The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations

The EPIC-InterAct Study

  1. Nicholas J. Wareham, FRCP1
  1. 1Medical Research Council, Epidemiology Unit, Cambridge, U.K.
  2. 2Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute, Barcelona, Spain
  3. 3Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany
  4. 4Navarre Public Health Institute, Pamplona, Spain
  5. 5CIBER Epidemiología y Salud Pública, Madrid, Spain
  6. 6Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
  7. 7Public Health Department of Gipuzkoa, BioDonostia Research Institute, Health Department of Basque Region, San Sebastián, Spain
  8. 8National Food Institute, Technical University of Denmark, Moerkhoej, Denmark
  9. 9INSERM, Centre for Research in Epidemiology and Population Health, U1018, Nutrition, Hormones and Women's Health, Villejuif, France
  10. 10Paris South University, Unité Mixte de Recherche 1018, Villejuif, France
  11. 11Division of Human Nutrition, Section of Nutrition and Epidemiology, University of Wageningen, Wageningen, the Netherlands
  12. 12Genetic and Molecular Epidemiology Unit, Clinical Research Center, Skåne University Hospital, Lund University, Malmö, Sweden
  13. 13Nutritional Epidemiology Unit, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy
  14. 14Department of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany
  15. 15Cancer Epidemiology Unit, University of Oxford, Oxford, U.K.
  16. 16Department of Public Health and Primary Care, University of Cambridge, Cambridge, U.K.
  17. 17Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy
  18. 18Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
  19. 19Andalusian School of Public Health. Granada, Spain
  20. 20Department of Clinical Sciences, Lund University, Malmö, Sweden
  21. 21Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
  22. 22Public Health Directorate, Asturias, Spain
  23. 23Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
  24. 24Center for Cancer Prevention in Piemonte, and Human Genetic Foundation, Torino, Italy
  25. 25National Institute for Public Health and the Environment, Bilthoven, the Netherlands
  26. 26Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
  27. 27Epidemiology Department, Murcia Regional Health Council, Murcia, Spain
  28. 28Department of Health and Social Sciences, Universidad de Murcia, Spain
  29. 29Cancer Registry and Histopathology Unit, “Civile M.P. Arezzo” Hospital, ASP Ragusa, Italy
  30. 30School of Public Health, Imperial College, London, U.K.
  1. Corresponding author: Nita G. Forouhi, nita.forouhi{at}
  1. R.Z.-R. and N.G.F. contributed equally to this study.


OBJECTIVE To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.

RESEARCH DESIGN AND METHODS The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.

RESULTS In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77–1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72–1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69–0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68–0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57–0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes.

CONCLUSIONS Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.

  • Received April 15, 2013.
  • Accepted July 21, 2013.

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