Cytokine status and subpopulations of peripheral blood lymphocytes in patients with type 2 diabetes and nonalcoholic fatty liver disease

Abstract

Among the mechanisms of type 2 diabetes mellitus (T2DM), one of the leading roles is attributed to the immunopathological link of pathogenesis. At the manifestation  stage, in response to the impact of triggering factors, immune disorders determine the further character of this disease, including the development and  severity of its specific complications, in particular, non-alcoholic fatty liver disease (NAFLD). The aim of the study was an analysis of the content of cytokines and  major lymphocyte subpopulations in patients with T2DM and NAFLD. We followed up 118 patients, including 64 patients with T2DM and NAFLD (group 1), 26  patients – with T2DM (group 2), and 28 patients with NAFLD (group 3). The control group consisted of 25 conditionally healthy donors. The study has established that  each of the studied pathologies, namely T2DM, NAFLD, or its combination was characterized by a particular cytokine status which reflects both the presence of  inflammatory processes and orientation of immunopathological reactions in the body. The changes observed in cytokine level and lymphocyte subpopulation  composition in the presence of a combination of T2DM with NAFLD can be used both for the diagnosis and prediction of an unfavorable development of this disease,  in particular, development of an inflammatory response in the liver (increased IL-1β level), intensity and orientation of immunopathological reactions (increased   IFN-γ  level, decreased IL-4 level, changes in NK cell content), intensity of proliferation of connective tissue and fibrosis degree (increased IL- 10 level). The authors came to  the following conclusions: 1) In patients with T2DM, NAFLD, or a combination of these disorders, changes in cytokine status are observed, that reflect the intensity of  the inflammatory immune responses, their orientation and possible fibrosis in the liver. 2) Increased blood levels of IL-1β, IL-17 and IFN-γ indicate the  presence of  high inflammatory and immunopathological reactions in patients with T2DM and NAFLD. 3) An imbalance has been established in lymphocyte subpopulation  composition, expressed by decreased blood levels of CD8+ and CD16+ cells in case of a relatively stable level of T helper (CD4+) cells and increased content of CD20+  cells, which develops in the presence of an increased level of circulating immune complexes. 4) Patients with NAFLD and T2DM showed an increased apoptotic  willingness of lymphocytes, which manifests itself as an increased content of CD95+ cells in the blood. 5) The changes revealed in cytokine level and lymphocyte  subpopulation composition in T2DM patients with NAFLD can be used to diagnose and assess the severity of disorders in this pathology.