Although insulin resistance and hyperinsulinemia can be attributed to these complications, they may occur with or without insulin resistance because several other mechanisms including advanced glycation end products, autonomic nervous instability, imbalance between the renin-angiotensin system and nitric oxide, hemodynamic changes and endothelial dysfunction with subsequent ADMA accumulation (an inhibitor for nitric oxide synthesis) and adiponectin deficiency also contribute in the process [44-46]. Here, REN is linked to Insulin resistance.