Functional Improvement of Progenitor Cells and Endothelial Function by Vildagliptin in Diabetes Mellitus (FINNjA-DM). (FINNjA-DM)

Functional Improvement of Progenitor Cells and Endothelial Function by Vildagliptin in Diabetes Mellitus (FINNjA-DM).

Functional Improvement of Progenitor Cells and Endothelial Function by Vildagliptin in Diabetes Mellitus (FINNjA-DM).

SDF-1, an important cytokine for neovascularisation is cleaved by (dipeptidyl peptidase IV) DPPIV. The aim of this study is to assess the effect of the dipeptidyl peptidase IV inhibitor vildagliptin (Galvus®) on endothelial function as well as number and functional activity of progenitor cells in patients with documented diabetes mellitus.

The peptidase CD26 (DPPIV/dipeptidyl peptidase IV) removes dipeptides from the amino terminus of proteins and thereby inactivates these cleaved proteins. It was shown, that CD26 cleaves SDF-1 into a non-mitogenic molecule. Inhibition or deletion of CD26 leads to an increased homing of hematopoietic progenitor cells to the bone marrow after transplantation by increasing the invasion capacity of these cells {Campbell et al. 2008; Christopherson et al. 2004}. The cytokine SDF-1 is released in response to hypoxia, is crucial for progenitor cell homing and recruitment of cells for neovascularisation. Invasion capacity is closely related to the cytokine SDF-1 and the SDF-1 receptor CXCR4 {Ceradini et al. 2004}. The in vivo neovascularisation capacity of progenitor cells is closely correlated to their functional capacity as SDF-1 induced invasion or colony-forming capacity {Heeschen et al. 2004; Britten et al. 2003; Assmus et al. 2007}. Therefore, the aim of this study is to assess the effect of the dipeptidyl peptidase IV inhibitor vildagliptin on endothelial function as well as number and functional activity of progenitor cells in patients with documented diabetes mellitus.

SDF-1 is an Important Cytokine for Neovascularization. Cleavage of SDF-1 is Reduced by DPPIV Inhibitors

Inclusion Criteria: Patients with diabetes mellitus type 2 under stable medication HbA1c between 7% an 10% age between 18 and 80 years signed informed consent Exclusion Criteria: Atrial fibrillation (plethysmographic recordings can only obtained in sinus-rhythm) CAD with reduced left ventricular ejection fraction (LVEF <45%) Pregnancy, chronic or acute infection, fever Diabetes mellitus type 1 Newly diagnosed diabetes, uncontrolled diabetes Neoplasm Known allergy to study drug Severe liver/kidney disease HIV, Hepatitis Participation at other studies within the last 30 days