Lower HOMA-β values are detected among individuals with variant of E23K polymorphism of potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene

Background: Type 2 Diabetes Mellitus (T2DM) is a multifactorial disease involving both genetic and also environmental factors. Potassium inwardly-rectifying channel, subfamily J, member 11 (KCNJ11) gene, an ATP-sensitive potassium channel-coding gene, contributes to insulin secretion.Objectives: This research aimed to investigate E23K polymorphism in KCNJ11 gene and insulin secretion in individuals with family history of T2DM (cases) and without family history of T2DM (controls).Method: This research was a case-control study involving 34 cases and 34 controls. E23K polymorphism of KCNJ11 was detected with PCR-RFLP. All of the obtained data were statistically analyzed with T-test, Mann–Whitney U-test, Chi-Square and One-Way ANOVA.Result: Frequency of AA genotype in individuals with family history of T2DM (41%) was higher than in individuals without family history of T2DM (6%) (p=0.001). Frequency of A allele in individuals with family history of T2DM (68%) was higher than in individuals without family history of T2DM(38%) (p=0.001). The risk of A allele in individuals with family history of T2DMwas 3 times higher than in individuals without family history of T2DM (p=0.001, OR 3.38, CI 95% 1.67–6.84). Homeostasis Model Assessment b (HOMA-β) values of AA genotype (85.44%±39.55) were lower than that of GA (212.20%±79.30) and GG (254.00%±61.98) genotypes (p=0.000).Conclusion: The risk of having A allele in individuals with family history of T2DM is higher than that in individuals without family history of T2DM. HOMA-β values of AA genotype are lower than that of GA and GG genotypes

STEADY-STATE PHARMACOKINETICS OF METFORMIN IN OBESE PATIENTS WITH TYPE 2 DIABETES MELLITUS: A PRELIMINARY STUDY

Objective: This study aimed to determine the metformin plasma steady-state concentration (PSSC) either trough and peak level in Type 2 diabetesmellitus patients with obesity and the impact of SLC22A1 gene organic cation transporter 1 (OCT) rs628031 A>G on PSSC of metformin.Methods: Validated reversed-phase high-performance liquid chromatography method with ultraviolet detector was used to determine the metforminPSSC, as well as genotype variation was performed using the restriction fragment length polymorphisms-polymerase chain reaction method.Results: A total of 13 patients were recruited from five Primary Health Centers in Yogyakarta Province of Indonesia. The results showed that themeans of their trough and peak PSSC were 0.285±0.192 and 1.175±0.814 μg/ml, respectively. Only 10 patients (77%) had peak PSSC within theplasma therapeutic level (PTL) of metformin, and 14-fold variability was observed for the peak PSSC. None of the patients achieved the PTL ofmetformin with regard to their trough PSSC. The PSSC of metformin was independent of the OCT1 genotype in rs628031 (A>G) 408M/V SLC22A1.Conclusion: This study found a huge variability in the trough concentration of metformin (>100-fold) and 14-fold for the peak PSSC, and no impactof a variant of rs628013 SLC22A1 OCT1 on metformin PSSC was revealed.Keywords: Metformin, Steady-state pharmacokinetics, Obesity, Type 2 diabetes mellitus

Level of Adipokines and Insulin Resistance in Obese Javanese Population

Introduction: Obesity is a condition involving low-level chronic inflammation as indicated by increased levels of C-reactive protein (CRP), TNF, interleukin and other inflammatory markers in the blood. Some endocrine mediators, such as paracrine and autocrine derived from adipose tissue play an important role in regulating the function of adipocytes, especially related to insulin sensitivity. Significant complications of obesity, including insulin resistance as a risk factor of Type 2 diabetes are associated with myocardial infarction, stroke, and peripheral vascular disease. Aim:  The purpose of this study is to determine the level of C-reactive protein (CRP), TNF-alpha, interleukin, resistin and insulin resistance in the obese group compared to controls  sampled from a Javanese population. Method: This study is a preliminary study of 120 people, consisting of 60 obese and 60 controls. Lipid profiles, levels of C-reactive protein (CRP), TNF-alpha, interleukin, resistin were examined with Elisa methods and insulin resistance was calculated by HOMA IR index. Results: This study found levels of glucose, insulin, CRP, and HOMA-IR were higher and significantly different in obese group than control (P 0.05) Conclusion: The study showed that there were increased levels of adipokines and insulin resistance in obese group compared with the control in the sample of Javanese population. Keywords:  Obese, insulin resistance, CRP, TNF-Alpha, Interleukin, Resisti