Angiogenic T cells are decreased in people with type 2 diabetes mellitus and recruited by the dipeptidyl peptidase‐4 inhibitor Linagliptin: A subanalysis from a randomized, placebo‐controlled trial (RELEASE study)

Abstract

Angiogenic T (Tang) cells are mediators of vascular repair, and are characterized by surface expression of CXCR4. This receptor for stromal cell‐derived factor‐1α (SDF‐1α) is cleaved by dipeptidyl peptidase‐4 (DPP‐4). Tang cell levels were investigated in people with type 2 diabetes mellitus (T2DM) compared with matched healthy controls and after treatment with the DPP‐4 inhibitor Linagliptin. People with T2DM were randomized to 5 mg/day Linagliptin (n = 20) or placebo (n = 21) for 26 weeks. Tang cell frequency was identified in peripheral blood mononuclear cells (CD3+CD31+CXCR4+) and levels of endothelial progenitor cells (EPCs) (CD34+CD133+KDR+) were also assessed in whole blood. Circulating Tang cell levels were significantly lower in people with T2DM compared with the healthy control group. SDF‐1α levels increased significantly in Linagliptin‐treated people with T2DM compared to placebo, and a trend was observed in change of Tang cell levels, while EPC count did not change. In conclusion, circulating Tang cell levels were considerably lower in people with T2DM, while a trend was observed in recruitment of Tang cells after 26 weeks of treatment with Linagliptin. These data suggest that DPP‐4 inhibitors may potentially exert beneficial effects on bone marrow‐driven vascular repair.