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.
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- 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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