Abstract 457: Type 1 and 2 Diabetic Patients Under Chronic Aspirin Treatment Exhibit A Persistent Platelet Thromboxane-A2 Production
Background: Clinical trials have highlighted that aspirin (ASA) is less effective in reducing cardiovascular events in both type 1 and 2 diabetic patients, compared to nondiabetics. We have recently demonstrated that platelets from patients under chronic aspirin treatment still retain the capability to generate thromboxane A2 (TxA2) with a wide inter-individual variability. Then, persistent TxA2 might account for the limited benefit of ASA in diabetic patients.
Methods: We investigated TxA2 production in serum and following platelet stimulation with collagen in 100 type 2 diabetics, in 26 type 1 diabetics and in 100 nondiabetics, all under chronic aspirin treatment. Platelet COX-1 and COX-2 expression was evaluated in 20 type 2 diabetics, 15 type 1 diabetics and 20 nondiabetics.
Results: Serum TxA2 production in response to collagen was significantly higher (p<0.001 and 0,003, respectively) both in type 1 (1726.6Â 27>478.3 pg/108 cells) and in type 2 (1521.3Â 27>187.7 pg/108 cells) diabetic patients compared to nondiabetics (864.6Â 27>31.5 pg/108 cells). Collagen-induced TxA2 production was also significantly higher (p<0.001) both in type 1 (845.4Â 27>381.9 pg/108 cells) and in type 2 (854.0Â 27>165.7 pg/108 cells) diabetic patients compared to nondiabetics (130.5Â 27>31.5 pg/108 cells). Expression of both COX isoforms, demonstrated that while COX-1 was highly expressed in all groups, COX-2 was expressed in all diabetic patients, both of type 1 and type 2, analyzed but only in 46% nondiabetics.
Conclusion: Diabetic patients present persistent TxA2 production during ASA treatment which might account for the lower clinical benefit of ASA. The similar persistent TxA2 production in type 1 and 2 diabetes, suggests that it is caused by hyperglycemia and not by the metabolic abnormalities associated to type 2 diabetes.