OE Oral Presentation-Endocrine (1-6

OD-01

THE ROLES OF ADIPOSITY ON INSULIN RESISTANCE, GLUCOSE EFFECTIVENESS, FIRST AND SECOND PHASE IN AGED SUBJECTS

1DEE PEI, 2JIUNN-DIANN LIN, 3YEN-LIN CHEN, 2CHUNG-ZE WU, 1TE-LIN HSIA

1Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.; 2Division of Endocrinology, Department of Internal Medicine, Shuang-Ho Hospital, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 3Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, R.O.C.

Aims:

The aim of study is to evaluate the relative influence of body mass index (BMI) on insulin

Methods:

In total, we enrolled 265 individuals with the same fasting plasma glucose level 5.56 mmol/l and same age 60 years old. In this way, the effects of both confounders could be adjusted. Their body mass index ranged (BMI) between 20.0-34.2 kg/m2. IR, FPIS, SPIS and GE were estimated by the equations we built previously. Since the units of the correlation lines are different, the absolute units of these four factors were transformed to relative units, the percentage. Thus, they can be compared.

Results:

which were higher those reported previously. For men, SPIS is most profoundly affected by the BMI, followed by IR, FPIS and GE. For women, the order is a slightly different from that of the men, the the slopes between FPIS and SPIS in women (p = 0.534) and between IR and FPIS in men (p = 0.258).

Conclusions:

The contribution of the obesity to these factors except GE were higher than that those reported previously. The BMI has the most profound effect on insulin secretion in men and on IR in women in this old cohort.

OD-02

MAJOR URINARY PROTEIN 1 INTERACTS WITH CANNABINOID RECEPTOR TYPE 1 IN FATTY ACID-INDUCED HEPATIC INSULIN RESISTANCE IN A MOUSE HEPATOCYTE MODEL

1CHIN-CHANG CHEN, 2CHING-FAI KWOK, 3YUNG-PEI HSU, 4KUANG-CHUNG SHIH, 5YAN-JIE LIN, 2,3LOW-TONE HO

1Division of Urology, Department of Surgery, Chang Gung Memorial Hospital Linkou, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.; 3Department of Medical Research, Taipei Veterans General Hospital, Taiwan, R.O.C.; 4Department of Medicine-Metabolism, Cheng Hsin General Hospital, Taiwan, R.O.C.; 5Department of Research Planning and Development, National Health Research Institutes, Taiwan, R.O.C.

Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids. Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance. The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA). Firstly we observed that treatment of AM251, a selective CB1R antagonist, obviously reversed the HFFA-induced reduction of MUP1 protein expression both in vivo and in vitro. Additionally, our results revealed that AM251 also reverted HFFA-mediated decrease of the mRNA level of mitochondrial biogenesis-related factors, mtDNA amount, ATP production, mitochondrial respiratory complexes-I and-III, and mitochondrial membrane potential, thus consequently might correlate with a parallel reduction of ROS production. Meanwhile, AM251 attenuated HFFA-induced impairment of insulin signaling phosphorylation and elevation of phosphoenolpyrvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), two key enzymes of gluconeogenesis. Silence of MUP1 gene abolished the inhibitory effect of AM251 on HFFA-mediated elevation of PEPCK and G6Pase expression, whereas the suppression of insulin signaling and mRNA level of mitochondrial biogenesis-related factors were only partially recovered. functions might occur in a MUP1-dependent manner.

OD-03

ASSOCIATION OF ANTIHYPERGLYCEMIC AGENTS AND GUT MICROBIOTA IN TYPE 2 DIABETES MELLITUS

WEI-WEN HUNG, WEI-CHUN HUNG, YI-CHUN TSAI, HE-JIUN JIANG, SHYI-JANG SHIN, PI-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 Type 2 diabetes mellitus is one of the most prevalent disease in the modern era and cause a great threat to our health due to its multiple chronic diabetic complications. Recent studies suggest the impact of gut microbiota on metabolic functions. In addition, drug is one of the most antihyperglycemic agents and gut microbiota in type 2 diabetes mellitus.

MATERIALS AND METHODS Patients with type 2 diabetes mellitus were recruited from the outpatient clinic in an university hospital. The present analysis was done based on 44 participants diagnosed with type 2 diabetes mellitus. We used 16S rRNA gene sequencing to analyze the fecal microbiota. Student’s t-test was used as statistical analysis. Based on the usage of antihyperglycemic agents, we compared the difference of gut microbiota with or without metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitor, and insulin. RESULTS We found an association between usage of antihyperglycemic agents and gut microbiota. Dipeptidyl peptidase-4 inhibitor was associated with higher relative abundance of Clostridium leptum group, while sulfonylureas and insulin were associated with less genus Bacteroides and less genus Bifidobacterium, respectively. There were no statistical differences observed with Faecalibacterium prausnitzii, phylum Firmicutes, or phylum Bacteroidetes with or without metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitor, and insulin.

DISCUSSION Our data proved the association of certain antihyperglycemic agents and gut microbiota in type 2 diabetes mellitus. Further research is needed to clarify the impact of gut microbiota on glycemic status and evaluate the cause-effect relationship between glucose metabolism and gut microbiota. In the future, gut microbiota has the potential to serve as a new therapeutic tool or target in treating type 2 diabetes mellitus.

OD-04

INPATIENT SCREEN OF RETINOPATHY PREDICTING LONG-TERM MORTALITY IN THE DIABETIC PATIENTS WITHOUT ALBUMINURIA- AN OBSERVATIONAL STUDY

1I-TE LEE, 1YA-MEI HSIEH

1Taichung Veterans General Hospital

Aims: There is a high hospitalization rate in the subjects with diabetes mellitus. Since retinopathy and albuminuria are both important manifestations of microvascular diseases in diabetes, we aimed to investigate the effect of retinopathy and albuminuria on long-term mortality in diabetic inpatients in this observational cohort study.

Materials and Methods: Diabetic inpatients with a primary diagnosis of poor glucose control were consecutively enrolled during hospitalization. Clinical information was collected by review of medical records and mortality data were obtained from the national registry in Taiwan.

Results: A total of 779 diabetic inpatients were included in the study. Over a median followup period of 6.7 years (interquartile range, 4.1–9.6 years), there were 412 (52.9%) subjects who died during the study. Patients with albuminuria has highest risk of mortality (HR = 2.600, 95%CI = without albuminuria, those with retinopathy had higher risk of mortality (HR = 1.633, 95% CI = CI = = 0.001) but not retinopathy in diabetic inpatients with albuminuria.

Conclusions: Albuminuria is a strong predictor of long-term mortality in diabetic inpatients after discharge. Retinopathy is an independent predictor of mortality in diabetic inpatients without albuminuria, but not in those with albuminuria. Low estimated glomerular filtration rate is a better predictor of mortality than retinopathy in diabetic inpatients with albuminuria.

OD-05

INCIDENCE OF CHRONIC KIDNEY DISEASE IS RELATED WITH HYPERTRIGLYCERIDEMIA IN TYPE 2 DIABETES PATIENTS - A PROSPECTIVE COHORT STUDY IN A COMMUNITY HOSPITAL

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

1TONG-YUAN TAI

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

Background. Diabetic nephropathy accounts for more than 45% of end-stage renal disease in Taiwan. However, incidence of chronic kidney disease (CKD) for type 2 diabetic (T2D) patients and risk factors contributing to CKD development in T2D has not been well studied. This study aimed at assessing CKD incidence and its attributable factors.

Methods. We recruited 512 T2D patients from a community hospital in Taipei from 2006 to 2014 rate (eGFR) < 60 ml/min/1.73 m2, and advanced CKD as eGFR < 45 ml/min/1.73 m2. The incidence of CKD was calculated by the corresponding events divided by person-years observed for those with 2 in the initial recruitment. Cox proportional hazards models were used to identify risk factors contributing to development of CKD or advanced CKD in the follow-up period.

Results. The baseline characteristics of our study subjects were as follows: age: 61.9 ± 10.2 years, T2D duration: 7.5 ± 7.3 years, mean follow-up: 5.9 ± 2.4 years, BMI: 26.6 ± 11.6, HbA1c: 7.5 ± 2.1%, systolic blood pressure: 134.1 ± 10.1 mmHg, diastolic blood pressure: 74.4 ± 5.9 mmHg, LDL: 111.7 ± 17.0 mg/dL, HDL: 52.6 ± 17.2 mg/dL, and TG: 140.2 ± 69.5 mg/dL. There were 144 subjects who developed CKD and 31 subjects who developed advanced CKD. The incidence rate of CKD and advanced CKD was 55.6 and 10.2 per 1000 person-years, respectively. The multivariable Cox models 1.21-1.62] compared to those < 50 years) and triglyceride > 150 mg/dL (HR = 2.02 [95% CI: 1.37 CKD development was HbA1c in 7-9% (HR = 8.85 [95% CI: 1.96-39.91] compared to those < 7%), HbA1c > 9% (HR = 14.16 [95% CI: 2.19-91.56] compared to those < 7%), and triglyceride > 150 mg/ dL (HR = 4.78 [95% CI: 2.05-11.12] compared to those < 150 mg/dL).

Conclusion. T2D patients were the high risk group to develop CKD. In addition to poor glycemic control, hypertriglyceridemia was found as an Independent risk factor causing CKD development in T2D patients.

OD-06

ASSOCIATION BETWEEN DRB1 AND AUTOIMMUNE THYROID DISEASES IN PATIENTS WITH TYPE 1 DIABETES

1,2,3,4,5YJ LEE,

1,6CY HUANG, 1,6WH TING, 7,8FS LO, 1YT CHIANG, 1CI CHAN, 9CH LIN, 9BW CHENG, 10WL WU, 11CM HUNG, 12HJ LI, 2CL LIN

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

Type 1 diabetes (T1D) is heterogeneous in form and number of autoantibodies. At diagnosis and during follow-up of T1D, additional autoimmune phenomena are frequently observed. In descending and Addison disease. Autoimmune thyroid disease (AITD) including Hashimoto disease and Graves disease are usually preceded by appearance of antithyroid autoantibodies (anti-microsomal, anti-TPO, anti-thyroglobulin, or anti-TSH receptor antibodies). We screened thyroid function on a cohort of T1D patients annually and as indicated by clinical manifestations for AITD. HLA complex is associated with various autoimmune diseases. Therefore we genotyped the DRB1 gene on these patients to evaluate the genetic inclination for developing AITD in T1D patients.

Material and Methods

The subjects were 467 patients with T1D. T1D was diagnosed on the basis of clinical mg/dl) with diabetic symptoms, and at least one of autoantibodies to islet cell antigens, glutamic acid decarboxylasee (GAD) and Islet antigen-2 (IA-2) or c-peptide level < 0.7 mmol/l (2.1 ng/ml) at random or < 1.1 mmol/l (3.3 ng/ml) at the peak by a glucagon test. anti-TOP antibody) with/without anti-thyroglobulin antibody, elevated TSH levels, and decreased or anti-thyroid antibodies detected for 2 times or more and persisting till the last examination with a euthyroid status. Euthyroid T1D patients without any anti-thyroid antibodies were as controls.

Genotyping of DRB1

We genotyped DRB1 using HLAssure SE DRB Locus SBT Kit (Texas BioGene Inc., Taipei, Taiwan) on an ABI 3730XL DNA Analyzers (Applied Biosystems, Foster City, CA) with uTYPE6.0 SBT software (Invitrogen).

Statistical analysis

Allele frequencies were determined by allele counting. Differences, ORs, and 95%CIs for the association of genotype, allele, and carrier between patients with AITD and EuPTA and controls were determined. The Bonferroni correction, Pc = 1 –(1-P)n, was used for multiple comparisons where Pc was the corrected P value, P the uncorrected value, and n the number of comparisons. In this study, n

Results

198 (90 male and 108 female) patients contracted AITD or EuPTA. Their mean (SD) age at diagnosis was 7.2 (3.9) (ranged 0.8-17.8) years. The current age 26.0 (6.8) (9.3-39.7) years. Controls were 269 (128 male and 141 female) patients. Their mean age at diagnosis was 8.5 (4.4) (ranged 1.019.0) years. The current age 22.3 (7.9) (5.9-44.4) years.

Alleles DRB1*03:01, *09:01, and *04:05 were major alleles. Allele DRB1 more frequent in patients with AITD or EuPTA than in controls, 121/396 (30.6%) vs 123/538 (22.9%). The allele conferred a risk to AITD or EuPTA, OR (95%CI) = 1.48 (1.11-1.99), P = 0.008, Pc = 0.056.

Conclusion

T1D patients are prone to AITD or EuPTA. The inclination might be influenced by genetic factors. Allele DRB1*09:01 might confer a risk to AITD or EuPTA. Other genes in the HLA complex should be genotyped to further understand the mechanism.