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Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study
BACKGROUND: Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were inves...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653597/ https://www.ncbi.nlm.nih.gov/pubmed/34876126 http://dx.doi.org/10.1186/s12933-021-01419-y |
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author | Chevli, Parag Anilkumar Freedman, Barry I. Hsu, Fang-Chi Xu, Jianzhao Rudock, Megan E. Ma, Lijun Parks, John S. Palmer, Nicholette D. Shapiro, Michael D. |
author_facet | Chevli, Parag Anilkumar Freedman, Barry I. Hsu, Fang-Chi Xu, Jianzhao Rudock, Megan E. Ma, Lijun Parks, John S. Palmer, Nicholette D. Shapiro, Michael D. |
author_sort | Chevli, Parag Anilkumar |
collection | PubMed |
description | BACKGROUND: Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). METHODS: The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. RESULTS: At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. CONCLUSIONS: Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-021-01419-y. |
format | Online Article Text |
id | pubmed-8653597 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86535972021-12-08 Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study Chevli, Parag Anilkumar Freedman, Barry I. Hsu, Fang-Chi Xu, Jianzhao Rudock, Megan E. Ma, Lijun Parks, John S. Palmer, Nicholette D. Shapiro, Michael D. Cardiovasc Diabetol Original Investigation BACKGROUND: Incidence rates of cardiovascular disease (CVD) are increasing, partly driven by the diabetes epidemic. Novel prediction tools and modifiable treatment targets are needed to enhance risk assessment and management. Plasma metabolite associations with subclinical atherosclerosis were investigated in the Diabetes Heart Study (DHS), a cohort enriched for type 2 diabetes (T2D). METHODS: The analysis included 700 DHS participants, 438 African Americans (AAs), and 262 European Americans (EAs), in whom coronary artery calcium (CAC) was assessed using ECG-gated computed tomography. Plasma metabolomics using liquid chromatography-mass spectrometry identified 853 known metabolites. An ancestry-specific marginal model incorporating generalized estimating equations examined associations between metabolites and CAC (log-transformed (CAC + 1) as outcome measure). Models were adjusted for age, sex, BMI, diabetes duration, date of plasma collection, time between plasma collection and CT exam, low-density lipoprotein cholesterol (LDL-C), and statin use. RESULTS: At an FDR-corrected p-value < 0.05, 33 metabolites were associated with CAC in AAs and 36 in EAs. The androgenic steroids, fatty acid, phosphatidylcholine, and bile acid metabolism subpathways were associated with CAC in AAs, whereas fatty acid, lysoplasmalogen, and branched-chain amino acid (BCAA) subpathways were associated with CAC in EAs. CONCLUSIONS: Strikingly different metabolic signatures were associated with subclinical coronary atherosclerosis in AA and EA DHS participants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12933-021-01419-y. BioMed Central 2021-12-07 /pmc/articles/PMC8653597/ /pubmed/34876126 http://dx.doi.org/10.1186/s12933-021-01419-y Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Original Investigation Chevli, Parag Anilkumar Freedman, Barry I. Hsu, Fang-Chi Xu, Jianzhao Rudock, Megan E. Ma, Lijun Parks, John S. Palmer, Nicholette D. Shapiro, Michael D. Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title | Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title_full | Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title_fullStr | Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title_full_unstemmed | Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title_short | Plasma metabolomic profiling in subclinical atherosclerosis: the Diabetes Heart Study |
title_sort | plasma metabolomic profiling in subclinical atherosclerosis: the diabetes heart study |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653597/ https://www.ncbi.nlm.nih.gov/pubmed/34876126 http://dx.doi.org/10.1186/s12933-021-01419-y |
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