Diabetologia

, Volume 57, Issue 8, pp 1737–1741 | Cite as

Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3

  • Katharina Hess
  • Saad H. Alzahrani
  • Jackie F. Price
  • Mark W. Strachan
  • Natalie Oxley
  • Rhodri King
  • Tobias Gamlen
  • Verena Schroeder
  • Paul D. Baxter
  • Ramzi A. Ajjan
Short Communication

Abstract

Aims/hypothesis

Plasminogen activator inhibitor-1 (PAI-1) has been regarded as the main antifibrinolytic protein in diabetes, but recent work indicates that complement C3 (C3), an inflammatory protein, directly compromises fibrinolysis in type 1 diabetes. The aim of the current project was to investigate associations between C3 and fibrinolysis in a large cohort of individuals with type 2 diabetes.

Methods

Plasma levels of C3, C-reactive protein (CRP), PAI-1 and fibrinogen were analysed by ELISA in 837 patients enrolled in the Edinburgh Type 2 Diabetes Study. Fibrin clot lysis was analysed using a validated turbidimetric assay.

Results

Clot lysis time correlated with C3 and PAI-1 plasma levels (r = 0.24, p < 0.001 and r = 0.22, p < 0.001, respectively). In a multivariable regression model involving age, sex, BMI, C3, PAI-1, CRP and fibrinogen, and using log-transformed data as appropriate, C3 was associated with clot lysis time (regression coefficient 0.227 [95% CI 0.161, 0.292], p < 0.001), as was PAI-1 (regression coefficient 0.033 [95% CI 0.020, 0.064], p < 0.05) but not fibrinogen (regression coefficient 0.003 [95% CI −0.046, 0.051], p = 0.92) or CRP (regression coefficient 0.024 [95% CI −0.008, 0.056], p = 0.14). No correlation was demonstrated between plasma levels of C3 and PAI-1 (r = −0.03, p = 0.44), consistent with previous observations that the two proteins affect different pathways in the fibrinolytic system.

Conclusions/interpretation

Similarly to PAI-1, C3 plasma levels are independently associated with fibrin clot lysis in individuals with type 2 diabetes. Therefore, future studies should analyse C3 plasma levels as a surrogate marker of fibrinolysis potential in this population.

Keywords

Complement C3 C-reactive protein CRP Diabetes Fibrinolysis 

Abbreviations

C3

Complement C3

CRP

C-reactive protein

ET2DS

Edinburgh Type 2 Diabetes Study

PAI-1

Plasminogen activator inhibitor-1

Supplementary material

125_2014_3267_MOESM1_ESM.pdf (65 kb)
ESM Table 1(PDF 65 kb)
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ESM Table 6(PDF 62 kb)

References

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Katharina Hess
    • 1
  • Saad H. Alzahrani
    • 2
    • 3
  • Jackie F. Price
    • 4
  • Mark W. Strachan
    • 5
  • Natalie Oxley
    • 2
  • Rhodri King
    • 2
  • Tobias Gamlen
    • 2
  • Verena Schroeder
    • 6
  • Paul D. Baxter
    • 7
  • Ramzi A. Ajjan
    • 2
  1. 1.Department of CardiologyUniversity Hospital RWTH AachenAachenGermany
  2. 2.Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics, Health and Therapeutics, LIGHT Laboratories, Clarendon WayUniversity of LeedsLeedsUK
  3. 3.Specialized Diabetes and Endocrine CentreKing Fahad Medical CityRiyadhKingdom of Saudi Arabia
  4. 4.Centre for Population Health SciencesUniversity of EdinburghEdinburghUK
  5. 5.Metabolic UnitWestern General HospitalEdinburghUK
  6. 6.University Clinic of Hematology and Central Hematology Laboratory, Hemostasis Research LaboratoryUniversity Hospital and University of BernBernSwitzerland
  7. 7.Division of Epidemiology and BiostatisticsLeeds Institute of Genetics, Health and Therapeutics, University of LeedsLeedsUK

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