Association of plasma biomarkers of fruit and vegetable intake with incident type 2 diabetes: EPIC-InterAct case-cohort study in eight European countries.

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 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.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 (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust). Professor John Danesh is funded by the National Institute for Health Research (Senior Investigator Award). Professors Nicholas J Wareham and Nita G Forouhi 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). Dr Ju-Sheng Zheng has received funding from Westlake University (No. YSYY0209) and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701708. Dr Tammy YN Tong has received funding from the Cancer Research UK (C570/A16491 and C8221/A19170), UK Medical Research Council (MR/M012190/1). Professor Paul W Franks has received funding from Swedish Research Council, Novo Nordisk, Swedish Diabetes Association, Swedish Heart-Lung Foundation, European Research Council. Professor Kay-Tee Khaw has received funding from Medical Research Council UK, Cancer Research UK. Dr Tilman Kühn has received funding from German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF). Professor Peter M Nilsson has received funding from Swedish Research Council. Professor Kim Overvad has received funding from Danish Cancer Society. Professor Salvatore Panico has received funding from Compagnia di San Paolo. Dr J. Ramón Quirós has received funding from Regional Government of Asturias. Dr Olov Rolandsson has received funding from the Västerboten County Council. Professor Elio Riboli 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 study design, data collection, data analysis, data interpretation, or report preparation