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Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
BACKGROUND: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasmino...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538597/ https://www.ncbi.nlm.nih.gov/pubmed/23249721 http://dx.doi.org/10.1186/1475-2840-11-152 |
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author | Hernestål-Boman, Jenny Norberg, Margareta Jansson, Jan-Hakan Eliasson, Mats Eriksson, Jan W Lindahl, Bernt Johansson, Lars |
author_facet | Hernestål-Boman, Jenny Norberg, Margareta Jansson, Jan-Hakan Eliasson, Mats Eriksson, Jan W Lindahl, Bernt Johansson, Lars |
author_sort | Hernestål-Boman, Jenny |
collection | PubMed |
description | BACKGROUND: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM. METHODS: We conducted a prospective incident case-referent study within the Västerbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L). RESULTS: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments. CONCLUSIONS: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance. |
format | Online Article Text |
id | pubmed-3538597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35385972013-01-10 Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study Hernestål-Boman, Jenny Norberg, Margareta Jansson, Jan-Hakan Eliasson, Mats Eriksson, Jan W Lindahl, Bernt Johansson, Lars Cardiovasc Diabetol Original Investigation BACKGROUND: Diabetic patients experience stimulated coagulation and dysfibrinolysis, which is associated with an increased risk of cardiovascular events. This imbalance may precede the manifest diagnosis. We investigated whether elevated antigen levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), the tPA/PAI-1 complex, or von Willebrand Factor (VWF) precede type 2 diabetes mellitus (T2DM) diagnosis, and whether this elevation occurs before increased fasting plasma glucose (FPG) or 2-hour plasma glucose (2hPG) in individuals who later develop T2DM. METHODS: We conducted a prospective incident case-referent study within the Västerbotten Intervention Programme. Cardiovascular risk factor data as well as FPG and 2hPG and blood samples for future research were collected at a baseline health examination between 1989 and 2000, (n= 28 736). During follow-up in January 2001, 157 cases had developed T2DM. Referents without T2DM were matched for sex, age, and year of participation (n=277). Subgroup analysis was performed for cases with normal baseline glucose levels (FPG <6.1 mmol/L and 2hPG < 8.9 mmol/L) and cases with elevated levels (FPG 6.1-6.9 mmol/L and/or 2hPG 8.9-12.1 mmol/L). RESULTS: After adjusting for BMI, family history of diabetes, physical activity, smoking, systolic blood pressure and levels of C-reactive protein and triglycerides, independent associations were found between incident T2DM and elevated levels of tPA (OR=1.54, 95% CI 1.06-2.23), PAI-1 (OR=1.61, 95% CI 1.14-2.28), and tPA/PAI-1 complex (OR=2.45, 95% CI 1.56-3.84). In participants with normal glucose levels, PAI-1 (OR=2.06, 95% CI 1.10 - 3.86) exhibited an independent relationship with incident T2DM after the adjustments. CONCLUSIONS: Elevated levels of fibrinolytic variables precede the manifestation of T2DM after adjusting for metabolic and cardiovascular risk factors and can be detected several years before changes in glucose tolerance. BioMed Central 2012-12-18 /pmc/articles/PMC3538597/ /pubmed/23249721 http://dx.doi.org/10.1186/1475-2840-11-152 Text en Copyright © 2012 Hernestal-Boman et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Investigation Hernestål-Boman, Jenny Norberg, Margareta Jansson, Jan-Hakan Eliasson, Mats Eriksson, Jan W Lindahl, Bernt Johansson, Lars Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title | Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title_full | Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title_fullStr | Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title_full_unstemmed | Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title_short | Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
title_sort | signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3538597/ https://www.ncbi.nlm.nih.gov/pubmed/23249721 http://dx.doi.org/10.1186/1475-2840-11-152 |
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