Aspirin as antiplatelet agent in diabetes. PROS

Macrovascular complications in diabetes mellitus (DM) manifest themselves as accelerated atherosclerosis, clinically resulting in premature coronary artery disease (CAD), increased risk of cerebrovascular disease, and severe peripheral vascular disease [1]. Patients with type 2 diabetesmellitus (T2DM) have a twoto four-fold increase in the risk of CAD and patients with DM but without previous myocardial infarction (MI) carry the same level of risk for subsequent acute coronary events as non-diabetic patients with previous MI [2]. The abnormal metabolic state that accompanies diabetes is responsible for abnormalities in endothelial and platelet function, which may contribute to the cellular events that cause atherosclerosis and subsequently increase the risk of the adverse cardiovascular events. In particular, an altered platelet metabolism and changes in intraplatelet signalling pathways may contribute to the pathogenesis of atherothrombotic complications of diabetes. It is still under debate whether enhanced platelet activation is merely a consequence of more prevalent atherosclerotic lesions (relevant to a risk of thrombosis complicating plaque rupture) or reflects the influence of the accompanyingmetabolic disturbances on platelet biochemistry and function [3]. Since 1965 many studies demonstrated a variety of platelet alterations in diabetes [4]. Chronic hyperglycemia has been clearly identified as a causal factor for in vivo platelet activation in DM patients [3,5]. In 1990, Davi et al. demonstrated enhanced thromboxane (TX) biosynthesis in T2DM and provided evidence for its platelet origin [6]. Tightmetabolic control led to a reduction of TX levels in the same study [6]. We subsequently reported that the release of a platelet-derived inflammatorymolecule, soluble CD40 ligand, able to activate platelets, is largely thromboxane dependent, thus suggesting a potential mechanismof amplificationof thromboxane-dependent platelet activation [7]. Interestingly, the metabolic disorder rather than the attendant vasculardiseaseappears tobe responsible forpersistentplatelet activation in this setting [3]. This important issue has been further proven by the detection of enhanced TX biosynthesis in type 1 diabetic children and adolescents at diagnosis, presumably driven by the underlying inflammatory burden [8], as well as in newly-diagnosed type 2 diabetic subjects free of vascular disease. In the latter the biochemical abnormality is reversible by dampening postprandial glycemic spikes with acarbose treatment [9]. Consistently, acute, short-term hyperglycemia induces increased activation of platelets exposed to high shear stress conditions