RT Journal Article
T1 Association of Plasma Vitamin D Metabolites With Incident Type 2 Diabetes: EPIC-InterAct Case-Cohort Study.
A1 Zheng, Ju-Sheng
A1 Imamura, Fumiaki
A1 Sharp, Stephen J
A1 van der Schouw, Yvonne T
A1 Sluijs, Ivonne
A1 Gundersen, Thomas E
A1 Ardanaz, Eva
A1 Boeing, Heiner
A1 Bonet, Catalina
A1 Gómez, Jesus Humberto
A1 Dow, Courtney
A1 Fagherazzi, Guy
A1 Franks, Paul W
A1 Jenab, Mazda
A1 Kühn, Tilman
A1 Kaaks, Rudolf
A1 Key, Timothy J
A1 Khaw, Kay-Tee
A1 Lasheras, Cristina
A1 Mokoroa, Olatz
A1 Mancini, Francesca Romana
A1 Nilsson, Peter M
A1 Overvad, Kim
A1 Panico, Salvatore
A1 Palli, Domenico
A1 Rolandsson, Olov
A1 Sieri, Sabina
A1 Salamanca-Fernández, Elena
A1 Sacerdote, Carlotta
A1 Spijkerman, Annemieke M W
A1 Stepien, Magdalena
A1 Tjonneland, Anne
A1 Tumino, Rosario
A1 Butterworth, Adam S
A1 Riboli, Elio
A1 Danesh, John
A1 Langenberg, Claudia
A1 Forouhi, Nita G
A1 Wareham, Nicholas J
K1 25-hydroxyvitamin D
K1 Diabetes Mellitus, Type 2
K1 Stereoisomerism
K1 Vitamin D
K1 Calcifediol
K1 Vitamins
K1 Ergocalciferols
AB 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. 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. 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)]. 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.
PB Oxford University Press
YR 2019
FD 2019
LK http://hdl.handle.net/10668/13170
UL http://hdl.handle.net/10668/13170
LA en
NO The InterAct project was funded bythe European Union Sixth Framework Program (Grant LSHM_CT_2006_037197). Biomarker measurements for vitamin Dmetabolites were funded jointly by the MRC Cambridge Initiative (Grants RG71466 and SJAH/004), and by the EPIC-CVDproject. EPIC-CVD has been supported by the European UnionSeventh Framework Program (Grant HEALTH-F2-2012-279233), the European Research Council (Grant 268834), theUK Medical Research Council (Grants G0800270 and MR/L003120/1), the British Heart Foundation (Grants SP/09/002,RG/08/014, and RG13/13/30194), and by the UK NationalInstitutes of Health Research. Additionally, InterAct investigators acknowledge funding from the following agencies:MedicalResearchCouncilEpidemiologyUnitMC_UU_12015/1and MC_UU_12015/5, NIHR Biomedical Research CentreCambridge: Nutrition, Diet, and Lifestyle Research Theme(Grant IS-BRC-1215-20014), the Regional Government ofAsturias, and the Regional Governments of Basque Country. I.S.is supported by Junior Dr. Dekker Grant 2015T019 from theDutch Heart Foundation. G.F. is supported by Agence Nationalede la Recherche via “Investissement d’Avenir” Grant ANR-10-COHO-0006 and by the IDEX Paris Saclay Nutriperso Project.This project has received funding from the European Union’sHorizon 2020 research and innovation program under MarieSklodowska-Curie Grant 701708.
DS RISalud
RD Apr 6, 2025