title: Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers.
abstract: BACKGROUND
  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).
  
  
  METHODS
  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].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Mario
authors.initials: M
authors.lastname: Gössl
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Martin
authors.initials: M
authors.lastname: Reriani
authors.forename: Darrell
authors.initials: D
authors.lastname: Loeffler
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001772:Blood Cell Count; D001773:Blood Cells / Q000166:cytology* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology; D011236:Prediabetic State / Q000097:blood* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human