Determinants of aspirin loss of efficacy in type 2 diabetic patients

Background Aspirin is clinically less effective for preventing atherosclerotic events in type-2 diabetic patients (T2DP). Aspirin loss of efficacy (ALE) in T2DP is mainly related to an accelerated platelet turnover with persistent platelet reactivity 24 h after last aspirin intake. Purpose To investigate the main mechanisms associated with ALE in T2DP. Methods This prospective study included consecutive stable T2DP coming for yearly check-up between March and July 2016. ALE was defined as a persistent high platelet reactivity (HPR) using light transmission aggregometry (LTA) with arachidonic acid (threshold > 20% residual aggregation) and confirmed with serum thromboxane B2 measurement (TXB2), 24 h after last aspirin intake. Diabetes status, insulin resistance and inflammation were explored. Results 116 T2DP (mean age 65 ± 9 y.o., 69% men) were included. Mean duration of diabetes was 15 years and 50% were treated with insulin for 9 y. Using LTA, HPR was found in 27 (23%) patients. Population's characteristics are presented in Table 1 and Fig. 1 . Median duration of diabetes and insulin treatment were significantly longer in patients with HPR ( P  = 0.01). HPR was strongly related to all markers of insulin resistance: waist circumference ( P  = 0.007), HOMA-IR ( P  = 0.002), QUICKI index ( P  = 0.002), leptin ( P  = 0.01) and mean dose of long-lasting insulin/kg ( P  = 0.006). Surprisingly, there was no relationship with thrombopoietin ( P  = 0.38) and inflammatory markers: IL6 ( P  = 0.86), IL10 ( P  = 0.68), IDO activity ( P  = 0.98), TNFalpha ( P  = 0.31), usCRP ( P  = 0.08). TXB2 concentration was also strongly correlated with all insulin resistance parameters, especially with HOMA–IR ( r  = −0.42, P  = 0.002), QUICKI index ( r  = −0.44, P  = 0.0006) and long lasting insulin dose/kg ( r  = −0.43, P  = 0.0007) but not to inflammatory parameters. Conclusion ALE is frequent in T2DP and appears to be strongly related to insulin resistance. This could help to select T2DP who could benefit to alternative antiplatelet treatment.