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

Zheng, Ju Sheng; Imamura, Fumiaki; Sharp, Stephen J.; Van Der Schouw, Yvonne T.; Sluijs, Ivonne; Gundersen, Thomas E.; Ardanaz, Eva LU ; Boeing, Heiner; Bonet, Catalina and Gómez, Jesus Humberto, et al. (2019) In Journal of Clinical Endocrinology and Metabolism 104(4). p.1293-1303
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)D
3
stereoisomers, and 25(OH)D
2
, the minor component of 25(OH)D. We aimed to investigate the prospective associations of circulating levels of the sum... (More)


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)D
3
stereoisomers, and 25(OH)D
2
, 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)D
3
, and 25(OH)D
2
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)D
3
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)D
3
was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D
2
[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)D
3
with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.

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published
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in
Journal of Clinical Endocrinology and Metabolism
volume
104
issue
4
pages
11 pages
publisher
The Endocrine Society
external identifiers
  • scopus:85064061197
ISSN
0021-972X
DOI
10.1210/jc.2018-01522
language
English
LU publication?
yes
id
bc5b6236-35a2-4292-bd48-583ffae4daf6
date added to LUP
2019-04-26 11:00:01
date last changed
2019-10-15 07:02:18
@article{bc5b6236-35a2-4292-bd48-583ffae4daf6,
  abstract     = {<p><br>
                                                         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)D                             <br>
                            <sub>3</sub><br>
                                                          stereoisomers, and 25(OH)D                             <br>
                            <sub>2</sub><br>
                                                         , 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)D                             <br>
                            <sub>3</sub><br>
                                                         , and 25(OH)D                             <br>
                            <sub>2</sub><br>
                                                          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)D                             <br>
                            <sub>3</sub><br>
                                                          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)D                             <br>
                            <sub>3</sub><br>
                                                          was positively associated [per 1 SD HR = 1.16 (1.09, 1.25)]. There was no statistically significant association with T2D for 25(OH)D                             <br>
                            <sub>2</sub><br>
                                                          [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)D                             <br>
                            <sub>3</sub><br>
                                                          with incident T2D provides novel information to assess the biological relevance of vitamin D epimerization and vitamin D subtypes in diabetes etiology.                         <br>
                        </p>},
  author       = {Zheng, Ju Sheng and Imamura, Fumiaki and Sharp, Stephen J. and Van Der Schouw, Yvonne T. and Sluijs, Ivonne and Gundersen, Thomas E. and Ardanaz, Eva and Boeing, Heiner and Bonet, Catalina and Gómez, Jesus Humberto and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Jenab, Mazda and Kuhn, Tilman and Kaaks, Rudolf and Key, Timothy J. and Khaw, Kay Tee and Lasheras, Cristina and Mokoroa, Olatz and Mancini, Francesca Romana and Nilsson, Peter M. and Overvad, Kim and Panico, Salvatore and Palli, Domenico and Rolandsson, Olov and Sieri, Sabina and Salamanca-Fernández, Elena and Sacerdote, Carlotta and Spijkerman, Annemieke M.W. and Stepien, Magdalena and Tjonneland, Anne and Tumino, Rosario and Butterworth, Adam S. and Riboli, Elio and Danesh, John and Langenberg, Claudia and Forouhi, Nita G. and Wareham, Nicholas J.},
  issn         = {0021-972X},
  language     = {eng},
  number       = {4},
  pages        = {1293--1303},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  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},
}