Published online before print April 24, 2003, doi: 10.1161/01.ATV.0000072968.00157.6B
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© 2003 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Endothelium-Dependent and -Independent Vascular Dysfunction in Type 1 Diabetes
Role of Conventional Risk Factors, Sex, and Glycemic Control
From EURODIAB, Department of Epidemiology (N.N.C., H.M.C.) and Centre for Clinical Pharmacology (P.V.), University College London, UK.
Correspondence to Dr Norman Chan, Department of Medicine & Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail nnchan{at}cuhk.edu.hk
Objective— Defective NO release/response may contribute to increased coronary risk and the loss of sex difference in coronary heart disease in diabetes. We aimed to determine whether NO release/response is impaired in type 1 diabetes and whether any defects are greater in women than men.
Methods and Results— Forearm blood flow response to vasoactive drugs was assessed by venous plethysmography in 88 diabetic and 69 control subjects aged 30 to 53 years. In diabetic patients, response was 18% lower for acetylcholine (ACh) (P=0.002), 6% lower for bradykinin (P=0.14), and 17% lower for glyceryl trinitrate (GTN) (P<0.001). Women had a higher response to ACh than men (17%, P=0.006). The diabetes-associated defect in ACh was greater in women (25% lower, P=0.01) than men (13% lower, P=0.08), although not significantly (P=0.26 for the interaction). Poorer glycemic control was associated with ACh response (P=0.003) and contributed to the greater defect in diabetic women than men.
Conclusions— The diabetes-associated defect in GTN response was similar in men and women. Established coronary heart disease risk factors did not explain any of the defects in ACh or GTN response associated with diabetes. Type 1 diabetes is associated with impaired responsiveness to NO and with an impairment in ACh-stimulated NO release.
Key Words: nitric oxide • endothelial dysfunction • diabetes mellitus • plethysmography
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