title: Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nita G
authors.initials: NG
authors.lastname: Forouhi
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Fumiaki
authors.identifier: 0000-0002-6841-8396
authors.initials: F
authors.lastname: Imamura
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Stephen J
authors.identifier: 0000-0003-2375-1440
authors.initials: SJ
authors.lastname: Sharp
authors.affiliation: MRC Human Nutrition Research, Cambridge, UK.
authors.forename: Albert
authors.identifier: 0000-0001-9998-051X
authors.initials: A
authors.lastname: Koulman
authors.affiliation: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Schulze
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jusheng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Ye
authors.affiliation: University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Ivonne
authors.identifier: 0000-0001-7758-4911
authors.initials: I
authors.lastname: Sluijs
authors.affiliation: Navarre Public Health Institute (ISPN), Pamplona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
authors.forename: Marcela
authors.identifier: 0000-0001-9242-6364
authors.initials: M
authors.lastname: Guevara
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
authors.forename: José María
authors.identifier: 0000-0002-9637-3869
authors.initials: JM
authors.lastname: Huerta
authors.affiliation: Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Kröger
authors.affiliation: MRC Human Nutrition Research, Cambridge, UK.
authors.forename: Laura Yun
authors.initials: LY
authors.lastname: Wang
authors.affiliation: MRC Human Nutrition Research, Cambridge, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Summerhill
authors.affiliation: MRC Human Nutrition Research, Cambridge, UK.
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.affiliation: Wageningen University, The Netherlands.
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.affiliation: Inserm, CESP, U1018, Villejuif, France.|Univ Paris-Sud, UMRS 1018, Villejuif, France.|Gustave Roussy Institute, Villejuif, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Affret
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Public Health Division of Gipuzkoa, San Sebastian, Spain.|Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: German Institute of Human Nutrition Potsdam-Rehbruecke, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.affiliation: Inserm, CESP, U1018, Villejuif, France.|Univ Paris-Sud, UMRS 1018, Villejuif, France.|Gustave Roussy Institute, Villejuif, France.
authors.forename: Courtney
authors.initials: C
authors.lastname: Dow
authors.affiliation: Inserm, CESP, U1018, Villejuif, France.|Univ Paris-Sud, UMRS 1018, Villejuif, France.|Gustave Roussy Institute, Villejuif, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Fagherazzi
authors.affiliation: Lund University, Malmö, Sweden.|Umeå University, Umeå, Sweden.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.affiliation: Catalan Institute of Oncology (ICO), Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.affiliation: University of Oxford, Oxford, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.affiliation: University of Cambridge, Cambridge, United Kingdom.
authors.forename: Kay Tee
authors.initials: KT
authors.lastname: Khaw
authors.affiliation: German Cancer Research Centre (DKFZ), Heidelberg, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Kühn
authors.affiliation: Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.|Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.
authors.forename: Lotte Maxild
authors.initials: LM
authors.lastname: Mortensen
authors.affiliation: Lund University, Malmö, Sweden.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Nilsson
authors.affiliation: Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark.|Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.affiliation: Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
authors.affiliation: Cancer Research and Prevention Institute (ISPO), Florence, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panico
authors.affiliation: Public Health Directorate, Asturias, Spain.
authors.forename: J Ramón
authors.initials: JR
authors.lastname: Quirós
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
authors.forename: Miguel
authors.identifier: 0000-0002-9972-9779
authors.initials: M
authors.lastname: Rodriguez-Barranco
authors.affiliation: Umeå University, Umeå, Sweden.
authors.forename: Olov
authors.initials: O
authors.lastname: Rolandsson
authors.affiliation: Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Turin, Italy.|Human Genetics Foundation (HuGeF), Turin, Italy.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Sacerdote
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Augustin
authors.initials: A
authors.lastname: Scalbert
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Slimani
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Annemieke M W
authors.initials: AM
authors.lastname: Spijkerman
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tjonneland
authors.affiliation: Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Spain.|Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
authors.forename: Maria-Jose
authors.identifier: 0000-0003-1474-5233
authors.initials: MJ
authors.lastname: Tormo
authors.affiliation: Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
authors.forename: Daphne L
authors.initials: DL
authors.lastname: van der A
authors.affiliation: University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Yvonne T
authors.identifier: 0000-0002-4605-435X
authors.initials: YT
authors.lastname: van der Schouw
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Claudia
authors.identifier: 0000-0002-5017-7344
authors.initials: C
authors.lastname: Langenberg
authors.affiliation: School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.affiliation: MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Nicholas J
authors.identifier: 0000-0003-1422-2993
authors.initials: NJ
authors.lastname: Wareham
mesh_terms: D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology*; D015525:Fatty Acids, Omega-3 / Q000009:adverse effects / Q000097:blood*; D043371:Fatty Acids, Omega-6 / Q000009:adverse effects / Q000097:blood*; D005231:Fatty Acids, Unsaturated / Q000009:adverse effects / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated