Indicators of endothelial dysfunction in type 2 diabetes mellitus as factors for the development of complications

Abstract

Background. To determine the pathogenetic role of the main factors reflecting the development of endothelial dysfunction (EDF), an attempt was made within the framework of one study to calculate their effect on the occurrence of vascular complications of diabetes mellitus 2 type (DM2T). These include endothelin-1 (ET1), tumor necrosis factor α (TNFα), and diene conjugates. Two protective factors were also chosen: nitric oxide (NO) and endothelial NO-synthase. The purpose of study was to investigate the effect of EDF indices in DM2T on the development of its complications. Materials and methods. The study involved 152 patients with DM2T, the age of patients ranged from 34 to 80 years, on ave-rage 53.9 ± 8.4 years. Women were 95 (62.5 %), men — 57 (37.5 %). According to the clinical recommendations, the results of clinical and laboratory tests determined the presence of retinopathy, nephropathy according to the levels of albuminuria and glomerular filtration rate (GFR), sensory polyneuropathy, macroangiopathy of the lower extremities, and arterial hypertension. The blood plasma content of EDF factors was determined by enzyme and biochemical methods. For mathematical processing of the obtained data, the program Statistica 10 (StatSoft, Inc., USA), GLZ package was used. Results. The presence of retinopathy was strongly influenced by blood levels of ET1 (β = 3.1; p = 2.77E-05), as well as TNFα (β = 0.019; p = 0.050). In the presence of macroangiopathy of the lower extremities — by the blood levels of NO (β = 27.5; p = 0.021) and TNFα (β = –0.48; p = 0.017). For polyneuropathy, only one indicator was significant — ET1 (β = 1.8; p = 0.016). The presence of nephropathy for GFR was influenced by the blood levels of ET1 (β = 2.7; p = 7.58E-07) and TNFα (β = 0.013; p = 0.047). ET1 led to the development of nephropathy on microalbuminuria (β = 4.5; p = 0.043). The presence of arterial hypertension was influenced by ET1 (β = 1.69; p = 2.54E-04) and TNFα (β = 0.017; p = 0.014). By means of multivariate logistic regression, models for predicting the risk of DM2T complications are constructed based on the studied factors of EDF. All models are adequate and have a high level of predictive accuracy (60.5–90.8 %). Conclusions. The development of DM2T complications was influenced differently by EDF factors: ET1 directly influenced the development of all complications of DM2T (in addition to macroangiopathy of the lower extremities); TNFα had an effect on the development of retinopathy, nephropathy for GFR and arterial hypertension; NO accumulation in the blood led to the development of macroangiopathy of the lower extremities.

Keywords

• diabetes mellitus type 2
• complications
• endothelial dysfunction
• endothelin-1
• nitric oxide
• tumor necrosis factor α