© 1995 American Heart Association, Inc.
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Relations Between Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Insulin Resistance, Glucose Intolerance, Hyperinsulinemia, and Dyslipidemia
From the Falk Cardiovascular Research Center, Divisions of Cardiovascular Medicine (T.K., M.H., G.K., R.E.P., V.J.D.) and Gerontology, Endocrinology, and Metabolism (Y.-D.I.C., G.M.R.), Department of Medicine, Stanford University School of Medicine and Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Palo Alto, Calif.
Correspondence to Gerald M. Reaven, MD, Department of Veterans Affairs Medical Center, GRECC 182B, 3801 Miranda Ave, Palo Alto, CA 94304.
Abstract Recent reports have shown that the frequency of the homozygous deletion genotype (DD) of the angiotensin-converting enzyme (ACE) gene is highly associated with myocardial infarction and cardiomyopathy, particularly in those considered to be at low risk for coronary heart disease (CHD) on the basis of their apoB or LDL cholesterol concentrations. The present study was initiated to extend this inquiry by exploring the possibility that the ACE/DD genotype might be associated with risk factors not evaluated in the initial reports. Consequently, we determined the ACE genotype in 181 subjects, 124 with normal glucose tolerance and 57 with non–insulin-dependent-diabetes mellitus (NIDDM), and compared various aspects of glucose, insulin, and lipoprotein metabolism in the three ACE genotypes. In general, normal subjects with the DD genotype had a lower body mass index, were more insulin sensitive (as assessed by the insulin suppression test), and had lower plasma glucose and insulin responses to oral glucose. In addition, plasma triglyceride and cholesterol concentrations were lowest and HDL cholesterol concentrations highest in the DD group. However, the only statistically significant differences were between the ID and DD groups; the latter had lower values for body mass index, was more insulin sensitive, and had a lower plasma insulin response to oral glucose. Similar but insignificant trends were noted in the patients with NIDDM. The present results show that subjects with the ACE/DD genotype are not at increased risk for CHD because of insulin resistance, relative hyperglycemia and hyperinsulinemia, or a dyslipidemia characterized by a high triglyceride and low HDL cholesterol concentration. Indeed, the risk for CHD from these variables seems to be decreased in subjects with the ACE/DD genotype.
Key Words: insertion/deletion polymorphism • coronary heart disease risk factors • steady-state plasma glucose • insulin response to glucose • lipoproteins
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