Insulin Resistance and Platelet Hyperactivity: Hematological Insights and Nutritional Strategies for Vascular Protection

Insulin resistance (IR) promotes a prothrombotic milieu by enhancing platelet hyperactivity, oxidative stress, and endothelial dysfunction, driving both microvascular and macrovascular complications in type 2 diabetes. Our review synthesizes mechanistic evidence showing that insulin-resistant platelets exhibit increased basal activation, elevated sensitivity to agonists, and reduced responsiveness to inhibitory signals, with distinct pro-aggregatory subpopulations amplifying thrombotic risk. Molecular pathways underlying platelet hyperactivation include reactive oxygen species accumulation, advanced glycation end-product signaling, disrupted calcium homeostasis, and impaired nitric oxide/prostacyclin pathways. Clinically, these mechanisms contribute to heightened arterial thrombosis, coronary artery disease, stroke, and microvascular injury, including nephropathy and retinopathy. Nutritional interventions emerge as effective modulators of platelet function and vascular health. Diets such as the Mediterranean, DASH, low-glycemic-index, and plant-based regimens, alongside bioactive compounds-including omega-3 fatty acids, polyphenols, vitamins D, E, C, and minerals like magnesium and zinc-may reduce platelet aggregation, oxidative stress, and systemic inflammation while restoring endothelial function. Clinical and epidemiological evidence demonstrates improvements in flow-mediated dilation, arterial elasticity, and stabilization of atherosclerotic plaques following dietary interventions. Integrating whole-diet strategies with targeted nutrients provides synergistic benefits, suggesting that personalized nutritional approaches can mitigate IR-induced platelet hyperactivity and lower vascular risk. These findings highlight nutrition as a practical, evidence-based adjunct to pharmacotherapy for cardiovascular protection in insulin-resistant populations.