Evidence map›Paper›PMID 25281353›Full record

Trial reportThe lancet. Diabetes & endocrinology2015

Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study.

Zheng Ye, Stephen J Sharp, Stephen Burgess, Robert A Scott, Fumiaki Imamura, InterAct Consortium, Claudia Langenberg, Nicholas J Wareham, Nita G Forouhi

Erratum issuedOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The lancet. Diabetes & endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 102 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed, 13 pooled it
13.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

102 citing papers in PubMed, 13 syntheses or guidelines pooled it, 184 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Guideline
  11. Pooled it
  12. Pooled it
  13. Pooled it
  14. Trial
  15. Trial
  16. Trial
  17. CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017
    Trial
  18. Trial
  19. Trial
  20. Trial

42 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Zheng YeMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Stephen J SharpMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Stephen BurgessDepartment of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Robert A ScottMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Fumiaki ImamuraMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
InterAct Consortium
Claudia LangenbergMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Nicholas J WarehamMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK.
Nita G ForouhiMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge, UK. Electronic address: nita.forouhi@mrc-epid.cam.ac.uk.
MRC Epidemiology Unit · GBUniversity of Cambridge · GB

Funding

British Heart Foundation RG/08/014/24067Medical Research Council MC_U106179471Medical Research Council MC_UP_A100_1003Medical Research Council MC_UU_12015/1Medical Research Council MC_UU_12015/5Medical Research Council MR/L003120/1Wellcome Trust 100114
6 · The paper itself

Abstract

backgroundLow circulating concentrations of 25-hydroxyvitamin D (25[OH]D), a marker of vitamin D status, are associated with an increased risk of type 2 diabetes, but whether this association is causal remains unclear. We aimed to estimate the unconfounded, causal association between 25(OH)D concentration and risk of type 2 diabetes using a mendelian randomisation approach.

methodsUsing several data sources from populations of European descent, including type 2 diabetes cases and non-cases, we did a mendelian randomisation analysis using single nucleotide polymorphisms (SNPs) within or near four genes related to 25(OH)D synthesis and metabolism: DHCR7 (related to vitamin D synthesis), CYP2R1 (hepatic 25-hydroxylation), DBP (also known as GC; transport), and CYP24A1 (catabolism). We assessed each SNP for an association with circulating 25(OH)D concentration (5449 non-cases; two studies), risk of type 2 diabetes (28 144 cases, 76 344 non-cases; five studies), and glycaemic traits (concentrations of fasting glucose, 2-h glucose, fasting insulin, and HbA1c; 46 368 non-cases; study consortium). We combined these associations in a likelihood-based mendelian randomisation analysis to estimate the causal association of 25(OH)D concentration with type 2 diabetes and the glycaemic traits, and compared them with that from a meta-analysis of data from observational studies (8492 cases, 89 698 non-cases; 22 studies) that assessed the association between 25(OH)D concentration and type 2 diabetes.

findingsAll four SNPs were associated with 25(OH)D concentrations (p<10(-6)). The mendelian randomisation-derived unconfounded odds ratio for type 2 diabetes was 1·01 (95% CI 0·75-1·36; p=0·94) per 25·0 nmol/L (1 SD) lower 25(OH)D concentration. The corresponding (potentially confounded) relative risk from the meta-analysis of data from observational studies was 1·21 (1·16-1·27; p=7·3 × 10(-19)). The mendelian randomisation-derived estimates for glycaemic traits were not significant (p>0·25).

interpretationThe association between 25(OH)D concentration and type 2 diabetes is unlikely to be causal. Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence. These findings warrant further investigations to identify causal factors that might increase 25(OH)D concentration and also reduce the risk of type 2 diabetes.

fundingUK Medical Research Council Epidemiology Unit and European Union Sixth Framework Programme.

Indexed as

Diabetes Mellitus, Type 2FemaleHumansIncidenceMaleMendelian Randomization AnalysisMiddle AgedPolymorphism, Single NucleotideRisk FactorsVitamin D25-hydroxyvitamin DVitamin D

Identifiers

PMID25281353
PMCPMC4286815
OpenAlexW2156810420

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.