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.