STUDY OF INSULIN RECEPTOR GENE POLYMORPHISM IN TYPE 2 DIABETES MELLITUS

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is common metabolic disease with hyperglycemia and insulin resistance. Much of the rising prevalence is driven by lifestyle factors, but hereditary determinants, including insulin receptor gene polymorphisms, are widely considered contributory. Objectives: To study insulin receptor gene polymorphism in T2DM patients, to analyze gene polymorphism, and to assess lifestyle-associated and other risk factors. Methods: This was an observational study conducted for a period of 18 months at Narayana Medical College and Hospital, Nellore among the T2DM patients attending the Endocrinology OPD. Inclusion criteria were age 35-55 years, both sexes, known diabetics on oral hypoglycemic agents (not insulin), and able to comply with the protocol. Exclusion criteria included type 1 diabetes, pregnancy, psychiatric illness, thyroid or other endocrine disorders, and steroid use. Anthropometric measures were taken (height, weight, waist-hip ratio, and BMI). Fasting and postprandial samples were collected and insulin, fasting and postprandial glucose, HOMA-IR, and HbA1c were estimated. For analysis of chromosome 19 insulin receptor gene polymorphism, whole blood was collected for DNA extraction. Results: FBS (117.22±13.22 versus 88.46±6.17 mg/dl), PPBS (191.94±28.33 versus 118.18±1.01 mg/dl), insulin (319.67±1424.49 versus 47.08±11.71 μU/ml), HbA1c (9.84±1.59% versus 5.08±0.60%), HOMA-IR (4.6±1.16 versus 1.39±0.26), and BMI (28±2.3 versus 24.3±1.93 kg/m²) were significantly higher in cases compared to controls (p<0.0001). The IRS-1 G972R polymorphism was present in 19% of T2DM patients, and both groups were heterozygotes. Conclusions: IRS-1 G972R polymorphism was not significantly associated with insulin resistance, β-cell function, and lipid parameters in overweight/obese T2DM patients. However, the higher frequency of the mutant allele in patients with BMI < 25 kg/m² suggests a possible risk role even in normal-weight individuals. HOMA-IR is a reliable and low-cost surrogate of insulin resistance assessment.