The insertion/deletion polymorphism of the ACE gene is related to insulin sensitivity in overweight women

OBJECTIVE - The ACE insertion/deletion (I/D) polymorphism has been identified as a genetic risk factor for coronary heart disease (CHD). The deletion (D) allele of the ACE gene may be associated with higher insulin sensitivity. Individuals who are homozygous for the DD allele have higher ACE levels and possibly more angiotensin II, which, when infused exogenously, causes an increase in insulin sensitivity. The purpose of this study was to investigate the association of the I/D polymorphism of the ACE gene with insulin sensitivity and CHD risk factors. RESEARCH DESIGN AND METHODS - The study included 66 women (ages 57 ± 1 years) who were overweight or obese (means ± SEM, BMI = 33 ± 1 kg/m²) and sedentary (Vo_2max = 19.6 ± 0.4 ml · kg^-1 · min¹). Total body fat mass and percent fat were determined by dual-energy X-ray absorptiometry, and abdominal fat was by computed tomography. Insulin sensitivity was measured during the last 30 min of 3-h hyperinsulinemic-euglycemic clamps (40 mU · m^-2 · min^-1). Comparisons were made among women with the II (n = 9), ID(n = 36), and DD (n = 21) genotypes. RESULTS - Age, percent body fat, waist-to-hip ratio, visceral and subcutaneous abdominal fat areas, plasma lipid levels, and systolic and diastolic blood pressures did not differ by ACE genotype. Fasting glucose and 2-h glucose levels were similar among genotypes, but fasting plasma insulin levels were lower in DD women than in ID women (P < 0.05). Glucose utilization was higher in women with the DD genotype than in women with the II genotype (53.1 ± 3.9 vs. 36.0 ± 3.8 μmol · kg^-1 FFM · min^-1, P = 0.01) and was higher in ID women than in II women (48.5 ± 2.5 μmol · kg^-1 FFM · min^-1, P = 0.04). CONCLUSIONS - These data suggest that the I/D polymorphism is not associated with risk factors for CHD in overweight sedentary women; however, women who are homozygous for the D allele of the ACE gene are more insulin sensitive, whereas women who are homozygous for the I allele of the ACE gene have greater insulin resistance and potential risk for type 2 diabetes.