[The pathogenesis of type 2 diabetes--new aspects and clinical consequences]

Type 2 diabetes mellitus manifests itself in individuals who lose the ability to produce sufficient quantities of insulin to maintain normoglycemia in the face of insulin resistance. The ability to secrete adequate amounts of insulin depends on beta-cell function and mass. The endocrine pancreas has a remarkable capacity to adapt to conditions of increased insulin demand and only a minority of individuals fail to adapt and become diabetic with time. Secondary events that further reduce the function of beta-cells in type 2 diabetes mellitus are the so-called beta-cell gluco- and lipotoxicity: chronic stimulation of islets by high glucose and free fatty acid levels results in the reduction of insulin secretion. Part of these effects are reversible once these metabolites are normalized and the beta-cell re-exposed to a physiologic environment. The essential role of the beta-cell failure in type 2 diabetes is reminiscent to the pathophysiology of type 1 diabetes. The possible link between both diseases and the therapeutic implications are discussed.