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 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 (HC) and after treatment with the DPP4‐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⁺) in whole blood. Circulating Tang cell levels were significantly lower in people with T2DM compared with HC. SDF‐1α levels increased significantly in Linagliptin treated people with T2DM compared to placebo, and a trend was observed in change of Tang cells, while EPC count did not change. In conclusion, circulating Tang cells were considerably lower in T2DM, while a trend was observed in recruitment of Tang cells after 26 weeks of treatment with Linagliptin. These data suggest that DPP4‐inhibitors may potentially exert beneficial effects on bone marrow driven vascular repair.