Improved insulin action and glycemic control after long-term angiotensin-converting enzyme inhibition in subjects with arterial hypertension and type II diabetes

Diabetes Care. 1993 Oct;16(10):1347-55. doi: 10.2337/diacare.16.10.1347.

Abstract

Objective: To determine the long-term effects of the angiotensin-converting enzyme inhibitor captopril on insulin sensitivity in subjects with type II diabetes and arterial hypertension. The chronic effects of angiotensin-converting enzyme inhibition on insulin-sensitive individuals are presently controversial.

Research design and methods: Sixteen subjects, with type II diabetes (on diet and/or diet plus oral hypoglycemic agents) and arterial hypertension, were studied. During a 1-mo run-in period no antihypertensive drugs were administered, but oral hypoglycemic agents were continued in subjects already in therapy. The subjects were then randomly assigned to two 3-mo treatment periods, with either captopril or placebo (single blind, cross-over design). At the end of each treatment period, insulin sensitivity was assessed by means of a euglycemic-hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1 mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3-3H]glucose (for calculation of hepatic glucose output and peripheral glucose utilization, rates of glucose disappearance), and indirect calorimetry (for calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid oxidation). The percentage of HbA1c was measured to assess long-term glycemic control.

Results: Comparing data at the end of placebo and captopril treatment, captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3 mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in hyperglycemic conditions (total amount of insulin infused and time of insulin infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58 +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater insulin sensitivity in euglycemic conditions at liver level (hepatic glucose output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp), muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1 mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately 29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/- 0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2 vs. 7.3 +/- 0.2%, P < 0.05).

Conclusions: Long-term captopril administration in type II diabetic subjects improves insulin sensitivity in the postprandial state, not in the fasting state, and improves glycemic control.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Antihypertensive Agents / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Blood Pressure
  • Captopril / therapeutic use*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy*
  • Diet, Diabetic
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypertension / blood
  • Hypertension / drug therapy*
  • Hypoglycemic Agents / therapeutic use
  • Infusions, Intravenous
  • Insulin / administration & dosage
  • Insulin / blood
  • Insulin / pharmacology*
  • Lipid Metabolism
  • Male
  • Middle Aged

Substances

  • Antihypertensive Agents
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Captopril
  • Glucose