OBJECTIVE: Vascular disease in type 1 diabetes is a complex and multifactorial process, which probably begins in childhood in association with the onset of diabetes. To determine the possible factors involved, we measured microvascular responses to endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilators in 56 patients with type 1 diabetes (aged 9-22 years) and 22 control subjects. RESEARCH DESIGN AND METHODS: Skin perfusion was measured at the dorsum of the foot using laser Doppler flowmetry during low-current iontophoresis of acetylcholine and sodium nitroprusside. Maximum vasodilator function was measured during local 44 degrees C skin heating. RESULTS: Vascular responses were significantly reduced in patients with type 1 diabetes compared with responses in control subjects: acetylcholine (P<0.01, analysis of variance [ANOVA]), sodium nitroprusside (P<0.01, ANOVA), and local heating (P<0.02. Mann-Whitney U test). Endothelium-dependent responses were related to duration of diabetes (r = -0.38, P<0.01) and to glycemic control (r = 0.37, P<0.01). Significant correlations were found in the patient group between responses to acetylcholine and sodium nitroprusside (r = 0.28, P<0.05) but not to heating, suggesting that a common factor (e.g., nitric oxide activity) may be responsible for the abnormal vascular responses to these chemicals. CONCLUSIONS: Early changes in microvascular function are present in young patients with type 1 diabetes, long before the initial clinical presentation. These abnormalities may be related to complex interactions between structural abnormalities and functional changes in the endothelium, smooth muscle, and nitric oxide activity.
Khan, F., Elhadd, T. A., Greene, S. A., & Belch, J. J. (2000). Impaired skin microvascular function in children, adolescents, and young adults with type 1 diabetes. Diabetes Care, 23(2), 215-220. https://doi.org/10.2337/diacare.23.2.215