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Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes
OBJECTIVE: Reduction of bone marrow–derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent and potential mechanisms of progenitor cell reduction during the natural history of type...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858183/ https://www.ncbi.nlm.nih.gov/pubmed/20150295 http://dx.doi.org/10.2337/dc09-1999 |
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author | Fadini, Gian Paolo Boscaro, Elisa de Kreutzenberg, Saula Agostini, Carlo Seeger, Florian Dimmeler, Stefanie Zeiher, Andreas Tiengo, Antonio Avogaro, Angelo |
author_facet | Fadini, Gian Paolo Boscaro, Elisa de Kreutzenberg, Saula Agostini, Carlo Seeger, Florian Dimmeler, Stefanie Zeiher, Andreas Tiengo, Antonio Avogaro, Angelo |
author_sort | Fadini, Gian Paolo |
collection | PubMed |
description | OBJECTIVE: Reduction of bone marrow–derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent and potential mechanisms of progenitor cell reduction during the natural history of type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified 425 individuals, divided into seven categories according to carbohydrate metabolism status (normal glucose tolerance [NGT], impaired fasting glucose, impaired glucose tolerance [IGT], and newly diagnosed type 2 diabetes) and diabetes duration (0–9, 10–19, and ≥20 years). These categories were examined as ideally describing the natural history of type 2 diabetes development and progression. We measured CD34+ and CD34+KDR+ progenitor cells by flow cytometry. We also evaluated progenitor cells in 20 coupled bone marrow and peripheral blood samples and examined progenitor cell apoptosis in 34 subjects. RESULTS: In comparison to NGT, CD34+ cells were significantly reduced in IGT and had a first nadir in newly diagnosed type 2 diabetes and a second nadir after 20 years of diabetes. Statistical adjustment for possible confounders confirmed that CD34+ cell counts are deeply reduced at time of diagnosis, that they partially recover during the subsequent 0–19 years, and that they dip again after ≥20 years. A similar, but less consistent, trend was detected for CD34+KDR+ cells. Peripheral blood CD34+ cells were directly correlated with bone marrow CD34+ cells and inversely correlated with CD34+ cell apoptosis. CONCLUSIONS: Circulating progenitor cell reduction marks the clinical onset of type 2 diabetes. Both defective mobilization and increased apoptosis may account for this phenomenon. While a partial recovery occurs during subsequent years, bone marrow reserve seems exhausted in the long term. |
format | Text |
id | pubmed-2858183 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-28581832011-05-01 Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes Fadini, Gian Paolo Boscaro, Elisa de Kreutzenberg, Saula Agostini, Carlo Seeger, Florian Dimmeler, Stefanie Zeiher, Andreas Tiengo, Antonio Avogaro, Angelo Diabetes Care Original Research OBJECTIVE: Reduction of bone marrow–derived circulating progenitor cells has been proposed as a novel mechanism of cardiovascular disease in type 2 diabetes. The present study was designed to describe the extent and potential mechanisms of progenitor cell reduction during the natural history of type 2 diabetes. RESEARCH DESIGN AND METHODS: We identified 425 individuals, divided into seven categories according to carbohydrate metabolism status (normal glucose tolerance [NGT], impaired fasting glucose, impaired glucose tolerance [IGT], and newly diagnosed type 2 diabetes) and diabetes duration (0–9, 10–19, and ≥20 years). These categories were examined as ideally describing the natural history of type 2 diabetes development and progression. We measured CD34+ and CD34+KDR+ progenitor cells by flow cytometry. We also evaluated progenitor cells in 20 coupled bone marrow and peripheral blood samples and examined progenitor cell apoptosis in 34 subjects. RESULTS: In comparison to NGT, CD34+ cells were significantly reduced in IGT and had a first nadir in newly diagnosed type 2 diabetes and a second nadir after 20 years of diabetes. Statistical adjustment for possible confounders confirmed that CD34+ cell counts are deeply reduced at time of diagnosis, that they partially recover during the subsequent 0–19 years, and that they dip again after ≥20 years. A similar, but less consistent, trend was detected for CD34+KDR+ cells. Peripheral blood CD34+ cells were directly correlated with bone marrow CD34+ cells and inversely correlated with CD34+ cell apoptosis. CONCLUSIONS: Circulating progenitor cell reduction marks the clinical onset of type 2 diabetes. Both defective mobilization and increased apoptosis may account for this phenomenon. While a partial recovery occurs during subsequent years, bone marrow reserve seems exhausted in the long term. American Diabetes Association 2010-05 2010-02-11 /pmc/articles/PMC2858183/ /pubmed/20150295 http://dx.doi.org/10.2337/dc09-1999 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Original Research Fadini, Gian Paolo Boscaro, Elisa de Kreutzenberg, Saula Agostini, Carlo Seeger, Florian Dimmeler, Stefanie Zeiher, Andreas Tiengo, Antonio Avogaro, Angelo Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title | Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title_full | Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title_fullStr | Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title_full_unstemmed | Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title_short | Time Course and Mechanisms of Circulating Progenitor Cell Reduction in the Natural History of Type 2 Diabetes |
title_sort | time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858183/ https://www.ncbi.nlm.nih.gov/pubmed/20150295 http://dx.doi.org/10.2337/dc09-1999 |
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