No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach

作者：Pfister R; Barnes D; Luben R; Forouhi N G; Bochud M; Khaw K T; Wareham N J; Langenberg C^*

来源：Diabetologia, 2011, 54(10): 2561-2569.

DOI：10.1007/s00125-011-2235-0

• Hyperuricaemia
• Mendelian randomisation
• Meta-analysis
• Type 2 diabetes
• Uric acid

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.
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.
The genetic score showed a linear association with uric acid levels, with a difference of 12.2 mu mol/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 mu mol/l.
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.

• 出版日期2011-10