Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study

Cardiothoracic Unit, Great Ormond Street Hospital for Children National Health Service Trust, London, England, United Kingdom.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

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