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

Circulation. 1999 Jan 19;99(2):224-9. doi: 10.1161/01.cir.99.2.224.


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)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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes Mellitus / blood*
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / therapy
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / therapy
  • Dinoprost / analogs & derivatives*
  • Dinoprost / biosynthesis
  • Dinoprost / urine
  • F2-Isoprostanes
  • Female
  • Humans
  • Lipid Peroxidation
  • Male
  • Middle Aged
  • Platelet Activation / physiology*
  • Thromboxane B2 / analogs & derivatives
  • Thromboxane B2 / urine
  • Vitamin E / pharmacology*


  • F2-Isoprostanes
  • Vitamin E
  • 8-epi-prostaglandin F2alpha
  • Thromboxane B2
  • 11-dehydro-thromboxane B2
  • Dinoprost