title: Platelets and diabetes mellitus.
abstract: Platelet activation plays a key role in atherothrombosis in type 2 diabetes mellitus (T2DM) and increased in vivo platelet activation with enhanced thromboxane (TX) biosynthesis has been reported in patients with impairment of glucose metabolism even in the earlier stages of disease and in the preclinical phases. In this regards, platelets appear as addresses and players carrying and transducing metabolic derangement into vascular injury. The present review critically addresses key pathophysiological aspects including (i) hyperglycemia, glycemic variability and insulin resistance as determinants and predictors of platelet activation, (ii) inflammatory mediators derived from platelets, such as soluble CD40 ligand, soluble CD36, Dickkopf-1 and probably soluble receptor for advanced glycation-end-products (sRAGE), which expand the functional repertoire of platelets from players of hemostasis and thrombosis to powerful amplifiers of inflammation by promoting the release of cytokines and chemokines, cell activation, and cell-cell interactions; (iii) molecular mechanisms underpinning the less-than-expected antithrombotic protection by aspirin (ASA), despite regular antiplatelet prophylaxis at the standard dosing regimen, and (iv) stratification of patients deserving different antiplatelet strategies, based on the metabolic phenotype. Taken together, these pathophysiological aspects may contribute to the development of promising mechanism-based therapeutic strategies to reduce the progression of atherothrombosis in diabetic subjects.
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University of Chieti, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Santilli
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University of Chieti, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Simeone
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University of Chieti, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Liani
authors.affiliation: Internal Medicine and Center of Excellence on Aging, "G. D'Annunzio" University of Chieti, Italy. Electronic address: gdavi@unich.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Davì
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes
keywords: ASA responsiveness; Diabetes mellitus; Oxidative stress; Platelet activation; Platelet turnover; Platelet-derived inflammatory proteins