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.
A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes / Sluijs, Ivonne; Holmes, Michael V; van der Schouw, Yvonne T; Beulens, Joline W. J; Asselbergs, Folkert W; Huerta, José María; Palmer, Tom M; Arriola, Larraitz; Balkau, Beverley; Barricarte, Aurelio; Boeing, Heiner; Clavel Chapelon, Françoise; Fagherazzi, Guy; Franks, Paul W; Gavrila, Diana; Kaaks, Rudolf; Khaw, Kay Tee; Kühn, Tilman; Molina Montes, Esther; Mortensen, Lotte Maxild; Nilsson, Peter M; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Schmidt, Julie A; Scott, Robert A; Sieri, Sabina; Slimani, Nadia; Spijkerman, Annemieke M. W; Tjonneland, Anne; Travis, Ruth C; Tumino, Rosario; van der A, Daphne L; Sharp, Stephen J; Forouhi, Nita G; Langenberg, Claudia; Riboli, Elio; Wareham, Nicholas J.. - In: DIABETES. - ISSN 1939-327X. - 64:8(2015), p. 3028-36. [10.2337/db14-0742]
A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes
PANICO, SALVATORE;
2015
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
