Endothelial dysfunction and increased arterial intima-media thickness in children with type 1 diabetes

Background - Endothelial dysfunction may play a pathophysiological role in the development of atherosclerosis in subjects with type 1 diabetes. We examined whether alterations in vascular endothelial function exist in children with type 1 diabetes and tested the hypothesis that endothelial dysfunction is associated with early structural atherosclerotic vascular changes in these children. Methods and Results - Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid artery intima-media thickness (IMT) in 75 children ( mean age 11 +/- 2 years), 45 with type 1 diabetes (diabetes duration 4.4 +/- 2.9 years) and 30 healthy control children. Children with diabetes had lower peak FMD response (4.4 +/- 3.4% versus 8.7 +/- 3.6%, P < 0.001) and increased IMT (P < 0.001) compared with controls. Sixteen children with diabetes (36%) had endothelial dysfunction defined as total FMD response in the lowest decile for normal children. These children had increased carotid IMT (0.58 +/- 0.05 versus 0.54 +/- 0.04 mm, P = 0.01) and higher LDL cholesterol concentration (2.63 +/- 0.76 versus 2.16 +/- 0.60 mmol/L, P = 0.03) compared with diabetic children without endothelial dysfunction. Multivariate correlates of increased IMT included diabetes group (P = 0.03), low FMD (P = 0.03), and high LDL cholesterol (P = 0.08). Conclusions - Impaired FMD response is a common manifestation in children with type 1 diabetes and is associated with increased carotid artery IMT. These data suggest that endothelial dysfunction in children with type 1 diabetes may predispose them to the development of early atherosclerosis.