Journal
PLOS MEDICINE
Volume 13, Issue 7, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.1002094
Keywords
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Categories
Funding
- EU [LSHM_CT_2006_037197]
- Medical Research Council Epidemiology Unit [MC_UU_12015/1, MC_UU_12015/5]
- Medical Research Council Human Nutrition Research [MC_UP_A090_1006]
- Cambridge Lipidomics Biomarker Research Initiative [G0800783]
- Cancer Research UK
- Health Research Fund of the Spanish Ministry of Health
- Murcia Regional Government [6236]
- Regional Government of Navarre
- Dutch Ministry of Public Health, Welfare and Sports
- Netherlands Cancer Registry
- LK Research Funds
- Dutch Prevention Funds
- Dutch ZON (Zorg Onderzoek Nederland)
- World Cancer Research Fund (WCRF)
- Statistics Netherlands
- NL Agency grant [IGE05012]
- Board of the UMC Utrecht
- Swedish Research Council
- Novo Nordisk
- Swedish Diabetes Association
- Swedish Heart-Lung Foundation
- German Cancer Aid
- German Ministry of Research (BMBF)
- Medical Research Council UK
- Danish Cancer Society
- Asturias Regional Government
- Vasterboten County Council
- AIRE-ONLUS Ragusa
- AVIS-Ragusa
- Sicilian Regional Government
- Imperial College Biomedical Research Centre
- Cancer Research UK [16491] Funding Source: researchfish
- Medical Research Council [MR/N003284/1, MC_UP_A090_1006, MC_EX_G0800783, MC_UU_12015/1, G0401527, MR/P011705/1, MR/L00002/1, G1000143, MC_UU_12015/5, MC_U105960396, MC_PC_13030, MR/P01836X/1] Funding Source: researchfish
- National Institute for Health Research [CL-2011-18-004, NF-SI-0512-10135, NF-SI-0512-10114] Funding Source: researchfish
- MRC [MC_EX_G0800783, MC_PC_13030, MR/P011705/1, MC_UU_12015/5, MR/N003284/1, MC_UU_12015/1, MC_U105960396, MC_UP_A090_1006, MR/P01836X/1] Funding Source: UKRI
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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, a-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.
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