INS and Hyperglycemia: Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1) hypoglycemia; (2) body weight gain; (3) peripheral hyperinsulinemia and (4) postprandial hyperglycemia, which are all associated with inappropriate insulin supplementation, again underpinning the important role of endogenous and physiological insulin secretion in the management of T2DM.