Lucie Sromova1, Petr Busek2, Helena Posova3, Jana Potockova4, Pavel Skrha5, Michal Andel6, Aleksi Sedo7. 1. Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U nemocnice 5, 12853 Prague 2, Czech Republic. Electronic address: lsrom@lf1.cuni.cz. 2. Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U nemocnice 5, 12853 Prague 2, Czech Republic. Electronic address: busekpetr@seznam.cz. 3. Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University in Prague, Studnickova 7, 12000 Prague 2, Czech Republic. Electronic address: hmare@lf1.cuni.cz. 4. 2nd Department of Internal Medicine, 3rd Faculty of Medicine and Faculty Hospital Královské Vinohrady, Charles University in Prague, Srobarova 1150, 10034 Prague 10, Czech Republic. Electronic address: potocko@fnkv.cz. 5. 2nd Department of Internal Medicine, 3rd Faculty of Medicine and Faculty Hospital Královské Vinohrady, Charles University in Prague, Srobarova 1150, 10034 Prague 10, Czech Republic. Electronic address: pavel.skrha@email.cz. 6. 2nd Department of Internal Medicine, 3rd Faculty of Medicine and Faculty Hospital Královské Vinohrady, Charles University in Prague, Srobarova 1150, 10034 Prague 10, Czech Republic. Electronic address: andel@fnkv.cz. 7. Laboratory of Cancer Cell Biology, Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, Charles University in Prague, U nemocnice 5, 12853 Prague 2, Czech Republic. Electronic address: aleksi@cesnet.cz.
Abstract
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 100mg once daily) and then after 4weeks and 12months. 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 4weeks 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.
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 100mg once daily) and then after 4weeks and 12months. 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 4weeks 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.
Authors: Stefanie A de Boer; Melanie Reijrink; Wayel H Abdulahad; Elisa S Hoekstra; Riemer H J A Slart; Hiddo J L Heerspink; Johanna Westra; Douwe J Mulder Journal: Diabetes Obes Metab Date: 2020-03-27 Impact factor: 6.577