Sitagliptin, a DPP-4 inhibitor, alters the subsets of circulating CD4+T cells in patients with type 2 diabetes
Sitagliptin, a DPP-4 inhibitor, alters the subsets of circulating CD4+T cells in patients with type 2 diabetes
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DOI：
10.1016/j.diabres.2015.10.012
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发表时间：
2015-12-01
影响因子：
5.1
通讯作者：
Inukai, Toshihiko
中科院分区：
文献类型：
--
作者：
Aso, Yoshimasa;Fukushima, Maiko;Inukai, Toshihiko
目的：CD 26/DPP-4由T细胞，特别是CD 4 + T细胞（T辅助细胞; Th）高度表达，并且可以调节这些细胞的分化、成熟或增殖。我们研究了西格列汀，DPP-4抑制剂，对循环中的CD 4 + T细胞的各种亚群的绝对数量和百分比的影响与2型diabetes.Methods：我们招募了30例连续的患者（16名女性和14名男性）与2型糖尿病在一项前瞻性，随机，开放标签，盲终点研究。合格的受试者以2：1的比例随机分配至西格列汀组（西格列汀50 mg/天）或活性对照组（格列美脲1 mg/天）。随访12周，每月复查一次。通过流式细胞术检测外周血单个核细胞的细胞因子（IFN-γ作为Th 1细胞的标志物，IL-4用于Th 2细胞，IL-17用于Th 17细胞）的细胞内表达以及CD 4、CD 25和Foxp 3（调节性T细胞[Treg]）的表达。CD 4 + T细胞总数在西格列汀治疗后降低，而在对照组中没有变化。西格列汀组Th 17细胞和Treg细胞的数量和百分比均显著降低，而对照组无此变化。西格列汀治疗后Th 17细胞和Treg细胞的百分比变化之间存在显著正相关性。结论：西格列汀治疗12周可降低2型糖尿病患者循环中CD 4 + T细胞的数量，尤其是Th 17和Treg细胞。(C)2015爱思唯尔爱尔兰有限公司版权所有。
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 50 mg/day) or an active control group (glimepiride at 1 mg/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-gamma 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.