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@article{Zheng:2019:10.1210/jc.2018-01522,
author = {Zheng, J-S and Imamura, F and Sharp, SJ and van, der Schouw YT and Sluijs, I and Gundersen, TE and Ardanaz, E and Boeing, H and Bonet, C and Gómez, JH and Dow, C and Fagherazzi, G and Franks, PW and Jenab, M and Kühn, T and Kaaks, R and Key, TJ and Khaw, K-T and Lasheras, C and Mokoroa, O and Mancini, FR and Nilsson, PM and Overvad, K and Panico, S and Palli, D and Rolandsson, O and Sieri, S and Salamanca-Fernández, E and Sacerdote, C and Spijkerman, AM and Stepien, M and Tjonneland, A and Tumino, R and Butterworth, AS and Riboli, E and Danesh, J and Langenberg, C and Forouhi, NG and Wareham, NJ},
doi = {10.1210/jc.2018-01522},
journal = {Journal of Clinical Endocrinology and Metabolism},
pages = {1293--1303},
title = {Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study},
url = {http://dx.doi.org/10.1210/jc.2018-01522},
volume = {104},
year = {2019}
}

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TY  - JOUR
AB  - 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.
AU  - Zheng,J-S
AU  - Imamura,F
AU  - Sharp,SJ
AU  - van,der Schouw YT
AU  - Sluijs,I
AU  - Gundersen,TE
AU  - Ardanaz,E
AU  - Boeing,H
AU  - Bonet,C
AU  - Gómez,JH
AU  - Dow,C
AU  - Fagherazzi,G
AU  - Franks,PW
AU  - Jenab,M
AU  - Kühn,T
AU  - Kaaks,R
AU  - Key,TJ
AU  - Khaw,K-T
AU  - Lasheras,C
AU  - Mokoroa,O
AU  - Mancini,FR
AU  - Nilsson,PM
AU  - Overvad,K
AU  - Panico,S
AU  - Palli,D
AU  - Rolandsson,O
AU  - Sieri,S
AU  - Salamanca-Fernández,E
AU  - Sacerdote,C
AU  - Spijkerman,AM
AU  - Stepien,M
AU  - Tjonneland,A
AU  - Tumino,R
AU  - Butterworth,AS
AU  - Riboli,E
AU  - Danesh,J
AU  - Langenberg,C
AU  - Forouhi,NG
AU  - Wareham,NJ
DO  - 10.1210/jc.2018-01522
EP  - 1303
PY  - 2019///
SN  - 0021-972X
SP  - 1293
TI  - Association of plasma vitamin D metabolites with incident type 2 diabetes: EPIC-InterAct case-cohort study
T2  - Journal of Clinical Endocrinology and Metabolism
UR  - http://dx.doi.org/10.1210/jc.2018-01522
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30418614
UR  - http://hdl.handle.net/10044/1/66282
VL  - 104
ER  -

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