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 HbA1c compared 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. (J Clin Endocrinol Metab 97: 4761-4768, 2012)