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Paul Franks

Paul Franks

Principal investigator

Paul Franks

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

Author

  • Ju Sheng Zheng
  • Fumiaki Imamura
  • Stephen J. Sharp
  • Yvonne T. Van Der Schouw
  • Ivonne Sluijs
  • Thomas E. Gundersen
  • Eva Ardanaz
  • Heiner Boeing
  • Catalina Bonet
  • Jesus Humberto Gómez
  • Courtney Dow
  • Guy Fagherazzi
  • Paul W. Franks
  • Mazda Jenab
  • Tilman Kuhn
  • Rudolf Kaaks
  • Timothy J. Key
  • Kay Tee Khaw
  • Cristina Lasheras
  • Olatz Mokoroa
  • Francesca Romana Mancini
  • Peter M. Nilsson
  • Kim Overvad
  • Salvatore Panico
  • Domenico Palli
  • Olov Rolandsson
  • Sabina Sieri
  • Elena Salamanca-Fernández
  • Carlotta Sacerdote
  • Annemieke M.W. Spijkerman
  • Magdalena Stepien
  • Anne Tjonneland
  • Rosario Tumino
  • Adam S. Butterworth
  • Elio Riboli
  • John Danesh
  • Claudia Langenberg
  • Nita G. Forouhi
  • Nicholas J. Wareham

Summary, in English


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.

Department/s

  • Genetic and Molecular Epidemiology
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Internal Medicine - Epidemiology

Publishing year

2019

Language

English

Pages

1293-1303

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

104

Issue

4

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 0021-972X