Agonistic Autoantibodies, a Risk Factor in Patients with Type 2 Diabetes

Abstract

In addition to insulin intolerance, patients with type 2 diabetes suffer from hypertension, renal insufficiency, retinopathy, wound healing disorders, coronary heart disease, heart attacks, strokes, and amputations. In addition to metabolic syndrome, many patients have pathological changes in macro- and microcirculation. One of the causes might be agonistic autoantibodies (agAAB), an immunological component. This specialized group of autoantibodies activates the G protein-coupled receptors similar to the way natural agonists do and triggers receptor-specific reactions in the cell (1). The pathological potential of agAAB has been described in numerous publications. The pathological processes triggered by agAAB for the ß-1-adrenoceptors (AR), AT1 AR, and α 1 AR (2,3,4,5) have been particularly well researched. Animal experiments provided valuable insights into the causality of receptor-specific autoantibodies for the development of diseases and disease-relevant symptoms. These autoantibodies can only be removed with specific antagonists at the receptor or by plasmapheresis or immunoadsorption. The agAAB do not respond to immunosuppression as classical autoantibodies do. Patients in whom agAAB was removed by extracorporeal treatment benefited from it. In patients with dilated cardiomyopathy, cardiac output improved (6,7); those with Alzheimer's disease (8) achieved stabilization of cognition. In subjects with Thromboangiitis obliterans (9), further amputations were able to be avoided after removal of the autoantibodies, and in patients with inadequate control of hypertension through pharmacological means, blood pressure was considerably reduced (10). In only a few cases did agAAB reappear. These positive treatment results for various diseases formed the basis for screening diabetics with respect to the prevalence of agonistic autoantibodies.