Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
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Authors
Schulze, Matthias B
Ye, Zheng
Sluijs, Ivonne
Guevara, Marcela
Huerta, José María
Kröger, Janine
Wang, Linlin
Summerhill, Keith
Feskens, Edith JM
Affret, Aurélie
Amiano, Pilar
Boeing, Heiner
Dow, Courtney
Fagherazzi, Guy
Franks, Paul W
Gonzalez, Carlos
Kaaks, Rudolf
Key, Timothy J
Kühn, Tilman
Mortensen, Lotte Maxild
Nilsson, Peter M
Overvad, Kim
Pala, Valeria
Palli, Domenico
Panico, Salvatore
Quirós, J Ramón
Rodriguez-Barranco, Miguel
Rolandsson, Olov
Sacerdote, Carlotta
Scalbert, Augustin
Slimani, Nadia
Spijkerman, Annemieke MW
Tjonneland, Anne
Tormo, Maria-Jose
Tumino, Rosario
van, der A Daphne L
van, der Schouw Yvonne T
Riboli, Elio
Publication Date
2016-07-19Journal Title
PLoS Medicine
ISSN
1549-1277
Volume
13
Pages
e1002094
Language
English
Type
Article
This Version
VoR
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Forouhi, N., Imamura, F., Sharp, S., Koulman, A., Schulze, M. B., Zheng, J., Ye, Z., et al. (2016). Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.. PLoS Medicine, 13 e1002094. https://doi.org/10.1371/journal.pmed.1002094
Abstract
BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.
Keywords
Humans, Diabetes Mellitus, Type 2, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Fatty Acids, Omega-6, Case-Control Studies, Middle Aged, Male
Sponsorship
MRC (MC_UU_12015/1)
MRC (MC_UU_12015/5)
MRC (MR/P011705/1)
MEDICAL RESEARCH COUNCIL (MR/N003284/1)
MRC (MR/P01836X/1)
MRC (G1000143)
MRC (G0401527)
MEDICAL RESEARCH COUNCIL (MR/L00002/1)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701708)
Medical Research Council (MC_PC_13030)
Identifiers
External DOI: https://doi.org/10.1371/journal.pmed.1002094
This record's URL: https://www.repository.cam.ac.uk/handle/1810/259989
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/http://creativecommons.org/licenses/by/4.0/