Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers

Context: Vascular calcification, an important feature of diabetic vasculopathy, is an active process potentially mediated by endothelial progenitor cells (EPCs) coexpressing the osteoblastic marker osteocalcin (OCN). Objective: In this study we tested the hypothesis that cells expressing these markers are associated with the presence of elevated glycated hemoglobin (HbA1c). Design, Setting, and Patients: This was a cross-sectional comparison. Patients (n = 133, aged 57.4 ±15.7 yr) were divided into two groups according to the presence of an HbA1c in a (pre-)diabetic (>5.6) or normal range at the time of blood sampling. Methods: Using flow cytometry of peripheral blood mononuclear cells (MNCs), cells positive for OCN, the EPC markers (CD34/KDR and CD133⁺/CD34^-/KDR⁺) and OCN ⁺ EPCs were counted. Results: Patients with elevated HbA1 ccompared with those with normal HbA1c had a significantly higher percentage of circulating OCN⁺ MNCs [4.6 (interquartile range 2.68-7.81%) vs. 3.12 (0.99-7.81%), P =0.035], higher numbers of OCN⁺/CD133 ⁺/CD34^-/KDR⁺ cells [20(9-74)vs. 8(0-19) counts per 100,000 gated events, P < 0.001] and a higher fraction of CD133 ⁺/CD34^-/KDR⁺ and CD34/KDR cells coexpressing OCN (23.7 ± 24.3 vs. 40.5 ± 34.6%, P = 0.002 and 37.1 ± 39.5 vs. 59.7 ± 37.7%, P = 0.002, respectively). The association between circulating OCN⁺/CD133⁺/CD34^-/KDR⁺ cells and an HbA1c in the (pre-) diabetic range remained strong, even after adjusting for differences in obesity and cardiovascular risk factors, disease,and medications in a multivariate model [odds ratio 1.72 (1.21-2.61), P = 0.002]. Conclusion: This study demonstrated that patients with HbA1c in the (pre-)diabetic range have a significant increase in OCN⁺ MNCs, and OCN⁺/CD133⁺/CD34^-/KDR⁺ cells, in particular. Whether these cells increase vascular calcification in (pre-)diabetes warrants further studies.