Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort

OBJECTIVE: Limited Mendelian randomization (MR) studies have assessed the causal relationship between serum uric acid levels and diabetes risk. Here we investigated causality between the serum uric acid concentration and diabetes risk in Chinese population. RESEARCH DESIGN AND METHODS: The observational analysis, based on the Dongfeng-Tongji prospective cohort (n=15 195) we tested the association of serum uric acid levels with incident diabetes risk. In the instrumental variable analysis, we examined the association of the genetic risk score (GRS) of serum uric acid with diabetes risk in case-control design (2539 cases and 4595 controls) via MR analysis. RESULTS: During a mean (SD) follow-up of 4.5 (0.5) years, 1156 incident diabetes cases were identified. Compared with those in the lowest quintile of serum uric acid levels, the HRs of incident diabetes were 1.19 (95% CI 0.96 to 1.48), 1.12 (95% CI 0.90 to 1.40), 1.38 (95% CI 1.12 to 1.70), and 1.51 (95% CI 1.23 to 1.87) for Q2, Q3, Q4 and Q5, respectively (P-trend <0.001). The GRS was strongly associated with serum uric acid levels (β=0.17, 95% CI 0.15 to 0.19; P=2.81×10(-67)). However, no significant association was observed between the GRS and diabetes risk (OR=1.01, 95 CI 0.95 to 1.06; P=0.75). CONCLUSIONS: Even though serum uric acid levels were significantly associated with increased incident diabetes risk, the results did not provide evidence for a causal relationship between them.