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

Andreas J. Flammer, Mario Gössl, Jing Li, Yoshiki Matsuo, Martin Reriani, Darrell Loeffler, Robert D. Simari, Lilach O Lerman, Sundeep Khosla, Amir Lerman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4761-4768
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number12
DOIs
StatePublished - Dec 2012

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Osteocalcin
Endothelial cells
Cell Count
Vascular Calcification
Glycosylated Hemoglobin A
Blood
Endothelial Progenitor Cells
Flow cytometry
Medical problems
Blood Cells
Flow Cytometry
Reference Values
Obesity
Odds Ratio
Cells
Sampling

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers. / Flammer, Andreas J.; Gössl, Mario; Li, Jing; Matsuo, Yoshiki; Reriani, Martin; Loeffler, Darrell; Simari, Robert D.; Lerman, Lilach O; Khosla, Sundeep; Lerman, Amir.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 12, 12.2012, p. 4761-4768.

Research output: Contribution to journalArticle

Flammer, Andreas J. ; Gössl, Mario ; Li, Jing ; Matsuo, Yoshiki ; Reriani, Martin ; Loeffler, Darrell ; Simari, Robert D. ; Lerman, Lilach O ; Khosla, Sundeep ; Lerman, Amir. / Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers. In: Journal of Clinical Endocrinology and Metabolism. 2012 ; Vol. 97, No. 12. pp. 4761-4768.
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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 = "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.",
author = "Flammer, {Andreas J.} and Mario G{\"o}ssl and Jing Li and Yoshiki Matsuo and Martin Reriani and Darrell Loeffler and Simari, {Robert D.} and Lerman, {Lilach O} and Sundeep Khosla and Amir Lerman",
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T1 - Patients with an HbA1c in the prediabetic and diabetic range have higher numbers of circulating cells with osteogenic and endothelial progenitor cell markers

AU - Flammer, Andreas J.

AU - Gössl, Mario

AU - Li, Jing

AU - Matsuo, Yoshiki

AU - Reriani, Martin

AU - Loeffler, Darrell

AU - Simari, Robert D.

AU - Lerman, Lilach O

AU - Khosla, Sundeep

AU - Lerman, Amir

PY - 2012/12

Y1 - 2012/12

N2 - 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.

AB - 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.

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