Cargando…

Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype

OBJECTIVE—Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-...

Descripción completa

Detalles Bibliográficos
Autores principales: Asleh, Rabea, Blum, Shany, Kalet-Litman, Shiri, Alshiek, Jonia, Miller-Lotan, Rachel, Asaf, Roy, Rock, Wasseem, Aviram, Michael, Milman, Uzi, Shapira, Chen, Abassi, Zaid, Levy, Andrew P.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551691/
https://www.ncbi.nlm.nih.gov/pubmed/18599520
http://dx.doi.org/10.2337/db08-0450
_version_ 1782159464242085888
author Asleh, Rabea
Blum, Shany
Kalet-Litman, Shiri
Alshiek, Jonia
Miller-Lotan, Rachel
Asaf, Roy
Rock, Wasseem
Aviram, Michael
Milman, Uzi
Shapira, Chen
Abassi, Zaid
Levy, Andrew P.
author_facet Asleh, Rabea
Blum, Shany
Kalet-Litman, Shiri
Alshiek, Jonia
Miller-Lotan, Rachel
Asaf, Roy
Rock, Wasseem
Aviram, Michael
Milman, Uzi
Shapira, Chen
Abassi, Zaid
Levy, Andrew P.
author_sort Asleh, Rabea
collection PubMed
description OBJECTIVE—Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction. RESEARCH DESIGN AND METHODS—Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters. RESULTS—Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes. CONCLUSIONS—Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals.
format Text
id pubmed-2551691
institution National Center for Biotechnology Information
language English
publishDate 2008
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-25516912009-10-01 Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype Asleh, Rabea Blum, Shany Kalet-Litman, Shiri Alshiek, Jonia Miller-Lotan, Rachel Asaf, Roy Rock, Wasseem Aviram, Michael Milman, Uzi Shapira, Chen Abassi, Zaid Levy, Andrew P. Diabetes Complications OBJECTIVE—Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of diabetic individuals). However, because of the large number of clinical trials that failed to demonstrate benefit from vitamin E coupled with the lack of a mechanistic explanation for why vitamin E should be beneficial only in diabetic individuals with the Hp 2-2 genotype, enthusiasm for this pharmacogenomic paradigm has been limited. In this study, we sought to provide such a mechanistic explanation based on the hypothesis that the Hp 2-2 genotype and diabetes interact to promote HDL oxidative modification and dysfunction. RESEARCH DESIGN AND METHODS—Hb and lipid peroxides were assessed in HDL isolated from diabetic individuals or mice with the Hp 1-1 or Hp 2-2 genotypes. HDL function was assessed based on its ability to promote cholesterol efflux from macrophages. A crossover placebo-controlled study in Hp 2-2 diabetic humans and in Hp 1-1 and Hp 2-2 diabetic mice assessed the ability of vitamin E to favorably modify these structural and functional parameters. RESULTS—Hb and lipid peroxides associated with HDL were increased and HDL function was impaired in Hp 2-2 diabetic individuals and mice. Vitamin E decreased oxidative modification of HDL and improved HDL function in Hp 2-2 diabetes but had no effect in Hp 1-1 diabetes. CONCLUSIONS—Vitamin E significantly improves the quality of HDL in Hp 2-2 diabetic individuals. American Diabetes Association 2008-10 /pmc/articles/PMC2551691/ /pubmed/18599520 http://dx.doi.org/10.2337/db08-0450 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Complications
Asleh, Rabea
Blum, Shany
Kalet-Litman, Shiri
Alshiek, Jonia
Miller-Lotan, Rachel
Asaf, Roy
Rock, Wasseem
Aviram, Michael
Milman, Uzi
Shapira, Chen
Abassi, Zaid
Levy, Andrew P.
Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title_full Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title_fullStr Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title_full_unstemmed Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title_short Correction of HDL Dysfunction in Individuals With Diabetes and the Haptoglobin 2-2 Genotype
title_sort correction of hdl dysfunction in individuals with diabetes and the haptoglobin 2-2 genotype
topic Complications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551691/
https://www.ncbi.nlm.nih.gov/pubmed/18599520
http://dx.doi.org/10.2337/db08-0450
work_keys_str_mv AT aslehrabea correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT blumshany correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT kaletlitmanshiri correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT alshiekjonia correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT millerlotanrachel correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT asafroy correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT rockwasseem correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT avirammichael correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT milmanuzi correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT shapirachen correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT abassizaid correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype
AT levyandrewp correctionofhdldysfunctioninindividualswithdiabetesandthehaptoglobin22genotype