Increased Platelet Arachidonic Acid Metabolism in Diabetes Mellitus

Platelets obtained from some diabetic patients show enhanced in vitro platelet aggregation. This study sought to determine if platelets obtained from insulindependent diabetic subjects synthesize increased quantities of the labile aggregating substance, thromboxane A₂ (TXA₂), and if it may play a role in the enhanced platelet aggregation. Arachidonic acid (1 mM)-stimulated TXA2 synthesis, as determined via radioimmunoassay of its stable metabolite TXB₂, was significantly greater (P < 0.01, N = 12) in platelet-rich plasma obtained from diabetics compared with matched controls. Arachidonic acid-stimulated TXB₂ synthesis in the diabetic platelet-rich plasma was positively correlated with the ambient fasting plasma glucose (r = 0.61, P < 0.02, N = 15). Platelet aggregation induced by arachidonic acid (0.4–0.8 mM) was inhibited significantly less by 13-azaprostanoic acid (P < 0.04, N = 14), a competitive antagonist of the actions of prostaglandin H₂ or TXA₂ on platelets, compared with matched controls. The results support the notion that platelets obtained from some insulin-dependent diabetic subjects manifest increased synthesis of TXA₂, which may contribute to the enhanced platelet aggregation.