THROMBOXANE BIOSYNTHESIS AND PLATELET-FUNCTION IN TYPE-II DIABETES-MELLITUS

It has been suggested that platelet hyperreactivity in patients with diabetes mellitus is associated with increased platelet production of thromboxane. We therefore compared the excretion of a thromboxane metabolite and platelet function in 50 patients with Type II diabetes mellitus who had normal renal function and clinical evidence of macrovascular disease and in 32 healthy controls. The mean (±SD) excretion rate of urinary 11-dehydro-thromboxane B2 was significantly higher in the patients than in the controls (5.94±3.68 vs. 1.50±0.79 nmol per day; P<0.001), irrespective of the type of macrovascular complication. Tight metabolic control achieved with insulin therapy reduced the levels of 11-dehydro-thromboxane B2 by approximately 50 percent. The fractional conversion of exogenous thromboxane B2 (infused at a rate of 4.5,45.3, or 226.4 fmol per kilogram of body weight per second) to urinary 11-dehydro-thromboxane B2 was assessed in four patients, in whom it averaged 5.4±0.1 percent; this value did not differ from that measured in healthy subjects. Aspirin in low doses (50 mg per day for seven days) reduced urinary excretion of the metabolite by approximately 80 percent in four patients. The fact that thromboxane biosynthesis recovered over the following 10 days was consistent with a platelet origin of the urinary metabolite. We conclude that in Type II diabetes (1) increased 11-dehydro-thromboxane B2 excretion reflects enhanced biosynthesis of thromboxane A2 by platelets rather than a shift in its metabolic disposition; (2) this is likely to reflect in vivo platelet activation; and (3) improved metabolic control as well as low-dose aspirin therapy may correct these abnormalities in platelet function to a variable extent. PLATELETS from patients with diabetes and from diabetic rats have been reported to synthesize more thromboxane than normal platelets in response to a variety of agonists that induce deacylation of arachidonate from membrane phospholipids.1 Di Minno et al.2 have suggested that the increased fibrinogen binding and aggregation of platelets from diabetic subjects in response to adenosine diphosphate or collagen is mediated by increased formation of prostaglandin H2, thromboxane A2, or both. Several lines of evidence indicate that increased thromboxane production may be related primarily to high concentrations of blood glucose or lipids (or both), rather than… © 1990, Massachusetts Medical Society. All rights reserved.