GLYCEMIA CONTROL, INSULIN RESISTANCE, AND FUNCTIONAL ACTIVITY OF T-HELPER SUBPOPULATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Aim. To study the functional activity of T-helper subpopulations (pro-inflammatory T-helpers-17 (Th17) and T-helpers-1 (Th1) and immune-suppressing FoxP3+ T-regulators (Treg)) and its association with clinical parameters, glycemic control levels, and insulin resistance severity among patients with arterial hypertension (AH) and Type 2 diabetes mellitus (DM-2).

Material and methods. The study included 35 patients (17 men and 18 women) with Stage 1-2 AH and DM-2, aged 47-63 years. The control group included 24 healthy volunteers, comparable by age and gender. All participants underwent standard clinical examination and assessment of carbohydrate and lipid metabolism parameters. Flow cytometry method was used for the assessment of Treg levels and activated Th1 and Th17 numbers in the peripheral blood mononuclear cell fraction. Functional status of blood cells was assessed by the secretion levels of interleukin (IL) 1p, IL-2, IL-6, IL-17, IL-10, tumor necrosis factor (TFN) a, and interferon (IFN) y. Results. In diabetic patients, there was an increase in activated Th1 numbers and IL-17, IL-6, and TNF-a secretion, combined with a decrease in IL-10 secretion, FoxP3+ Treg numbers, and Treg/Th17 ratio, compared to the control group. In patients with HbA_1c >7%, more pronounced abdominal obesity was associated with reduced Treg numbers and Treg/Th17 and Treg/Th1 ratios, as well as with elevated IL-17 secretion, compared to patients with adequate glycemia control. According to the cluster analysis results, DM-2 patients could be divided into two subgroups by the severity of insulin resistance and HOMA index levels. Among patients with higher HOMA levels, more pronounced abdominal obesity, hyperglycemia, and hyperinsulinemia were associated with increased Th1 numbers and pro-inflammatory cytokine (IL-2, IL-1p, and IL-17) secretion, compared to their peers with less severe insulin resistance.

Conclusion. Our results suggest an important association between insulin resistance, inadequate glycemia control, and functional dysbalance of T-helper subpopulations in patients with DM-2.

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