Evaluation of the Effect of Empagliflozin Therapy on T Helper 22 Cell-Related Factors in Patients with Type 2 Diabetes Mellitus

Abstract

Background and Objective: The increased response of T helper (Th) 22 cells might be involved in the pathogenesis of Type 2 Diabetes Mellitus (T2DM). The present study aimed to investigate the transcription factor of Th22 cells (aryl hydrocarbon receptor [AHR]) and interleukin 22 (IL-22) in CD4 T cells as well as the impact of oral empagliflozin treatment. The correlation between the aforementioned factors and clinical parameters was also determined among the patients. Materials and Methods: In this case-control study, 50 patients under the treatment of metformin and gliclazide were divided into two equal groups, including the patients receiving empagliflozin (EMPA) and not receiving empagliflozin (EMPA, as the control group). The peripheral blood CD4 T cells were isolated on the initiation day of the study and after 6 months of therapy, and the gene expression levels of AHR and IL-22 were evaluated by real-time polymerase chain reaction. In addition, the production of IL-22 after activation was measured using enzyme-linked immunosorbent assay. Results: The levels of fasting plasma glucose and hemoglobin A1c diminished in the EMPA group after empagliflozin therapy, compared to those reported at the baseline (initiation day; P<0.001 and P=0.04). The gene expression level of IL-22 and production of IL-22 significantly reduced after 6 months of empagliflozin therapy (P=0.011 and P=0.001). A significant positive correlation between IL-22 production and its gene expression with AHR as well as between fasting plasma glucose and hemoglobin A1c was observed in the EMPA patients after therapy (P˂0.05). Conclusion: In addition to antidiabetic effects, empagliflozin has antiinflammatory impacts on the immune system, especially on Th22 cell-