Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.

Zaccardi, F., Rizzi, A., Petrucci, G., Ciaffardini, F., Tanese, L., Pagliaccia, F., Cavalca, V., Ciminello, A. M., Habib, A., Squellerio, I., Rizzo, P., Tremoli, E., Rocca, B., Pitocco, D., Patrono, C., In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes, <<DIABETES>>, 2016; 65 (2): 503-509. [doi:10.2337/db15-0936] [http://hdl.handle.net/10807/70852]

In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes

Zaccardi, Francesco;Rizzi, Alessandro;Petrucci, G;Ciaffardini, Flavia;Tanese, Luigi;Pagliaccia, Francesca;Ciminello, Angela Maria;Rizzo, Paola;Rocca, Bianca;Pitocco, Dario;Patrono, Carlo
2016

Abstract

Platelet activation is persistently enhanced, and its inhibition by low-dose aspirin is impaired in type 2 diabetes mellitus. We investigated in vivo thromboxane (TX) and prostacyclin (PGI2) biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus (T1DM) without overt cardiovascular disease and stable glycemic control. The biosynthesis of TXA2 was persistently increased in subjects with T1DM versus matched healthy subjects, with females showing higher urinary TX metabolite (TXM) excretion than male subjects with T1DM. Microalbuminuria and urinary 8-iso-PGF2α, an index of in vivo oxidative stress, independently predicted TXM excretion in T1DM. No homeostatic increase in PGI2 biosynthesis was detected. Platelet COX-1 suppression by low-dose aspirin and the kinetics of its recovery after drug withdrawal were similar in patients and control subjects and were unaffected by glucose variability. We conclude that patients with T1DM and stable glycemic control display enhanced platelet activation correlating with female sex and microvascular and oxidative damages. Moreover, aspirin responsiveness is unimpaired in T1DM, suggesting that the metabolic disturbance per se is unrelated to altered pharmacodynamics. The efficacy and safety of low-dose aspirin in T1DM warrant further clinical investigation.
Inglese
Zaccardi, F., Rizzi, A., Petrucci, G., Ciaffardini, F., Tanese, L., Pagliaccia, F., Cavalca, V., Ciminello, A. M., Habib, A., Squellerio, I., Rizzo, P., Tremoli, E., Rocca, B., Pitocco, D., Patrono, C., In Vivo Platelet Activation and Aspirin Responsiveness in Type 1 Diabetes, <<DIABETES>>, 2016; 65 (2): 503-509. [doi:10.2337/db15-0936] [http://hdl.handle.net/10807/70852]
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