Abstract 1719: A Potential Mechanism for the Reduced Efficacy of Aspirin in Individuals with Diabetes
The protective effects of aspirin are reduced in individuals with diabetes by mechanisms that remain unclear. Diabetes is associated with changes in clot structure making it more resistant to lysis, which may be due to increased glycation of the fibrinogen molecule. In contrast, we have recently found that acetylation of fibrinogen enhances fibrinolysis of the fibrin clot. The aim of this study was to assess whether the reduced efficacy of aspirin in diabetes is due to an interaction between acetylation and glycation in fibrinogen and clotting factors.Type 1 diabetes subjects with poor diabetes control (n = 18) were recruited and insulin treatment was intensified. Blood samples were obtained before and after improving glycaemic control over a period of 7.3 months (CI 5.5, 9.2). Plasma samples were incubated with 0, 1, 10 and 100 mg L-1 aspirin for 5 h at 37°C, subsequently treated with thrombin and tissue plasminogen activator, and time to 50% lysis was assessed using turbidity measurements. Electron microscopy was used to study the structure of clots made from plasma-purified fibrinoge.HbA1c was reduced significantly post-intervention [10.52% (9.56, 11.48) vs. 9.23% (8.31, 10.15)]. In the absence of aspirin, improvement in glycaemic control significantly reduced lysis time [357 (312, 402) and 323 (278, 368) seconds at baseline and after intervention respectively; p < 0.05]. Low dose aspirin (1 mg L−1 and 10 mg L−1) had an adverse effect on lysis time in the presence of poor diabetes control [367 (323, 413) and 385 (332, 437) seconds respectively, p < 0.05], whereas high dose aspirin (100 mg L−1) had a beneficial effect on lysis time only in individuals with improved glycaemic control [299 (264, 333) seconds, p < 0.05]. Experiments on plasma-purified fibrinogen showed the formation of thicker fibres and bigger pores with improved glycaemic control and after treatment with high dose aspirin. This study has shown that improvement in glycaemic control has a beneficial effect on fibrinolysis. Our work has also demonstrated that aspirin treatment can adversely affects lysis time in the presence of poor glycaemic control, which may explain the reduced efficacy of this agent in individuals with diabetes.