Lack of impact of angiotensin-converting enzyme gene polymorphism and salt intake on insulin resistance and limb blood flow.

Abstract

We postulated the mechanism for the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and insulin sensitivity might relate to changes in blood flow regulation. We studied the association of this polymorphism with insulin action, and insulin-mediated changes in limb blood flow (LBF), under conditions of high and low salt intake. We also studied effects of genotype and salt loading on renin-angiotensin-aldosterone system (RAAS) activity. Twenty people with (10 I/I; 10 D/D) and 23 without (10 I/I; 13 D/D), type 2 diabetes were studied during 6 days of 40 mmol/day and 220 mmol/day sodium diet in a randomized, double-blind cross-over fashion. On the sixth day of each condition, we measured 24-h blood pressure, plasma volume, LBF and insulin sensitivity during hyperinsulinaemic clamp at low (40 mU/m(2) /min) and high (600 mU/m(2) /min) dose insulin infusion. Salt intake variation produced greater effects on the renin-angiotensin-aldosterone system than ACE genotype. Diabetes status and insulin infusion were associated with differences in the metabolic clearance rate of glucose, (P < 0·001 for each) and insulin infusion increased LBF (P < 0·001). However, ACE genotype and salt intake had no consistent impacts on either variable in nondiabetic and diabetic subgroups, or in the combined group. Reported differences in insulin sensitivity between ACE genotypes were not found in this study under strict regulation of sodium intake. Insulin sensitivity was also unaffected in either group by sodium loading. ACE genotype and salt status do not impact on insulin sensitivity through changes in limb blood flow during hyperinsulinaemia.