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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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Peer-reviewed

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Article

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Abstract

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 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363860.

Description

Funder: Associazione Iblea per la Ricerca Epidemiologica


Funder: Health Data Research UK


Funder: Institut Gustave-Roussy


Funder: Ligue Contre le Cancer


Funder: Zorg Onderzoek Nederland


Funder: Catalan Institute of Oncology


Funder: Dutch Prevention Funds


Funder: German Institute of Human Nutrition Potsdam-Rehbruecke


Funder: NIHR Imperial Biomedical Research Centre


Funder: Imperial College Biomedical Research Centre


Funder: Institut National de la Santé et de la Recherche Médicale


Funder: Mutuelle Générale de l’Education Nationale


Funder: Associazione Italiana per la Ricerca sul Cancro


Funder: Swedish Heart-Lung Foundation


Funder: German Cancer Aid


Funder: Ministerie van Volksgezondheid, Welzijn en Sport


Funder: National Research Council and Sicilian Regional Government


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


Funder: Bundesministerium für Bildung und Forschung


Funder: Compagnia di San Paolo


Funder: LK Research Funds


Funder: Netherlands Cancer Registry


Funder: School of Public Health, Imperial College London


Funder: Statistics Netherlands


Funder: Swedish Cancer Society


Funder: Swedish Research Council


Funder: Wereld Kanker Onderzoek Fonds


Funder: Centre International de Recherche sur le Cancer


Funder: Councils of Skåne and Västerbotten


Funder: Danish Cancer Society


Funder: Instituto de Salud Carlos III


Funder: German Cancer Research Center


Funder: Novo Nordisk


Funder: Swedish Diabetes Association

Keywords

Adult, Humans, Diet, Mediterranean, Australia, Cohort Studies, Diabetes Mellitus, Type 2, Biomarkers, Neoplasms, Risk Factors

Journal Title

PLoS Med

Conference Name

Journal ISSN

1549-1277
1549-1676

Volume Title

20

Publisher

Public Library of Science (PLoS)
Sponsorship
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 and Care Research (IS-BRC-1215-20014)