Background: Expression of HLA class II molecules on islet endothelial cells (EC) is a central vascular event in the pathogenesis of type 1 diabetes (T1D). Previous studies demonstrated the ability of other vascular EC to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for T1D, is associated with early atherosclerosis in youths with this disease. Methods: Brachial artery flow-mediated dilation (FMD) and carotid artery intima-media thickness (IMT), as well as CRP, LDL, HDL and total cholesterol (TC), were assessed in 86 children and adolescents with T1D (mean age: 15 years). HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. Results: HLA-DQ2/8 was detected in 34 patients. When this group was compared to the remaining patients (n=52), there were no differences in age, diabetes duration, HbA1C, body mass index, inflammatory markers, IMT, and TC (p>0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated as compared to the non-DQ2/8 group (1.8 vs 1.3, respectively; p=0.001), while FMD did not significantly differ between the groups (5.3 vs 6.7%, respectively; p=0.08) . When patients were further categorized in relation to CRP (cut-off value 1 mg/l), FMD was significantly lower (3%, p<0.01), whereas LDL-to-HDL ratio increased further (2.2, p<0.001) in the subgroup of DQ2/8 & CRP>1 patients compared to the remaining three subgroups. These associations remain significant after adjustment for age, diabetes duration, and HbA1C by ANCOVA. The brachial artery responses to nitroglycerine were similar in all subgroups. Conclusion: In youths with T1D, HLA-DQ2/8 appears to interfere with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways.