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


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, ?-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 ?-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.

SUBMITTER: Forouhi NG 

PROVIDER: S-EPMC4951144 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Forouhi Nita G NG   Imamura Fumiaki F   Sharp Stephen J SJ   Koulman Albert A   Schulze Matthias B MB   Zheng Jusheng J   Ye Zheng Z   Sluijs Ivonne I   Guevara Marcela M   Huerta José María JM   Kröger Janine J   Wang Laura Yun LY   Summerhill Keith K   Griffin Julian L JL   Feskens Edith J M EJ   Affret Aurélie A   Amiano Pilar P   Boeing Heiner H   Dow Courtney C   Fagherazzi Guy G   Franks Paul W PW   Gonzalez Carlos C   Kaaks Rudolf R   Key Timothy J TJ   Khaw Kay Tee KT   Kühn Tilman T   Mortensen Lotte Maxild LM   Nilsson Peter M PM   Overvad Kim K   Pala Valeria V   Palli Domenico D   Panico Salvatore S   Quirós J Ramón JR   Rodriguez-Barranco Miguel M   Rolandsson Olov O   Sacerdote Carlotta C   Scalbert Augustin A   Slimani Nadia N   Spijkerman Annemieke M W AM   Tjonneland Anne A   Tormo Maria-Jose MJ   Tumino Rosario R   van der A Daphne L DL   van der Schouw Yvonne T YT   Langenberg Claudia C   Riboli Elio E   Wareham Nicholas J NJ  

PLoS medicine 20160719 7


<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-specifi  ...[more]

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