Association of blood endothelial dysfunction markers with type 2 diabetes mellitus complications

Abstract

Type 2 diabetes mellitus (T2DM)is associated with endothelial dysfunction (ED) which contributes to pathogenesis of the disease. The major markers of ED are endothelial hormone — endothelin 1 (ET1), nitric oxide (NO), endothelial NO-synthase (eNOS), tumor necrosis factor (TNF-α) and oxidative stress marker — diene conjugates (DCs). Objective — to assess of potential association of blood ED markers (ET1, eNOS, NO, TNFα, DCs) with T2DM complications. Materials and methods. 152 patients with T2DM and 95 generally healthy subjects (control)were examined. According to the results of clinical and laboratory examinations, the stage of the disease and the presence of complications were determined. Content of ET1 (Biomedica Immunoassays, Austria), eNOS (BCM Diagnostics, USA) and TNF-α (Bender Medsystems, Austria) were determined in blood plasma. NO level in blood was determined by its terminal metabolites (NOx) in the Gris reaction, and the content of DCs of unsaturated fatty acids by Z. Placer in VB Gavrilov modification. Statistica 10 (StatSoft, Inc., USA) was used for statistical processing of the obtained data. Results and discussion. The blood content of ET1, TNFα, NOx and DCs increased significantly, corres­ponding to the severity of the disease (especially for TNF-α and ET1); eNOS content was declining. ET1 higher than 1.990 fmol/ml determined nephropathy on the level of microalbuminuria, and above 2.309 fmol/ml — other complications. An increase in blood TNF-α content above 102.0 pg/ml and 105.1 pg/ml determined retinopathy and nephropathy, respectively. The development of nephropathy by the level of microalbuminuria, in addition to ET1, was confirmed by a decrease in blood eNOS content below 250,4 pg/ml and DCs below 5,368 U/ml. Critical levels for the formation of lower extremity macroangiopathy and almost all (except eNOS) hypertension have been established for all markers. Conclusions. The association of ED markers with diabetic complications was shown and thresholds(critical values) were set, indicating that the markers (especially ET1 and TNF-α), in particular, could be used to predict T2DM complications.