Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial

Randomized, double-blind, placebo-controlled crossover trial in adults with type 1 diabetes. Hp genotype stratified (Hp1-1, Hp2-1, Hp2-2). ITT sample: Hp1-1 n=27; Hp2-1 n=31; Hp2-2 n=29; total 87. Mean ages ~49–51 years; roughly half female; diabetes duration ~37–40 years.

Vitamin E (α-tocopherol acetate), 400 IU daily, taken orally in capsules, for 8 weeks; 4-week washout.

Vitamin E increased HDL-mediated cholesterol efflux in Hp2-2 carriers (β=0.79, p=0.03) and tended to increase HDL-associated lipid peroxides in Hp1-1 and Hp2-1 carriers (Hp1-1: β=0.18, p=0.05; Hp2-1: β=0.21, p=0.07); HDL particle size decreased in Hp1-1 carriers (β=-0.07, p=0.03). There were no significant genotype-by-treatment interactions (p=0.25 for cholesterol efflux; p=0.63 for lipid peroxides). Conclusion: HDL function worsens with more Hp2 alleles in type 1 diabetes; α-tocopherol may improve HDL function in Hp2-2 carriers but could adversely affect lipid peroxide levels and lipoprotein subfractions in Hp1 carriers. Replication in larger trials is required to confirm a pharmacogenetic effect.

Small, underpowered pilot; not powered to detect Hp genotype-by-treatment interactions; short duration; limited covariate data; no clinical cardiovascular outcomes; incomplete HbA1c data; limited generalizability to Hp genotype distribution in type 1 diabetes.