ACE gene polymorphism and insulin action in older subjects and healthy centenarians

OBJECTIVES: To evaluate the possible relationship between angiotensin-conve rting enzyme (ACE) insertion-deletion (ID) genotype and insulin resistance in a population of healthy older Italian subjects. DESIGN: Prospective recruitment of a convenience sample. SETTING: Outpatient clinic. PARTICIPANTS: One hundred twenty-five subjects age 62 to 105 in good health and not taking any drug known to interfere with glucose metabolism. MEASUREMENTS: Anthropometric measurements; fasting plasma glucose (FPG), an d fasting plasma insulin (FPI) concentrations; oral glucose tolerance test; homeostatic method assessment (HOMA) to estimate degree of insulin resista nce; and ACE genotype by polymerase chain reaction. RESULTS: In the sample population, the relative frequencies of the ACE geno types deletion-deletion (DD) (0.424), ID (0.400), and insertion-insertion ( II) (0.176) were not significantly different from values predicted by Hardy -Weinberg equilibrium. The genotype distribution was similar in men and wom en. Subjects carrying the II genotype had a higher FPG (P < .001) and FPI ( P < .001) than did subjects with DD or ID genotype. Subjects with II genoty pe also had a significantly higher HOMA index than did subjects with DD or ID genotype (P for trend < .002). In a multivariate stepwise regression ana lysis, the ACE ID polymorphism was significantly and independently associat ed with the HOMA index (P < .001). The same result was confirmed performing multivariate analysis in the younger group and centenarians separately. CONCLUSION: In an older population, the presence of II ACE genotype is asso ciated with a high degree of insulin resistance independent of other anthro pometric variables known to interfere with insulin action; this association is significant in both the younger subjects and the centenarians.