Type2 diabetes mellitus (T2DM) is a highly inheritable disease. Transcription factor 7-like 2 (TCF7L2) gene regulates the expression of glucagon-like peptide1 (GLP-1) in L cells of small intestine. GLP1 plays a critical role in blood glucose homeostasis by stimulating postprandial insulin secretion and increasing insulin sensitivity. Hence, it is postulated that TCF7L2 gene variants may affect the susceptibility to Type 2 diabetes by altering GLP-1 levels. This case control study was conducted with 90 newly diagnosed patients with Type2 diabetes mellitus as cases and 90 age and sex matched healthy volunteers as controls. TCF7L2 rs7903146 genotyping was done and we also estimated Fasting and postprandial GLP-1 level, Fasting and Postprandial insulin level and calculated HOMA-IR in both cases and controls. Results showed that T+ genotype, lower fasting GLP-1 level and lower postprandial GLP-1 levels were more observed among cases as compared to controls. Low mean GLP 1 activity, high Mean HOMA-IR, low postprandial insulin, low percentage rise in insulin were observed among T+ genotype than among T-genotypic individuals. Hence, the study concludes that T+ genotype causes a decrease in GLP-1 levels, which in turn by decreasing postprandial insulin levels and by increasing insulin resistance increases the risk of Type2 diabetes.
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