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.
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).
Milman
Uzi
U
Clalit Health Services, Haifa, Israel.
Blum
Shany
S
Shapira
Chen
C
Aronson
Doron
D
Miller-Lotan
Rachel
R
Anbinder
Yefim
Y
Alshiek
Junia
J
Bennett
Lawrence
L
Kostenko
Maria
M
Landau
Michele
M
Keidar
Shlomo
S
Levy
Yishai
Y
Khemlin
Alexander
A
Radan
Arman
A
Levy
Andrew P
AP
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*
D000975:Antioxidants; D006242:Haptoglobins; D024505:Tocopherols