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PLoS Med. 2016 Jul 19;13(7):e1002094. doi: 10.1371/journal.pmed.1002094. eCollection 2016 Jul.

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

Author information

1
MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
2
MRC Human Nutrition Research, Cambridge, UK.
3
Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
4
University Medical Center Utrecht, Utrecht, the Netherlands.
5
Navarre Public Health Institute (ISPN), Pamplona, Spain.
6
CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
7
Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
8
Wageningen University, The Netherlands.
9
Inserm, CESP, U1018, Villejuif, France.
10
Univ Paris-Sud, UMRS 1018, Villejuif, France.
11
Gustave Roussy Institute, Villejuif, France.
12
Public Health Division of Gipuzkoa, San Sebastian, Spain.
13
Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.
14
German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
15
Lund University, Malmö, Sweden.
16
Umeå University, Umeå, Sweden.
17
Catalan Institute of Oncology (ICO), Barcelona, Spain.
18
German Cancer Research Centre (DKFZ), Heidelberg, Germany.
19
University of Oxford, Oxford, United Kingdom.
20
University of Cambridge, Cambridge, United Kingdom.
21
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.
22
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
23
Aalborg University Hospital, Aalborg, Denmark.
24
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
25
Cancer Research and Prevention Institute (ISPO), Florence, Italy.
26
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
27
Public Health Directorate, Asturias, Spain.
28
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
29
Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy.
30
Human Genetics Foundation (HuGeF), Turin, Italy.
31
International Agency for Research on Cancer, Lyon, France.
32
National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
33
Danish Cancer Society Research Center, Copenhagen, Denmark.
34
Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
35
Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy.
36
School of Public Health, Imperial College London, London, United Kingdom.

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.

PMID:
27434045
PMCID:
PMC4951144
DOI:
10.1371/journal.pmed.1002094
[Indexed for MEDLINE]
Free PMC Article

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