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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.; Imamura, Fumiaki; Sharp, Stephen J.; Koulman, Albert; Schulze, Matthias B.; Zheng, Jusheng; Ye, Zheng; Sluijs, Ivonne; Guevara, Marcela and Huerta, José María, et al. (2016) In PLoS Medicine 13(7).
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... (More)

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.

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PLoS Medicine
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  • Scopus:84980332028
ISSN
1549-1277
DOI
10.1371/journal.pmed.1002094
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English
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8e17009c-c060-4b63-886b-f7e55f29351c
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2016-09-08 14:41:27
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2016-10-28 12:09:54
@misc{8e17009c-c060-4b63-886b-f7e55f29351c,
  abstract     = {<p>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.</p>},
  author       = {Forouhi, Nita G. and Imamura, Fumiaki and Sharp, Stephen J. and Koulman, Albert and Schulze, Matthias B. and Zheng, Jusheng and Ye, Zheng and Sluijs, Ivonne and Guevara, Marcela and Huerta, José María and Kröger, Janine and Wang, Laura Yun and Summerhill, Keith and Griffin, Julian L. and Feskens, Edith J M and Affret, Aurélie and Amiano, Pilar and Boeing, Heiner and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Gonzalez, Carlos and Kaaks, Rudolf and Key, Timothy J. and Khaw, Kay Tee and Kühn, Tilman and Mortensen, Lotte Maxild and Nilsson, Peter M. and Overvad, Kim and Pala, Valeria and Palli, Domenico and Panico, Salvatore and Quirós, J. Ramón and Rodriguez-Barranco, Miguel and Rolandsson, Olov and Sacerdote, Carlotta and Scalbert, Augustin and Slimani, Nadia and Spijkerman, Annemieke M W and Tjonneland, Anne and Tormo, Maria Jose and Tumino, Rosario and van der A, Daphne L. and van der Schouw, Yvonne T. and Langenberg, Claudia and Riboli, Elio and Wareham, Nicholas J.},
  issn         = {1549-1277},
  language     = {eng},
  month        = {07},
  number       = {7},
  publisher    = {ARRAY(0xb61be08)},
  series       = {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},
  url          = {http://dx.doi.org/10.1371/journal.pmed.1002094},
  volume       = {13},
  year         = {2016},
}