Thromboxane biosynthesis and platelet function in type I diabetes mellitus.
It has been speculated that platelet activation may contribute to the evolution of vascular complications in patients with Type I diabetes mellitus. To address this hypothesis, we measured the plasma and urinary metabolites of thromboxane, presumably of platelet origin, and of prostacyclin, derived from endothelial cells, in addition to more conventional indexes of platelet function. Urinary excretion of the metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha did not differ between diabetics with or without retinopathy and nondiabetic controls. Furthermore, measurement of platelet granule constituents, the aggregation responses to ADP or arachidonic acid, and levels of serum thromboxane B2 failed to discriminate between the groups. The institution of tight diabetic control with multiple daily injections of insulin failed to alter either urinary metabolite excretion or plasma levels of 11-dehydro-thromboxane B2. Conversely, insulin-induced hypoglycemia failed to alter the concentrations of plasma or urinary thromboxane metabolites in nondiabetic volunteers, despite a mean 60-fold increase in plasma epinephrine. These studies suggest that platelet activation does not precede the development of microvascular complications in patients with Type I diabetes who lack clinical evidence of macrovascular disease and have normal renal function. Furthermore, it is unlikely that platelet activation due to intermittent hypoglycemia contributes to the reportedly accelerated development of retinopathy in such patients, when they are subject to tight diabetic control.
Alessandrini
P
P
Division of Clinical Pharmacology, Vanderbilt University, Nashville, TN 37232.
McRae
J
J
Feman
S
S
FitzGerald
G A
GA
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000293:Adolescent; D000328:Adult; D001792:Blood Platelets / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology; D011464:Epoprostenol / Q000097:blood; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D010974:Platelet Aggregation; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*
D007328:Insulin; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; C049235:11-dehydro-thromboxane B2; D011464:Epoprostenol