, Estonia; 10Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA

Background: Empagliflozin reduced the risks of cardiovascular (CV) death and hospitalization for heart failure (HHF) in type 2 diabetes mellitus (T2DM) patients and established CV disease in the EMPA-REG OUTCOME trial. The Empagliflozin Comparative Effectiveness and Safety Study (EMPRISE) is comparing the effectiveness, safety, and healthcare utilization of empagliflozin versus dipeptidyl peptidase-4 inhibitors (DPP-4i) in routine clinical care across the CV risk continuum in Asia, Europe, and the US. Analyses of EMPRISE in the US showed that empagliflozin was associated with a lower risk of CV outcomes.

Methods: We analyzed data from three East Asian countries in EMPRISE (Japan, South Korea, and Taiwan) for T2DM patients aged ≥ 18 years before initiated empagliflozin or a DPP-4i. Exclusion criteria included prescription of any SGLT2i/DPP-4i in the prior 12 months, diagnosis of type 1 diabetes mellitus/gestational diabetes at any time, or diagnosis of end-stage renal disease (ESRD) in the prior 12 months. Sub-cohorts of empagliflozin and DPP-4i initiators were identified by propensity score matching (1:1) with > 120 covariates. The meta-analyses were conducted for the primary effectiveness outcomes (HHF, ESRD and all-cause mortality [ACM]).

Results: In total, 892,355 patients initiated either empagliflozin or a DPP-4i (Japan 343,329; South Korea 263,524; Taiwan 285,502), with 28,712 matched pairs of patients (Japan 5,592 pairs; South Korea 9,072 pairs; Taiwan 14,048 pairs). Empagliflozin was associated with significant 21% (p-value = 0.023), 36% (p-value < 0.001) and 63% (p-value < 0.001) reductions in the risk of HHFspecific, ACM and ESRD, respectively.

Conclusions: The results provide insight into the effectiveness of empagliflozin in routine care of T2DM in East Asia.

OD-2 THE RISK FACTORS OF LATENT TUBERCULOSIS INFECTION IN PATIENTS WITH TYPE 2 DIABETES

1,2CHING-JUNG HSIEH, 1SUN WU, 1I-CHIN HUANG, 1HSIN-HONG HSIEH, 1CHUN-HUI WU

1Department of Internal Medicine, Pao Chien Hospital, Ping Tung, Taiwan; 2Department of Nursing, College of Health and Nursing, Mei Ho University, Ping Tung, Taiwan

Background: There is growing evidence that diabetes mellitus (DM) is an important factor for tuberculosis and might affect disease presentation and treatment response. Otherwise, tuberculosis might induce glucose intolerance and worsen glycemic control in people with diabetes. Adults with diabetes and latent tuberculosis infection (LTBI) are at high risk for progressing to active tuberculosis (TB) disease if they are not treated. Studies have shown that this risk is 2 to 6 times higher than in patients without diabetes. T-cell interferon-γ release assay (IGRA) to test for LTBI at least once after diabetes diagnosis has been recommended. Screening and treatment of LTBI and TB disease could reduce DM associated TB. The aim of this study is to investigate the risk factors of LTBI among patients with type 2 DM in a single institution.

Methods: Patients with more than 5 years of type 2 DM under medication control underwent LTBI screening using IGRA testing. TB was investigated by sputum smear, culture and x-ray if positive finding of IGRA. Risk factors measuring from electronic medical record included average and standard deviation (SD) of glycated hemoglobin (HbA1c) between 1 month before and 5 years after IGRA testing. The serum lipid profile, creatinine, urine albumin/creatinine ratio (UACR), and blood pressure were measured before IGRA testing. The duration of diabetes, body weight, and body high were also recorded.

Results: Of 90 patients with DM screened, 81 (90%) were eligible and LTBI prevalence was 19.8% (16/81). No active TB was investigated in the patients with LTBI. Patients who had LTBI had longer duration of diabetes (10.6 ± 2.0 vs. 7.3 ± 1.3 years, p = 0.001), higher SD of HbA1cs than control (3.1 ± 0.4 vs. 1.9 ± 0.4 %, p < 0.001) and higher UACR (723.3 ± 605.7 vs.181.8 ± 374.4 mg/ g, p = 0.005) but not average of HbA1cs (8.8 ± 1.0 vs. 8.4 ± 1.4 %, p = 0.065). There were no group differences in gender, body weight, blood pressure, lipid profile, renal function.

Conclusion: Patients with longer duration of DM, HbA1cs fluctuation and severe albuminuria may have increased risk of LTBI. Therefore, stable blood glucose control and lower HbA1c oscillation may improve T cell function and prevent LTBI in patients with diabetes. Less HbA1c fluctuation may also decreasing microvascular complication, especially for nephropathy.

OD-3 SODIUM HYDROSULFIDE RESTORES TUMOR NECROSIS FACTOR-ALPHA-INDUCED MITOCHONDRIAL DYSFUNCTION AND METABOLIC DYSREGULATION IN HL-1 CELLS

1,2,3T-I LEE, 4,5Y-H KAO, 4L BAIGALMAA, 2,3T-W LEE, 6Y-Y LU LU, 7Y-C CHEN, 8,9Y-J CHEN

1Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; 4Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University; 5Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University; 6Division of Cardiology, Department of Internal Medicine, Sijhih Cathay General Hospital; 7Department of Biomedical Engineering, National Defense Medical Center; 8Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University; 9Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University Taiwan

Background: Tumor necrosis factor (TNF)-alpha induces cardiac metabolic disorder, and mitochondrial dysfunction. Hydrogen sulfide (H2S) contains anti-inflammatory and biological effects in cardiomyocytes. This study investigated whether H2S modulates TNF-alpha-dysregulated mitochondrial function and metabolism in cardiomyocytes.

Materials and Methods: HL-1 cells were incubated with TNF-alpha (25 ng/mL) with or without sodium hydrosulfide (NaHS, 0.1 mM) for 24 hours. Cardiac peroxisome proliferator-activated receptor (PPAR) isoforms, proinflammatory cytokines, receptor for advanced glycation end products (RAGE), and fatty acid metabolism were evaluated through Western blotting. The mitochondrial oxygen consumption rate and adenosine triphosphate (ATP) production were investigated using Seahorse XF24 extracellular flux analyzer and bioluminescence assay. Fluorescence intensity using 2′, 7′-dichlorodihydrofluorescein diacetate was used to evaluate mitochondrial oxidative stress.

Results: NaHS attenuated the impaired basal and maximal respiration, ATP production, and ATP synthesis, and enhanced mitochondrial oxidative stress in TNF-alpha-treated HL-1 cells. TNFalpha-treated HL-1 cells exhibited lower expression of PPAR-alpha, PPAR-delta, phosphorylated 5′ adenosine monophosphate-activated protein kinase-alpha2, phosphorylated acetyl CoA carboxylase, carnitine palmitoyltransferase-1, PPAR-gamma coactivator 1-alpha, and diacylglycerol acyltransferase 1 protein, but higher expression of interleukin-6 and RAGE protein than control or combined NaHS and TNF-alpha-treated HL-1 cells.

Conclusion: NaHS modulates the effects of TNF-alpha on mitochondria and the cardiometabolic system, suggesting its therapeutic potential for inflammation-induced cardiac dysfunction.

OD-4 GLP-1 SIGNALING ACTIVATION AND HMB SUPPLEMENTATION ATTENUATE GLUCOLIPOTOXICITY-INDUCED MUSCLE WASTING

1HSIN-HUA LI, 2CHIH-LI LIN, 3YI-SUN YANG, 3EDY KORNELIUS, 3SHIH-CHANG LO, 4CHIUNG-HUEI PENG, 2LING-YEN CHIU, 3CHIEN-NING HUANG

1Clinical Research Center, Chung Shan Medical University Hospital, Taichung, Taiwan; 2Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Division of Endocrinology and Metabolism, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Division of Nursing, Hung Kuang University, Taichung, Taiwan

Background: Type 2 diabetes (T2D) is characterized by a failure to mediate glucose homeostasis, and hence numerous complicated conditions are induced by tissues exposure to high glucose. Although the causes of T2D are multifactorial, nearly 80% of T2D patients suffer obese and insulin resistance simultaneously. Evidence is now revealed that T2D patients typically show high circulating levels of glucose, palmitic and oleic fatty acids (also called as glucolipotoxicity), which can mediate oxidative stress and insulin resistance. Among various complications of diabetes, the continuously loss of muscle is one of the most important adverse effects. Since muscle loss is at high risk for physical disability and mortality in diabetes, the investigation of molecular mechanisms may help developing therapeutic strategies. To this, previous studies have suggested that the supplementation of β-Hydroxy-βmethylbutyrates (HMBs) may be a dietary strategy to minimize diabetic muscle wasting. Interestingly, recent studies have found that GLP-1 agonists appear to slow muscle wasting during T2D. However, the detailed mechanism is still not well understood.

Methods: To provide a better understanding the role of GLP-1 signaling, we evaluated whether co-treatment of GLP-1 analogue and HMBs is a workable strategy against glucolipotoxicity-induced muscle wasting.

Results: Our results found that activation of GLP-1 signaling protect against glucolipotoxicityinduced muscle damages, including oxidative stress, mitochondria dysfunction, glucose uptake and insulin resistance. Moreover, co-treatment with GLP-1 analogues can better strengthen the above protection mechanisms, and this protection may be effective by activating the AMPK/SIRT1 pathway.

Conclusions: These results can confirm and extend the contributing role of GLP-1 signaling and HMBs in glucolipotoxicity-induced oxidative stress and insulin resistance in myotube cells.

OD-5 SOLUBLE TUMOR NECROSIS FACTOR RECEPTOR TYPE 1 IS ASSOCIATED WITH RENAL OUTCOMES IN CHINESE SUBJECTS WITH TYPE 2 DIABETES MELLITUS

1,2LIANG-YU LIN, 3,4LI-HSIN CHANG

1Division 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, 4Department of Nursing, Hsin Sheng Junior College of Medical Care and Management, Taoyuan, Taiwan

Background: Chinese subjects with type 2 diabetes mellitus (T2D) are at higher risk of diabetic kidney disease (DKD) than Caucasian. Soluble tumor necrosis factor receptor type 1(sTNFR1) is associated with advancing of DKD and predicts renal outcomes in the Caucasian but the association has not been validated in Chinese subjects. The purpose of the study is to exam the association of sTNFR1 and renal outcomes in the Chinese cohort with T2D.

Methods: Two hundred and eighty three Chinese subjects with T2D were enrolled in the prospectively observational cohort after excluding those with estimating glomerular filtration rate (eGFR) < 30 ml/min/1.73m2. The renal outcomes were composited by more than 30% decline of eGFR or worsening status of albuminuria confirmed by consecutive sampling of blood and urine.

Results: sTNFR1 was associated with renal outcomes. sTNFR1 979 pg/mL showed the best area under curve (AUC), sensitivity, and specificity to predict renal outcomes in receiver operating curve (AUC 0.68, p < 0.001; sensitivity 78.3%, specificity 48.9%). The portion of renal events were higher in subjects with sTNFR1 ≥ 979 pg/mL comparing with subjects whose sTNFR1 < 979 pg/mL (29% versus 10%, p < 0.001 by log-rank test). sTNFR1 ≥ 979 pg/mL was associated with renal outcomes after adjusting other covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18-5.02, p = 0.01) and the association was consistent in all subgroups stratified by age, gender, blood pressure, eGFR, status of albuminuria, and use of blockade of renin-angiotensin system.

Conclusions: sTNFR1 was associated with progression of DKD in Chinese subjects with T2D.

OD-6 COMPARISON OF THE EFFICACY AND SAFETY OF EMPAGLIFLOZIN AND LINAGLIPTIN ADDED TO PREMIXED INSULIN IN PATIENTS WITH UNCONTROLLED TYPE 2 DIABETES

1SUNG-CHEN LIU, 1CHUN-CHUAN LEE, 1SHIH-MING CHUANG, 2FANG-JU SUN, 1YI-HONG ZENG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan; 2Research Assistant, Department of Medical research, Mackay Memorial Hospital, Taipei, Taiwan

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors added to insulin regimen in patients with type 2 diabetes (T2DM) can improve glycemic control. The aim of this study was to compare the efficacy and safety of empagliflozin and linagliptin added to premixed insulin therapy in patients with poorly controlled T2DM.

Methods: This was a 24-week, open-label, parallel, randomized controlled trial. Patients with poorly controlled T2DM, who were on premixed insulin were randomized to receive 5 mg linagliptin (n = 53) or 25 mg empagliflozin (n = 53) for 24 weeks.

Results: At week 24, the changes in glycated hemoglobin (HbA1c) from baseline were -0.06 ± 0.17 % and -1.01 ± 0.16 % in the linagliptin and empagliflozin groups, respectively. The mean treatment difference in HbA1c was -0.88 % (95 % CI -1.33, -0.43). At week 24, empagliflozin group showed significant reduction compared with linagliptin group in terms of fasting plasma glucose, body weight (p < 0.001), and systolic blood pressure (p = 0.003). Hypoglycemia was reported to be slightly higher but not significantly in the empagliflozin group than in the linagliptin group (30.2 % vs. 22.6 %; p = 0.51). A similar percentage of patients had urinary tract infection in the two groups (1.9 %).

Conclusions: In patients with inadequately controlled T2DM on premixed insulin, the addition of empagliflozin over 24 weeks provided better glycemic control and greater reduction in body weight and systolic blood pressure than the addition of linagliptin.