SynthesisPLoS medicine2020
The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis.
Synthesis in PLoS medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 4 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 4 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Association between asthma, allergic rhinitis, atopic dermatitis, and dental caries: evidence from systematic review with meta-analysis and Mendelian randomisation investigation.Journal of global health · 2026Pooled it
- Vitamin D and human health: evidence from Mendelian randomization studies.European journal of epidemiology · 2024Pooled it
- What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: a systematic review and meta-analysis of randomized controlled trails.BMC endocrine disorders · 2023Pooled it
- The impacts of vitamin D supplementation in adults with metabolic syndrome: A systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2022Pooled it
- Association between serum 25-hydroxyvitamin D levels and bilateral vestibulopathy: A case-control study.Clinics (Sao Paulo, Brazil) · 2026Article
- Type 2 Diabetes Causally Reduces Circulating Vitamin D Levels: A Multi-Ancestry Mendelian Randomization Study.Nutrients · 2026Article
- Vitamin D and Health Outcomes: State-of-the-Art Review of Triangulated Evidence and Ongoing Controversies.Current nutrition reports · 2026Review
- Associations between vitamin D insufficiency, health beliefs, and quality of life in metabolic syndrome: A northeastern Taiwanese community study.Asia Pacific journal of clinical nutrition · 2026Article
- Vitamin D status and type 2 diabetes incidence in Finnish adults-a longitudinal survey and register-based study using standardized serum 25-hydroxyvitamin D data.European journal of nutrition · 2026Article
- Modifiable risk factors and skin cancers: a multi-omics Mendelian randomization study from causal inference to drug target discovery.Frontiers in genetics · 2026Article
- Circulating vitamin D concentrations and the risk of urticaria: A bidirectional two-sample Mendelian randomization study.Asia Pacific journal of clinical nutrition · 2025Article
- Non-Skeletal Roles of Vitamin D in Skin, Gut, and Cardiovascular Disease: Focus on Epithelial Barrier Function and Immune Regulation in Chronic Disease.International journal of molecular sciences · 2025Review
- Non-Linear Associations Between Serum Vitamin D and Uric Acid in Korean Adults: 2022-2023 KNHANES Data.Nutrients · 2025Article
- The causal associations of 25(OH)D and its metabolites with oropharyngeal cancer risk: a Mendelian randomization study.Acta odontologica Scandinavica · 2025Article
- Levels of plasma 25-hydroxy vitamin D and risk of developing type 2 diabetes in a large Danish primary health care population.Acta diabetologica · 2025Article
- Potential of Vitamin D and l-Cysteine Co-supplementation to Downregulate Mammalian Target of Rapamycin: A Novel Therapeutic Approach to Diabetes.Metabolic syndrome and related disorders · 2025Review
- Expert consensus on vitamin D in osteoporosis.Annals of joint · 2025Review
- Differential seasonal performance of C3-epi-D3 level and proportion on multiple metabolic disorders in patients with type 2 diabetes mellitus.European journal of medical research · 2024Article
- Evaluating the Effect of Vitamin D Supplementation on Type 2 Diabetes Risk: A Systematic Review.Cureus · 2024Review
- Causal role of immune cells in muscle atrophy: mendelian randomization study.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
50 authors at 20 institutions in 12 countries.
Funding
Abstract
backgroundPrior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND
findingsWe performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities.
conclusionsOur study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.
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