Thromboxane Biosynthesis and Platelet Function in Type II Diabetes Mellitus

Abstract

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 less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)

Tight Glycemic Control in Diabetic Coronary Artery Bypass Graft Patients Improves Perioperative Outcomes and Decreases Recurrent Ischemic Events

“…Patients with diabetes also have impaired platelet function characterized by increased levels of plasminogen activator inhibitor-1 and adhesion molecules. 15,16 This enhances platelet adhesiveness and hyperaggregability and predisposes to coronary thrombosis, which may ultimately affect long-term vein graft patency. Intravenous infusions of insulin after CABG surgery have been shown to decrease levels of free fatty acids and increase myocardial uptake of glucose.…”

“…It upwardly regulates the L-arginine-NO pathway, which improves endothelial function, and it decreases serum levels of plasminogen activator inhibitor-1. 15 Several studies have shown that hyperglycemia is associated with adverse outcomes during acute coronary syndromes. Wahab and colleagues 19 studied the effects of increased blood glucose in 1664 patients admitted with an acute MI.…”

Beyond Hyperglycemia in Diabetes: Role of Statin Treatment on Thrombogenesis Triggered by Inflammation

“…Chronic hyperglycemia has been clearly identified as a causal factor for in vivo platelet activation [11]. Our group firstly demonstrated enhanced thromboxane (TX) biosynthesis in T2D, providing evidence for its platelet origin.…”

“…Our group firstly demonstrated enhanced thromboxane (TX) biosynthesis in T2D, providing evidence for its platelet origin. Moreover, tight metabolic control led to reduction of TX metabolite urinary levels [11]. Interestingly, inflammatory mediators (such as CD40L) derived from platelets 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 [12].…”

Platelet activation in type 2 diabetes mellitus

“…Increased platelet aggregation in DM was recognized already in 1965 [20]; since then many studies have demonstrated that platelet degranulation and synthesis of TX derivatives mediating further platelet activation are increased in DM [21,22], whereas platelet-mediated vasodilatation is impaired [23]. Furthermore, platelets from DM patients have been shown to have diminished sensitivity to natural antiaggregating Fig.…”