In vivo supplementation studies of the antioxidant α-tocopherol in human Type II diabetes have used surrogate, rather than direct, markers of oxidative damage/antioxidant protection and have used higher doses of α-tocopherol than used in coronary secondary prevention trials. We tested the hypothesis that oral α-tocopherol in a dosage regimen used in secondary prevention trials would reduce directly observed oxidatively induced single-strand breaks in lymphocyte DNA in Type II diabetes. We studied 40 people with Type II diabetes and 30 controls in a randomized, double-blind, placebo-controlled trial of 400 i.u. of oral α-tocopherol daily for 8 weeks. Lymphocyte DNA single-strand breaks and low-density lipoprotein (LDL) particle size and oxidizability were measured at baseline, after 8 weeks, and after 4 weeks washout. Polymorphisms in the gene for the antioxidant enzyme paraoxonase-1 gene (position 192) were measured. The diabetics had increased DNA oxidative susceptibility (P = 0.008), without increased LDL oxidative susceptibility. There was a direct relationship between DNA oxidative susceptibility and baseline plasma α-tocopherol in the diabetes group alone (r = 0.421, r2 = 0.177 and P = 0.023), but DNA and LDL oxidative susceptibility were not influenced by α-tocopherol supplementation in either group in this regimen. Paraoxonase-1 gene polymorphisms did not contribute to LDL or DNA oxidative susceptibility or response to α-tocopherol. Increased DNA oxidative susceptibility, therefore, can occur in Type II diabetes without increased LDL oxidative susceptibility, but α-tocopherol supplementation in this regimen has no influence on DNA or LDL oxidative susceptibility in Type II diabetes or controls. Polymorphisms in the paraoxonase gene (position 192) are not associated with differences in oxidative susceptibility or responses to α-tocopherol.
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August 03 2001
Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of α-tocopherol supplementation
Michael J. SAMPSON;
Michael J. SAMPSON
*Bertram Diabetes Research Unit, Department of Endocrinology and Diabetes, Norfolk and Norwich Healthcare NHS Trust, Brunswick Road, Norwich NR1 3SR, U.K.
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Sian ASTLEY;
Sian ASTLEY
†Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, U.K.
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Tristan RICHARDSON;
Tristan RICHARDSON
*Bertram Diabetes Research Unit, Department of Endocrinology and Diabetes, Norfolk and Norwich Healthcare NHS Trust, Brunswick Road, Norwich NR1 3SR, U.K.
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Gavin WILLIS;
Gavin WILLIS
‡Department of Molecular Genetics, Norfolk and Norwich Healthcare NHS Trust, Norwich NR1 3SR, U.K.
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Isabel R. DAVIES;
Isabel R. DAVIES
*Bertram Diabetes Research Unit, Department of Endocrinology and Diabetes, Norfolk and Norwich Healthcare NHS Trust, Brunswick Road, Norwich NR1 3SR, U.K.
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David A. HUGHES;
David A. HUGHES
†Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, U.K.
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Sue SOUTHON
Sue SOUTHON
†Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, U.K.
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Publisher: Portland Press Ltd
Received:
April 03 2001
Accepted:
May 04 2001
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2001
2001
Clin Sci (Lond) (2001) 101 (3): 235–241.
Article history
Received:
April 03 2001
Accepted:
May 04 2001
Citation
Michael J. SAMPSON, Sian ASTLEY, Tristan RICHARDSON, Gavin WILLIS, Isabel R. DAVIES, David A. HUGHES, Sue SOUTHON; Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of α-tocopherol supplementation. Clin Sci (Lond) 1 September 2001; 101 (3): 235–241. doi: https://doi.org/10.1042/cs1010235
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