Pathophysiology and pharmacological treatment of insulin resistance

Diabetes mellitus type 2 is a world-wide growing health problem affecting m ore than 150 million people at the beginning of the new millennium. It is b elieved that this number will double in the next 25 yr. The pathophysiologi cal hallmarks of type 2 diabetes mellitus consist of insulin resistance,pan creatic beta -cell dysfunction, and increased endogenous glucose production . To reduce the marked increase of cardiovascular mortality of type 2 diabe tic subjects, optimal treatment aims at normalization of body weight, glyce mia, blood pressure, and lipidemia. This review focuses on the pathophysiol ogy 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, sulfonyl ureas, and insulin. Finally, a rational treatment approach is proposed base d on the dynamic pathophysiological abnormalities of this highly heterogene ous and progressive disease.