Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.

<h4>Background</h4>Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.<h4>Methods and findings</h4>Plasma phospholipid PUFAs were measured by...

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Main Authors: Nita G Forouhi, Fumiaki Imamura, Stephen J Sharp, Albert Koulman, Matthias B Schulze, Jusheng Zheng, Zheng Ye, Ivonne Sluijs, Marcela Guevara, José María Huerta, Janine Kröger, Laura Yun Wang, Keith Summerhill, Julian L Griffin, Edith J M Feskens, Aurélie Affret, Pilar Amiano, Heiner Boeing, Courtney Dow, Guy Fagherazzi, Paul W Franks, Carlos Gonzalez, Rudolf Kaaks, Timothy J Key, Kay Tee Khaw, Tilman Kühn, Lotte Maxild Mortensen, Peter M Nilsson, Kim Overvad, Valeria Pala, Domenico Palli, Salvatore Panico, J Ramón Quirós, Miguel Rodriguez-Barranco, Olov Rolandsson, Carlotta Sacerdote, Augustin Scalbert, Nadia Slimani, Annemieke M W Spijkerman, Anne Tjonneland, Maria-Jose Tormo, Rosario Tumino, Daphne L van der A, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, Nicholas J Wareham
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-07-01
Series:PLoS Medicine
Online Access:https://doi.org/10.1371/journal.pmed.1002094
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author Nita G Forouhi
Fumiaki Imamura
Stephen J Sharp
Albert Koulman
Matthias B Schulze
Jusheng Zheng
Zheng Ye
Ivonne Sluijs
Marcela Guevara
José María Huerta
Janine Kröger
Laura Yun Wang
Keith Summerhill
Julian L Griffin
Edith J M Feskens
Aurélie Affret
Pilar Amiano
Heiner Boeing
Courtney Dow
Guy Fagherazzi
Paul W Franks
Carlos Gonzalez
Rudolf Kaaks
Timothy J Key
Kay Tee Khaw
Tilman Kühn
Lotte Maxild Mortensen
Peter M Nilsson
Kim Overvad
Valeria Pala
Domenico Palli
Salvatore Panico
J Ramón Quirós
Miguel Rodriguez-Barranco
Olov Rolandsson
Carlotta Sacerdote
Augustin Scalbert
Nadia Slimani
Annemieke M W Spijkerman
Anne Tjonneland
Maria-Jose Tormo
Rosario Tumino
Daphne L van der A
Yvonne T van der Schouw
Claudia Langenberg
Elio Riboli
Nicholas J Wareham
author_facet Nita G Forouhi
Fumiaki Imamura
Stephen J Sharp
Albert Koulman
Matthias B Schulze
Jusheng Zheng
Zheng Ye
Ivonne Sluijs
Marcela Guevara
José María Huerta
Janine Kröger
Laura Yun Wang
Keith Summerhill
Julian L Griffin
Edith J M Feskens
Aurélie Affret
Pilar Amiano
Heiner Boeing
Courtney Dow
Guy Fagherazzi
Paul W Franks
Carlos Gonzalez
Rudolf Kaaks
Timothy J Key
Kay Tee Khaw
Tilman Kühn
Lotte Maxild Mortensen
Peter M Nilsson
Kim Overvad
Valeria Pala
Domenico Palli
Salvatore Panico
J Ramón Quirós
Miguel Rodriguez-Barranco
Olov Rolandsson
Carlotta Sacerdote
Augustin Scalbert
Nadia Slimani
Annemieke M W Spijkerman
Anne Tjonneland
Maria-Jose Tormo
Rosario Tumino
Daphne L van der A
Yvonne T van der Schouw
Claudia Langenberg
Elio Riboli
Nicholas J Wareham
author_sort Nita G Forouhi
collection DOAJ
description <h4>Background</h4>Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.<h4>Methods and findings</h4>Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.<h4>Conclusions</h4>These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.
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spelling doaj-art-d5be1b1cc1184d37b7a18e645082bfe72025-08-20T02:22:25ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762016-07-01137e100209410.1371/journal.pmed.1002094Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.Nita G ForouhiFumiaki ImamuraStephen J SharpAlbert KoulmanMatthias B SchulzeJusheng ZhengZheng YeIvonne SluijsMarcela GuevaraJosé María HuertaJanine KrögerLaura Yun WangKeith SummerhillJulian L GriffinEdith J M FeskensAurélie AffretPilar AmianoHeiner BoeingCourtney DowGuy FagherazziPaul W FranksCarlos GonzalezRudolf KaaksTimothy J KeyKay Tee KhawTilman KühnLotte Maxild MortensenPeter M NilssonKim OvervadValeria PalaDomenico PalliSalvatore PanicoJ Ramón QuirósMiguel Rodriguez-BarrancoOlov RolandssonCarlotta SacerdoteAugustin ScalbertNadia SlimaniAnnemieke M W SpijkermanAnne TjonnelandMaria-Jose TormoRosario TuminoDaphne L van der AYvonne T van der SchouwClaudia LangenbergElio RiboliNicholas J Wareham<h4>Background</h4>Whether and how n-3 and n-6 polyunsaturated fatty acids (PUFAs) are related to type 2 diabetes (T2D) is debated. Objectively measured plasma PUFAs can help to clarify these associations.<h4>Methods and findings</h4>Plasma phospholipid PUFAs were measured by gas chromatography among 12,132 incident T2D cases and 15,919 subcohort participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study across eight European countries. Country-specific hazard ratios (HRs) were estimated using Prentice-weighted Cox regression and pooled by random-effects meta-analysis. We also systematically reviewed published prospective studies on circulating PUFAs and T2D risk and pooled the quantitative evidence for comparison with results from EPIC-InterAct. In EPIC-InterAct, among long-chain n-3 PUFAs, α-linolenic acid (ALA) was inversely associated with T2D (HR per standard deviation [SD] 0.93; 95% CI 0.88-0.98), but eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were not significantly associated. Among n-6 PUFAs, linoleic acid (LA) (0.80; 95% CI 0.77-0.83) and eicosadienoic acid (EDA) (0.89; 95% CI 0.85-0.94) were inversely related, and arachidonic acid (AA) was not significantly associated, while significant positive associations were observed with γ-linolenic acid (GLA), dihomo-GLA, docosatetraenoic acid (DTA), and docosapentaenoic acid (n6-DPA), with HRs between 1.13 to 1.46 per SD. These findings from EPIC-InterAct were broadly similar to comparative findings from summary estimates from up to nine studies including between 71 to 2,499 T2D cases. Limitations included potential residual confounding and the inability to distinguish between dietary and metabolic influences on plasma phospholipid PUFAs.<h4>Conclusions</h4>These large-scale findings suggest an important inverse association of circulating plant-origin n-3 PUFA (ALA) but no convincing association of marine-derived n3 PUFAs (EPA and DHA) with T2D. Moreover, they highlight that the most abundant n6-PUFA (LA) is inversely associated with T2D. The detection of associations with previously less well-investigated PUFAs points to the importance of considering individual fatty acids rather than focusing on fatty acid class.https://doi.org/10.1371/journal.pmed.1002094
spellingShingle Nita G Forouhi
Fumiaki Imamura
Stephen J Sharp
Albert Koulman
Matthias B Schulze
Jusheng Zheng
Zheng Ye
Ivonne Sluijs
Marcela Guevara
José María Huerta
Janine Kröger
Laura Yun Wang
Keith Summerhill
Julian L Griffin
Edith J M Feskens
Aurélie Affret
Pilar Amiano
Heiner Boeing
Courtney Dow
Guy Fagherazzi
Paul W Franks
Carlos Gonzalez
Rudolf Kaaks
Timothy J Key
Kay Tee Khaw
Tilman Kühn
Lotte Maxild Mortensen
Peter M Nilsson
Kim Overvad
Valeria Pala
Domenico Palli
Salvatore Panico
J Ramón Quirós
Miguel Rodriguez-Barranco
Olov Rolandsson
Carlotta Sacerdote
Augustin Scalbert
Nadia Slimani
Annemieke M W Spijkerman
Anne Tjonneland
Maria-Jose Tormo
Rosario Tumino
Daphne L van der A
Yvonne T van der Schouw
Claudia Langenberg
Elio Riboli
Nicholas J Wareham
Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
PLoS Medicine
title Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
title_full Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
title_fullStr Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
title_full_unstemmed Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
title_short Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
title_sort association of plasma phospholipid n 3 and n 6 polyunsaturated fatty acids with type 2 diabetes the epic interact case cohort study
url https://doi.org/10.1371/journal.pmed.1002094
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