Effects of angiotensin-converting enzyme inhibitors, Ca²⁺ channel antagonists, and α-adrenergic blockers on glucose and lipid metabolism in NIDDM patients with hypertension

We compared the effects of captopril, nifedipine, and doxazosin on glucose and lipid metabolism in 30 hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients (age = 50 ± 3 years; body mass index = 30 ± 1 kg/m²). Of these patients, 9 were treated with captopril, 11 with nifedipine, and 10 with doxazosin for 12 weeks. Blood pressure, fasting plasma glucose (FPG) concentration, HbA(1c), oral glucose tolerance test (OGTT), euglycemic insulin clamp, and plasma lipids were measured before and after a 3-month period. Mean arterial blood pressure (114 ± 2 mmHg) was similar in all groups before initiating antihypertensive therapy and declined to 102 ± 2 (captopril), 103 ± 1 (nifedipine), and 103 ± 2 (doxazosin) mmHg (P < 0.001). Baseline FPG (148 ± 11 mg/dl) and HbA(1c) (6.3 ± 1%) were similar in all groups and did not change significantly with treatment. Plasma glucose, insulin, and free fatty acid (FFA) concentrations during the OGTT were similar in all groups before antihypertensive treatment and did not change with captopril and nifedipine; after doxazosin, plasma glucose and FFA concentrations during the OGTT decreased (both P < 0.05) without change in plasma insulin response. Insulin-mediated glucose uptake (144 ± 11 mg · m^{- 2} · min^-1), glucose oxidation (76 ± 4 mg · m^-2 · min^-1), and nonoxidative glucose disposal (71 ± 6 mg · m^-2 · min^-1) were similar in all groups before the start of antihypertensive treatment and did not change in captopril and nifedipine groups. After doxazosin, total glucose uptake (180 ± 25 mg · m^-2 · min^-1) and glucose oxidation (108 ± 8 mg · m^-2 · min^-1) increased significantly (P < 0.01); nonoxidative glucose disposal did not change. Plasma lipid levels improved after doxazosin therapy: high-density lipoprotein rose from 40 ± 3 to 44 ± 3 mg/dl (P < 0.01) and triglycerides fell from 210 ± 18 to 178 ± 17 (P < 0.05). No changes in plasma lipid levels were observed with captopril or nifedipine. We concluded that in hypertensive NIDDM subjects, 1) captopril, nifedipine, and doxazosin are equally effective in lowering blood pressure; 2) captopril and nifedipine have no adverse effects on glucose tolerance, insulin sensitivity, or plasma lipid profile; and 3) doxazosin significantly improves insulin sensitivity during the euglycemic insulin clamp, enhances OGTT while decreasing the plasma insulin response, and improves the plasma lipid profile.