The effect of dipeptidyl peptidase-IV inhibition on circulating T cell subpopulations in patients with type 2 diabetes mellitus

Aim: To assess intraindividually the effects of DPP-IV inhibition on the subpopulations of immune cells in type 2 diabetes mellitus (DM2) patients during the course of treatment with sitagliptin. Methods: In this open label non-randomized observational study with a control group DM2 patients were examined before the initiation of the DPP-IV inhibitor administration (sitagliptin 100 mg once daily) and then after 4 weeks and 12 months. Inhibition of the blood plasma DPP-IV enzymatic activity was determined by a chromogenic assay, the immunophenotyping of the blood cell subpopulations was performed using flow cytometry and blood plasma cytokine concentrations were quantified using an array-based multiplex ELISA. All parameters were evaluated in relation to the entry values in individual patients. Results: The blood plasma DPP-IV enzymatic activity was effectively inhibited during the sitagliptin treatment. A significant decrease of the proportion of Treg cells (to 86 +/- 31% (median +/- SD) of entry values, p = 0.001) and an increase of Th1 cells (to 120 +/- 103% (median +/- SD) of entry values, p = 0.004) were observed after 4 weeks but not after one year of the sitagliptin treatment. No changes were observed in the ratio of CD4+/CD8+ cells, in the quantity of NK and Th2 cells and blood plasma cytokine levels. Conclusions: Sitagliptin treatment may cause temporary changes of the proportion of lymphocyte subpopulations in patients with DM2. The consequent deregulation of the immune system should be considered as a possible cause of the eventual side effects of long term DPP-IV inhibition. (C) 2016 Elsevier Ireland Ltd. All rights reserved.