Impaired Vascular Reactivity in Insulin-Dependent Diabetes Mellitus Is Related to Disease Duration and Low Density Lipoprotein Cholesterol Levels

OBJECTIVES: This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors. BACKGROUND: Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes. METHODS: We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [+/- SD] diabetes duration 13 +/- 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation). RESULTS: Flow-mediated dilation was significantly impaired in diabetic subjects (5.0 +/- 3.7% vs. 9.3 +/- 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 +/- 5.6% vs. 19.7 +/- 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = -0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = -0.38, p < 0.005). CONCLUSIONS: Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.