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A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study.

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BACKGROUND: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet. METHODS AND FINDINGS: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22,202 participants, of whom 9,453 were T2D cases, with relevant biomarkers from an original case-cohort of 27,779 participants sampled from a cohort of 340,234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding. CONCLUSIONS: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12613000602729


Funder: Health Data Research UK

Funder: Centre International de Recherche sur le Cancer; funder-id:

Funder: School of Public Health, Imperial College London; funder-id:

Funder: NIHR Imperial Biomedical Research Centre; funder-id:

Funder: Danish Cancer Society

Funder: Ligue Contre le Cancer; funder-id:

Funder: Institut Gustave-Roussy; funder-id:

Funder: Mutuelle Générale de l’Education Nationale

Funder: Institut National de la Santé et de la Recherche Médicale (INSERM)

Funder: German Cancer Aid

Funder: German Cancer Research Center

Funder: German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)

Funder: Bundesministerium für Bildung und Forschung; funder-id:

Funder: Associazione Iblea per la Ricerca Epidemiologica; funder-id:

Funder: Associazione Italiana per la Ricerca sul Cancro; funder-id:

Funder: Compagnia di San Paolo; funder-id:

Funder: National Research Council and Sicilian Regional Government

Funder: Ministerie van Volksgezondheid, Welzijn en Sport; funder-id:

Funder: Netherlands Cancer Registry

Funder: LK Research Funds

Funder: Dutch Prevention Funds

Funder: Zorg Onderzoek Nederland

Funder: Wereld Kanker Onderzoek Fonds; funder-id:

Funder: Statistics Netherlands

Funder: Instituto de Salud Carlos III; funder-id:

Funder: Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra

Funder: Catalan Institute of Oncology

Funder: Swedish Cancer Society

Funder: Swedish Research Council

Funder: Councils of Skåne and Västerbotten

Funder: Novo Nordisk; funder-id:

Funder: Swedish Diabetes Association

Funder: Swedish Heart-Lung Foundation

Funder: European Research Council

Funder: Imperial College Biomedical Research Centre


32 Biomedical and Clinical Sciences, 3210 Nutrition and Dietetics, 42 Health Sciences, Prevention, Nutrition, Clinical Trials and Supportive Activities, Clinical Research, Diabetes, Cancer, Obesity, Cancer, Metabolic and endocrine

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PLoS Med

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Public Library of Science (PLoS)
MRC (MC_UU_00006/3)
Medical Research Council (G1000143)
European Research Council (268834)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701708)
British Heart Foundation (RG/18/13/33946)
MRC (MC_UU_00006/1)
National Institute for Health Research (IS-BRC-1215-20014)