Long-Term Effects of the Angiotensin Converting Enzyme Inhibitor Captopril on Metabolic Control in Non – Insulin-Dependent Diabetes Mellitus

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Abstract
The role of angiotensin converting enzyme (ACE) inhibitors in improving insulin-mediated glucose uptake has been described. However, their effects on long-term glucose control in diabetes mellitus are less well established. This study examines the effect of 4 months of captopril treatment on blood pressure (BP) and glucose control in 130 subjects with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. Therapy for glycemic control was adjusted during a 3 month period prior to entry into active BP treatment and was not changed during 4 months of captopril administration. Fasting blood glucose and sitting BP were measured before and at 1, 2, 3, and 4 months of captopril monotherapy. Hemoglobin (Hb) A1c, serum electrolytes, creatinine, total cholesterol, and triglycerides were measured before and at 4 months. There were significant reductions in fasting blood glucose from baseline at 1 month (P < .01) and further stepwise decreases in values at 2, 3, and 4 months. Differences in glucose from month to month were highly significant. HbA1c was stable over a 3-month pretrial period, then decreased (P < .001) from baseline at 4 months of active treatment. Mean serum potassium increased from 4.4 to 4.7 (P < .001) at month 4 and there was an inverse correlation (r = −0.2, P < .025) between changes in potassium and HbA1c. Total serum cholesterol fell (P < .01) at month 4 of treatment. Serum creatinine and blood urea were unchanged, but of 18 patients with mild proteinuria pretrial, 12 of 18 were negative for protein at 4 months. Mean systolic and diastolic BP fell (P < .001) at 1, 2, 3, and 4 months of captopril. Seventy of 130 NIDDM attained goal BP on 25 mg captopril daily, and overall 83% responded to captopril at 4 months. There were no discontinuations or withdrawals from the study. As diabetic therapy was held constant, captopril appeared to have effects on long-term glycemic control in the NIDDM subjects. Our results suggest that increased potassium levels may contribute in part to improved glucose control with ACE inhibitor administration. As previously reported, ACE inhibitor monotherapy is highly effective for BP control in hypertensive NIDDM subjects and is well tolerated. Am J Hypertens 1993;6:337–343

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