No Evidence for a Causal Link Between Uric Acid and Type 2 Diabetes: A Mendelian Randomisation Approach

Diabetologia. 2011 Oct;54(10):2561-9. doi: 10.1007/s00125-011-2235-0. Epub 2011 Jun 30.

Abstract

Aims/hypothesis: Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes.

Methods: We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association.

Results: The genetic score showed a linear association with uric acid levels, with a difference of 12.2 μmol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p = 0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 μmol/l.

Conclusions/interpretation: Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Mendelian Randomization Analysis
  • Middle Aged
  • Uric Acid / blood*

Substances

  • Uric Acid