Original Articles
Epidemiology of insulin resistance and its relation to coronary artery disease

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Abstract

The relation of insulin resistance to cardiovascular risk, particularly for coronary artery disease (CAD), has been well established in many prospective studies. The clustering of insulin resistance and/or hyperinsulinemia, hypertriglyceridemia, hypertension, and low HDL is now considered a feature of the insulin resistance syndrome. However, the association is complex and the pathways by which elevated insulin adversely affects both CAD risk factors and the risk of developing CAD have yet to be elucidated. Postprandial lipemia may be a mechanistic link between insulin resistance and CAD. Hyperinsulinemia appears to be a weak, but positive, independent cardiovascular risk factor. The strongest relations are seen in middle-aged rather than older persons and at higher elevations of plasma insulin levels. Individuals with type 2 diabetes have a risk of myocardial infarction (MI) equivalent to that of nondiabetic persons who have had a previous MI. Given the relatively weak association between duration of diabetes and severity of hyperglycemia and cardiovascular disease, common antecedents may underlie both CAD and type 2 diabetes.

Section snippets

Selected studies of insulin resistance and coronary artery disease risk factors

Hundreds of studies have assessed the effect of the insulin resistance syndrome on cardiovascular risk, particularly CAD. Some prospective studies examining the relation of insulin to cardiovascular disease are listed in Table I. Many of the key epidemiologic studies are cited or discussed below.

Zavaroni et al1 performed a cross-sectional study of the relation of hyperinsulinemia to CAD risk in pasta factory workers in Italy. Subjects were nondiabetic, nonobese persons who had impaired glucose

Insulin and the risk of cardiovascular disease

A recent meta-analysis of prospective population-based or nested case–control studies examined the relation between insulin and cardiovascular disease.8 Twelve of 17 studies provided sufficient information to be analyzed. The meta-analysis found that insulin was a weak but positive indicator of cardiovascular disease risk. Upon assessment of each study individually, one sees that the relation is stronger in middle-aged than in older persons. Studies in the elderly have generally yielded

Insulin resistance and diabetes

Recent data reveal that patients with type 2 diabetes mellitus have a risk of first myocardial infarction equal to that of nondiabetic individuals who have had a previous infarction.19 Diabetic patients who have had a previous infarction are at even higher risk. This equivalency of risk in nondiabetics with a history of infarction compared with diabetic patients without that history extends earlier observations of the increased risk of CAD in diabetes: Compared with the nondiabetic population,

Conclusion

Many studies have investigated the relation between cardiovascular disease and insulin resistance, hyperinsulinemia, and type 2 diabetes. It has been demonstrated that elevated insulin levels have a negative impact on both CAD risk factors and the risk of developing CAD itself. Still, it is clear that this association is complex, and the mechanistic pathways by which insulin effects these changes are still being studied. Ongoing trials need to elucidate these mechanisms, as well as determine

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