Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study
Year: 2018
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Existing evidence for the prospective association of vitamin D status with type 2 diabetes (T2D) is focused almost exclusively on circulating total 25-hydroxyvitamin D [25(OH)D] without distinction between its subtypes: nonepimeric and epimeric 25(OH)D3 stereoisomers, and 25(OH)D2, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum and each of these three metabolites with incident T2D. METHODS: This analysis in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13,562 subcohort members. Plasma vitamin D metabolites were quantified by liquid chromatography-mass spectrometry. We used a multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates were combined across countries using random-effects meta-analysis. RESULTS: The mean concentrations (SD) of total 25(OH)D, nonepimeric 25(OH)D3, epimeric 25(OH)D3, and 25(OH)D2 were 41.1 (17.2), 40.7 (17.3), 2.13 (1.31), and 8.16 (6.52) nmol/L, respectively. Plasma total 25(OH)D and nonepimeric 25(OH)D3 were inversely associated with incident T2D [multivariable-adjusted HR per 1 SD = 0.81 (95% CI, 0.77, 0.86) for both variables], whereas epimeric 25(OH)D3 was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D2 [per 1 SD HR = 0.94 (0.76, 1.18)]. CONCLUSIONS: Plasma nonepimeric 25(OH)D3 was inversely associated with incident T2D, consistent with it being the major metabolite contributing to total 25(OH)D. The positive association of the epimeric form of 25(OH)D3 with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.
Authors: Ju-Sheng Zheng, Fumiaki Imamura, Stephen J Sharp, Yvonne T van der Schouw, Ivonne Sluijs, Thomas E Gundersen, Eva Ardanaz, Heiner Boeing, Catalina Bonet, Jesus Humberto Gómez, Courtney Dow, Guy Fagherazzi, Paul W Franks, Mazda Jenab, Tilman Kühn, Rudolf Kaaks, Timothy J Key, Kay-Tee Khaw, Cristina Lasheras, Olatz Mokoroa, Francesca Romana Mancini, Peter M Nilsson, Kim Overvad, Salvatore Panico, Domenico Palli, Olov Rolandsson, Sabina Sieri, Elena Salamanca-Fernández, Carlotta Sacerdote, Annemieke M W Spijkerman, Magdalena Stepien, Anne Tjonneland, Rosario Tumino, Adam S Butterworth, Elio Riboli, John Danesh, Claudia Langenberg, Nita G Forouhi, Nicholas J Wareham
Institutions: University of Cambridge, MRC Epidemiology Unit, Utrecht University, University Medical Center Utrecht, Vitas (Norway), Instituto de Salud Pública de Navarra, Navarre Institute of Health Research, German Institute of Human Nutrition, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, Instituto Murciano de Investigación Biosanitaria, Université Paris-Sud, Inserm, Université Paris-Saclay, Institut Gustave Roussy, Centre de recherche en Epidémiologie et Santé des Populations, Lund University, Centre international de recherche sur le cancer, German Cancer Research Center, University of Oxford, Universidad de Oviedo, Biogipuzkoa Health Research Institute, Aarhus University, Federico II University Hospital, University of Naples Federico II, Umeå University, Fondazione IRCCS Istituto Nazionale dei Tumori, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Andalusian School of Public Health, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Turin, National Institute for Public Health and the Environment, Danish Cancer Society, British Heart Foundation, National Institute for Health and Care Research, Medical Research Council, Imperial College London, Wellcome Sanger Institute, Addenbrooke's Hospital
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,750
Funders: World Health Organization, Cancer Research UK, National Institute for Health and Care Research, British Heart Foundation, European Commission, Agence Nationale de la Recherche, National Institutes of Health, Seventh Framework Programme, Sixth Framework Programme, Medical Research Council, European Research Council, H2020 Marie Skłodowska-Curie Actions
Awards: G1075599542, Aetiology of type 2 diabetes and related metabolic disorders, Nutritional epidemiology, G1422564005, NIHR Senior Investigator Award, NIHR Senior Investigator Award, Nutritional biomarkers to advance understanding of association between diet and type 2 diabetes, G2826529823, G2892497062, G299057155, G370598735, G385907487, G4211044638, G434337789, G4577085396, G4584873075, G4733990475, Etude Epidémiologique des Enfants de femmes de l'Education Nationale, G567453067, G5787426001, G5897142711, NIHR Senior Investigator Award, G6206044308, EPIC-CVD: Individualised CVD risk assessment: tailoring targeted and cost-effective approaches to Europe's diverse populations, G6594529311, G6641991021, G6723261869, G6957823285, Nutritional biomarkers to advance understanding of association between diet and type 2 diabetes, G7240651115, Global initiative on gene-environment interaction on diabetes/obesity risk, Large-scale integrative studies of risk factors in coronary heart disease: from discovery to application (renewal). (Joint funding with MRC), G810980811, NIHR Senior Investigator Award, NIHR Senior Investigator Award, G892496435, G8946560635
OpenAlex ID: W2900077198