Trandolapril does not affect insulin sensitivity in patients with essential hypertension and impaired glucose tolerance/NIDDM

J. R. Petrie*, A. D. Morris, S. Ueda, R. Donnelly, J. M C Connell, H. L. Elliot

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Objective It has frequently been reported that angiotensin-converting enzyme (ACE) inhibitors improve insulin sensitivity in patients with essential hypertension. However, few of the relevant trials have used a crossover design, and many have used surrogate measures of insulin sensitivity. We have therefore assessed the effect of the ACE inhibitor trandolapril on insulin sensitivity in patients with essential hypertension and impaired glucose tolerance/NIDDM. Design and methods In a randomised double-blind, placebo-controlled crossover study, 16 patients (mean ± SD age 58 ± 10.6 years) with mild-to-moderate systolic or diastolic essential hypertension (initial blood pressure 173 ± 14.5/93 ± 8.0 mmHg), obesity (body mass index 30.4 ± 5.4 kg/m2), and impaired glucose intolerance (n = 4) or diet-controlled NIDDM (n = 12) entered a two-week placebo run-in, at the end of which insulin sensitivity (M-value) was measured using the euglycaemic hyperinsulinaemic clamp technique (soluble insulin 1.5 mU/kg/min). Patients were either previously untreated (n = 9) or withdrawn from previously unsatisfactory treatment (n = 7); those who had been treated with thiazide diuretics in the previous 6 months were excluded. After the baseline assessment of insulin sensitivity, patients were randomised to two four-week periods of treatment with trandolapril 2 mg or placebo, with a two-week intercalated washout phase; insulin sensitivity was reassessed at the end of each period. Results The euglycaemic clamps were well tolerated and there were no significant adverse effects. Serum insulin concentrations at steady state during the three conditions (placebo run-in, placebo crossover, trandolapril) were not significantly different (mean ± SD at 120 minutes 148 ± 55.4, 133 ± 40.1, 150 ± 47.3 μU/ml). Mean ± SD systolic blood pressure measurements during euglycaemic hyper-insulinaemia were 152 ± 2.1 (placebo), 149 ± 2.0 (placebo), and 135 ± 1.9 (trandolapril) mmHg (P < 0.001 trandolapril versus placebo, ANOVA). The corresponding values for diastolic blood pressure were 80 ± 0.9 (placebo), 78 ± 1.1 (placebo), and 71 ± 0.8 mmHg (P < 0.01 for trandolapril versus placebo, ANOVA). Treatment with trandolapril was not associated with a change in insulin sensitivity (M-value; mean ± SD): placebo (run-in) 5.2 ± 1.98 mg/kg/min; placebo (crossover) 5.2 ± 1.67 mg/kg/min; trandolapril (crossover) 5.2 ± 1.68 mg/kg/min. 95% confidence intervals (crossover comparison) were −0.52, +0.66 i.e. the study had sufficient power to exclude a 10% (or greater) increase in insulin sensitivity. Conclusion In this double-blind placebo-controlled crossover study in patients with essential hypertension and glucose intolerance, trandolapril had no effect on insulin sensitivity. This finding is consistent with recently reported crossover studies in non-diabetic subjects which have examined the effects of enalapril and captopril on insulin sensitivity. Previous reports of increases in insulin sensitivity during ACE inhibitor treatment may have been attributable to use of surrogate measures and/or suboptimal study designs.
Original languageEnglish
Pages (from-to)1542
JournalJournal of Hypertension
Volume15
Issue number12
Publication statusPublished - 1 Dec 1997

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