The pathogenetic significance of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes mellitus

Abstract

Objective: to determine the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vfV), endothelial NO-synthase (e‑NOS)) in the blood serum of patients with type 2 diabetes mellitus (DM), as well as to assess the pathogenetic significance endothelial dysfunction in the development of diabetic nephropathy.Materials and methods: the study included 93 patients with type 2 DM, including 28 men (30.1%) and 65 women (69.9%), aged 30 to 79 years, the average age of patients was 59.7±8.4 of the year. The main group included patients with both newly diagnosed type 2 DM and a long-term diabetic history. The duration of the disease averaged 9.5±7.5 years. The majority of patients with DM type 2 (92.5%) at the time of inclusion in the study had various variants of microvascular complications of diabetes, only a small number of patientsin this group (7.5%) had no signs of diabetic angiopathy. Signs of various stages of diabetic nephropathy were observed in 60 patients (69.2%). The comparison group consisted of 30 patients with essential arterial hypertension, including 12 men (40%) and 18 women (60%), aged 34 to 70 years, on average 56.1 ± 8.1 years. The control group consisted of 32 apparently healthy individuals. In all patients, along with routine methods of clinical, laboratory and instrumental examination, the level of circulating markers of endothelial dysfunction (endothelin‑1, von Willebrand factor (vWF), endothelial NO-synthase (e‑NOS)) in blood serum was measured using enzyme-linked immunosorbent assay (ELISA).Results: in patients with DM type 2 and diabetic nephropathy, a statistically significant increase in the concentration of circulating markers of endothelial dysfunction was revealed in comparison with hypertensive patients and healthy individuals. An increase in the level of endothelin‑1 relative to the borderline reference value was found in 73 (78.5±4.1%), vfV in 63 (67.7±4.8%) and e‑NOS in 65 (69.9±4.7%) of patients with DM type 2. In the groups of participants with hypertension and healthy individuals, endothelial imbalance was noted by us significantly less often than in patients with DM type 2, the levels of endothelin‑1 and vfV in people with hypertension were increased in more cases than in healthy individuals. It was noted that the levels of circulating markers of endothelial dysfunction increase with an increase in the duration of DM type 2, and also significantly increase under conditions of carbohydrate decompensation.Conclusion: the results obtained confirm the pathogenetic role of endothelial dysfunction in the development of diabetic nephropathy in patients with type 2 diabetes, increasing endothelial imbalance in persons with a long diabetic history and lack of compensation for carbohydrate metabolism.