Prevalence of Insulin Receptor Substrate-1 Gene (G972R) Polymorphism, Insulin Resistance, and Determination of β-Cell Function among Overweight and Obese Persons with Type 2 Diabetes Mellitus

BACKGROUND: Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder and its pathogenesis is characterized by a combination of peripheral insulin resistance and impaired insulin secretory capacity of pancreatic β cell. Genetic predisposition interacts with environmental factors including diet, physical activity, and age leading to the development of diabetes. OBJECTIVE: To determine the proportion of overweight and obese persons with type 2 diabetes and to compare the fasting blood sugar, fasting serum insulin, insulin resistance and β-cell function in G972R carrier and non-carrier overweight and obese persons with type 2 diabetes. METHODOLOGY: One hundred overweight and obese patients with T2DM were recruited from persons with diabetes attending the Diabetes Outpatient Department of Yangon General Hospital. History taking and physical examination were done and blood samples were collected. Plasma glucose level was determined by the glucose oxidase method and fasting serum insulin was measured by enzyme linked immunoassay (ELISA) kit method. Polymerase chain reaction and Restriction Fragment Length Polymorphism were done for genetic polymorphism. RESULTS: Among 100 overweight and obese subjects with T2DM, 81 patients were of homozygous (G/G) genotype, 18 patients were of heterozygous (G/A) and only one patient of homozygous (A/A) genotype. There was no statistically significant difference in the proportion of genotypes between overweight and obese subjects with T2DM. There was no significant difference in fasting blood sugar (FBS), fasting serum insulin, HOMA-IR, β-cell function, lipid parameters between IRS-1 (G972R) carriers and non-carriers. There is significant negative correlation between insulin resistance and TG level (r(2)=0.0529, p=0.01). CONCLUSION: It was concluded that IRS-1 G972R polymorphism was not important in insulin resistance, β-cell function and lipid parameters in overweight and obese T2DM. There could be a number of candidate genes in the pathophysiology of diabetes mellitus, genetic sequencing of IRS-1 and other genes in the insulin signaling pathway, and finding out the alteration in their genetic patterns would provide clues for the association of the site-specific polymorphisms of these genes with insulin resistance in T2DM.