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

Hess, Katharina; Alzahrani, Saad H; Price, Jackie F; Strachan, Mark W; Oxley, Natalie; King, Rhodri; Gamlen, Tobias; Schroeder, Verena; Baxter, Paul D; Ajjan, Ramzi A (2014). Hypofibrinolysis in type 2 diabetes: the role of the inflammatory pathway and complement C3. Diabetologia, 57(8), pp. 1737-1741. Springer 10.1007/s00125-014-3267-z

Preview

Text art%3A10.1007%2Fs00125-014-3267-z.pdf - Published Version Available under License Publisher holds Copyright. Download (157kB) | Preview

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.

Interest & Impact

Downloads

65 since deposited on 29 Apr 2015
22 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item