Effect of short-term ACE inhibitor treatment on peripheral insulin sensitivity in obese insulin-resistant subjects

Abstract

This study was designed to investigate the effect of short-term ACE inhibitor treatment on insulin sensitivity and to examine possible underlying metabolic and haemodynamic effects in obese insulin-resistant subjects. A randomised, double-blind placebo-controlled trial was performed in 18 obese insulin-resistant men (age, 53 +/- 2 years; BMI, 32.6 +/- 0.8 kg/m(2); homeostasis model assessment of insulin resistance, 5.6 +/- 0.5; systolic blood pressure [SBP], 140.8 +/- 3.2; diastolic blood pressure [DBP], 88.8 +/- 1.6 mmHg), who were free of any medication. The aim was to examine the effects of 2 weeks of ACE inhibitor treatment (ramipril, 5 mg/day) on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and intramuscular triacylglycerol (IMTG) content. Ramipril treatment decreased ACE activity compared with placebo (-22.0 +/- 1.7 vs 0.2 +/- 1.1 U/l, respectively, p < 0.001), resulting in a significantly reduced blood pressure (SBP, -10.8 +/- 2.1 vs -2.7 +/- 2.0 mmHg, respectively, p = 0.01; DBP, -10.1 +/- 1.3 vs -4.2 +/- 2.1 mmHg, respectively, p = 0.03). Ramipril treatment had no effect on whole-body insulin-mediated glucose disposal (before: 17.9 +/- 2.0, after: 19.1 +/- 2.4 micromol kg body weight(-1) min(-1), p = 0.44), insulin-mediated glucose uptake across the forearm (before: 1.82 +/- 0.39, after: 1.92 +/- 0.29 micromol 100 ml forearm tissue(-1) min(-1), p = 0.81) and IMTG content (before: 45.4 +/- 18.8, after: 48.8 +/- 27.5 micromol/mg dry muscle, p = 0.92). Furthermore, the increase in carbohydrate oxidation (p < 0.001) and forearm blood flow (p < 0.01), and the decrease in fat oxidation (p < 0.001) during insulin stimulation were not significantly different between treatments. Short-term ramipril treatment adequately reduced ACE activity and blood pressure, but had no significant effects on insulin sensitivity, forearm blood flow, substrate fluxes across the forearm, whole-body substrate oxidation and IMTG content in obese insulin-resistant subjects.