Factors Contributing to Increased Platelet Reactivity in People With Diabetes

Abstract

People with diabetes, particularly those with type 2 diabetes, exhibit increased platelet reactivity. Hyperglycemia contributes to greater platelet reactivity through direct effects and by promoting glycation of platelet proteins. Hypertriglyceridemia increases platelet reactivity. Both insulin resistance and insulin deficiency increase platelet reactivity. Insulin antagonizes activation of platelets. Thus, relative or absolute deficiency of insulin would be expected to increase platelet reactivity. Diabetes is associated with oxidative stress and inflammation. Resultant endothelial dysfunction promotes activation of platelets by decreasing production of nitric oxide (NO) that attenuates platelet reactivity. Oxidative stress accentuates this effect by attenuating activity of NO and promoting platelet activation. Inflammation and platelet activation are reciprocally related. Inflammation promotes platelet activation that, in turn, promotes inflammation. Accordingly, improved metabolic control achieved with regimens that improve insulin sensitivity and preserve pancreatic β-cell function is likely to decrease platelet reactivity and enhance effects of antiplatelet agents. Platelets from subjects with diabetes exhibit increased reactivity (i.e., increased propensity to activate in response to a stimulus) (1). This review highlights factors that contribute to increased platelet reactivity. Type 2 diabetes is more prevalent than type 1 diabetes and is associated with a substantially increased risk of macrovascular complications. Accordingly, this review focuses on platelet reactivity in subjects with type 2 diabetes. Key aspects of type 2 diabetes are insulin resistance, metabolic abnormalities including hyperglycemia, and systemic abnormalities including oxidative stress and inflammation. The influence of each of these abnormalities on platelet function is addressed. ### Metabolic abnormalities and platelet function Induction of hyperglycemia and hyperinsulinemia in healthy subjects without diabetes increases platelet reactivity (2). Consistent with this observation, improved glycemic control has been associated with decreased platelet …