title: Effect of vitamin E supplementation on HDL function by haptoglobin genotype in type 1 diabetes: results from the HapE randomized crossover pilot trial.
abstract: OBJECTIVE
  Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes.
  
  
  METHODS
  Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout.
  
  
  RESULTS
  Baseline CE decreased with the number of Hp 2 alleles (p-trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (β = 0.79, p = 0.03) and LP in Hp 1 allele carriers (β Hp 1-1 = 0.18, p = 0.05; β Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (β = -0.07, p = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp.
  
  
  CONCLUSIONS
  In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. costacout@edc.pitt.edu.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: Department of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Levy
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Miller
authors.affiliation: Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Janet
authors.initials: J
authors.lastname: Snell-Bergeon
authors.affiliation: Department of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Rabea
authors.initials: R
authors.lastname: Asleh
authors.affiliation: Department of Anatomy and Cell Biology, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Farbstein
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Fickley
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Georgia
authors.initials: G
authors.lastname: Pambianco
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Rona
authors.initials: R
authors.lastname: de la Vega
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Rhobert W
authors.initials: RW
authors.lastname: Evans
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000628:therapy; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014810:Vitamin E / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*
chemical_list: D006242:Haptoglobins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014815:Vitamins; D014810:Vitamin E
keywords: Double-blinded placebo-controlled randomized trial; HDL function; Haptoglobin genotype; NMR lipoprotein subfractions; Type 1 diabetes; Vitamin E