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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-...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2008
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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 |
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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 |
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