Sitagliptin, a DPP-4 inhibitor, alters the subsets of circulating CD4+ T cells in patients with type 2 diabetes.
OBJECTIVE
CD26/DPP-4 is highly expressed by T cells, especially CD4+ T cells (T helper cells; Th) and may regulate the differentiation, maturation, or proliferation of these cells. We investigated the effects of sitagliptin, a DPP-4 inhibitor, on the absolute number and percentage of various subsets of circulating CD4+ T cells in patients with type 2 diabetes.


METHODS
We enrolled 30 consecutive patients (16 women and 14 men) with type 2 diabetes in a prospective, randomized, open-label, blinded endpoint study. Eligible participants were randomly assigned at a 2:1 ratio to either a sitagliptin group (sitagliptin at 50mg/day) or an active control group (glimepiride at 1mg/day). Patients were followed for 12 weeks with monthly review. Peripheral blood mononuclear cells were examined by flow cytometry for intracellular expression of cytokines (IFN-γ as a marker of Th1cells, IL-4 for Th2 cells, and IL-17 for Th17 cells) and for expression of CD4, CD25, and Foxp3 (regulatory T cells [Treg]).


RESULTS
Both groups showed similar improvement of glycemic control. The total number of CD4+ T cells was decreased by treatment with sitagliptin, while it did not change in the control group. The number and percentage of Th17 cells and Treg cells both decreased significantly in the sitagliptin group, but not in the control group. There was a significant positive correlation between changes in the percentage of Th17 cells and Treg cells after treatment with sitagliptin.


CONCLUSIONS
Treatment with sitagliptin for 12 weeks reduced the number of circulating CD4+ T cells, especially Th17 and Treg cells, in patients with type 2 diabetes.
Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan. Electronic address: yaso@dokkyomed.ac.jp.
Yoshimasa
Y
Aso
LSI Medience Corporation, Itabashi, Tokyo, Japan.
Maiko
M
Fukushima
Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan.
Masaaki
M
Sagara
Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan.
Teruo
T
Jojima
Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan.
Toshie
T
Iijima
Department of Endocrinology and Metabolism, Dokkyo Medical University, Mibu, Tochigi, Japan.
Kunihiro
K
Suzuki
LSI Medience Corporation, Itabashi, Tokyo, Japan.
Atsushi
A
Momobayashi
Department of Medicine, Ishibashi General Hospital, Shimotsuke, Tochigi, Japan.
Kikuo
K
Kasai
Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, Koshigaya, Saitama, Japan.
Toshihiko
T
Inukai
D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; C573415:IFNG protein, human; C508717:IL17A protein, human; C508598:IL4 protein, human; D020381:Interleukin-17; D013453:Sulfonylurea Compounds; D015847:Interleukin-4; C057619:glimepiride; D007371:Interferon-gamma; D000068900:Sitagliptin Phosphate
CD4+ T cell; DPP-4 inhibitor; Regulatory T cell; T-helper 17 cell