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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1737-1741
Number of pages5
JournalDiabetologia
Volume57
Issue number8
DOIs
Publication statusPublished - Aug 2014

Keywords

  • Complement C3
  • C-reactive protein
  • CRP
  • Diabetes
  • Fibrinolysis
  • COAGULATION
  • DISEASE

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