Aim: The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects.
Materials and methods: 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp. Blood samples taken before and at the end of the clamp were used for the flow cytometry analysis of lymphocyte and monocyte populations and for the assessment of cytokine levels.
Results: At fasting conditions, FDR showed a higher CD4/CD8 ratio of peripheral lymphocytes, a higher percentage of Th17 lymphocytes, and a lower content of intermediate monocytes when compared to controls. The CD4/CD8 ratio correlated with fat mass, insulin, and HOMA-IR in the entire group of subjects. Hyperinsulinemia decreased a relative content of peripheral CD4+ and increased a relative content of CD8+ T lymphocytes, thus decreasing the CD4/CD8 ratio by 18-22% in both groups of subjects. In FDR but not in controls, the decrease of CD4+ T lymphocyte content was partially based on the decrease of TH2 and TH17 lymphocyte subpopulations. In control subjects but not in FDR, the number of intermediate monocytes has declined in response to hyperinsulinemia.
Conclusion: The alterations of the CD4/CD8 lymphocyte ratio, relative content of TH17 cells, and intermediate monocytes in FDR are features of genetic predisposition to T2DM and may play a role in pathogenesis of T2DM. Short-term hyperinsulinemia affected mostly the immune cell populations deregulated in FDR subjects, which suggests important interplay between immune system homeostasis and insulin levels.