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- Ivonne Sluijs
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
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- Michael V. Holmes
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
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- Yvonne T. van der Schouw
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
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- Joline W.J. Beulens
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
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- Folkert W. Asselbergs
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
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- José María Huerta
- Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain
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- Tom M. Palmer
- Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, U.K.
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- Larraitz Arriola
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
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- Beverley Balkau
- Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France
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- Aurelio Barricarte
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
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- Heiner Boeing
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
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- Françoise Clavel-Chapelon
- Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France
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- Guy Fagherazzi
- Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France
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- Paul W. Franks
- Lund University, Malmö, Sweden
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- Diana Gavrila
- Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain
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- Rudolf Kaaks
- German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Kay Tee Khaw
- University of Cambridge, Cambridge, U.K.
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- Tilman Kühn
- German Cancer Research Center (DKFZ), Heidelberg, Germany
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- Esther Molina-Montes
- CIBER Epidemiología y Salud Pública (CIBERESP), Spain
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- Lotte Maxild Mortensen
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
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- Peter M. Nilsson
- Lund University, Malmö, Sweden
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- Kim Overvad
- Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
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- Domenico Palli
- Cancer Research and Prevention Institute (ISPO), Florence, Italy
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- Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
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- J. Ramón Quirós
- Public Health Directorate, Asturias, Spain
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- Olov Rolandsson
- Umeå University, Umeå, Sweden
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- Carlotta Sacerdote
- Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital, University of Turin and Center for Cancer Prevention (CPO), Turin, Italy
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- Núria Sala
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, and Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain
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- Julie A. Schmidt
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
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- Robert A. Scott
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
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- Sabina Sieri
- Epidemiology and Prevention Unit, Milan, Italy
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- Nadia Slimani
- International Agency for Research on Cancer, Lyon, France
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- Annemieke M.W. Spijkerman
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
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- Anne Tjonneland
- Danish Cancer Society Research Center, Copenhagen, Denmark
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- Ruth C. Travis
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
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- Rosario Tumino
- ASP Ragusa, Ragusa, Italy
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- Daphne L. van der A
- National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
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- Stephen J. Sharp
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
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- Nita G. Forouhi
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
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- Claudia Langenberg
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
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- Elio Riboli
- School of Public Health, Imperial College London, U.K.
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- Nicholas J. Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
抄録
<jats:p>We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid–associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid–lowering therapies may therefore not be beneficial in reducing diabetes risk.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 64 (8), 3028-3036, 2015-04-27
American Diabetes Association