title: The effect of dipeptidyl peptidase-IV inhibition on circulating T cell subpopulations in patients with type 2 diabetes mellitus.
abstract: OBJECTIVE
  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.affiliation: 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.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sromova
authors.affiliation: 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.
authors.forename: Petr
authors.initials: P
authors.lastname: Busek
authors.affiliation: 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.
authors.forename: Helena
authors.initials: H
authors.lastname: Posova
authors.affiliation: 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.
authors.forename: Jana
authors.initials: J
authors.lastname: Potockova
authors.affiliation: 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.
authors.forename: Pavel
authors.initials: P
authors.lastname: Skrha
authors.affiliation: 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.
authors.forename: Michal
authors.initials: M
authors.lastname: Andel
authors.affiliation: 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.
authors.forename: Aleksi
authors.initials: A
authors.lastname: Sedo
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000068900:Sitagliptin Phosphate
keywords: Diabetes mellitus type 2; Dipeptidyl peptidase 4 inhibition; Gliptins; Immune cells