Cutaneous microvascular dysfunction is associated with human leukocyte antigen-DQ in youths with type 1 diabetes

Functional disturbances in microcirculation in juvenile type 1 diabetes (T1D) are believed to underlie, in part, the later occurrence of cardiovascular complications. Some epidemiologic studies suggested greater risk of microvascular complications in those with T1D-risk genotypes of human leukocyte antigen (HLA). We investigated whether HLA-DQ2/8, which is linked to highest T1D morbidity, influences microvascular function in young diabetic patients. Cutaneous microvascular endothelium-dependent and independent reactivity and HLA genotypes were assessed in young patients (age: 9-21 y) with T1D (duration: 2-20 y). HLA-DQ2/8 was identified in 29 of 75 patients. The DQ2/8 and non-DQ2/8 groups were similar in age, body mass index, diabetes duration, glycosylated hemoglobin, and C-reactive protein (CRP). Compared with the non-DQ2/8 group, the DQ2/8 group showed decreased endothelium-dependent responses (p = 0.03 after adjustment for age, diabetes duration, glycosylated hemoglobin, and CRP) and elevated soluble intercellular adhesion molecule-1 (p = 0.05). In these but not in non-DQ2/8 patients, CRP correlated with both systolic (r = 0.76; p < 0.001) and diastolic (r = 0.50; p = 0.01) blood pressure. HLA-DQ2/8 is associated with endothelial microvascular dysfunction in young patients with T1D, and future studies are needed to provide mechanistic insights. The findings could explain in part the previously reported epidemiologic link between T1D-risk HLA and microvascular complications.