Plasma F2 Isoprostanes
Direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes
- Michael J. Sampson, MD1,
- Nitin Gopaul, PHD2,
- Isabel R. Davies, PHD3,
- David A. Hughes, PHD3 and
- Martin J. Carrier, PHD2
- 1Bertram Diabetes Research Unit, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, U.K.
- 2William Harvey Research Institute, St. Bartholomews Hospital, London, U.K.
- 3Institute of Food Research, Norwich Research Park, Colney, Norwich, U.K.
Abstract
OBJECTIVES—Acute hyperglycemia in type 2 diabetes increases the generation of plasma 8-epi-prostaglandin F2 (8-epi-PGF2α) isoprostane, a sensitive direct marker of in vivo free radical oxidative damage to membrane phospholipids.
RESEARCH DESIGN AND METHODS—A total of 21 patients with type 2 diabetes underwent an oral 75-g glucose tolerance test. Plasma 8-epi-PGF2α isoprostane concentrations (by gas chromatography [GC]/mass spectrometry [MS]), intralymphocyte reduced-to-oxidized glutathione ratios, and plasma total antioxidant capacity were measured at baseline and 90 min after glucose loading.
RESULTS—Plasma 8-epi-PGF2α isoprostane concentrations rose significantly (P=0. 010) from 0.241± 0.1 to 0.326± 0.17 ng/l after 90 min. Intracellular oxidative balance and plasma antioxidant capacity did not change in either group.
CONCLUSIONS—Plasma concentrations of 8-epi-PGF2α isoprostane increase during acute hyperglycemia in type 2 diabetes, providing direct evidence of free radical–mediated oxidative damage and demonstrating a pathway for an association between acute rather than fasting hyperglycemia and macrovascular risk in type 2 diabetes.
- ABTS, 2,2-azino-bis-3-ethylbensthiazoline-6-sulfonic acid
- BHT, butylated hydroxytoluene
- 8-epi-PGF2α, 8-epi-prostaglandin F2α
- GC, gas chromatography
- GSH, glutathione
- MS, mass spectrometry
- TAOS, total antioxidant status
Footnotes
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Address correspondence and reprint requests to Dr. M.J. Sampson, Department of Endocrinology and Diabetes, Norfolk and Norwich University Hospital NHS Trust, Brunswick Rd., Norwich NR1 3SR, U.K. E-mail: mike.sampson{at}norfolk-norwich.thenhs.com.
Received for publication 25 July 2001 and accepted in revised form 30 November 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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