Altered T‐cell subsets and transcription factors in latent autoimmune diabetes in adults taking sitagliptin, a dipeptidyl peptidase‐4 inhibitor: A 1‐year open‐label randomized controlled trial. Issue 2 (3rd August 2018)

• Record Type: Journal Article
• Authors: Wang, Xia; Yang, Lin; Cheng, Ying; Zheng, Peilin; Hu, Jingping; Huang, Gan; Zhou, Zhiguang
• Is Part Of: Journal of diabetes investigation. Volume 10:Issue 2(2019)
• Page Start: 375
• Page End: 382
• Publication Date: 2018-08-03
• Subjects: Dipeptidyl peptidase‐4 inhibitor -- Latent autoimmune diabetes in adults -- T‐lymphocyte subsets; Diabetes -- Periodicals; Diabetes -- Research -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462005
• DOI: 10.1111/jdi.12873
• Languages: English
• ISSNs: 2040-1116

Abstract

Abstract: Aims/Introduction: Dipeptidyl peptidase‐4 inhibitor has been proven to improve glycemic control and β‐cell function in latent autoimmune diabetes in adults (LADA). The potential immune modulation mechanism is still unknown. Thus, we tested T‐lymphocyte subsets and expression of relevant transcription factors in LADA patients with sitagliptin intervention for up to 1‐year. Materials and Methods: A total of 40 LADA patients were randomly assigned to sitagliptin and/or insulin treatment (SITA group; n = 20) or insulin alone treatment (CONT group; n = 20). Peripheral blood mononuclear cells were isolated at baseline, 6 months and 12 months. The percentage of T‐lymphocyte subsets (T helper 1, T helper 2, T helper 17 and regulatory T cells) tested by flow cytometry, and the messenger ribonucleic acid expression (T box expressed in T cells [T‐BET], GATA binding protein 3 [GATA3], forkhead box protein 3 [FOXP3] and related orphan receptor C [RORC]) tested by real‐time polymerase chain reaction were determined at baseline, 6 months and 12 months. Results: The percentage of regulatory T cells in the SITA group was significantly lower than that of the CONT group at baseline. The percentage of T helper 2 cells was higher than that of the CONT group at 6 months and 12 months. At 12 months, the percentage of T helper 17 cells was lower in the SITA group than that of the CONT group. After a 1‐year visit, the messenger ribonucleic acid expression levels of T‐BET expressed in T cells and RORC in the SITA group were significantly lower than at baseline. Whereas that of RORC in the CONT group were significantly lower than that at baseline. Conclusions: The data confirmed that sitagliptin altered the phenotype of T cells and downregulated the expression of T‐BET and RORC in LADA patients, and ameliorated glycemic control in LADA patients. Abstract : Th2 was higher and Th17 was lower in SITA group than that in CONT group at 12M. Meanwhile, the mRNA expression levels of both T‐BET and RORC in SITA group were significantly lower than its baseline. We first implicated that sitagliptin, a DPP4 inhibitor, could alter the frequency of CD4 + T cell subsets on both cellular and mRNA level in LADA patients.