Cutaneous Microvascular Dysfunction Is Associated With Human Leukocyte Antigen-DQ in Youths With Type 1 Diabetes

Abstract

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 endotheliumdependent responses (p ϭ 0.03 after adjustment for age, diabetes duration, glycosylated hemoglobin, and CRP) and elevated soluble intercellular adhesion molecule-1 (p ϭ 0.05). In these but not in non-DQ2/8 patients, CRP correlated with both systolic (r ϭ 0.76; p Ͻ 0.001) and diastolic (r ϭ 0.50; p ϭ 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. A broad spectrum of cardiovascular risk factors including type 1 diabetes (T1D) has been linked to functional disturbances in microcirculation. The generalized microvascular dysfunction in T1D is an important mechanism in the development of microvascular diabetes complications in, for instance, eyes, kidneys, or myocardium (1). Although the precise pathophysiology of diabetes microvasculopathy remains elusive, it seems that both extrinsic (e.g., infection, socioeconomic status) and intrinsic (race, ethnicity, metabolic control) factors contribute to it, in part, through progressive injury to microvascular endothelial cells (2).Some, but not all, previous epidemiologic works suggested a possible link between the human leukocyte antigen (HLA) system and clinical manifestations of microvasculopathy in both diabetic and nondiabetic patients (3,4). Expression of diabetes-risk HLA class II molecules on islet endothelial cells could be a central vascular event in the pathogenesis of T1D (5). Previous studies showing the ability of endothelial cells in other vascular beds to express HLA class II support the assumption that HLA may be present in the entire vascular system (6,7). Whether diabetes-risk HLA is associated with systemic microvascular endothelial dysfunction has not yet been studied.Herein, we investigated the relationship between the HLA-DQ2/8 genotype, which confers the highest risk for T1D (8) and endothelial function of cutaneous microcirculation in young patients with T1D. METHODSSeventy-five children and adolescents (45 ...

Welche Rolle spielt die Therapieadhärenz?

“…Anodal iontophoresis was used for Ach, whereas SNP was delivered via cathodal iontophoresis. The current was set at 100 μA for 20 s for both drugs, based on previous work [20]. Five consecutive doses were applied for both drugs to generate dose-response curves.…”

HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

“…The genetic HLA-related susceptibility is recognized in more than 80% of young patients with T1D [ 14 ]. We have earlier reported in a cross-sectional study of children and young adults with T1D that diabetes duration, body mass index, and glycosylated haemoglobin were strongly associated with brachial artery and cutaneous microvascular endothelial dysfunction in patients with HLA-DQ 2/8 but not in those without this genotype [ 15 , 16 ]. The risk of endothelial damage seemed to increase further in patients with inflammatory activity, suggesting a possible interplay between systemic inflammation and HLA in vascular injury.…”