Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.
van der Schouw, Yvonne T
Gundersen, Thomas E
Gómez, Jesus Humberto
Franks, Paul W
Key, Timothy J
Mancini, Francesca Romana
Nilsson, Peter M
Spijkerman, Annemieke MW
The Journal of clinical endocrinology and metabolism
The Endocrine Society
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Zheng, J., Imamura, F., Sharp, S., van der Schouw, Y. T., Sluijs, I., Gundersen, T. E., Ardanaz, E., et al. (2019). Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.. The Journal of clinical endocrinology and metabolism, 104 (4), 1293-1303. https://doi.org/10.1210/jc.2018-01522
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: non-epimeric 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 EPIC-InterAct case-cohort study for T2D included 9671 incident T2D cases and 13562 subcohort members. Plasma vitamin D metabolites were quantified by liquid-chromatography mass-spectrometry. We used multivariable Prentice-weighted Cox regression to estimate hazard ratios (HRs) of T2D for each metabolite. Analyses were performed separately within country, and estimates combined across countries using random-effects meta-analysis. Results: The mean concentrations (standard deviation) of total 25(OH)D, non-epimeric 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 non-epimeric 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], while 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 non-epimeric 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.
Humans, Diabetes Mellitus, Type 2, Vitamin D, Incidence, Risk Factors, Prospective Studies, Stereoisomerism, Adult, Middle Aged, Europe, Female, Male, Biomarkers
The InterAct project was funded by the European Union Framework 6 (LSHM_CT_2006_037197). Biomarker measurements for vitamin D metabolites were funded jointly by the InterAct project, the MRC Cambridge Initiative (RG71466, SJAH/004) and the EPIC-CVD project. EPIC-CVD has been supported by the European Union Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the UK Medical Research Council (G0800270 and MR/L003120/1), the British Heart Foundation (SP/09/002 and RG/08/014 and RG13/13/30194) and the UK National Institute of Health Research. In addition, InterAct investigators acknowledge funding from the following agencies: Medical Research Council Epidemiology Unit MC_UU_12015/1 and MC_UU_12015/5, NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014), Regional Government of Asturias and Regional Governments of Basque Country. Dr. Ivonne Sluijs is supported by the Junior Dr. Dekker grant (2015T019) from the Dutch Heart Foundation. Dr. Guy Fagherazzi is supported by the French Research Agency (Agence Nationale de la Recherche) via an “Investissement d’Avenir” grant (investment for the future grant, ANR-10-COHO-0006) and by the IDEX Paris Saclay Nutriperso Project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 701708.
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
MEDICAL RESEARCH COUNCIL (MR/N003284/1)
British Heart Foundation (RG/13/13/30194)
European Research Council (268834)
European Commission (602068)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
External DOI: https://doi.org/10.1210/jc.2018-01522
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286655