INS and endothelial dysfunction: The known pathogenic mechanisms of DC are metabolic disturbance (depletion of glucose transporter 4, increased free fatty acids, carnitine deficiency, and changes in calcium homeostasis), myocardial fibrosis (associated with increase in Ang II, IGF-I, and inflammatory cytokines), small vessel disease (microangiopathy, impaired coronary flow reserve, and endothelial dysfunction), cardiac autonomic neuropathy (denervation and alterations in myocardial catecholamine levels), and insulin resistance (hyperinsulinemia and reduced insulin sensitivity) [72].