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

ABSTRACT: Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, ?-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 ?-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes.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 ?-tocopherol or placebo for 8 weeks with a 4-week washout.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, ?-tocopherol increased CE in Hp 2-2 (? = 0.79, p = 0.03) and LP in Hp 1 allele carriers (? Hp 1-1 = 0.18, p = 0.05; ? Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (? = -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.In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. ?-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.

SUBMITTER: Costacou T

PROVIDER: S-EPMC4826317 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Costacou Tina T Levy Andrew P AP Miller Rachel G RG Snell-Bergeon Janet J Asleh Rabea R Farbstein Dan D Fickley Catherine E CE Pambianco Georgia G de la Vega Rona R Evans Rhobert W RW Orchard Trevor J TJ

Acta diabetologica 20150524 2

<h4>Aims</h4>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.<h4>Methods</h4>Hp genotyp ...[more]

PMID: 26002590

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Project description:AimsVitamin E (Vit-E) may preferentially improve cardiovascular risk in haptoglobin 2-2 (Hp2-2) genotype diabetes individuals. We studied the impact of Vit-E supplementation on vascular function in diabetes individuals stratified by haptoglobin genotype in Singapore.MethodsIn this 24-week, double blind, placebo-controlled RCT, we recruited 187 subjects (101 Hp2-2, 86 non-Hp2-2).Interventionalpha-tocopherol-400 IU.Primary outcomeChange in EndoPAT-derived reactive-hyperaemia index (RHI) and augmentation index (AIx); Secondary Outcomes: Pulse-Wave velocity (Sphygmocor-PWV), carotid intima media thickness (CIMT), inflammation (hsCRP), derivatives of reactive-oxygen metabolites (dROMs), biological antioxidant-potential (BAPs), HbA1c, LDL-C, HDL-C and oxidised LDL-C (ox-LDL).ResultsOverall, with Vit-E supplementation no significant change in RHI, PWV, CIMT, hsCRP, dROMS, BAPs, HDL-C and HbA1c was observed (p > 0.05); an increase in LDL-C with concomitant decrease in ox-LDL, and incidentally increase in eGFR was observed (p < 0.05). No interaction effect with haptoglobin genotype was seen for all outcomes (p > 0.05). Subgroup analysis: In the non-Hp-2-2 group, Vit-E supplementation led to a higher EndoPAT-derived AIx, accompanied by higher LDL and ox-LDL concentrations (p < 0.05); Hp2-2 group: Vit-E supplementation led to higher eGFR when compared to the non-Hp2-2 group (exploratory) (p < 0.05). We observed an interaction effect for baseline haptoglobin concentration (threshold > 119 mg/dl) with intervention in terms of increased EndoPAT-derived AIx in the Hp > 119 mg/dl group whereas no change in the group with Hp ≤ 119 mg/dl.ConclusionVit-E supplementation did not show any preferential benefit or deleterious effect on vascular function in Hp2-2 diabetes subjects in Singapore. A possible deleterious effect of an increase in arterial stiffness in individuals with Hp > 119 mg/dl was observed. Future studies should consider personalisation based on baseline Hp concentrations in patients with T2DM rather than just Hp2-2 genotype to evaluate impact on the detailed lipid pathways, cardiac and renal physiology. The impact of ethnic differences needs to be explored in greater details.

Dataset Information

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

Publications

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

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