Persistent hyperglycemia induces hyperinsulinemia and insulin resistance, leading to abnormal glucose metabolism, myocardial cell apoptosis, and myocardial fibrosis, and the mechanisms involved include endoplasmic reticulum stress, oxidative stress, inflammation, calcium impaired processing, autophagy, mitochondrial autophagy, and renin–angiotensin–aldosterone system (17). Here, REN is linked to Insulin resistance.