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The most important thing to remember is that patients with insulin resistance syndrome are at increased risk for developing type 2 diabetes mellitus and accelerated atherosclerosis. Coronary artery disease (CAD) is the leading cause of death in patients with the insulin resistance syndrome, accounting for approximately 60% of mortality, and cerebrovascular and peripheral vascular disease also contribute significantly to mortality and morbidity. Therefore, the major goals of therapy are to prevent or treat diabetes and its complications and to reduce cardiovascular risk. Since obesity and physical inactivity are major contributing factors to insulin resistance, changes in lifestyle that emphasize weight reduction and regular exercise may be expected to reduce many features of the syndrome and should be a fundamental part of the treatment program.

Previous studies in China (50) and in Finland (51) have demonstrated that the incidence of progression from IGT to overt diabetes is significantly reduced by relatively modest decreases in body weight and increased physical activity and the recent announcement of the results of the NIH-sponsored Diabetes Prevention Program (DPP) (52) strongly supports the use of lifestyle modification to decrease the risk of developing diabetes in the U.S. population at risk by virtue of having IGT. In this study, a sustained weight loss of 10 to 15 pounds and an increase in exercise equivalent to brisk walking for 30 min 6 to 7 days a week reduced the risk of developing type 2 diabetes by 58% for at least 3 years. It is also encouraging that treatment with metformin also decreased the progression from IGT to type 2 diabetes mellitus by 31% in the DPP, although it was not as effective as weight reduction and increased physical activity. Several other studies are currently being conducted to determine if other medications, such as thiazoliden-diones, insulin secretogues, or angiotensin receptor blockers may also be effective in treating insulin resistance syndrome, reducing cardiovascular risk, and preventing progression to overt diabetes.

It is also very important to keep in mind that, in addition to preventing and/or treating type 2 diabetes mellitus, all other aspects of insulin resistance -o syndrome should be treated aggressively to reduce the risk of cardiovascular disease. New targets for blood pressure and lipid (53) management have been established recently and it is recommended that, unless contraindicated, all patients with type 2 diabetes mellitus should be treated with aspirin to reduce the risk of myocardial infarction. Many studies have demonstrated that controlling M

blood pressure markedly decreases the risk of both micro- and macrovascular complications of type 2 diabetes mellitus (54) and a target blood pressure of a

130/80 mmHg is now accepted for most patients. It is also clear that patients with diabetes respond well to lipid-lowering therapy with HMG CoA reductase inhibitors (statins) and fibric acid derivatives, often showing better reductions in cardiovascular events and death rates than patients without diabetes. Detailed approaches to treatment of diabetes and reduction in cardiovascular risk are presented in subsequent chapters and will not be discussed here.

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