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.
journal_name
Diabetesjournal_title
Diabetesauthors
Sluijs I,Holmes MV,van der Schouw YT,Beulens JW,Asselbergs FW,Huerta JM,Palmer TM,Arriola L,Balkau B,Barricarte A,Boeing H,Clavel-Chapelon F,Fagherazzi G,Franks PW,Gavrila D,Kaaks R,Khaw KT,Kühn T,Molina-Montes E,Modoi
10.2337/db14-0742subject
Has Abstractpub_date
2015-08-01 00:00:00pages
3028-36issue
8eissn
0012-1797issn
1939-327Xpii
db14-0742journal_volume
64pub_type
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