Platelets and Diabetes

It is increasingly recognized that platelets are the culprit cells implicated in the propensity to atherothrombosis in the setting of both type 1 and type 2 diabetes mellitus, making the study of platelet pathophysiology and platelet activation/inhibition some of the most intriguing fields of research related to diabetes vascular complications. Indeed, a platelet hyperreactive phenotype with biochemical evidence of persistent in vivo platelet activa- tion, with enhanced thromboxane (TX) biosynthesis, has been described in diabetic patients in different stages along the natural history of the impairment of glucose metabolism, even in the preclinical phases. This chapter highlights several issues within this field: (1) the variable contribution of sustained and acute hyperglycemia, glycemic instability, and insulin resistance to the observed changes in the platelet pathophysiology; (2) the role of oxidative stress and inflammation and namely of platelet-derived inflammatory molecules and microparticles, as secondary mediators of diabetes-induced platelet activation; and (3) the complex intertwining between the described pathophysiology and the anticipated epidemiological burden in terms of high risk of vascular events and lower protection from antithrombotic prophylaxis, with particular reference to aspirin. Availability of high-throughput techniques is rapidly changing the way we address the problem, with a deeper insight on transcriptomics and posttranscriptional regulation of platelets as a consequence of the above-described metabolic abnormalities.