Year: 2015
Type: article
Study design: Observational Study
Abstract: 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.
Source: Diabetes
DOI: 10.2337/db14-0742
Authors: Ivonne Sluijs, Michael V. Holmes, Yvonne T. van der Schouw, Joline W.J. Beulens, Folkert W. Asselbergs, José María Huerta, Tom M. Palmer, Larraitz Arriola, Beverley Balkau, Aurelio Barricarte, Heiner Boeing, Françoise Clavel-Chapelon, Guy Fagherazzi, Paul W. Franks, Diana Gavrila, Rudolf Kaaks, Kay Tee Khaw, Tilman Kühn, Esther Molina-Montes, Lotte Maxild Mortensen, Peter M. Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, J. Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Núria Sala, Julie A. Schmidt, Robert A. Scott, Sabina Sieri, Nadia Slimani, Annemieke M.W. Spijkerman, Anne Tjonneland, Ruth C. Travis, Rosario Tumino, Daphne L. van der A, Stephen J. Sharp, Nita G. Forouhi, Claudia Langenberg, Elio Riboli, Nicholas J. Wareham
Institutions: University Medical Center Utrecht, University of Oxford, University of Pennsylvania, Netherlands Heart Institute, Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, University of Warwick, Basque Government, Université Paris-Sud, Inserm, Centre de recherche en Epidémiologie et Santé des Populations, German Institute of Human Nutrition, Lund University, Umeå University, German Cancer Research Center, University of Cambridge, Andalusian School of Public Health, Aarhus University, Aalborg University Hospital, Istituto per lo Studio e la Prevenzione Oncologica, Federico II University Hospital, University of Naples Federico II, Gobierno del Principado de Asturias, Italian institute for Genomic Medicine, Piedmont Reference Center for Epidemiology and Cancer Prevention, University of Turin, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, MRC Epidemiology Unit, Centre international de recherche sur le cancer, National Institute for Public Health and the Environment, Danish Cancer Society, University of Ragusa, Imperial College London
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2127975509