title: Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: a prospective double-blinded clinical trial.
abstract: OBJECTIVE
  Clinical trials of vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major antioxidant protein, is a determinant of cardiovascular events in patients with Type 2 diabetes mellitus (DM). The Hp gene is polymorphic with 2 common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior antioxidant protection compared with the Hp 1 allelic product. We sought to test the hypothesis that vitamin E could reduce cardiovascular events in DM individuals with the Hp 2-2 genotype, a subgroup that comprises 2% to 3% of the general population.
  
  
  RESULTS
  1434 DM individuals > or = 55 years of age with the Hp 2-2 genotype were randomized to vitamin E (400 U/d) or placebo. The primary composite outcome was myocardial infarction, stroke, and cardiovascular death. At the first evaluation of events, 18 months after initiating the study, the primary outcome was significantly reduced in individuals receiving vitamin E (2.2%) compared with placebo (4.7%; P=0.01) and led to early termination of the study.
  
  
  CONCLUSIONS
  Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2-2 genotype (ClinicalTrials.gov NCT00220831).
authors.affiliation: Clalit Health Services, Haifa, Israel.
authors.forename: Uzi
authors.initials: U
authors.lastname: Milman
authors.forename: Shany
authors.initials: S
authors.lastname: Blum
authors.forename: Chen
authors.initials: C
authors.lastname: Shapira
authors.forename: Doron
authors.initials: D
authors.lastname: Aronson
authors.forename: Rachel
authors.initials: R
authors.lastname: Miller-Lotan
authors.forename: Yefim
authors.initials: Y
authors.lastname: Anbinder
authors.forename: Junia
authors.initials: J
authors.lastname: Alshiek
authors.forename: Lawrence
authors.initials: L
authors.lastname: Bennett
authors.forename: Maria
authors.initials: M
authors.lastname: Kostenko
authors.forename: Michele
authors.initials: M
authors.lastname: Landau
authors.forename: Shlomo
authors.initials: S
authors.lastname: Keidar
authors.forename: Yishai
authors.initials: Y
authors.lastname: Levy
authors.forename: Alexander
authors.initials: A
authors.lastname: Khemlin
authors.forename: Arman
authors.initials: A
authors.lastname: Radan
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
mesh_terms: D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000235:genetics; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010597:Pharmacogenetics; D011446:Prospective Studies; D020521:Stroke / Q000517:prevention & control*; D024505:Tocopherols / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D006242:Haptoglobins; D024505:Tocopherols