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No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach.
MedLine Citation:
PMID:  21717115     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
R Pfister; D Barnes; R Luben; N G Forouhi; M Bochud; K-T Khaw; N J Wareham; C Langenberg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-30
Journal Detail:
Title:  Diabetologia     Volume:  -     ISSN:  1432-0428     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
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