Vildagliptin, but not glibenclamide, increases circulating endothelial progenitor cell number: a 12-month randomized controlled trial in patients with type 2 diabetes

Abstract

BackgroundFewer circulating endothelial progenitor cells (EPCs) and increased plasma (C-term) stromal cell-derived factor 1α (SDF-1α), a substrate of DPP-4, are biomarkers, and perhaps mediators, of cardiovascular risk and mortality. Short-term/acute treatment with DPP-4 inhibitors improve EPC bioavailability; however, long-term effects of DPP-4i on EPCs bioavailability/plasma (C-term) SDF-1α are unknown.MethodsRandomized (2:1) open-label trial to compare the effects of vildagliptin (V) (100 mg/day) vs glibenclamide (G) (2.5 mg bid to a maximal dose of 5 mg bid) on circulating EPC levels at 4 and 12 months of treatment in 64 patients with type 2 diabetes in metformin failure. At baseline, and after 4 and 12 months, main clinical/biohumoral parameters, inflammatory biomarkers, concomitant therapies, EPC number (CD34+/CD133+/KDR+/106 cytometric events) and plasma (C-term) SDF-1α (R&D system) were assessed.ResultsBaseline characteristics were comparable in the two groups. V and G similarly and significantly (p < 0.0001) improved glucose control. At 12 months, V significantly increased EPC number (p < 0.05) and significantly reduced (C-term) SDF-1α plasma levels (p < 0.01) compared to G, with no differences in inflammatory biomarkers.ConclusionsV exerts a long-term favorable effect on EPC and (C-term) SDF-1α levels at glucose equipoise, thereby implying a putative beneficial effect on vascular integrity. Trial registration Clinical Trials number: NCT01822548; name: Effect of Vildagliptin vs. Glibenclamide on Circulating Endothelial Progenitor Cell Number Type 2 Diabetes. Registered 28 March, 2013

Vasculoprotective Effects of Vildagliptin. Focus on Atherogenesis

“…We can speculate that decreased circulating stem cells in DM2 might induce plasma SDF-1α, and administration of DPP-4 inhibitors decreased it by stem cell mobilization. Dei et al (2017) noted an increase in the number of EPCs after vildagliptin treatment, what may support this hypothesis [14]. In summary, by lowering SDF-1α levels and by stimulating EPCs, vildagliptin may have an impact on slowing the progression of atherosclerosis by reducing inflammation and by repairing endothelial injuries.…”

“…In the Framingham Heart Study of 3359 participants (10% of individuals with diabetes), high plasma SDF-1α were directly and independently associated with the risk of heart failure and 10-year all-cause mortality [56]. Two independent randomized double-blind control studies [14,32] in small groups of DM2 patients provide interesting evidence for the effect of vildagliptin on SDF-1α. Although DPP-4 degrades SDF-1α and its blockade should be associated with an increase in SDF-1α, the administration of vildagliptin resulted in a significant decrease in circulating SDF-1α.…”

Potential humoral mediators of remote ischemic preconditioning in patients undergoing surgical coronary revascularization

“…For the detection of GLP-1 95 (Abcam, Cambridge, UK) an antibody cocktail consisting of a capture and a detector antibody was supplemented. For the detection of GH 96 , IL-1α 97 , IL-2 98 , IL-15 99 , IL-17 99 , IL-33 100 , leptin 101 , pentraxin-3 102 , SDF-1α 103 and survivin 104 (R&D systems, Abingdon, UK) an enzyme-linked polyclonal horseradish peroxidase-conjugated antibody was supplemented. For the detection of GHRH 105 and GHRP 106 (ELISA Cloud-Immunoassay, Houston, USA) biotin-conjugated antibodies against the respective protein were added to the microplate, and the antibodies on the plate and the biotin-labeled antibodies then competed for each other.…”

Effects of a New Nutraceutical Formulation (Berberine, Red Yeast Rice and Chitosan) on Non-HDL Cholesterol Levels in Individuals with Dyslipidemia: Results from a Randomized, Double Blind, Placebo-Controlled Study

“…EPC levels were assessed by cytofluorimetric analysis and identified as cells co-expressing CD34, CD133, and Kinase insert Domain Receptor (KDR) surface antigens as previously described [ 42 , 43 , 44 , 45 ]. Briefly, 300 µL of blood collected in EDTA were stained with 15 μL fluorescein isothiocyanate (FITC)-conjugated anti-human CD34 monoclonal antibody (mAb) (Becton Dickinson Biosciences, Franklin Lakes, NJ, USA), 20 μL phycoerythrin (PE)-conjugated anti-human KDR mAb (R&D Systems, Minneapolis, MN, USA) and 20 µL allophycocyanin (APC)-conjugated anti-human CD133 mAb (Miltenyi Biotec, San Diego, CA, USA).…”