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Endocrine Reviews 21 (6): 585-618
Copyright © 2000 by The Endocrine Society

Pathophysiology and Pharmacological Treatment of Insulin Resistance1

Stephan Matthaei, Michael Stumvoll, Monika Kellerer and Hans-Ulrich Häring

Department of Internal Medicine IV (Endocrinology, Metabolism, Angiology, Pathobiochemistry and Clinical Chemistry), University of Tübingen, D-72076 Tübingen, Germany

Diabetes mellitus type 2 is a world-wide growing health problem affecting more than 150 million people at the beginning of the new millennium. It is believed that this number will double in the next 25 yr. The pathophysiological hallmarks of type 2 diabetes mellitus consist of insulin resistance, pancreatic ß-cell dysfunction, and increased endogenous glucose production. To reduce the marked increase of cardiovascular mortality of type 2 diabetic subjects, optimal treatment aims at normalization of body weight, glycemia, blood pressure, and lipidemia. This review focuses on the pathophysiology and molecular pathogenesis of insulin resistance and on the capability of antihyperglycemic pharmacological agents to treat insulin resistance, i.e., {alpha}-glucosidase inhibitors, biguanides, thiazolidinediones, sulfonylureas, and insulin. Finally, a rational treatment approach is proposed based on the dynamic pathophysiological abnormalities of this highly heterogeneous and progressive disease.




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