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Diabetologia
Published in: Diabetologia 8/2012

01-08-2012 | Article

Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies

Authors: N. G. Forouhi, Z. Ye, A. P. Rickard, K. T. Khaw, R. Luben, C. Langenberg, N. J. Wareham

Published in: Diabetologia | Issue 8/2012

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Abstract

Aims/hypothesis

Epidemiological evidence is suggestive, but limited, for an association between circulating 25-hydroxyvitamin D (25[OH]D) and risk of type 2 diabetes. We conducted a systematic review and meta-analysis that included new data from previously unpublished studies.

Methods

Using a nested case–cohort design in the European Prospective Investigation into Cancer (EPIC)-Norfolk study, we identified a random subcohort and incident type 2 diabetes cases occurring between baseline (1993–1997) and 2006. In the Ely prospective study we identified incident type 2 diabetes cases between 1990 and 2003. We conducted a systematic review of prospective studies on 25(OH)D and type 2 diabetes published in MEDLINE or EMBASE until 31 January 2012, and performed a random-effects meta-analysis combining available evidence with results from the EPIC-Norfolk and Ely studies.

Results

In EPIC-Norfolk, baseline 25(OH)D was lower among incident type 2 diabetes cases (mean [SD] 61.6 [22.4] nmol/l; n = 621) vs non-case subcohort participants (mean 65.3 [23.9] nmol/l; n = 826). There was an inverse association between baseline 25(OH)D and incident type 2 diabetes in multivariable-adjusted analyses: HR (95% CI) 0.66 (0.45, 0.97), 0.53 (0.34, 0.82), 0.50 (0.32, 0.76), p trend <0.001, comparing consecutive increasing 25(OH)D quartiles with the lowest. In Ely, 37 incident type 2 diabetes cases were identified among 777 participants. In meta-analysis, the combined RR of type 2 diabetes comparing the highest with lowest quartile of 25(OH)D was 0.59 (0.52, 0.67), with little heterogeneity (I 2 = 2.7%, p = 0.42) between the 11 studies included (3,612 cases and 55,713 non-cases).

Conclusions/interpretation

These findings demonstrate an inverse association between circulating 25(OH)D and incident type 2 diabetes. However, causal inference should be addressed through adequately dosed randomised trials of vitamin D supplementation or genetic Mendelian randomisation experiments.
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Metadata
Title
Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies
Authors
N. G. Forouhi
Z. Ye
A. P. Rickard
K. T. Khaw
R. Luben
C. Langenberg
N. J. Wareham
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 8/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2544-y

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