Endothelial Dysfunction and Increased Arterial Intima-Media Thickness in Children With Type 1 Diabetes

Abstract

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.