| Literature DB >> 25918230 |
Ivonne Sluijs1, Michael V Holmes2, Yvonne T van der Schouw3, Joline W J Beulens3, Folkert W Asselbergs4, José María Huerta5, Tom M Palmer6, Larraitz Arriola7, Beverley Balkau8, Aurelio Barricarte9, Heiner Boeing10, Françoise Clavel-Chapelon8, Guy Fagherazzi8, Paul W Franks11, Diana Gavrila5, Rudolf Kaaks12, Kay Tee Khaw13, Tilman Kühn12, Esther Molina-Montes14, Lotte Maxild Mortensen15, Peter M Nilsson16, Kim Overvad17, Domenico Palli18, Salvatore Panico19, J Ramón Quirós20, Olov Rolandsson21, Carlotta Sacerdote22, Núria Sala23, Julie A Schmidt24, Robert A Scott25, Sabina Sieri26, Nadia Slimani27, Annemieke M W Spijkerman28, Anne Tjonneland29, Ruth C Travis24, Rosario Tumino30, Daphne L van der A28, Stephen J Sharp25, Nita G Forouhi25, Claudia Langenberg25, Elio Riboli31, Nicholas J Wareham25.
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.Entities:
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Year: 2015 PMID： 25918230 PMCID： PMC6284788 DOI： 10.2337/db14-0742
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461