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Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study

AIMS/HYPOTHESIS: This biomarker study aimed to quantify the association of essential and other plasma fatty acid biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes. METHODS: A case-cohort study (N = 3576), including 654 macrovascular events, 34...

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Autores principales: Harris, Katie, Oshima, Megumi, Sattar, Naveed, Würtz, Peter, Jun, Min, Welsh, Paul, Hamet, Pavel, Harrap, Stephen, Poulter, Neil, Chalmers, John, Woodward, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351876/
https://www.ncbi.nlm.nih.gov/pubmed/32385604
http://dx.doi.org/10.1007/s00125-020-05162-z
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author Harris, Katie
Oshima, Megumi
Sattar, Naveed
Würtz, Peter
Jun, Min
Welsh, Paul
Hamet, Pavel
Harrap, Stephen
Poulter, Neil
Chalmers, John
Woodward, Mark
author_facet Harris, Katie
Oshima, Megumi
Sattar, Naveed
Würtz, Peter
Jun, Min
Welsh, Paul
Hamet, Pavel
Harrap, Stephen
Poulter, Neil
Chalmers, John
Woodward, Mark
author_sort Harris, Katie
collection PubMed
description AIMS/HYPOTHESIS: This biomarker study aimed to quantify the association of essential and other plasma fatty acid biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes. METHODS: A case-cohort study (N = 3576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of (median) follow-up, was undertaken as a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study (full details of the study design and primary endpoints of the ADVANCE trial and its case-cohort have been published previously). This current study considers new data: fatty acids measured from baseline plasma samples by proton NMR analysis. The fatty acids measured were n-3, docosahexaenoic acid (DHA), n-6, linoleic acid, and polyunsaturated, monounsaturated and saturated fatty acids. HRs were modelled per SD higher (percentage) fatty acid. C statistics and continuous net reclassification improvement were used to test the added value of fatty acids compared with traditional cardiovascular risk factors. RESULTS: After adjustment for traditional cardiovascular risk factors, an inverse association was observed for n-3 fatty acids and DHA with the risk of macrovascular events (HR [95% CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively, per 1 SD higher percentage), and for n-3 fatty acids with the risk of death (HR 0.91 [95% CI 0.84, 0.99] per 1 SD higher percentage). Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in the predictive ability of models when any fatty acid was added. CONCLUSIONS/INTERPRETATION: Plasma n-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, while n-3 fatty acids were also inversely associated with death. These results support the cardioprotective effects of n-3 fatty acids and DHA and further merit testing the role of high-dose supplementation with n-3 fatty acids in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05162-z) contains peer-reviewed but unedited supplementary material, which is available to authorized users.
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spelling pubmed-73518762020-07-14 Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study Harris, Katie Oshima, Megumi Sattar, Naveed Würtz, Peter Jun, Min Welsh, Paul Hamet, Pavel Harrap, Stephen Poulter, Neil Chalmers, John Woodward, Mark Diabetologia Article AIMS/HYPOTHESIS: This biomarker study aimed to quantify the association of essential and other plasma fatty acid biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes. METHODS: A case-cohort study (N = 3576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of (median) follow-up, was undertaken as a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) study (full details of the study design and primary endpoints of the ADVANCE trial and its case-cohort have been published previously). This current study considers new data: fatty acids measured from baseline plasma samples by proton NMR analysis. The fatty acids measured were n-3, docosahexaenoic acid (DHA), n-6, linoleic acid, and polyunsaturated, monounsaturated and saturated fatty acids. HRs were modelled per SD higher (percentage) fatty acid. C statistics and continuous net reclassification improvement were used to test the added value of fatty acids compared with traditional cardiovascular risk factors. RESULTS: After adjustment for traditional cardiovascular risk factors, an inverse association was observed for n-3 fatty acids and DHA with the risk of macrovascular events (HR [95% CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively, per 1 SD higher percentage), and for n-3 fatty acids with the risk of death (HR 0.91 [95% CI 0.84, 0.99] per 1 SD higher percentage). Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in the predictive ability of models when any fatty acid was added. CONCLUSIONS/INTERPRETATION: Plasma n-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, while n-3 fatty acids were also inversely associated with death. These results support the cardioprotective effects of n-3 fatty acids and DHA and further merit testing the role of high-dose supplementation with n-3 fatty acids in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05162-z) contains peer-reviewed but unedited supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2020-05-08 2020 /pmc/articles/PMC7351876/ /pubmed/32385604 http://dx.doi.org/10.1007/s00125-020-05162-z Text en © The Author(s) 2020 Open Access This 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/.
spellingShingle Article
Harris, Katie
Oshima, Megumi
Sattar, Naveed
Würtz, Peter
Jun, Min
Welsh, Paul
Hamet, Pavel
Harrap, Stephen
Poulter, Neil
Chalmers, John
Woodward, Mark
Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title_full Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title_fullStr Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title_full_unstemmed Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title_short Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study
title_sort plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the advance study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351876/
https://www.ncbi.nlm.nih.gov/pubmed/32385604
http://dx.doi.org/10.1007/s00125-020-05162-z
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