Type 2 diabetes: principles of pathogenesis and therapy.
Type 2 diabetes mellitus has become an epidemic, and virtually no physician is without patients who have the disease. Whereas insulin insensitivity is an early phenomenon partly related to obesity, pancreas beta-cell function declines gradually over time already before the onset of clinical hyperglycaemia. Several mechanisms have been proposed, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction for insulin resistance, and glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, but only a handful of genes have been identified so far: genes for calpain 10, potassium inward-rectifier 6.2, peroxisome proliferator-activated receptor gamma, insulin receptor substrate-1, and others. Management includes not only diet and exercise, but also combinations of anti-hyperglycaemic drug treatment with lipid-lowering, antihypertensive, and anti platelet therapy.
Stumvoll
Michael
M
Third Medical Department, University of Leipzig, Leipzig, Germany.
Goldstein
Barry J
BJ
van Haeften
Timon W
TW
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology