INS and atherosclerosis: Furthermore, ROS-induced inactivation of anti-atherosclerosis enzymes, AGE overproduction, upregulation of stress-sensitive signaling cascades, and impairment of insulin signaling pathways lead to the development of macrovascular (cardiomyopathy) and microvascular (neuropathy, nephropathy, retinopathy, atherosclerosis) diabetic complications 59, 60.