Content and ultrastructure of natural killer cells in the blood of patients with newly diagnosed type 2 diabetes mellitus

Abstract

Background. In patients with newly diagnosed type 2 diabetes mellitus (T2DM), a small but statistically significant decrease in absolute number of natural killer (NK) cells (CD56+) in the peripheral blood (PB) was found, especially pronounced with concomitant obesity. In connection with the above, one of the main aims of the present report was to further study the role of NK cells in patients with newly diagnosed T2DM, including those with obesity. For this purpose, a combination of flow cytometry methods with scanning and transmission electron microscopy was used to determine the number and function of CD56+ cells in the PB of patients with T2DM. Materials and methods. We examined 144 patients of both sexes with newly diagnosed T2DM aged 40–70 years who had no other acute or chronic diseases and had not previously taken any hypoglycemic drugs. The control group consisted of 50 healthy individuals with normoglycemia aged 40–65 years who had not COVID-19 disease. Results. Our studies have found that in untreated patients with newly diagnosed T2DM compared to healthy controls, there is a very small statistically significant decrease in the absolute number of CD56+ cells in the PB. When combining flow cytometry (FACS method), transmission and scanning electron microscopy in patients with T2DM, a significant change in the ultrastructure of CD56+ cells was revealed, indicating a decrease in their function (an increase in the number of cells with a smoother surface of the cell membrane, a sharp decrease in the number of azurophilic granules in the cytoplasm considered the main producer of cytokines and perforins, the appearance of parallel tubular structures, biomarkers of decreased cell function, a disruption of the Golgi apparatus structure, granular endoplasmic reticulum, etc.). The data obtained indicate that at the initial stage of T2DM development in humans, there is a pronounced weakening in the function of NK cells and, consequently, the natural immune defense of the body and explain the increased susceptibility of diabetics to various viruses and infections, including COVID-19, and also more severe clinical course and increased mortality. Conclusions. The conducted studies show that in patients with T2DM who are at the initial stage of T2DM, there is a sharp disturbance in the submicroscopic organization of CD56+ cells, the most important cellular element of natural immunity, which suggests a weakening of the function of natural immune defense. It is the main cause of increased sensitivity of diabetic patients to infection with various pathogens, including the SARS-CoV-2, as well as more severe clinical course and increased mortality rate.