RELATIONS BETWEEN DELETION POLYMORPHISM OF THE ANGIOTENSIN-CONVERTINGENZYME GENE AND INSULIN-RESISTANCE, GLUCOSE-INTOLERANCE, HYPERINSULINEMIA, AND DYSLIPIDEMIA

Recent reports have shown that the frequency of the homozygous deletio n genotype (DD) of the angiotensin-converting enzyme (ACE) gene is hig hly associated with myocardial infarction and cardiomyopathy, particul arly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. Th e present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk fac tors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance a nd 57 with noninsulin-dependent-diabetes mellitus (NIDDM), and compare d various aspects of glucose, insulin, and lipoprotein metabolism in t he three ACE genotypes. In general, normal subjects with the DD genoty pe had a lower body mass index, were more insulin sensitive (as assess ed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride an d cholesterol concentrations were lowest and HDL cholesterol concentra tions highest in the DD group. However, the only statistically signifi cant differences were between the ID and DD groups; the latter had low er values for body mass index, was more insulin sensitive, and had a l ower plasma insulin response to oral glucose. Similar but insignifican t trends were noted in the patients with NIDDM. The present results sh ow that subjects with the ACE/DD genotype are not at increased risk fo r CHD because of insulin resistance, relative hyperglycemia and hyperi nsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration. Indeed, the risk for CHD from thes e variables seems to be decreased in subjects with the ACE/DD genotype .