Insulin Resistance Atherosclerosis Study (IRAS)

BACKGROUND:

An association between overt diabetes and cardiovascular disease has been observed in multiple studies among populations across the world. The reason for this excess are only partly understood. In recent years, several studies have suggested that elevations in levels of insulin or insulin resistance are important risk factors for cardiovascular disease, not only in diabetic patients but also among those with normal or subclinical abnormalities in glucose tolerance.

Many reasons exist to investigate the role of insulin and insulin resistance in the development of cardiovascular disease. Insulin has effects on multiple metabolic pathways and has been shown to promote development of atherosclerotic lesions in animals. In addition, levels of insulin and insulin resistance are correlated with multiple abnormalities in other cardiovascular disease risk factors such as elevations in blood pressure, dyslipidemia, and alterations in coagulation factors.

It is particularly important to determine whether these associations are strongest with levels of insulin or of insulin resistance since this information will be valuable both for studies aimed at localizing the site of the defect and in developing new therapeutic interventions. Despite evidence from population studies, it is difficult to explain the excess of cardiovascular disease in diabetics solely as a consequence of elevations in insulin levels. Recent, small studies suggest that the risk previously associated with hyperinsulinemia may be correlated more strongly with increases in insulin resistance. Insulin resistance continues to increase as glucose levels increase, even in the presence of decreasing insulin secretion. Such observations may help to explain the higher risk of cardiovascular disease in overt diabetics. More detailed assessments of the role of insulin resistance in altering cardiovascular disease risk factors are also needed. Prior to the IRAS study, direct measures of insulin resistance had not been performed in population studies. The continuation of IRAS for an additional five years will provide the first longitudinal data on insulin resistance as a cardiovascular disease risk factor.

The IRAS was proposed by staff and approved by the Clinical Applications and Prevention Advisory Committee in May, 1990. The Request for Applications was released in November, 1990. Awards were first made in September, 1991. The study was extended for an additional five years in September, 1995 and in August, 1999.