(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.