Pathogenesis of type II DM.

(1) insulin resistance and

(2) β-cell dysfunction: inadequate insulin secretion in the face of insulin resistance and hyperglycemia

Sedentary lifestyle, obesity and insulin resistance

Among identical twins, the concordance rate is 50% to 90%, showing some genetic component also.

Loss-of-function abnormalities of either the insulin receptor or its down-stream signaling molecules cause insulin resistance

β cell dysfunction

hyperinsulinemic state is a compensation for peripheral resistance and can often maintain normal plasma glucose for years, but after some years the β cells are overwhelmed and can no longer secrete adequate insulin

adverse effects of high circulating FFAs ("lipotoxicity") or chronic hyperglycemia ("glucotoxicity") on β cells

decrease in β-cell mass, islet degeneration, and deposition of islet amyloid.