INS and obesity due to melanocortin 4 receptor deficiency: Consistent with our findings, prior investigations have shown that other IRS1 gene polymorphisms influence glucose intolerance, the survival of pancreatic β-cells, insulin secretion, serum insulin levels, insulin action, hyperinsulinemia, IR, T2DM, dyslipidemia, obesity, and hepatic fibrosis severity (9,11,12,19,21-24).