Background—Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2a, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation. Methods and Results—Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2a and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non–insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2a in this setting. Urinary 8-iso-PGF2a excretion was significantly higher (P50.0001) in NIDDM patients (4196208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208692; 41 to 433). Urinary 8-iso-PGF2a was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2a excretion was also significantly (P50.0001) higher in IDDM patients (4006146; 183 to 702) than in control subjects (197669; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2a (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P50.0001) reduction in 8-iso-PGF2a and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2a was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion. Conclusions—We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.

In vivo formation of 8-iso-prostaglandin f2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation.

DAVI', Giovanni;CIABATTONI, Giovanni;CONSOLI, Agostino;MEZZETTI, Andrea;FALCO, Angela;VITACOLONNA, Ester;BUCCIARELLI, Tonino;COSTANTINI, Fabrizio;CAPANI, Fabio;PATRONO, Carlo
1999

Abstract

Background—Diabetes mellitus (DM) is associated with enhanced lipid peroxidation and persistent platelet activation. We tested the hypothesis that the in vivo formation of the F2-isoprostane 8-iso-prostaglandin (PG)F2a, a bioactive product of arachidonic acid peroxidation, is enhanced in DM and contributes to platelet activation. Methods and Results—Urine samples were obtained from 85 diabetic patients and 85 age- and sex-matched healthy subjects for measurement of immunoreactive 8-iso-PGF2a and 11-dehydro-thromboxane B2 (TXM), an in vivo index of platelet activation. Sixty-two had non–insulin-dependent (NID)DM, and 23 had insulin-dependent (ID) DM. Vitamin E supplementation, metabolic control, and cyclooxygenase inhibitors were used to investigate the mechanisms of formation of 8-iso-PGF2a in this setting. Urinary 8-iso-PGF2a excretion was significantly higher (P50.0001) in NIDDM patients (4196208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208692; 41 to 433). Urinary 8-iso-PGF2a was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2a excretion was also significantly (P50.0001) higher in IDDM patients (4006146; 183 to 702) than in control subjects (197669; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2a (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P50.0001) reduction in 8-iso-PGF2a and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2a was unchanged after 2-week dosing with aspirin and indobufen despite profound suppression of TXM excretion. Conclusions—We conclude that DM is associated with increased formation of F2-isoprostanes, as a correlate of impaired glycemic control and enhanced lipid peroxidation. This may provide an important biochemical link between impaired glycemic control and persistent platelet activation. These results provide a rationale for dose-finding studies of antioxidant treatment in diabetes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/134557
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