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Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study

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Title: Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study
Authors: Zheng, J-S
Imamura, F
Sharp, SJ
Van der Schouw, YT
Sluijs, I
Gundersen, TE
Ardanaz, E
Boeing, H
Bonet, C
Gómez, JH
Dow, C
Fagherazzi, G
Franks, PW
Jenab, M
Kühn, T
Kaaks, R
Key, TJ
Khaw, K-T
Lasheras, C
Mokoroa, O
Mancini, FR
Nilsson, PM
Overvad, K
Panico, S
Palli, D
Rolandsson, O
Sieri, S
Salamanca-Fernández, E
Sacerdote, C
Spijkerman, AM
Stepien, M
Tjonneland, A
Tumino, R
Butterworth, AS
Riboli, E
Danesh, J
Langenberg, C
Forouhi, NG
Wareham, NJ
Item Type: Journal Article
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.
Issue Date: Apr-2019
Date of Acceptance: 6-Nov-2018
URI: http://hdl.handle.net/10044/1/66282
DOI: https://doi.org/10.1210/jc.2018-01522
ISSN: 0021-972X
Publisher: Oxford University Press (OUP)
Start Page: 1293
End Page: 1303
Journal / Book Title: Journal of Clinical Endocrinology and Metabolism
Volume: 104
Issue: 4
Copyright Statement: This article has been published under the terms of the Creative Commons Attribution License (CC BY; https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s).
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Endocrinology & Metabolism
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-11-09
Appears in Collections:School of Public Health