A Mendelian randomization study of circulating uric acid and type 2 diabetes

Sluijs, Ivonne and Holmes, Michael V. and van der Schouw, Yvonne T. and Beulens, Joline W. J. and Asselbergs, Folkert W. and Huerta, José María and Palmer, Tom M. and Arriola, Larraitz and Balkau, Beverley and Barricarte, Aurelio and Boeing, Heiner and Clavel-Chapelon, Françoise and Fagherazzi, Guy and Franks, Paul W. and Gavrila, Diana and Kaaks, Rudolf and Khaw, Kay Tee and Kühn, Tilman and Molina-Montes, Esther and Mortensen, Lotte Maxild and Nilsson, Peter M. and Overvad, Kim and Palli, Domenico and Panico, Salvatore and Quirós, J. Ramón and Rolandsson, Olov and Sacerdote, Carlotta and Sala, Núria and Schmidt, Julie A. and Scott, Robert A. and Sieri, Sabina and Slimani, Nadia and Spijkerman, Annemieke Mw and Tjonneland, Anne and Travis Dphil, Ruth C. and Tumino, Rosario and van der A, Daphne L. and Sharp, Stephen J. and Forouhi, Nita G. and Langenberg, Claudia and Riboli, Elio and Wareham, Nicholas J. and InterAct consortium (2015) A Mendelian randomization study of circulating uric acid and type 2 diabetes. Diabetes, 64 (8). pp. 3028-3036. ISSN 0012-1797

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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 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 type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a 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. Using the genetic score to estimate the unconfounded effect 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 DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR 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.

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This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals.org/content/64/8/3028
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27 Jul 2015 09:30
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18 Oct 2023 00:57