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(Circulation. 1997;95:560-561.)
© 1997 American Heart Association, Inc.

Articles

Insulin-Dependent Diabetes Mellitus and Nitrovasodilation

Important and Complex Interactions

Helmut O. Steinberg, MD; Alain D. Baron, MD

the Indiana University Medical Center (H.O.S., A.D.B.) and the Richard L. Roudebush VA Medical Center, Indianapolis, Ind.

Correspondence to Alain D. Baron, MD, Department of Medicine, Indiana University Medical Center, 541 N Clinical Dr, CL459, Indianapolis, IN 46202-5111.

Key Words: Editorials • acetylcholine • nervous system, autonomic • regional blood flow • vasodilation

	Introduction

 
Endothelial dysfunction in IDDM patients could contribute to their higher rates of macrovascular disease. The study of endothelial function in IDDM has yielded conflicting results,^{1 2 3 4} which is not surprising given the complexity of the IDDM state. First, endothelium-dependent vasodilation is modulated by insulin,^{5 6} and insulin levels fluctuate greatly in these subjects. Second, increased glucose levels, a hallmark of IDDM, have been shown to impair endothelium-dependent vasodilation in vitro^{7 8} and may contribute to endothelial dysfunction in vivo. Third, long-standing hyperglycemia with advanced glycosylated end-product formation causes dysregulation of the endothelium-derived NO system⁹ ; and fourth, autonomic nervous system function that regulates vascular tone and reactivity is often impaired early in the course of IDDM even in subjects who do not have clinically evident neuropathy.^{10 11 12 13}

The article by Makimattila and colleagues¹⁴ in this issue sheds some light on this complex problem. The authors assessed changes in forearm blood flow to the endothelium-dependent vasodilator ACh, the endothelium-independent vasodilator SNP, and the inhibitor of NO synthase L-NMMA in controls and in IDDM subjects. IDDM subjects were characterized by either normal or massively elevated albumin excretion (macroalbuminuria), which is a marker for increased risk of cardiovascular mortality and has been reported to be associated with severe endothelial dysfunction.¹⁵ It is important to note that, unlike previous studies, this study¹⁴ controlled for blood glucose and insulin levels while studying vascular responsiveness, thus removing important potential confounding factors. The authors also measured autonomic responses to a host of stimuli with the use of sophisticated techniques to uncover . . . [Full Text of this Article]

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