1. Association of plasma phospholipid n-3 and n-6 polyunsaturated fatty acids with type 2 diabetes: The EPIC-InterAct case-cohort study
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Forouhi, N, Imamura, F, Sharp, S, Koulman, A, Schulze, M, Zheng, J, Ye, Z, Sluijs, I, Guevara, M, Huerta, J, Kröger, J, Wang, L, Summerhill, K, Griffin, J, Feskens, E, Affret, A, Amiano, P, Boeing, H, Dow, C, Fagherazzi, G, Franks, P, Gonzalez, C, Kaaks, R, Key, T, Khaw, K, Kühn, T, Mortensen, L, Nilsson, P, Overvad, K, Pala, V, Palli, D, Panico, S, Quirós, J, Rodriguez-Barranco, M, Rolandsson, O, Sacerdote, C, Scalbert, A, Slimani, N, Spijkerman, A, Tjonneland, A, Tormo, M, Tumino, R, van der A, D, van der Schouw, Y, Langenberg, C, Riboli, E, Wareham, N, Forouhi, Nita G, Imamura, Fumiaki, Sharp, Stephen J, Koulman, Albert, Schulze, Matthias B, Zheng, Jusheng, Ye, Zheng, Sluijs, Ivonne, Guevara, Marcela, Huerta, José María, Kröger, Janine, Wang, Laura Yun, Summerhill, Keith, Griffin, Julian L, Feskens, Edith J. M, Affret, Aurélie, Amiano, Pilar, Boeing, Heiner, Dow, Courtney, Fagherazzi, Guy, Franks, Paul W, Gonzalez, Carlo, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Kühn, Tilman, Mortensen, Lotte Maxild, Nilsson, Peter M, Overvad, Kim, Pala, Valeria, Palli, Domenico, Panico, Salvatore, Quirós, J. Ramón, Rodriguez Barranco, Miguel, Rolandsson, Olov, Sacerdote, Carlotta, Scalbert, Augustin, Slimani, Nadia, Spijkerman, Annemieke M. W, Tjonneland, Anne, Tormo, Maria Jose, Tumino, Rosario, van der A, Daphne L, van der Schouw, Yvonne T, Langenberg, Claudia, Riboli, Elio, Wareham, Nicholas J., Apollo - University of Cambridge Repository, [Forouhi,NG, Imamura,F, Sharp,SJ, Zheng,J, Ye,Z, Langenberg,C, Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom. [Koulman,A, Wang,LY, Summerhill,K, Griffin,JL] MRC Human Nutrition Research, Cambridge, UK. [Schulze,MB, Kröger,J, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Sluijs,I, van der Schouw,YT] University Medical Center Utrecht, Utrecht, the Netherlands. [Guevara,M] Navarre Public Health Institute (ISPN), Pamplona, Spain. [Guevara,M, Huerta,JM, Amiano,P, Rodriguez-Barranco,M, Tormo,M] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Huerta,M, Tormo,M] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Feskens,EJM] Wageningen University, The Netherlands. [Affret,A, Dow,C, Fagherazzi,G] Inserm, CESP, U1018, Villejuif, France. Univ Paris-Sud, Villejuif, France, Gustave Roussy Institute, Villejuif, France. [Amiano,P] Public Health Division of Gipuzkoa, San Sebastian, Spain. Instituto BIO-Donostia, Basque Government, San Sebastian, Spain. [Boeing,H] German Institute of Human Nutrition Potsdam-Rehbruecke, Germany. [Franks,PW, Nilsson,PM] Lund University, Malmö, Sweden. [Franks,PW, Rolandsson,O] Umeå University, Umeå, Sweden. [Gonzalez,C] Catalan Institute of Oncology (ICO), Barcelona, Spain. [Kaaks,R, Kühn1,T] German Cancer Research Centre (DKFZ), Heidelberg, Germany. [Key1,TJ] University of Oxford, Oxford, United Kingdom. [Khaw,KT] University of Cambridge, Cambridge, United Kingdom. [Mortensen,M] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Mortensen,M, Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Overvad,K] Aalborg University Hospital, Aalborg, Denmark. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Palli,D] Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Rodriguez-Barranco,M] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sacerdote,C] 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. [Scalbert,A, Slimani,N] International Agency for Research on Cancer, Lyon, France. [Spijkerman,AMW, van der A,DL] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Tjonneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tormo,MJ] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Tumino,R] Cancer Registry and Histopathology Unit, Civic and M.P.Arezzo Hospital, ASP Ragusa, Italy. [Riboli,E] School of Public Health, Imperial College London, London, United Kingdom., Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197)., Imamura, Fumiaki [0000-0002-6841-8396], Sharp, Stephen J [0000-0003-2375-1440], Koulman, Albert [0000-0001-9998-051X], Sluijs, Ivonne [0000-0001-7758-4911], Guevara, Marcela [0000-0001-9242-6364], Huerta, José María [0000-0002-9637-3869], Rodriguez-Barranco, Miguel [0000-0002-9972-9779], Tormo, Maria-Jose [0000-0003-1474-5233], van der Schouw, Yvonne T [0000-0002-4605-435X], Langenberg, Claudia [0000-0002-5017-7344], and Wareham, Nicholas J [0000-0003-1422-2993]
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Male ,Physiology ,Social Sciences ,Diabetes Mellitus Tipo 2 ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6::Linoleic Acids [Medical Subject Headings] ,Anatomy::Fluids and Secretions::Body Fluids::Blood::Plasma [Medical Subject Headings] ,Biochemistry ,Plasma ,Mathematical and Statistical Techniques ,Endocrinology ,Sociology ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3 [Medical Subject Headings] ,Plant Products ,Estudios prospectivos ,Medicine and Health Sciences ,Fosfolípidos ,Ácidos grasos omega 3 ,Phospholipids ,Medicine(all) ,Schools ,Fatty Acids ,Geographicals::Geographic Locations::Europe [Medical Subject Headings] ,food and beverages ,Agriculture ,Ácido eicosapentaenoico ,11 Medical And Health Sciences ,Hematology ,Middle Aged ,Lipids ,Type 2 Diabetes ,Body Fluids ,Blood ,Ácidos Grasos Omega-6 ,Ácido 8,11,14-eicosanoico ,Endokrinologi och diabetes ,Physical Sciences ,Fatty Acids, Unsaturated ,Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Diabetes Mellitus::Diabetes Mellitus, Type 2 [Medical Subject Headings] ,Medicine ,Dieta ,lipids (amino acids, peptides, and proteins) ,Anatomy ,Europa ,Statistics (Mathematics) ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Arachidonic Acids [Medical Subject Headings] ,Research Article ,Cromatografía de gases ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings] ,Endocrine Disorders ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Eicosanoids::8,11,14-Eicosatrienoic Acid [Medical Subject Headings] ,Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings] ,Endocrinology and Diabetes ,Research and Analysis Methods ,Vegetable Oils ,Blood Plasma ,Education ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Docosahexaenoic Acids [Medical Subject Headings] ,General & Internal Medicine ,Fatty Acids, Omega-6 ,Fatty Acids, Omega-3 ,Ácidos docosahexaenoicos ,Diabetes Mellitus ,Journal Article ,Humans ,Statistical Methods ,Chemicals and Drugs::Lipids::Phospholipids [Medical Subject Headings] ,Ácido araquidónico ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Chromatography::Chromatography, Gas [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-6 [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Omega-3::Eicosapentaenoic Acid [Medical Subject Headings] ,Ácidos Grasos Insaturados ,Biology and Life Sciences ,Ácido linoleico ,Agronomy ,Diabetes Mellitus, Type 2 ,Metabolic Disorders ,Case-Control Studies ,Oils ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated [Medical Subject Headings] ,Mathematics ,Meta-Analysis ,Crop Science - 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., Using a large European cohort, Nita Forouhi and colleagues investigate the association between the concentration of polyunsaturated fatty acids measured in plasma and risk of developing type 2 diabetes., Author Summary Why Was This Study Done? Most dietary guidelines recommend the consumption of polyunsaturated fatty acids for cardiovascular health, but it is unclear whether or how n-3 and n-6 types of polyunsaturated fatty acids are related to type 2 diabetes. Health concerns have been raised previously about a diet high in linoleic acid (n-6 fatty acid), but its association with type 2 diabetes is unclear. Major limitations in previous studies have included the error-prone subjective assessment of the habitual consumption of polyunsaturated fatty acids when dietary intakes were evaluated and a small number of type 2 diabetes cases (n = 71 to 673) when objective biomarkers of polyunsaturated fatty acids were measured. What Did the Researchers Do and Find? We measured circulating individual polyunsaturated fatty acids in the blood samples of individuals within a large study from across eight countries of Europe among a reference sample of 15,919 individuals as well as 12,132 individuals who subsequently developed diabetes. Individuals were followed up for an average of approximately 10 y. We investigated the association between individual polyunsaturated fatty acids and the risk of future type 2 diabetes using statistical analyses that accounted for factors that could be potential alternative explanations for any observed associations. We found that higher levels of blood alpha-linolenic acid, a plant-origin n-3 fatty acid, and n-6 linoleic acid, the most abundant type of polyunsaturated fatty acid, were associated with a lower risk of future type 2 diabetes. In contrast, higher levels of four other minor individual n-6 fatty acids were associated with higher type 2 diabetes risk, while the blood marine-origin n-3 fatty acids were not associated with future diabetes. What Do These Findings Mean? Our findings show that it is important to consider individual circulating polyunsaturated fatty acids for association with type 2 diabetes risk, rather than placing emphasis on the class of circulating polyunsaturated fatty acids. We found that blood n-6 linoleic acid, the most abundant polyunsaturated fatty acid, is inversely associated with type 2 diabetes. We found no evidence that blood total n-6 polyunsaturated fatty acids may elevate the risk of type 2 diabetes, but several individual minor blood n-6 polyunsaturated fatty acids were associated with increased type 2 diabetes risk, highlighting the importance of polyunsaturated fatty acid metabolism in the development of type 2 diabetes.
- Published
- 2016
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