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Plasma F₂ Isoprostanes

Direct evidence of increased free radical damage during acute hyperglycemia in type 2 diabetes

¹ Bertram Diabetes Research Unit, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, U.K.
² William Harvey Research Institute, St. Bartholomews Hospital, London, U.K.
³ Institute of Food Research, Norwich Research Park, Colney, Norwich, U.K.

OBJECTIVES—Acute hyperglycemia in type 2 diabetes increases the generation of plasma 8-epi-prostaglandin F₂ (8-epi-PGF₂) 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-PGF₂ 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-PGF₂ 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-PGF₂ 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.

Abbreviations: ABTS, 2,2-azino-bis-3-ethylbensthiazoline-6-sulfonic acid • BHT, butylated hydroxytoluene • 8-epi-PGF₂, 8-epi-prostaglandin F₂ • GC, gas chromatography • GSH, glutathione • MS, mass spectrometry • TAOS, total antioxidant status

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