INS and obesity due to melanocortin 4 receptor deficiency: Although a compensatory increase in blood insulin levels is required to maintain glucose homeostasis in insulin resistance (IR) individuals6, sustained hyperinsulinemia in obesity or the early phase of T2D may further impair insulin signal transduction7,8, resulting in a vicious cycle between hyperinsulinemia and IR, thereby contributing to the development of cardiometabolic disease.