Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries
Zheng, Ju Sheng; Sharp, Stephen J.; Imamura, Fumiaki; Chowdhury, Rajiv; Gundersen, Thomas E.; Steur, Marinka; Sluijs, Ivonne; Van Der Schouw, Yvonne T.; Agudo, Antonio; Aune, Dagfinn; Barricarte, Aurelio; Boeing, Heiner; Chirlaque, María Dolores; Dorronsoro, Miren; Freisling, Heinz; El-Fatouhi, Douae; Franks, Paul W.; Fagherazzi, Guy; Grioni, Sara; Gunter, Marc J.; Kyrø, Cecilie; Katzke, Verena; Kühn, Tilman; Khaw, Kay Tee; Laouali, Nasser; Masala, Giovanna; Nilsson, Peter M.; Overvad, Kim; Panico, Salvatore; Papier, Keren; Quirós, J. Ramón; Rolandsson, Olov; Redondo-Sánchez, Daniel; Ricceri, Fulvio; Schulze, Matthias B.; Spijkerman, Annemieke M.W.; Tjønneland, Anne; Tong, Tammy Y.N.; Tumino, Rosario; Weiderpass, Elisabete; Danesh, John; Butterworth, Adam S.; Riboli, Elio; Forouhi, Nita G.; Wareham, Nicholas J.
(2020) The BMJ, volume 370
(Article)
Abstract
OBJECTIVE: To investigate the association of plasma vitamin C and carotenoids, as indicators of fruit and vegetable intake, with the risk of type 2 diabetes. DESIGN: Prospective case-cohort study. SETTING: Populations from eight European countries. PARTICIPANTS: 9754 participants with incident type 2 diabetes, and a subcohort of 13 662 individuals from
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the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 340 234 participants: EPIC-InterAct case-cohort study. MAIN OUTCOME MEASURE: Incident type 2 diabetes. RESULTS: In a multivariable adjusted model, higher plasma vitamin C was associated with a lower risk of developing type 2 diabetes (hazard ratio per standard deviation 0.82, 95% confidence interval 0.76 to 0.89). A similar inverse association was shown for total carotenoids (hazard ratio per standard deviation 0.75, 0.68 to 0.82). A composite biomarker score (split into five equal groups), comprising vitamin C and individual carotenoids, was inversely associated with type 2 diabetes with hazard ratios 0.77, 0.66, 0.59, and 0.50 for groups 2-5 compared with group 1 (the lowest group). Self-reported median fruit and vegetable intake was 274 g/day, 396 g/day, and 508 g/day for participants in categories defined by groups 1, 3, and 5 of the composite biomarker score, respectively. One standard deviation difference in the composite biomarker score, equivalent to a 66 (95% confidence interval 61 to 71) g/day difference in total fruit and vegetable intake, was associated with a hazard ratio of 0.75 (0.67 to 0.83). This would be equivalent to an absolute risk reduction of 0.95 per 1000 person years of follow up if achieved across an entire population with the characteristics of the eight European countries included in this analysis. CONCLUSIONS: These findings indicate an inverse association between plasma vitamin C, carotenoids, and their composite biomarker score, and incident type 2 diabetes in different European countries. These biomarkers are objective indicators of fruit and vegetable consumption, and suggest that diets rich in even modestly higher fruit and vegetable consumption could help to prevent development of type 2 diabetes.
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Keywords: Ascorbic Acid/blood, Biomarkers/blood, Carotenoids/blood, Case-Control Studies, Diabetes Mellitus, Type 2/blood, Diet, Europe, Female, Fruit, Humans, Male, Prospective Studies, Vegetables, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
ISSN: 0959-8146
Publisher: BMJ Publishing Group
Note: Funding Information: 39NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK 40British Heart Foundation Cambridge Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke’s Hospital, Cambridge, UK 41Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK We thank all EPIC participants and staff for their contribution to the study. We thank Nicola Kerrison (MRC Epidemiology Unit, Cambridge) for managing the data for the InterAct Project. We thank the technical and functional operational teams of the MRC Epidemiology Unit and laboratory team at VITAS AS, Norway, for the measurements of plasma vitamin C and carotenoids. We thank staff from the EPIC-CVD and EPIC-InterAct Coordinating Centres for carrying out sample preparation and data-handling work, particularly Sarah Spackman (EPIC-CVD Data Manager), and Cambridge Genomic Services for genotyping. Contributors: NGF and NJW contributed equally to this work. NJW was chief investigator and NGF and SJS were investigators of the InterAct project. J-SZ and NGF had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis; J-SZ performed the statistical analyses and drafted the manuscript with input from NGF. The working group (J-SZ, SJS, FI, TEG, MS, RC, YTvdS, IS, AB, NGF) and all authors contributed to interpretation of data, revised the article critically for important intellectual content, and approved the final version of the manuscript. NGF and NJW are the guarantors, and they contributed equally to the work. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Funding: The InterAct project was funded by the EU FP6 programme (grant number LSHM_CT_2006_037197). Biomarker measurements for vitamin C and carotenoids were funded jointly by the InterAct project, the EPIC-CVD project, and the MRC Cambridge Initiative (RG71466, SJAH/004). EPIC-CVD has been supported by the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946), the European Commission Framework Programme 7 (HEALTH-F2-2012-279233), the European Research Council (268834), and the National Institute for Health Research (NIHR; Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). JD is funded by the National Institute for Health Research (senior investigator award). NJW and NGF acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, and NIHR Biomedical Research Centre Cambridge: nutrition, diet, and lifestyle research theme (IS-BRC-1215-20014). JSZ has received funding from Westlake University (No YSYY0209) and European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701708. TYNT has received funding from the Cancer Research UK (C570/A16491 and C8221/A19170), UK Medical Research Council (MR/M012190/1). PWF has received funding from Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation, European Research Council. K-TK has received funding from Medical Research Council UK, Cancer Research UK. TK has received funding from German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF). PMN has received funding from Swedish Research Council. KO has received funding from Danish Cancer Society. SP has received funding from Compagnia di San Paolo. JRQ has received funding from regional government of Asturias. OR has received funding from the Västerboten County Council. ER has received funding from Imperial College Biomedical Research Centre. EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF). The coordination of EPIC-Spain was financially supported by the Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), regional governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and the Catalan Institute of Oncology (ICO) (Spain). The funders of the studies had no role in the study design, data collection, data analysis, data interpretation, or report preparation. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from European commission, UK Medical Research Council, British Heart Foundation, and National Institute for Health Research Cambridge Biomedical Research Centre for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/WHO. Ethical approval: All included studies were approved by local review boards, and all participants gave written informed consent to participate in the study. Data sharing: EPIC-InterAct Study data cannot be deposited publicly as these collaborative data originate from multiple research institutions across eight European countries with different legal frameworks. The authors confirm that researchers seeking the analysis dataset for this work can submit a data request to the EPIC-InterAct study central contact point by emailing interact@mrc-epid.cam.ac.uk. The corresponding author affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. Dissemination to participants and related patient and public communities: Findings will be disseminated via the communications team of the corresponding author’s institute. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. Publisher Copyright: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
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