COMPARISON OF THE EFFECTS OF CAPTOPRIL AND NICARDIPINE ON INSULIN SENSITIVITY AND THROMBOTIC PROFILE IN PATIENTS WITH HYPERTENSION AND ANDROID OBESITY

Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The,euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily (n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 mu IU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 mu IU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 mu IU/mL (-14%) for captopril v 6.7 +/- 79.4 mu IU/mL (6.6%) for nicardipine (P = .070). Baseline fasting insulin levels influenced the treatment effect (P = .037), with a greater effect on insulin AUC outcomes for patients with high baseline values in the captopril group (-29%) than in the nicardipine group (P = .011). No difference was observed between the two groups in blood pressure variation, PAI-1, IGF-I, F VII, fibrinogen, lipid profile, or glucose AUC. In conclusion, although glucose AUC did not change, the decrease in insulin AUC after captopril treatment strongly suggests that insulin sensitivity is improved by captopril independently of its effect on blood pressure reduction.