Temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes

Background/objectives: Although hyperuricemia and obesity are significantly correlated, their temporal relationship and whether this relationship is associated with future risk of diabetes are largely unknown. This study examined temporal relationship between hyperuricemia and obesity, and its association with future risk of type 2 diabetes. Subjects/methods: This study examined two longitudinal cohorts totally including 17,044 subjects from China with an average of 6.0 years follow-up. Measurements of body mass index (BMI), waist circumference (WC), percentage of body fat and fasting serum uric acid were obtained at two time points. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between hyperuricemia and obesity, and the association of this temporal relationship with follow-up diabetes. Results: In combined data of the two cohorts, the cross-lagged path coefficient (beta(1) = 0.121; 95% confidence interval (CI): 0.108-0.135) from baseline uric acid to the follow-up BMI was significantly greater than the path coefficient (beta(2) = 0.055, 95% CI: 0.038-0.072) from baseline BMI to the follow-up uric acid (P = 8.14e(-10) for the difference between beta(1) and beta(2)) with adjustment for covariates. The separate cross-lagged path models of uric acid with WC and percentage of body fat showed temporal patterns similar to that noted for uric acid with BMI. Further, the path coefficient (beta(1)) from baseline uric acid to follow-up BMI in the group with diabetes was significantly greater than without diabetes (P = 0.003 for the difference of beta(1)s in the two groups). BMI partially mediated the association of uric acid with risk of diabetes, and the percentage of mediated-association was estimated at 20.3% (95% CI: 15.7-24.8%). Results of these analyses in the combined data were consistent with those in the two cohorts, respectively. Conclusions: These findings indicated that increased uric acid levels probably associated with obesity and type 2 diabetes, and more definite research is needed to define any role for uric acid in relation to these diseases.