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

AbstractBACKGROUND:
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)F2alpha, 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-PGF2alpha 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-PGF2alpha in this setting. Urinary 8-iso-PGF2alpha excretion was significantly higher (P=0.0001) in NIDDM patients (419+/-208 pg/mg creatinine; range 160 to 1014) than in age-matched control subjects (208+/-92; 41 to 433). Urinary 8-iso-PGF2alpha was linearly correlated with blood glucose and urinary TXM. 8-iso-PGF2alpha excretion was also significantly (P=0. 0001) higher in IDDM patients (400+/-146; 183 to 702) than in control subjects (197+/-69; 95 to 353). Vitamin E supplementation (600 mg/d for 14 days) was associated with a statistically significant reduction in both urinary 8-iso-PGF2alpha (by 37%) and TXM (by 43%) in 10 NIDDM patients. Improved metabolic control was associated with a significant (P=0.0001) reduction in 8-iso-PGF2alpha and TXM excretion by 32% and 41%, respectively, in 21 NIDDM patients. 8-iso-PGF2alpha 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.
AuthorsG Davì, G Ciabattoni, A Consoli, A Mezzetti, A Falco, S Santarone, E Pennese, E Vitacolonna, T Bucciarelli, F Costantini, F Capani, C Patrono
JournalCirculation (Circulation) Vol. 99 Issue 2 Pg. 224-9 (Jan 19 1999) ISSN: 1524-4539 [Electronic] United States
PMID9892587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • F2-Isoprostanes
  • Vitamin E
  • 8-epi-prostaglandin F2alpha
  • Thromboxane B2
  • 11-dehydro-thromboxane B2
  • Dinoprost
Topics
  • Adult
  • Diabetes Mellitus (blood, metabolism, therapy)
  • Diabetes Mellitus, Type 1 (blood, metabolism, therapy)
  • Diabetes Mellitus, Type 2 (blood, metabolism, therapy)
  • Dinoprost (analogs & derivatives, biosynthesis, urine)
  • F2-Isoprostanes
  • Female
  • Humans
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Platelet Activation (physiology)
  • Thromboxane B2 (analogs & derivatives, urine)
  • Vitamin E (pharmacology)

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