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Andreas J. Flammer, Mario Gössl, Jing Li, Yoshiki Matsuo, Martin Reriani, Darrell Loeffler, Robert D. Simari, Lilach O. Lerman, Sundeep Khosla, Amir Lerman, Patients with an HbA1c in the Prediabetic and Diabetic Range Have Higher Numbers of Circulating Cells with Osteogenic and Endothelial Progenitor Cell Markers, The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 12, 1 December 2012, Pages 4761–4768, https://doi.org/10.1210/jc.2012-2642
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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).
In this study we tested the hypothesis that cells expressing these markers are associated with the presence of elevated glycated hemoglobin (HbA1c).
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.
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.
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].
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.
