OD：Oral Presentation-Diabetes (1-6

OD-1 ADAM10 MODULATES CALCITRIOL-REGULATED RAGE IN CARDIOMYOCYTES

1,2TING-WEI LEE, 1,3YU-HSUN KAO, 2,4TING-I LEE, 1,5YI-JEN CHEN

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C; 3Department of Medical Education and Research, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C; 4Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C; 5Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taiwan, R.O.C.

Background: Receptor for advanced glycation end products (RAGE) signaling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes.

Materials and methods: Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 hours.

Results: Calcitriol (10 nM) significantly reduced RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells. These changes were associated with increased protein expression and enzyme activity of ADAM10 and higher mRNA expression of esRAGE. In the presence of ADAM10 inhibitor, however, the suppressive effect of calcitriol on RAGE was diminished. Methylglyoxal (500 μM for 10 min)-mediated JNK phosphorylation was attenuated in the presence of calcitriol (10 nM). Moreover, control and NF-κB inhibitor-treated HL-1 cells had similar RAGE and sRAGE expression, suggesting that calcitriol-mediated RAGE modulation was independent of NF-κB signaling.

Conclusions: We showed that RAGE downregulation and increased sRAGE production by calcitriol was mediated through ADAM10 activation in cardiomyocytes. The results suggest that calcitriol has therapeutic potential in treating RAGE-mediated cardiovascular complications.

OD-2 THE CHANGE OF THE BONE STRUCTURE AND MICROARCHITECTURE AFTER ORAL ANTIDIABETIC DRUG TREATMENT IN DIET-INDUCED OBESITY MICE

1CHENG-FENG TSAO, 1JUNG-FU CHEN, 1CHIEN-HUNG KUO, 2SHAO-WEN WENG, 1PEI-WEN WANG

1Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 2Lee’s Endocrinology Clinic, Pingtung, Taiwan

Aims: The therapy of type 2 diabetes mellitus includes lifestyle modification, oral antidiabetic drug and insulin. Pioglitazone has been found associated with decreasing bone mineral density (BMD). However, the relation between Metformin, sulfonylureas (SU), Empagliflozin and bone structure and microarchitecture remain unclear.

Methods: 1-month-old mice underwent 5 months of treatment course. Mice were fed chow diet (CD), high-fat high-sucrose diet (HFD intervention 2nd-6th month), HFD+Metformin (Metformin intervention 3rd-6th month), HFD+SU (Glimepiride intervention 3rd-6th month), HFD+Empagliflozin (Empagliflozin intervention 3rd-6th month). We compared the different of bone structure and microarchitecture of femoral bone and tibia bone when mice was 6-month-old. The bone structure and microarchitecture was measured by micro computed tomography.

Results: There is no significantly different about BMD of femoral and tibia bone between the CD and the HFD group. The trabecular number of tibia bone of the HFD group, as compared with the CD group, showed decreased. However, the trabecular bone pattern factors, structural model index and trabecular thickness of tibia bone was higher in the HFD group than the CD group. The HFD group showed significantly increased more bone volume/tissue volume, trabecular thickness in femoral bone than the SU group. The HFD group, as compared with Metformin group, had increased bone volume/ tissue volume and decreased total porosity and open porosity in femoral bone. The BMD was not significantly different between the HFD group, the SU group and the Metformin group. The BMD, bone volume, trabecular number, trabecular thickness of tibia bone decreased significantly in the SU group, as compared with the CD group. The open porosity, structure model index of tibia bone in SU group shows more increased significant than the CD group. Besides, the trabecular bone pattern factor decreased less in the SU group than the CD group. The trabecular bone pattern factor of the tibia bone in the Empagliflozin group was higher than the CD group but the trabecular thickness of tibia bone was lower in the Empagliflozin group. Conclusion: The bone microarchitecture of tibia bone decreased more in the HFD group than in the CD group. Interestingly, the trabecular bone microarchitecture, BMD of tibia bone decreased significantly in the SU group in diet-induced obesity mice.

OD-3 CHANGES OF GUT MICROBIOTA IN NEWLY-DIAGNOSED TYPE 2 DIABETES TREATED WITH METFORMIN MONOTHERAPY

1WEI-WEN HUNG, 2WEI-CHUN HUNG, 3YI-CHUN TSAI, 1WEI-LUN WEN, 1HE-JIUN JIANG, 1SHYI-JANG SHIN, 1PI-JUNG HSIAO

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan, R.O.C. 2Department of Microbiology and Immunology, Kaohsiung Medical University, Taiwan, R.O.C. 3Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan, R.O.C.

OBJECTIVE: Current treatment guidelines all over the world suggest metformin as the first-line therapy to treat type 2 diabetes. Despite its use for 60 years, the precise mechanisms of metformin are still not fully discovered. Traditionally, liver was thought to be the main target of metformin action. More recently, gut has become the center of attention due to the increasing evidences suggesting that the antihypeglycemic effect of metformin is derived from the gut. We aim to evaluate the relation of antihypeglycemic effect and the changes of gut microbiota by metformin in newly-diagnosed and drug-naive type 2 diabetes.

MATERIALS AND METHODS: We recruited 22 patients with newly-diagnosed and drugnaive type 2 diabetes from the outpatient clinic in a university hospital in southern Taiwan. Before and after metformin monotherapy for three months, we collected the biochemical data and measured fecal microbiota by quantitative real-time PCR with 16S rRNA gene sequencing. At the end of three months, there were totally 14 patients continued on metformin monotherapy and completed the collection of stool samples. Wilcoxon signed rank test was used as statistical analysis.

RESULTS: Our results discovered that BMI (body-mass index), HbA1C, and fasting blood glucose decreased and HDL-C increased significantly after metformin monotherapy for three months. There were no significant changes in cholesterol, triglyceride, LDL-C, HOMA-IR, and UACR (urine albumin/creatinine ratio). Using quantitative real-time PCR with 16S rRNA gene sequencing, we found that Akkermansia and Escherichia increased significantly. The phylum of Firmicutes and Bacteroidetes did not have significant changes after three-month metformin therapy.

DISCUSSION: We revealed that the antihyperglycemic effect of metformin associated with the changes of microbiota including Akkermansia and Escherichia. Understanding the interaction between metformin and gut microbiota in newly-diagnosed type 2 diabetes can help to identify important microbiota species related to the antihypeglycemic effect of metformin. In the future, gut microbiota has the potential to serve as a new therapeutic tool or target in treating type 2 diabetes.

OD-4 LEVELS OF SERUM HIGH MOBILITY GROUP BOX 1 WERE INDEPENDENTLY ASSOCIATED WITH CARDIOVASCULAR RISK IN PATIENTS UNDERGOING CORONARY ANGIOGRAPHY

1JUN-SING WANG, 1WAYNE H-H SHEU, 2WEN-JANE LEE, 1I-TE LEE, 1SHIH-YI LIN, 3WEN-LIENG LEE, 3KAE-WOEI LIANG, 4SHING-JONG LIN

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; 4Department of Medical Research; Taipei Veterans General Hospital, Taipei, Taiwan.

Background: The aim of this study was to examine the association of serum high mobility group box 1 (HMGB1) level with cardiovascular risk in patients undergoing coronary angiography with no history of diabetes. Materials and methods: We enrolled patients with no history of diabetes who had been admitted for coronary angiography due to suspected or known coronary artery disease (CAD). Two to four weeks after the patients were discharged from the hospital, an oral glucose tolerance test (OGTT) was conducted and a blood sample was collected for the measurements of glucose, insulin, lipids, and HMGB1. Patients’ glucose regulation status was determined with the results of OGTT. Patients’ 10-year coronary heart disease (CHD) risk was assessed using the Framingham Risk Scoring. Results: A total of 476 patients were included in the analysis (mean age 61 ± 12 years, male 81.9%, mean body mass index 26.1 ± 3.7 kg/m2, CAD 57.8%). Overall, mean serum HMGB1 level was 6.1 ± 1.3 pg/ml. Using linear regression analysis, high-density lipoprotein cholesterol was negatively associated with serum HMGB1 (β coefficient -0.033, 95% CI -0.063 to -0.003, p = 0.033) after adjustment for several confounders. With regard to cardiovascular risk, levels of serum HMGB1 were positively associated with 10-year CHD risk (β coefficient 0.506, 95% CI 0.030 to 0.983, p = 0.037), independent of patients’ undiagnosed abnormal glucose regulation. Conclusions: In patients undergoing coronary angiography with no history of diabetes, levels of serum HMGB1 were positively associated with 10-year CHD risk, independent of patients’ undiagnosed abnormal glucose regulation.

OD-5 EVALUATION OF GLYCEMIC CONTROL AND SELF-EFFICACY AMONG PATIENTS RECEIVING CONTINUOUS GLUCOSE MONITORING WITH IMMEDIATE COUNSELING FEEDBACK COMPARED WITH DELAYED COUNSELING FEEDBACK

1,2YE-FONG DU, 2CHING-JU CHIU, 1HORNG-YIH OU, 1HAO-CHANG HUNG, 1MING-CHAO LEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; 2Institute of Gerontology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Objective

To explore the effect of immediate feedback or delayed feedback counseling using professional continuous glucose monitoring (CGM) feedback on glycemic control, self-efficacy, drug compliance, diabetes stress, depression, quality of life and life style among middle aged and older adults with poor controlled type 2 diabetes mellitus.

Method

This study enrolled patients aged 45 years and older with HbA1c more than 7%. Participants were assigned into immediate feedback (n = 7) or delayed feedback (n = 10) groups using 4-block randomization design. The immediate feedback group received counseling using CGM graphs on the day of sensor removal. The delayed feedback group received CGM-based counseling 3 months later as usual care schedule. All outcome measures were evaluated at baseline, 3 months, and 6 months.

Results

Participants received immediate feedback had lower depression scores (p = 0.024) and better selfefficacy score (p < .001) at 3 months, compared with delayed feedback group, and a better HbA1c level compared with baseline (p = 0.03). Participants at delayed feedback group had an improved MMAS-8 score after receiving CGM-based counseling (p = 0.05) and an improved diabetes stress at 6 months compared with baseline. There was no difference between groups, assessing change of all outcome measures at 3-months after CGM-based feedback counseling.

Conclusion

Professional CGM had potential benefit in improving glycemic control, especially if feedback counseling was carried out immediately after sensor removal.

OD-6 PREVALENCE, INCIDENCE, AND RISK FACTORS OF DIABETIC RETINOPATHY IN PATIENTS WITH TYPE 2 DIABETES - AN 8-YEAR PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL

1CHIH-CHENG HSU, 2JIUN-YIAN LIN, 2PI-YUAN WONG, 2I-CHUAN LIN, 2I-JU LIEN, 2TONG-YUAN TAI

1Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan ; 2Taipei Jen-Chi

Hospital, Taipei, Taiwan

Background. Incidence of sight-threatening diabetic retinopathy (DR) in Taiwan in 2011 estimated by the National Health Insurance Database was 0.6 and 2.2 per 100 person-years for women and men with type 2 diabetes (T2D), respectively. However, the recent epidemiological patterns of ophthalmologist-diagnosed DR in Taiwan are still unknown. This study aimed at assessing DR prevalence, incidence and its attributable factors for community T2D patients.

Methods. We recruited 553 T2D patients from a community hospital in Taipei from 2006 to 2014 and followed them up through December 31, 2014. Pupil-dilated retinal condition was checked by a well-trained ophthalmologist annually. The incidence of DR was calculated by the corresponding events divided by person-years observed. Cox proportional hazards models were used to identify risk factors contributing to development of DR in the follow-up period.

Results. The prevalence of DR at recruitment was 10.7% (7.2% with non-proliferative DR [NPDR] and 3.4% with proliferative DR [PDR]). The incidence of overall DR was 2.25 per 100 person-years. The incidence of PDR for those with NPDR was 3.2 per 100 person-years. The DR incidence for T2D without and with nephropathy was 2.0 and 2.9 per 100 person-years, respectively. Most significant risk factors contributing to DR were education < 6 years (HR = 2.36, 95% CI = 1.095.09), diabetes onset <45 years of age (HR = 3.62 [1.04-12.61]), diabetes duration ≥ 10 years (HR = 2.43, [1.06-5.56]), nephropathy with eGFR < 45 ml/min (HR = 2.82, [1.00-7.90]), and poor ABC control. Compared with those achieving at least two ABC control criteria (HbA1c < 7%, BP < 140/90 mmHg, and LDL < 100 mg/dL), HR for those with 0 or only 1 good control was 3.48 (1.24-9.76) and 3.76 (1.63-8.66), respectively.

Conclusion. The DR risks include lower education level, earlier diabetes onset and longer diabetes duration. Those with diabetic nephropathy at late stage were more likely to develop retinopathy. For DR prevention, it is essential to control all glucose, blood pressure and cholesterol at an optimal level.