Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3.
OBJECTIVE
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
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.
Department of Cardiology, University Hospital RWTH Aachen, Aachen, Germany.
Katharina
K
Hess
Saad H
SH
Alzahrani
Jackie F
JF
Price
Mark W
MW
Strachan
Natalie
N
Oxley
Rhodri
R
King
Tobias
T
Gamlen
Verena
V
Schroeder
Paul D
PD
Baxter
Ramzi A
RA
Ajjan
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D003176:Complement C3 / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*
D003176:Complement C3; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen; D002097:C-Reactive Protein