Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
J Clin Endocrinol Metab. 2012 Dec;97(12):4761-8. doi: 10.1210/jc.2012-2642. Epub 2012 Sep 26.
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).
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.
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.
血管钙化是糖尿病血管病变的一个重要特征，是一种潜在的活跃过程，可能由同时表达成骨细胞标志物骨钙素（OCN）的内皮祖细胞（EPC）介导。
本研究旨在验证以下假设，即在糖化血红蛋白（HbA1c）升高的患者中，存在表达这些标志物的细胞。
设计、地点和患者：这是一项横断面比较研究。患者（n=133，年龄 57.4±15.7 岁）根据采血时 HbA1c 的水平分为两组，即（前）糖尿病（>5.6）或正常范围。
采用外周血单个核细胞（MNCs）的流式细胞术，计数 OCN、EPC 标志物（CD34/KDR 和 CD133(+)/CD34(-)/KDR(+)）和 OCN(+)EPCs 阳性的细胞。
与 HbA1c 正常的患者相比，HbA1c 升高的患者循环中 OCN(+)MNCs 的百分比显著更高[4.6（四分位距 2.68-7.81%）vs. 3.12（0.99-7.81%），P=0.035]，OCN(+)/CD133(+)/CD34(-)/KDR(+)细胞数量更高[20（9-74）vs. 8（0-19）个/100,000 门控事件，P<0.001]，CD133(+)/CD34(-)/KDR(+)和 CD34/KDR 细胞共表达 OCN 的比例更高[23.7±24.3% vs. 40.5±34.6%，P=0.002 和 37.1±39.5% vs. 59.7±37.7%，P=0.002]。即使在校正肥胖和心血管危险因素、疾病和药物等混杂因素后，循环 OCN(+)/CD133(+)/CD34(-)/KDR(+)细胞与（前）糖尿病范围内的 HbA1c 之间的关联仍然很强[比值比 1.72（1.21-2.61），P=0.002]。
本研究表明，HbA1c 处于（前）糖尿病范围内的患者，尤其是 OCN(+)MNCs 和 OCN(+)/CD133(+)/CD34(-)/KDR(+)细胞显著增加。这些细胞是否会增加（前）糖尿病患者的血管钙化，需要进一步研究。
