A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study

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  • Fumiaki Imamura, University of Cambridge, United Kingdom
  • Stephen J Sharp, University of Cambridge, United Kingdom
  • Albert Koulman, Medical Research Council Epidemiology Unit Elsie Widdowson Laboratory, Cambridge, United Kingdom., Cambridge National Institute for Health Research (NIHR) Biomedical Research Centre (BRC), Department of Clinical Biochemistry, Addenbrooke's Hospital, National Institute for Health Research Biomedical Research Centres Core Metabolomics and Lipidomics Laboratory, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom
  • Matthias B Schulze, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, Germany
  • Janine Kröger, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, Germany
  • Julian L Griffin, Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom; Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom;, United Kingdom
  • José M Huerta, CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain., Spain
  • Marcela Guevara, Navarre Public Health Institute, Pamplona, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain., Spain
  • Ivonne Sluijs, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Netherlands
  • Antonio Agudo, Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), 08908 Barcelona, Spain., Spain
  • Eva Ardanaz, Navarre Public Health Institute, Pamplona, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain., Spain
  • Beverley Balkau, Center for Research in Epidemiology and Population Health, Inserm U1018, Paris-Sud University, University Versailles Saint-Quentin-en-Yvelines, Paris Saclay University, Villejuif, France., France
  • Heiner Boeing, Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany, Germany
  • Veronique Chajes, International Agency for Research on Cancer, 69372 Lyon, France., France
  • Christina C Dahm
  • Courtney Dow, Inserm, CESP, U1018, Villejuif, France; Univ Paris-Sud, UMRS 1018, Villejuif, France; Gustave Roussy Institute, F-94800 Villejuif, France., France
  • Guy Fagherazzi, Inserm, CESP, U1018, Villejuif, France; Univ Paris-Sud, UMRS 1018, Villejuif, France; Gustave Roussy Institute, F-94800 Villejuif, France., France
  • Edith J M Feskens, Department of Agrotechnology and Food Sciences, Wageningen University, Wageningen, Netherlands., Netherlands
  • Paul W Franks, Department of Clinical Sciences, Lund University, Skane University Hospital, Malmo, Sweden., Sweden
  • Diana Gavrila, Murcia BioHealth Research Institute-Hospital Virgen de la Arrixaca, Murcia, Spain., Spain
  • Marc Gunter, Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark; Aalborg University Hospital, Aalborg, Denmark., Denmark
  • Rudolf Kaaks, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Germany
  • Timothy J Key, Cancer Epidemiology Unit, Nuffield Department of Population Health University of Oxford, United Kingdom., United Kingdom
  • Kay-Tee Khaw, Department of Public Health and Primary Care, and Clinical Gerontology Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom;, United Kingdom
  • Tilman Kühn, Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Germany
  • Olle Melander, Department of Clinical Sciences, Lund University, Skane University Hospital, Malmo, Sweden., Sweden
  • Elena Molina-Portillo, Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, 18014 Granada, Spain., Spain
  • Peter M Nilsson, Department of Public Health and Primary Care, and Clinical Gerontology Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom;, United Kingdom
  • Anja Olsen
  • Kim Overvad
  • Domenico Palli, Cancer Risk Factors and Lifestyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy., Italy
  • Salvatore Panico, Dipartimento di Medicina Clinica e Chirurgia, Università degli Studi di Federico II University, Naples, Italy., Italy
  • Olov Rolandsson, Department of Public Health and Clinical Medicine, Family medicine, Umeå University, 901 87 Umeå, Sweden., Sweden
  • Sabina Sieri, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy., Italy
  • Carlotta Sacerdote, Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital-University of Turin and Center for Cancer Prevention (CPO), Torino, ItalyHuman Genetics Foundation (HuGeF), Torino, Italy., Italy
  • Nadia Slimani, International Agency for Research on Cancer, 69372 Lyon, France., France
  • Annemieke M W Spijkerman, National Institute for Public Health and the Environment, Bilthoven, Netherlands., Netherlands
  • Anne Tjønneland, Danish Cancer Society Research Center, Danish Cancer Society, Copenhagen, Denmark., Denmark
  • Rosario Tumino, Affiliation Cancer Registry, Department of Prevention, Azienda Sanitaria Provinciale di Ragusa, Ragusa, Italy., Italy
  • Yvonne T van der Schouw, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., Netherlands
  • Claudia Langenberg, University of Cambridge, United Kingdom
  • Elio Riboli, School of Public Health, Imperial College London, London, United Kingdom., United Kingdom
  • Nita G Forouhi, University of Cambridge, United Kingdom
  • Nick J Wareham, University of Cambridge, United Kingdom

BACKGROUND: Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.

METHODS AND FINDINGS: We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested case-cohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of γ-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.

CONCLUSIONS: A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

Original languageEnglish
JournalP L o S Medicine (Print)
Volume14
Issue10
Pages (from-to)e1002409
ISSN1549-1277
DOIs
Publication statusPublished - 11 Oct 2017

    Research areas

  • Journal Article

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