ANTIHYPERTENSIVE THERAPY WITH ENALAPRIL IMPROVES GLUCOSE STORAGE AND INSULIN SENSITIVITY IN HYPERTENSIVE PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS

A double-blind, placebo-controlled, 4-week trial was performed to determine the antihypertensive and metabolic effects of enalapril (20 to 40 mg/d) in 16 hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM) aged 55 +/- 2 years and with a body mass index of 29 +/- 1 kg/m(2). Glucose utilization was determined after an overnight fast and during insulin stimulation at 0 and 4 weeks (methods: euglycemic clamp, [3-H-3]glucose infusion, indirect calorimetry). Enalapril decreased systolic (166 +/- 4 v 152 +/- 5 mm Hg, P < .05) and diastolic (102 +/- 2 v 95 +/- 2 mm Hg, P < .05) blood pressure. Peripheral insulin sensitivity, ie, insulin stimulation of glucose utilization, increased approximately 30%, or by 4.3 +/- 1.7 mu mol/kg.min (13.1 +/- 2.0 v 17.4 +/- 3.5 mu mol/kg.min, P < .05, 0 v 4 weeks) during enalapril treatment, but remained unchanged during placebo treatment (15.4 +/- 2.8 v 15.3 +/- 2.7 mu mol/kg.min, respectively). The increase in glucose utilization during enalapril treatment was fully explained by an increase of 4.1 +/- 1.7 mu mol/kg.min in glucose storage (4.1 +/- 1.2 v 8.1 +/- 2.9 mu mol/kg.min, P < .05) while glucose oxidation remained unchanged. High-density lipoprotein (HDL) cholesterol increased by 8% (P < .05) and hemoglobin A(1c) (HbA(1c)) improved slightly (7.7% +/- 0.7% v 7.3% +/- 0.7%, P < .05) in the enalapril group, but not in the placebo group. We conclude that enalapril improves insulin sensitivity by increasing glucose storage in hypertensive patients with NIDDM. These data indicate that the beneficial metabolic effects of angiotensin-converting enzyme (ACE) inhibitors are not restricted to nondiabetic patients, and that insulin resistance is partially reversible in hypertensive NIDDM patients. Copyright (C) 1995 by W.B. Saunders Company