Transcription factor 7-like 2 single nucleotide polymorphisms are associated with lipid profile in the Balinese.

Transcription factor 7-like 2 (TCF7L2) protein plays an important role in glucose and lipid metabolisms. Single nucleotide polymorphisms (SNPs) in the TCF7L2 gene contribute to increased fasting plasma glucose (FPG) and body mass index (BMI), and altered lipid concentrations in various population. We investigated whether the TCF7L2 SNPs were associated with obesity, high FPG and altered lipid profile in the Balinese. A total of 608 Balinese from rural and urban Bali, Indonesia, were recruited. Triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and FPG were measured, and BMI was calculated. Ratios of TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were determined. Genotyping of SNPs rs7903146, rs10885406, and rs12255372 were done in all samples. Genetic association analyses under a dominant model showed that the rs7903146 (OR 5.50, 95% CI 2.34-12.91, p = 8.5 × 10-5), rs12255372 (OR 4.15, 95% CI 1.66-10.33, p = 0.003) and rs10885406 (OR 2.43, 95% CI 1.39-4.25, p = 0.003) were significantly associated with high TC/HDL-C ratio. The rs10885406 also presented a significant association with high TG (OR 2.21, 95% CI 1.29-3.81, p = 0.004) and low HDL-C (OR 3.02, 95% CI 1.58-5.80, p = 0.001) concentrations, as well as high TG/HDL-C ratio (OR 1.95, 95% CI 1.16-3.27, p = 0.013). None of the SNPs exhibited significant association with obesity or high FPG. SNPs in the TCF7L2 gene are associated with altered lipid profile in the Balinese.

Indonesia Cohort of IO HAT Study to Evaluate Diabetes Management, Control, and Complications in Retrospective and Prospective Periods Among Insulin-Treated Patients with Type 1 and Type 2 Diabetes.

BACKGROUND: hypoglycemia is a major adverse event of insulin therapy for diabetes mellitus patients. The study was conducted to evaluate the incidence of hypoglycemia among insulin treated patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in the Indonesian cohort. METHODS: this Indonesian cohort study consisted of retrospective and prospective evaluation of hypoglycemic episodes, using International Operations Hypoglycemia Assessment Tool (IO HAT) in 374 patients with diabetes (T1DM; n=17 or T2DM; n=357). The patients of ≥18 years of age and treated with insulin for >12 months were selected for this study (ClinicalTrials.gov number: NCT02306681). RESULTS: a total of 374 patients were enrolled in this study and completed SAQ1. All patients with T1DM (17 [100%]), and 347 (97.2%) patients with T2DM completed SAQ2. Almost all the patients in the 4-week prospective period reported at least one hypoglycemic event (T1DM 100%, T2DM 99.4%) and the incidence rate of any hypoglycemia was 67.5 events per patient-year (PPY) and 25.7 events PPY for T1DM and T2DM patients, respectively. Among patients with T1DM and T2DM, 5.9% and 36.4%, respectively, did not know what hypoglycemia was at baseline, also high proportion of patients had impaired hypoglycemic awareness in the study (82.4% and 62.7%, respectively). CONCLUSION: overall, high proportion of patients reported hypoglycemic events in the prospective period indicating under reporting during the retrospective period due to recall bias. Therefore, there is a need for patient education program to improve the awareness of hypoglycemia in diabetes patient in Indonesia.

Uncoupling protein 2 gene polymorphisms are associated with obesity.

BACKGROUND: Uncoupling protein 2 (UCP2) gene polymorphisms have been reported as genetic risk factors for obesity and type 2 diabetes mellitus (T2DM). We examined the association of commonly observed UCP2 G(-866)A (rs659366) and Ala55Val (C > T) (rs660339) single nucleotide polymorphisms (SNPs) with obesity, high fasting plasma glucose, and serum lipids in a Balinese population. METHODS: A total of 603 participants (278 urban and 325 rural subjects) were recruited from Bali Island, Indonesia. Fasting plasma glucose (FPG), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were measured. Obesity was determined based on WHO classifications for adult Asians. Participants were genotyped for G(-866)A and Ala55Val polymorphisms of the UCP2 gene. RESULTS: Obesity prevalence was higher in urban subjects (51%) as compared to rural subjects (23%). The genotype, minor allele (MAF), and heterozygosity frequencies were similar between urban and rural subjects for both SNPs. All genotype frequencies were in Hardy-Weinberg equilibrium. A combined analysis of genotypes and environment revealed that the urban subjects carrying the A/A genotype of the G(-866)A SNP have higher BMI than the rural subjects with the same genotype. Since the two SNPs showed strong linkage disequilibrium (D' = 0.946, r2 = 0.657), a haplotype analysis was performed. We found that the AT haplotype was associated with high BMI only when the urban environment was taken into account. CONCLUSIONS: We have demonstrated the importance of environmental settings in studying the influence of the common UCP2 gene polymorphisms in the development of obesity in a Balinese population.

Association of beta3-adrenergic receptor (ADRB3) Trp64Arg gene polymorphism with obesity and metabolic syndrome in the Balinese: a pilot study.

BACKGROUND: Prevalence of obesity is increasing all over the world. ADRB3 Trp64Arg gene polymorphism was proposed to be associated with obesity, although inconsistent findings and differences of the Arg64 allele frequency among various ethnics were reported. Westernization was reported to increase the prevalence of obesity in developing world. In this study we determined the prevalence of obesity and metabolic syndrome among urban and rural Balinese, and studied the association of ADRB3 Trp64Arg polymorphism with obesity and MetS. FINDINGS: A total of 528 Balinese (urban 282, rural 246) were recruited. Body mass index (BMI) and waist circumference (WC) were determined; high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic and diastolic blood pressure (SBP and DBP), and fasting plasma glucose (FPG) were measured using standard procedures. BMI and WC classifications were based on WHO classifications for Asian. Metabolic syndrome (MetS) was defined as described in the Joint Interim Statement. Chi-square test was employed to test the association between the ADRB3 Trp64Arg genotype and disease traits.Urban have higher BMI (p = 2.8 × 10-13), WC ( p < 2.2 × 10-16), TG (p = 0.0028), DBP (p = 1.8 × 10-5), and lower HDL-C (p = 0.0376) when compared to rural. Abdominal obesity and MetS prevalence were significantly higher in urban as compared to rural (both p < 0.001). The Arg64 allele frequency was similar between urban (0.06) and rural (0.05). The Arg64 rural female carriers have higher BMI and WC as compared to their Trp64 counterparts (p = 0.041 for BMI and p = 0.012 for WC), and consequently higher abdominal obesity prevalence (p = 0.007). Comparison between male and female, as well as urban and rural, showed different prevalence of MetS co-morbidities. Abdominal obesity and hypertriglyceridaemia were consistently appeared in all groups, suggesting to play a role as determinant of MetS in both urban and rural. CONCLUSIONS: Prevalence of obesity and MetS in urban were two times higher when compared to rural. Abdominal obesity and hypertriglyceridaemia appears to be the key determinant of MetS in both urban and rural Balinese. Our results indicated an association of the ADRB3 Trp64Arg gene polymorphism with obesity in the rural female.