title: Effects of Vitamin E on susceptibility of low-density lipoprotein and low-density lipoprotein subfractions to oxidation and on protein glycation in NIDDM.
abstract: OBJECTIVE
  To evaluate the effect of vitamin E supplementation on the susceptibility of low-density lipoprotein (LDL) and LDL subfractions to oxidation and on protein glycation in non-insulin-dependent diabetes mellitus (NIDDM).
  
  
  METHODS
  Twenty-one men with NIDDM (HbA1c = 6-10%), ages 50-70, were randomly assigned to either 1,600 IU/day of vitamin E or placebo for 10 weeks after a 4-week placebo period. LDL and LDL subfractions were isolated after 4 weeks of placebo and after 6 and 10 weeks of therapy. Susceptibility of LDL to copper-mediated oxidation was measured by conjugated diene formation (lag time) and formation of thiobarbituric acid-reactive substances (TBARS). Fasting serum glucose, mean weekly blood glucose, HbA1c, and glycated plasma protein concentrations were also determined at these time points.
  
  
  RESULTS
  Vitamin E content in plasma and LDL increased 4.0- and 3.7-fold, respectively, in the vitamin E-treated group. Vitamin E decreased the susceptibility of LDL to oxidation in comparison with placebo (lag time, 243 +/- 46 vs. 151 +/- 22 min, P < 0.01; 3 h TBARS, 24 +/- 12 vs. 66 +/- 18 nmol malondialdehyde/mg LDL, P < 0.05). Vitamin E content also increased significantly in both buoyant and dense LDL subfractions, and their oxidation was dramatically reduced. The lag time of LDL oxidation correlated well with the content of vitamin E in both LDL and its subfractions (r = 0.69-0.92). Glycemic indexes did not change significantly in either group during the study. Protein glycation, including glycated hemoglobin, glycated albumin, glycated total plasma proteins, and glycated LDL were unchanged in the vitamin E group.
  
  
  CONCLUSIONS
  Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.
authors.affiliation: Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla 92093-0682, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Reaven
authors.forename: D A
authors.initials: DA
authors.lastname: Herold
authors.forename: J
authors.initials: J
authors.lastname: Barnett
authors.forename: S
authors.initials: S
authors.lastname: Edelman
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003300:Copper; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D006031:Glycosylation; D006595:Hexosamines / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000032:analysis; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood / Q000627:therapeutic use*; D000093422:Glycated Serum Proteins; D000093423:Glycated Serum Albumin
chemical_list: D001786:Blood Glucose; D001798:Blood Proteins; D002784:Cholesterol; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003300:Copper; D019270:Fructosamine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D006023:Glycoproteins; D006595:Hexosamines; D007328:Insulin; D008077:Lipoproteins, LDL; D012709:Serum Albumin; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D014810:Vitamin E; D000093422:Glycated Serum Proteins; D000093423:Glycated Serum Albumin