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

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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 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.

Details

Authors
  • Ivonne Sluijs
  • Michael V Holmes
  • Yvonne T van der Schouw
  • Joline Wj Beulens
  • Folkert W Asselbergs
  • José María Huerta
  • Tom M Palmer
  • Larraitz Arriola
  • Beverley Balkau
  • Aurelio Barricarte
  • Heiner Boeing
  • Françoise Clavel-Chapelon
  • Guy Fagherazzi
  • Diana Gavrila
  • Rudolf Kaaks
  • Kay Tee Khaw
  • Tilman Kühn
  • Esther Molina-Montes
  • Lotte Maxild Mortensen
  • 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 Mw Spijkerman
  • Anne Tjonneland
  • Ruth C Travis Dphil
  • Rosario Tumino
  • Daphne L van der A
  • Stephen J Sharp
  • Nita G Forouhi
  • Claudia Langenberg
  • Elio Riboli
  • Nicholas J Wareham
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)3028-3036
JournalDiabetes
Volume64
Issue number8
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes