Agonistic autoantibodies against B2-adrenergic receptors correlating with macrovascular disease in longstanding diabetes type 2.

Abstract

Agonistic autoantibodies directed against adrenergic, endothelin, and angiotensin receptors are known as pathogenic factors in disease-causing vascular impairments such as Buergers' disease, dilatative cardiomyopathy, dementia, and preeclampsia. Diabetes mellitus also causes micro- and macrovascular damages, but pathogenesis is still not fully understood. Following indications for a pathogenic role of the mentioned antibodies from our preliminary investigations, we investigated the prevalence in a bigger cohort of patients with longstanding diabetes with or without diabetic complications. We included 200 patients in four groups (grouping due to duration of diabetes and presence of complications) from our university polyclinic with longstanding diabetes mellitus type 2 and evaluated the prevalence of the agonistic autoantibodies using ELISA technique. Antibodies directed against the alpha1-(39%), the first extracellular loop of the beta2-(34,5%), and the first extracellular loop of the beta1-adrenergic receptor (29,0%) were the most often detectable. With progression of diabetes and its complications, we found a decrease in the prevalence of the antibodies. Regression analyses revealed a positive association of antibodies against the first loop of the beta2-receptor and the presence of macrovascular complications. This investigation found mid frequent prevalence of agonistic autoantibodies in patients with longstanding diabetes mellitus type 2. The association between an antibody against one epitope and the presence of macrovascular complications may indicates a pathogenic linkage. This finding is inconsistent with our preliminary data and needs further evaluation, maybe by follow-up.