INS and obesity due to melanocortin 4 receptor deficiency: It has been suggested that insulin, particularly in high doses, may be atherogenic.40 All of the long-term insulin trials also have shown that insulin therapy is associated with weight gain and, of course, weight gain and obesity are independent risk factors for CVD.41 Some studies have also shown that insulin stimulates de novo lipogenesis and, in some cases, may aggravate underlying dyslipidemia.42 Thus, insulin may not be the ideal drug if one is concerned about reducing cardiovascular risk in T2D associated with overweight or obesity.