The online version of this article (doi:10.1186/1475-2840-11-152) contains supplementary material, which is available to authorized users.
The authors have no conflict of interest to disclose.
JHB: Data collection, analysis and interpretation of the results, drafting and revision of the manuscript. MN: Conception and design of the study, data collection, drafting and revision of the manuscript. JHJ: Data collection, analysis and interpretation of the results, drafting and revision of the manuscript. ME: Data collection, drafting and revision of the manuscript. JWE: Conception and design of the study, data collection, revision of the manuscript. BL: Conception and design of the study and revision of the manuscript. LJ: Data collection, analysis and interpretation of the results, drafting and revision of the manuscript. All authors read and approved the final manuscript.
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.
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).
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.
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.
American Diabetes Association: Implications of the United Kingdom prospective diabetes study. Diabetes Care. 2000, 23 (Suppl 1): S27-S31.
Eliasson MC, Jansson JH, Lindahl B, Stegmayr B: High levels of tissue plasminogen activator (tPA) antigen precede the development of type 2 diabetes in a longitudinal population study. The Northern Sweden MONICA study. Cardiovasc Diabetol. 2003, 2: 19-10.1186/1475-2840-2-19. PubMedCentralCrossRefPubMed
Juhan-Vague I, Pyke SD, Alessi MC, Jespersen J, Haverkate F, Thompson SG: Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT study group. European concerted action on thrombosis and disabilities. Circulation. 1996, 94: 2057-2063. 10.1161/01.CIR.94.9.2057. CrossRefPubMed
Johansson L, Jansson JH, Boman K, Nilsson TK, Stegmayr B, Hallmans G: Tissue plasminogen activator, plasminogen activator inhibitor-1, and tissue plasminogen activator/plasminogen activator inhibitor-1 complex as risk factors for the development of a first stroke. Stroke. 2000, 31: 26-32. 10.1161/01.STR.31.1.26. CrossRefPubMed
Wiman B, Andersson T, Hallqvist J, Reuterwall C, Ahlbom A, DeFaire U: Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. Arterioscler Thromb Vasc Biol. 2000, 20: 2019-2023. 10.1161/01.ATV.20.8.2019. CrossRefPubMed
Norberg M, Wall S, Boman K, Weinehall L: The Vasterbotten Intervention Programme: background, design and implications. Glob Health Action. 2010, 3: 4643.
Norberg M, Eriksson JW, Lindahl B, Andersson C, Rolandsson O, Stenlund H, Weinehall L: A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed. J Intern Med. 2006, 260: 263-271. 10.1111/j.1365-2796.2006.01689.x. CrossRefPubMed
World Health Organisation: Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation Part 1: Diagnosis and classification of diabetes mellitus. 1999, Geneva: WHO/NCD/NCS/99.2
Kanaya AM, Wassel Fyr C, Vittinghoff E, Harris TB, Park SW, Goodpaster BH, Tylavsky F, Cummings SR: Adipocytokines and incident diabetes mellitus in older adults: the independent effect of plasminogen activator inhibitor 1. Arch Intern Med. 2006, 166: 350-356. 10.1001/archinte.166.3.350. CrossRefPubMed
Cigolini M, Tonoli M, Borgato L, Frigotto L, Manzato F, Zeminian S, Cardinale C, Camin M, Chiaramonte E, De Sandre G, Lunardi C: Expression of plasminogen activator inhibitor-1 in human adipose tissue: a role for TNF-alpha?. Atherosclerosis. 1999, 143: 81-90. 10.1016/S0021-9150(98)00281-0. CrossRefPubMed
Alessi MC, Bastelica D, Morange P, Berthet B, Leduc I, Verdier M, Geel O, Juhan-Vague I: Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes. 2000, 49: 1374-1380. 10.2337/diabetes.49.8.1374. CrossRefPubMed
Alessi MC, Juhan-Vague I: Metabolic syndrome, haemostasis and thrombosis. Thromb Haemost. 2008, 99: 995-1000. PubMed
Czekay RP, Wilkins-Port CE, Higgins SP, Freytag J, Overstreet JM, Klein RM, Higgins CE, Samarakoon R, Higgins PJ: PAI-1: An Integrator of Cell Signaling and Migration. Int J Cell Biol. 2011, 2011 (Article ID:562481): 9.
Velazquez EM, Mendoza SG, Wang P, Glueck CJ: Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism. 1997, 46: 454-457. 10.1016/S0026-0495(97)90066-4. CrossRefPubMed
- Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
Jan W Eriksson
- BioMed Central
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