Plasma Uric Acid Is Associated with Increased Risk of Type 2 Diabetes Independent of Diet and Metabolic Risk Factors

Abstract

Current evidence suggests a direct association of uric acid with diabetes risk, but it is still unclear whether this is independent of risk factors such as obesity and diet. We aimed to investigate whether plasma uric acid concentrations are independently associated with incident type 2 diabetes and to investigate the role of a uric acid–related dietary pattern in this association. We used a case-cohort nested in the European Prospective Investigation into Cancer and Nutrition-Netherlands study. The study included 2318 subcohort members and 845 incident diabetes cases, with a mean follow-up of 10 y. At baseline, blood samples were taken and diet was assessed using a validated FFQ. A uric acid–related dietary pattern was derived with reduced rank regression. Diabetes was mainly self-reported and verified against general practitioner records. Plasma uric acid was (mean ± SD) 231 ± 54.6 μmol/L in the subcohort. After adjustment for established diabetes risk factors such as age, the HR (highest vs. lowest quartile of uric acid) for diabetes was 4.36 (95% CI: 3.22, 5.90). Further adjustment for adiposity attenuated the HR to 1.86 (95% CI: 1.32, 2.62). Additional adjustment for hypertension and biochemical markers, such as TG, slightly attenuated the association [HR = 1.43 (95% CI: 0.97, 2.10)]. A uric acid–related dietary pattern did not confound the association. In conclusion, this study supports that high uric acid concentrations are associated with increased diabetes risk, although a large part of the association can be explained by the degree of adiposity.