Metaanálisis2020Financiado por la industriaVínculos de autores con la industriaAcceso abierto

Financiado en parte por AstraZeneca, Sanofi, Biogen, Regeneron Pharmaceuticals, Novo Nordisk

The association between circulating 25-hydroxyvitamin D metabolites and type 2 diabetes in European populations: A meta-analysis and Mendelian randomisation analysis

Zheng JS, Luan J, Sofianopoulou E, Sharp SJ, Day FR, Imamura F, Gundersen TE, Lotta LA, Sluijs I, Stewart ID, Shah RL, van der Schouw YT, Wheeler E, Ardanaz E, Boeing H, Dorronsoro M, Dahm CC, Dimou N, El-Fatouhi D, Franks PW, Fagherazzi G, Grioni S, Huerta JM, Heath AK, Hansen L, Jenab M, Jakszyn P, Kaaks R, Kühn T, Khaw KT, Laouali N, Masala G, Nilsson PM, Overvad K, Olsen A, Panico S, Quirós JR, Rolandsson O, Rodríguez-Barranco M, Sacerdote C, Spijkerman AMW, Tong TYN, Tumino R, Tsilidis KK, Danesh J, Riboli E, Butterworth AS, Langenberg C, Forouhi NG, Wareham NJ

PLoS medicine · 61 citas

Etiquetas de revisión

Vínculos de autores con la industriaFinanciado por la industria

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Cómo se estudió

Diseño: Metaanálisis (indexado por PubMed)
Estudiado en: Personas
Resultado principal: Eventos clínicos como enfermedad o muerte

Quién lo pagó

Financiación: Financiado por la industria
Empresa: AstraZeneca
Empresa: Sanofi
Gobierno: World Health Organization
Empresa: Biogen
Organización sin fines de lucro: Compagnia di San Paolo
Universidad u hospital: Deutsches Krebsforschungszentrum
Universidad u hospital: Centre International de Recherche sur le Cancer
Empresa: Regeneron Pharmaceuticals
Universidad u hospital: Westlake University
Organización sin fines de lucro: Cancer Research UK
Gobierno: National Institute for Health and Care Research
Organización sin fines de lucro: British Heart Foundation
Universidad u hospital: University of Cambridge
Universidad u hospital: Imperial College London
Gobierno: European Commission
Gobierno: Bundesministerium für Bildung und Forschung
Gobierno: Generalitat de Catalunya
Universidad u hospital: Cambridge University Hospitals
Organización sin fines de lucro: Hjärt-Lungfonden
Empresa: Novo Nordisk
Gobierno: Vetenskapsrådet
Organización sin fines de lucro: Deutsche Krebshilfe
Gobierno: Medical Research Council
Organización sin fines de lucro: World Cancer Research Fund
Gobierno: Agència de Gestió d'Ajuts Universitaris i de Recerca
Gobierno: Sixth Framework Programme
Gobierno: NIHR Cambridge Biomedical Research Centre
Gobierno: H2020 Marie Skłodowska-Curie Actions
Gobierno: FP7 Health
Gobierno: MRC Cambridge Initiative
Gobierno: European Research Council
Gobierno: National Institute for Health Research (NIHR)
Gobierno: Medical Research Council Epidemiology Unit
Universidad u hospital: NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme
Autores: Al menos un autor declara un vínculo económico con la industria
Subvenciones: Medical Research Council (IS-BRC-1215-20014); Medical Research Council (MC_UU_12015/1); Medical Research Council (MC_UU_12015/5); Medical Research Council (M012190/1); Westlake University (YSYY0209); NIHR Cambridge Biomedical Research Centre ((BRC-1215-20014)); Bundesministerium für Bildung und Forschung (IS-BRC-1215-20014); European Commission (IS-BRC-1215-20014); Agència de Gestió d'Ajuts Universitaris i de Recerca (SGR 726); Cancer Research UK (C570/ A16491); National Institute for Health and Care Research (C8221/A19170); British Heart Foundation (MR/L003120/1); World Cancer Research Fund (IS-BRC-1215-20014); Medical Research Council (C570/A16491); British Heart Foundation (RG/13/13/30194; RG/18/13/33946); H2020 Marie Skłodowska-Curie Actions (701708); World Cancer Research Fund (MR/M012190/1); British Heart Foundation (RG/18/13/33946); European Commission (LSHM_CT_2006_037197); Deutsche Krebshilfe (MR/M012190/1); Compagnia di San Paolo (MR/M012190/1); Compagnia di San Paolo (IS-BRC-1215-20014); Medical Research Council (MC_UU_12015/5); Deutsches Krebsforschungszentrum (C8221/A19170); World Cancer Research Fund (C8221/A19170); Medical Research Council (MC_UU_12015); National Institute for Health and Care Research ([IS-BRC-1215-20014); Bundesministerium für Bildung und Forschung (C8221/A19170); FP7 Health (HEALTH-F2-2012-279233); Sixth Framework Programme (LSHM_CT_2006_037197); Medical Research Council (MR/M012190); World Cancer Research Fund (C570/A16491); Deutsche Krebshilfe (IS-BRC-1215-20014); NIHR Cambridge Biomedical Research Centre (1215-20014); National Institute for Health and Care Research (BRC1215-20014); National Institute for Health and Care Research (C570/A16491); Bundesministerium für Bildung und Forschung (MR/M012190/1); Cancer Research UK (IS-BRC-1215-20014); NIHR Cambridge Biomedical Research Centre (MR/L003120/1); Vetenskapsrådet (IS-BRC-1215-20014); Medical Research Council (C8221/A19170); European Commission (C570/A16491); European Commission (C8221/A19170); Medical Research Council (MR/L003120/1); European Commission (HORIZON2020); Medical Research Council (MR/M012190/1); Deutsche Krebshilfe (C570/A16491); NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014); Centre International de Recherche sur le Cancer (MR/M012190/1); Medical Research Council (RG/18/13/33946); Cancer Research UK (BRC-1215-20014); European Commission (MR/M012190/1); Generalitat de Catalunya (2014 SGR 726); Medical Research Council (MC_UU_12015/2); Deutsche Krebshilfe (C8221/A19170); National Institute for Health and Care Research (MC_UU_12015/1); Vetenskapsrådet (BRC-1215-20014); University of Cambridge (BRC-1215-20014); NIHR Cambridge Biomedical Research Centre (BRC-1215); National Institute for Health and Care Research (IS-BRC-1215); Cancer Research UK (MR/M012190/1); European Commission (279233); Medical Research Council (BRC-1215-20014); Deutsches Krebsforschungszentrum (IS-BRC-1215-20014); Centre International de Recherche sur le Cancer (C570/A16491); National Institute for Health and Care Research (RG/18/13/33946); Cancer Research UK (C8221/A19170); Medical Research Council (MC_UU_12015/1); Cancer Research UK (A16491); European Commission (701708); Deutsches Krebsforschungszentrum (C570/A16491); British Heart Foundation (RG/13/13/30194); Agència de Gestió d'Ajuts Universitaris i de Recerca (MR/M012190/1); Cancer Research UK (A19170); Medical Research Council (MR/L003120); Deutsches Krebsforschungszentrum (MR/M012190/1); Bundesministerium für Bildung und Forschung (C570/A16491); Centre International de Recherche sur le Cancer (C8221/A19170); Vetenskapsrådet (C8221/A19170); British Heart Foundation (IS-BRC-1215-20014); National Institute for Health and Care Research (NF-SI-0617-10149); Cancer Research UK (30194); National Institute for Health and Care Research (MR/M012190/1); Vetenskapsrådet (C570/A16491); Vetenskapsrådet (MR/M012190/1); Cancer Research UK (MC-UU_12015/1); Medical Research Council (MR/L003120/1); Generalitat de Catalunya (2014SGR)

Según 34 financiadores declarados y la declaración de financiación del texto completo.

Publicación

Publicado: 2020-10-16 · PLoS Med · vol. 17 · número 10 · pág. e1003394
Editorial: Public Library of Science
Citado: 74 citas · más que el 93% de estudios similares · 2.9× el promedio de su campo
Impacto: Entre el 10 % más citado de su campo
Referencias: 43 trabajos
Acceso: Acceso abierto (revista) · CC-BY
Áreas de investigación: Vitamin D Research Studies · Genetic Associations and Epidemiology · Nutrition, Genetics, and Disease
Palabras clave: Type 2 diabetes, Meta-analysis, Observational study, Vitamin D and neurology, Medicine, Genetic association, Confounding, European Prospective Investigation into Cancer and Nutrition, Internal medicine, Genome-wide association study, Mendelian randomization, Diabetes mellitus, Oncology, Genetics, Prospective cohort study, Biology, Endocrinology, Single-nucleotide polymorphism, Gene, Genotype, Genetic variants
MeSH: humans, diabetes mellitus, type 2, vitamin d, risk factors, prospective studies, dietary supplements, adult, middle aged, female, male, genome-wide association study, mendelian randomization analysis, white people

DOI ↗PubMed Central ↗OpenAlex ↗

50 autores

Ju‐Sheng Zheng🇬🇧🇨🇳 · autor de correspondenciaUniversity of Cambridge; Westlake University; MRC Epidemiology Unit
Jian’an Luan🇬🇧University of Cambridge; MRC Epidemiology Unit
Eleni Sofianopoulou🇬🇧University of Cambridge; National Institute for Health and Care Research
Stephen J. Sharp🇬🇧University of Cambridge; MRC Epidemiology Unit
Felix R. Day🇬🇧University of Cambridge; MRC Epidemiology Unit
Fumiaki Imamura🇬🇧University of Cambridge; MRC Epidemiology Unit
Thomas E. Gundersen🇳🇴Vitas (Norway)
Luca Andrea Lotta🇬🇧University of Cambridge; MRC Epidemiology Unit
Ivonne Sluijs🇳🇱Utrecht University; University Medical Center Utrecht
Isobel D. Stewart🇬🇧University of Cambridge; MRC Epidemiology Unit
Rupal L. Shah🇬🇧University of Cambridge; MRC Epidemiology Unit
Yvonne T. van der Schouw🇳🇱Utrecht University; University Medical Center Utrecht
Eleanor Wheeler🇬🇧University of Cambridge; MRC Epidemiology Unit
Eva Ardanáz🇪🇸Instituto de Salud Pública de Navarra; Navarre Institute of Health Research; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Heiner Boeing🇩🇪German Institute of Human Nutrition
Miren Dorronsoro
Christina Catherine Dahm🇩🇰Aarhus University
Niki L. Dimou🇫🇷Centre international de recherche sur le cancer
Douae El-Fatouhi🇫🇷Inserm; Université Paris-Saclay; Institut Gustave Roussy; Centre de recherche en Epidémiologie et Santé des Populations
Paul W. Franks🇸🇪Lund University
Guy Fagherazzi🇫🇷🇱🇺Inserm; Université Paris-Saclay; Institut Gustave Roussy; Luxembourg Institute of Health; Centre de recherche en Epidémiologie et Santé des Populations
Sara Grioni🇮🇹National Centre for Disease Prevention and Control
José María Huerta🇪🇸Instituto Murciano de Investigación Biosanitaria; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública
Alicia K. Heath🇬🇧Imperial College London
Louise Hansen🇩🇰Danish Cancer Society
Mazda Jenab🇫🇷Centre international de recherche sur le cancer
Paula Gabriela Jakszyn🇪🇸Institut d'Investigació Biomédica de Bellvitge; Institut Català d'Oncologia; Universitat Ramon Llull
Rudolf Kaaks🇩🇪German Cancer Research Center; Heidelberg University
Tilman E. Kuhn🇩🇪German Cancer Research Center; Heidelberg University
Kay‐Tee Khaw🇬🇧University of Cambridge
Nasser Laouali🇫🇷Inserm; Université Paris-Saclay; Institut Gustave Roussy; Centre de recherche en Epidémiologie et Santé des Populations
Giovanna Masala🇮🇹Piedmont Reference Center for Epidemiology and Cancer Prevention
Peter M. Nilsson🇸🇪Lund University
Kim Overvad🇩🇰Aarhus University; Aalborg University Hospital
Anja Olsen🇩🇰Danish Cancer Society
Salvatore Panico🇮🇹University of Naples Federico II
José Ramón Quirós🇪🇸Gobierno del Principado de Asturias
Olov Rolandsson🇸🇪Umeå University
Miguel Rodríguez‐Barranco🇪🇸Universidad de Granada; Instituto de Investigación Biosanitaria de Granada; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública; Andalusian School of Public Health
Carlotta Sacerdote🇮🇹Azienda Ospedaliera Citta' della Salute e della Scienza di Torino; Piedmont Reference Center for Epidemiology and Cancer Prevention; University of Turin
Annemieke M. W. Spijkerman🇳🇱National Institute for Public Health and the Environment
Tammy Y. N. Tong🇬🇧University of Oxford
Rosario Tumino🇮🇹Agenzia Regionale Sanitaria della Puglia
Konstantinos K. Tsilidis🇬🇷🇬🇧University of Ioannina; Imperial College London
John Danesh🇬🇧University of Cambridge; Wellcome Sanger Institute; British Heart Foundation; National Institute for Health and Care Research; Addenbrooke's Hospital
Elio Ríboli🇬🇧Imperial College London
Adam S. Butterworth🇬🇧University of Cambridge; National Institute for Health and Care Research
Claudia Langenberg🇬🇧University of Cambridge; MRC Epidemiology Unit
Nita G. Forouhi🇬🇧 · autor de correspondenciaUniversity of Cambridge; MRC Epidemiology Unit
Nicholas J. Wareham🇬🇧 · autor de correspondenciaUniversity of Cambridge; MRC Epidemiology Unit

Resumen

El texto original del estudio, en el idioma en que se publicó.

Background

Prior 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 findings

We 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.

Conclusions

Our 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.

Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).

Leer el texto completo ↗Ver en PubMed ↗

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