INS and Hyperinsulinemia: In particular, IR or hyperinsulinemia is responsible for the development of diabetic cardiomyopathy by pathophysiological mechanisms including impaired insulin signaling, cardiac mitochondrial dysfunction, endoplasmic reticulum stress, impaired autophagy, impaired myocardial calcium handling, abnormal coronary microcirculation, inappropriate neurohumoral activation and maladaptive immune responses (27, 28).