Forouhi, Nita GImamura, FumiakiSharp, Stephen JKoulman, AlbertSchulze, Matthias BZheng, JushengYe, ZhengSluijs, IvonneGuevara, MarcelaHuerta, José MaríaKröger, JanineWang, Laura YunSummerhill, KeithGriffin, Julian LFeskens, Edith J MAffret, AurélieAmiano, PilarBoeing, HeinerDow, CourtneyFagherazzi, GuyFranks, Paul WGonzalez, CarlosKaaks, RudolfKey, Timothy JKhaw, Kay TeeKühn, TilmanMortensen, Lotte MaxildNilsson, Peter MOvervad, KimPala, ValeriaPalli, DomenicoPanico, SalvatoreQuirós, J RamónRodriguez-Barranco, MiguelRolandsson, OlovSacerdote, CarlottaScalbert, AugustinSlimani, NadiaSpijkerman, Annemieke M WTjonneland, AnneTormo, Maria-JoseTumino, Rosariovan der A, Daphne Lvan der Schouw, Yvonne TLangenberg, ClaudiaRiboli, ElioWareham, Nicholas J2016-09-062016-09-062016-07-19Forouhi NG, Imamura F, Sharp SJ, Koulman A, Schulze MB, Zheng J, et al. Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study. PLoS Med. 2016; 13(7): e10020941549-1277http://hdl.handle.net/10668/2395Journal Article;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.enDiabetes Mellitus Tipo 2Ácidos Grasos Omega-6Ácidos Grasos InsaturadosFosfolípidosPlasmaÁcido 8,11,14-eicosanoicoÁcido araquidónicoCromatografía de gasesDietaÁcidos docosahexaenoicosÁcido eicosapentaenoicoEuropaÁcidos grasos omega 3Ácido linoleicoEstudios prospectivosMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, UnsaturatedMedical Subject Headings::Chemicals and Drugs::Lipids::PhospholipidsMedical Subject Headings::Anatomy::Fluids and Secretions::Body Fluids::Blood::PlasmaMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Eicosanoids::8,11,14-Eicosatrienoic AcidMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic AcidsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Chromatography::Chromatography, GasMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::DietMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Docosahexaenoic AcidsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Eicosapentaenoic AcidMedical Subject Headings::Geographicals::Geographic Locations::EuropeMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6::Linoleic AcidsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studiesresearch article27434045open access10.1371/journal.pmed.10020941549-1676PMC4951144