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

Autor: Zheng JS; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.; Westlake Laboratory of Life Sciences and Biomedicine, Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China., Luan J; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Sofianopoulou E; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom., Sharp SJ; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Day FR; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Imamura F; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Gundersen TE; VITAS, Oslo, Norway., Lotta LA; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Sluijs I; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Stewart ID; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Shah RL; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., van der Schouw YT; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands., Wheeler E; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Ardanaz E; Navarra Public Health Institute, Pamplona, Spain.; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain., Boeing H; Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany., Dorronsoro M; Public Health Division of Gipuzkoa, San Sebastian, Spain., Dahm CC; Department of Public Health, Aarhus University, Aarhus, Denmark., Dimou N; International Agency for Research on Cancer, Lyon, France., El-Fatouhi D; Center of Research in Epidemiology and Population Health, UMR 1018 Inserm, Institut Gustave Roussy, Paris South-Paris Saclay University, Villejuif, France., Franks PW; Department of Clinical Sciences, Lund University, Malmö, Sweden., Fagherazzi G; Center of Research in Epidemiology and Population Health, UMR 1018 Inserm, Institut Gustave Roussy, Paris South-Paris Saclay University, Villejuif, France.; Department of Population Health, Luxembourg Institute of Health, Strassen, Luxembourg., Grioni S; Epidemiology and Prevention Unit, Milan, Italy., Huerta JM; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Department of Epidemiology, Murcia Regional Health Council, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca, Murcia, Spain., Heath AK; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom., Hansen L; Danish Cancer Society Research Center, Copenhagen, Denmark., Jenab M; International Agency for Research on Cancer, Lyon, France., Jakszyn P; Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-Institut d'Investigació Biomédica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain.; Facultat Ciències Salut Blanquerna, Universitat Ramon Llull, Barcelona, Spain., Kaaks R; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Kühn T; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany., Khaw KT; Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom., Laouali N; Center of Research in Epidemiology and Population Health, UMR 1018 Inserm, Institut Gustave Roussy, Paris South-Paris Saclay University, Villejuif, France., Masala G; Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy., Nilsson PM; Department of Clinical Sciences, Lund University, Malmö, Sweden., Overvad K; Department of Public Health, Aarhus University, Aarhus, Denmark.; Department of Cardiology, Aalborg University Hospital, Aarhus, Denmark., Olsen A; Danish Cancer Society Research Center, Copenhagen, Denmark., Panico S; Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy., Quirós JR; Public Health Directorate, Asturias, Spain., Rolandsson O; Family Medicine Division, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden., Rodríguez-Barranco M; CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain.; Andalusian School of Public Health (EASP), Granada, Spain.; Instituto de Investigación Biosanitaria de Granada, Universidad de Granada, Granada, Spain., Sacerdote C; Unit of Cancer Epidemiology, Città della Salute e della Scienza di Torino University Hospital-University of Turin and Center for Cancer Prevention (CPO), Torino, Italy., Spijkerman AMW; National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands., Tong TYN; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom., Tumino R; Azienda Sanitaria Provinciale, Ragusa, Italy., Tsilidis KK; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.; Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Danesh J; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; British Heart Foundation Cambridge Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.; Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom., Riboli E; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom., Butterworth AS; MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.; National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom., Langenberg C; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Forouhi NG; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom., Wareham NJ; MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS medicine [PLoS Med] 2020 Oct 16; Vol. 17 (10), pp. e1003394. Date of Electronic Publication: 2020 Oct 16 (Print Publication: 2020).
DOI: 10.1371/journal.pmed.1003394
Abstrakt: 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.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: FI and CL are Academic Editors on PLOS Medicine’s editorial board. LAL is Employee and shareholder of Regeneron Pharmaceuticals Inc. ASB has received grants unrelated to this work from AstraZeneca, Biogen, Bioverativ, Merck, Novartis and Sanofi, and personal fees from Novartis. Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.
Databáze: MEDLINE
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