REN and Insulin resistance: Hyperinsulinemia and insulin resistance can cause alterations in vascular homeostasis, decreases in nitric oxide and increases in reactive oxygen species levels, leading to myocardial dysfunction, and together with aberrant activation or immune dysregulation of the renin–angiotensin–aldosterone system, they promote interstitial fibrosis in cardiac tissue [27], providing an explanation for subclinical LV myocardial systolic dysfunction in T2DM patients.