Pathogenesis and glycemic management of type 2 diabetes mellitus: a physiological approach

Type 2 diabetes (T2DM) is an incompletely understood chronic, progressive multifactorial disease with insulin resistance and decreased β-cell function playing dominant roles in its genesis.  The worldwide incidence of the disease is rapidly increasing to pandemic proportions.  The increase in incidence of T2DM is attributable to changes in lifestyle, diet and obesity, but other causes remain to be defined.  The disease is a major cause of early mortality due to atherosclerosis and cardiovascular disease (CVD), and is the leading cause of blindness, leg amputations, and chronic renal disease.  Hyperglycemia inT2DM becomes manifest once insulin secretion is no longer adequate for the metabolic demands of the individual. The approach to glycemic management of the disease is increasingly based on understanding the underlying pathophysiology.  Efforts to maintain and preserve β-cell function during the earlier phases of the disease may have important implications in prevention of subsequent complications of T2DM.  Finally, the approach to glycemic management of the disease should be individualized by considering the psycho-socio-economic condition of each patient, and glycemic targets should reflect presence of comorbid conditions, age of the patient, the stage of their disease in terms of duration, presence of macro- and micro-vascular complications, and propensity for severe hypoglycemia.