Vitamin E Reduces Cardiovascular Disease in Individuals with Diabetes Mellitus and the Haptoglobin 2-2 Genotype

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Abstract
Aims: Individuals with both diabetes mellitus (DM) and the Haptoglobin (Hp) 2-2 genotype are at increased risk of cardiovascular disease. As the antioxidant function of the Hp 2-2 protein is impaired, we sought to test the pharmacogenomic hypothesis that antioxidant vitamin E supplementation would provide cardiovascular protection to Hp 2-2 DM individuals. Materials & methods: We determined the Hp genotype on DM participants from two trials (HOPE and ICARE) and assessed the effect of vitamin E by Hp genotype on their common prespecified outcome, the composite of stroke, myocardial infarction and cardiovascular death. Data was analyzed with a fixed-effect model. These results were input into a simulation model, the Evidence Based Medicine Integrator, in order to estimate their long-term implications in a real-world population from Kaiser Permanente (CA, USA). Results: Meta-analysis of the two trials demonstrated a significant overall reduction in the composite end point in Hp 2-2 DM individuals with vitami...
Funding Information
  • United States–Israel Binational Science Foundation
  • Israel Science Foundation
  • Juvenile Diabetes Research Foundation
  • Kennedy Leigh Charitable Trust
  • National Institutes of Health (RO1KD085226)
  • US Agency for Healthcare Research (R21HS017643-01)

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