Circulating levels of tumor necrosis factor-alpha in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease taking into account the vascular complications

Abstract

The relationship between non-alcoholic fatty liver disease (NAFLD) and risk factors for vascular disorders and type 2 diabetes mellitus (T2D) remains the subject of discussion. Therefore, the purpose of our work was to determine the circulatory levels of tumor necrosis factor-alpha (TNF-α) in patients with T2D and to determine the nature of the effect of vascular complications in the presence and absence of NAFLD on this indicator. 146 patients with T2D aged from 28 to 80 years old (68 men / 78 women) were examined, with varying degrees of glycemic control and overweight, without renal insufficiency. 95 surveyed people had NAFLD. 21 practically healthy persons were studied as controls. Compared to controls, patients with T2D at the background of impaired glucose homeostasis were characterized by a marked increase in body mass index (BMI), increased levels of free fatty acids, triglycerides (TG), TNF-α, basal insulin, HOMA-IR indices, and decreased insulin sensitivity. It was found that the average level of TNF-α in patients with T2D (17.88 ± 3.42 pg/ml) was 3-fold higher than in the control group — 5.47 ± 3.44 pg/ml (p < 0.05). Patients with T2D with NAFLD have a greater BMI (35.10 ± 0.77 kg/m2 ) than T2D patients without NAFLD (32.13 ± 0.82 kg/m2, p < 0.001). Stratification of the diabetic population on the base of the presence/absence of NAFLD shown a more pronounced increase in circulating levels of TNF-α in the presence of NAFLD (20.36 ± 4.81 pg/ml vs 10.05 ± 1.62 pg/ml, p < 0.05), which substantiates this parameter utility for further applications as a diagnostic marker. It was found the difference between TNF-α levels in non-NAFLD diabetic patients with different types of vascular complications (p < 0.05 – p < 0.02). There were almost 2-fold higher TNF-α levels in patients with T2D and NAFLD regardless of vascular complication type (p < 0.05). In general, the group of patients without the liver disease had lower levels of TNF-α, but the lowest levels of TNF-α were noted in patients with T2D without the liver or vascular complications (p < 0.05). There was no significant differences in the TNF-α levels in T2D patients with NAFLD regardless macro/microvascular complications, which confirms the leading influence of hepatic insulin resistance and a possible presence of additional factors, that modulate the general level of this proinflammatory cytokine.