INS and Hyperglycemia: Additionally, the hyperglycemia seen in T2DM, depletes cellular NAD+ pools due to the reduction in mitochondrial NAD+ recycling due to mitochondrial damage caused by ROS, resulting in a compensatory upregulation of NAD+ synthesis via the kynurenine pathway and elevated glycolysis, fatty acid oxidation, the TCA cycle in insulin-independent tissues and the polyol pathway.