Increased DNA oxidative susceptibility without increased plasma LDL oxidizability in Type II diabetes: effects of alpha-tocopherol supplementation

In vivo supplementation studies of the antioxidant alpha -tocopherol in hum an Type II diabetes have used surrogate, rather than direct, markers of oxi dative damage/antioxidant protection and have used higher doses of alpha -t ocopherol than used in coronary secondary prevention trials. We tested the hypothesis that oral alpha -tocopherol in a dosage regimen used in secondar y prevention trials would reduce directly observed oxidatively induced sing le-strand breaks in lymphocyte DNA in Type II diabetes. We studied 40 peopl e with Type II diabetes and 30 controls in a randomized, double-blind, plac ebo-controlled trial of 400 i.u. of oral alpha -tocopherol daily for 8 week s. Lymphocyte DNA single-strand breaks and low-density lipoprotein (LDL) pa rticle size and oxidizability were measured at baseline, after 8 weeks, and after 4 weeks washout. Polymorphisms in the gene for the antioxidant enzym e paraoxonase-1 gene (position 192) were measured. The diabetics had increa sed DNA oxidative susceptibility (P = 0.008), without increased LDL oxidati ve susceptibility. There was a direct relationship between DNA oxidative su sceptibility and baseline plasma alpha -tocopherol in the diabetes group al one (r = 0.421, r(2) = 0.177 and P = 0.023), but DNA and LDL oxidative susc eptibility were not influenced by alpha -tocopherol supplementation in eith er group in this regimen. Paraoxonase-1 gene polymorphisms did not contribu te to LDL or DNA oxidative susceptibility or response to alpha -tocopherol. Increased DNA oxidative susceptibility, therefore, can occur in Type II di abetes without increased LDL oxidative susceptibility, but alpha -tocophero l supplementation in this regimen has no influence on DNA or LDL oxidative susceptibility in Type II diabetes or controls. Polymorphisms in the paraox onase gene (position 192) are not associated with differences in oxidative susceptibility or responses to alpha -tocopherol.