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Diabetes. 2015 Aug;64(8):3028-36. doi: 10.2337/db14-0742. Epub 2015 Apr 27.

A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes.

Author information

1
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands i.sluijs-2@umcutrecht.nl.
2
Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, U.K. Division of Transplantation and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
3
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands Department of Cardiology, Heart Long Institute, University Medical Center Utrecht, Utrecht, the Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, the Netherlands.
5
Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
6
Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry, U.K.
7
CIBER Epidemiología y Salud Pública (CIBERESP), Spain Public Health Division of Gipuzkoa, San Sebastian, Spain Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.
8
Inserm, Center for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France Université Paris-Sud, UMRS 1018, Villejuif, France.
9
CIBER Epidemiología y Salud Pública (CIBERESP), Spain Navarre Public Health Institute (ISPN), Pamplona, Spain.
10
German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
11
Lund University, Malmö, Sweden Umeå University, Umeå, Sweden.
12
German Cancer Research Center (DKFZ), Heidelberg, Germany.
13
University of Cambridge, Cambridge, U.K.
14
CIBER Epidemiología y Salud Pública (CIBERESP), Spain Andalusian School of Public Health, Granada, Spain.
15
Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
16
Lund University, Malmö, Sweden.
17
Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark Aalborg University Hospital, Aalborg, Denmark.
18
Cancer Research and Prevention Institute (ISPO), Florence, Italy.
19
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
20
Public Health Directorate, Asturias, Spain.
21
Umeå University, Umeå, Sweden.
22
Unit of Cancer Epidemiology, Citta' della Salute e della Scienza Hospital, University of Turin and Center for Cancer Prevention (CPO), Turin, Italy Human Genetics Foundation (HuGeF), Turin, Italy.
23
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, and Translational Research Laboratory, Catalan Institute of Oncology (IDIBELL), Barcelona, Spain.
24
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, U.K.
25
MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
26
Epidemiology and Prevention Unit, Milan, Italy.
27
International Agency for Research on Cancer, Lyon, France.
28
National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
29
Danish Cancer Society Research Center, Copenhagen, Denmark.
30
ASP Ragusa, Ragusa, Italy AIRE ONLUS, Ragusa, Italy.
31
School of Public Health, Imperial College London, U.K.

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.

PMID:
25918230
PMCID:
PMC6284788
DOI:
10.2337/db14-0742
[Indexed for MEDLINE]
Free PMC Article

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