umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Fibrinolytic factors in relation to anthropometry and incident type 2 diabetes.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. (Skellefteå Research Unit)
2014 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Fibrinolysfaktorer i relation till antropometri och incident typ 2 diabetes. (Swedish)
Abstract [en]

Fibrinolytic imbalance is associated with cardiovascular disease and its risk factors. The longitudinal changes in the fibrinolytic factors tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and tPA/PAI-1 complex have been inadequately studied in the general population and in relation to incident type 2 diabetes mellitus (T2DM). The measurements, questionnaires and blood samples prospectively collected in the World Health Organisation-project MONItoring trends and determinants in CArdiovascular disease (MONICA) and in the Västerbotten Intervention Programme (VIP) enable such studies. The samples have been stored since 1985, at the Northern Sweden Medical Research Biobank. However, it is unknown how these factors are affected by long-term storage.

The aims of this thesis were to evaluate the effects of long-term storage on fibrinolytic factors, and to determine how these factors are related to incident T2DM, how these factors change over time and how these factors are related to changes in anthropometric measurements.

Storage time was shown to have a negligible impact on plasma antigen levels of fibrinolytic factors. After adjustments for traditional diabetic and cardiovascular risk markers the fibrinolytic factors tPA, PAI-1 and tPA/PAI-1 complex were associated with incident T2DM. PAI-1 was associated with incident T2DM in subjects with normal fasting and 2-hour plasma glucose levels. In MONICA-Västerbotten, tPA, PAI-1 and tPA/PAI-1 complex increased over 9 years in both men and women. PAI-1 appears to interact in a complex manner with anthropometric, inflammatory, glycaemic and lipidemic measurements, but the pattern of components correlating with the changes in PAI-1 differed markedly between the sexes.

In conclusion, PAI-1 is a potential risk marker of incident T2DM. PAI-1 increased markedly over nine years, but the pathophysiological background to these findings needs to be further investigated, separately for each sex.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2014. , 81 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1626
National Category
Endocrinology and Diabetes Cardiac and Cardiovascular Systems Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public health; Medicine, cardiovascular disease
Identifiers
URN: urn:nbn:se:umu:diva-86360ISBN: 978-91-7459-796-7 (print)OAI: oai:DiVA.org:umu-86360DiVA: diva2:698568
Public defence
2014-03-21, Forumsalen, Campus, Skellefteå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2014-02-28 Created: 2014-02-24 Last updated: 2014-03-17Bibliographically approved
List of papers
1. Long-term stability of fibrinolytic factors stored at -80 degrees C.
Open this publication in new window or tab >>Long-term stability of fibrinolytic factors stored at -80 degrees C.
Show others...
2010 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 125, no 5, 451-456 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits.

MATERIALS AND METHODS: Plasma samples stored at -80( degrees )C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n=1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n=1558) and re-analysed 2001 (n=78) and 2005 (n=828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1.

RESULTS: Long-term storage for a median time of 11.6years (range 5 to 20) showed an effect of time on tPA antigen R(2)=0.01, PAI-1 antigen R(2)=0.01 and tPA-PAI-1 complex R(2) = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R(2) 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R(2) 0.67 - 0.93).

CONCLUSIONS: This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.

Place, publisher, year, edition, pages
Elsevier, 2010
Keyword
fibrinolysis, tissue plasminogen activator, plasminogen activator inhibitor 1, long-term storage, biobank
National Category
Public Health, Global Health, Social Medicine and Epidemiology Endocrinology and Diabetes Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-32967 (URN)10.1016/j.thromres.2009.12.007 (DOI)000277209200015 ()20053424 (PubMedID)
Available from: 2010-03-31 Created: 2010-03-31 Last updated: 2017-12-12Bibliographically approved
2. Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
Open this publication in new window or tab >>Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study
Show others...
2012 (English)In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 11, 152- p.Article in journal (Refereed) Published
Abstract [en]

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 Vasterbotten 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.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keyword
Diabetes mellitus type 2, Tissue plasminogen activator, Plasminogen activator inhibitor-1, Von Willebrand factor, Fibrinolysis, Population study, Vasterbotten Intervention Programme
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-64956 (URN)10.1186/1475-2840-11-152 (DOI)000313126800001 ()
Available from: 2013-03-07 Created: 2013-02-04 Last updated: 2017-12-06Bibliographically approved
3. Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.
Open this publication in new window or tab >>Individual changes in fibrinolytic factors, von Willebrand factor, and C-reactive protein over a nine-year period.
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Intra-individual changes in haemostatic factor concentrations over time are unknown, in the general population.

Objective: To describe intra-individual longitudinal changes in tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), tPA/PAI-1 complex, von Willebrand factor (VWF), and C-reactive protein (CRP) over nine years, in different age groups, stratified for sex.

Methods: The MONICA survey in 1990 examined randomly selected men and women in four age groups (25–64 years) who were re-examined in 1999. A total of 309 individuals donated venous blood samples in Stabilyte tubes for both surveys during the morning hours, after an overnight fast. We analysed tPA activity and antigens of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP.

Results: Over nine years, in both men and women, we found significant intra-individual increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP (P < 0.001). PAI-1 antigen levels increased by 75% for men and 95% for women. Compared to men, women had a significantly higher CRP increase (0.92 vs. 0.22 mg/L; P = 0.044). The P for trend for mean Δ1999–1990 across age groups showed a significant linear trend for VWF (P = 0.001 for men; P < 0.001 for women), but not for the other studied variables.

Conclusions: There were intra-individual longitudinal increases in the antigen levels of tPA, PAI-1, tPA/PAI-1 complex, VWF, and CRP over nine years in both men and women, with PAI-1 showing the highest relative increase. VWF increased significantly across age groups; however, fibrinolytic variables did not.

Keyword
fibrinolysis, haemostasis, longitudinal studies, tissue plasminogen activator, plasminogen activator inhibitor -1
National Category
Hematology
Research subject
Medicine, cardiovascular disease
Identifiers
urn:nbn:se:umu:diva-86358 (URN)
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2014-02-28Bibliographically approved
4. Individual PAI-1 increase over nine years relates differently in men and women to changes in anthropometric, glycaemic, inflammatory and lipid markers.
Open this publication in new window or tab >>Individual PAI-1 increase over nine years relates differently in men and women to changes in anthropometric, glycaemic, inflammatory and lipid markers.
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Levels of plasminogen activator inhibitor-1 (PAI-1) is known to correlate to factors related to the metabolic syndrome. We have previously shown that PAI-1 antigen increased by 75% in men and 95% in women over nine years.

Objective: The aim of this study was to explore relationships between intra-individual changes in PAI-1 and changes in anthropometric measurements, blood pressure, glycaemic, lipid and inflammatory markers, separately for men and women.

Method: In northern Sweden, 125 men and 116 women were examined first in 1990 and re-examined in 1999 during the morning hours. Changes over time (Δ) were calculated as the value at 1999 minus the value at 1990.

Results: In men, ΔPAI-1 was significantly correlated to ΔBMI (r =0.33), ΔCRP (r =0.25), Δtriglycerides (r =0.39), Δfasting plasma glucose (r =0.41) and Δ2-hour plasma glucose (r =0.29). In women, ΔPAI-1 was significantly correlated to ΔBMI (r =0.36), Δwaist circumference (r =0.38), Δhip circumference (r =0.27), ΔCRP (r =0.27) and Δtotal cholesterol (r =0.19). The multivariate linear regression analysis showed that ΔPAI-1 was significantly related to Δfasting plasma glucose and ΔCRP in men (R2 for the complete model was 0.31). In women, ΔPAI-1 was significantly related to Δwaist circumference (R2 for the complete model was 0.17).

Conclusion: We expected that changes in anthropometric, glycaemic, inflammatory and lipid markers would explain a large part of the observed PAI-1 increase. However, the multivariate analysis explained only 20% of the variation in ΔPAI-1 in women and 30% in men. Interestingly, the patterns of components correlating with the changes in PAI-1 differed between sexes.

Keyword
fibrinolysis, plasminogen activator inhibitor 1, longitudinal studies, gender
National Category
Public Health, Global Health, Social Medicine and Epidemiology Hematology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-86359 (URN)
Available from: 2014-02-24 Created: 2014-02-24 Last updated: 2014-02-28Bibliographically approved

Open Access in DiVA

fulltext(2031 kB)337 downloads
File information
File name FULLTEXT01.pdfFile size 2031 kBChecksum SHA-512
052a51377d4c04b957b402ad17fcc0e15369329f4950229f6774572144d2bbf6371f3ac3e770430c83446a39efb3c9a3f7ab1a2077a4db4b977302a973d1380d
Type fulltextMimetype application/pdf

Authority records BETA

Hernestål Boman, Jenny

Search in DiVA

By author/editor
Hernestål Boman, Jenny
By organisation
Department of Public Health and Clinical Medicine
Endocrinology and DiabetesCardiac and Cardiovascular SystemsPublic Health, Global Health, Social Medicine and Epidemiology

Search outside of DiVA

GoogleGoogle Scholar
Total: 337 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 191 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf