High serum uric acid and increased risk of type 2 diabetes: a systemic review and meta-analysis of prospective cohort studies

Abstract

Objective: Current evidence suggests high serum uric acid may increase the risk of type 2 diabetes, but the association is still uncertain. The aim of the study was to evaluate the association between serum uric acid and future risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies.

Design and methods: We conducted a systematic literature search of the PubMed database through April 2012. Prospective cohort studies were included in meta-analysis that reported the multivariate adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs) for the association between serum uric acid and risk of type 2 diabetes. We used both fix-effects and random-effects models to calculate the overall effect estimate. The heterogeneity across studies was tested by both Q statistic and I(2) statistic. Begg's funnel plot and Egger's regression test were used to assess the potential publication bias.

Results: We retrieved 7 eligible articles derived from 8 prospective cohort studies, involving a total of 32016 participants and 2930 incident type 2 diabetes. The combined RR of developing type 2 diabetes for the highest category of serum uric acid level compared with the lowest was 1.56(95% CI, 1.39-1.76). Dose-response analysis showed the risk of type 2 diabetes was increased by 6% per 1 mg/dl increment in serum uric acid level (RR 1.06, 95% CI: 1.04-1.07). The result from each subgroup showed a significant association between serum uric acid and risk of type 2 diabetes. In sensitive analysis, the combined RR was consistent every time omitting any one study. Little evidence of heterogeneity and publication bias was observed.

Conclusions: Our meta-analysis of prospective cohort studies provided strong evidence that high level of serum uric acid is independent of other established risk factors, especially metabolic syndrome components, for developing type 2 diabetes in middle-aged and older people.

Figure 1. Flowchart of the study selection.

Figure 2. Serum uric acid and risk of incident type 2 diabetes.

Fix-effects model analysis for the overall RR (1.56, 95% CI = 1.39–1.76) of incident type 2 diabetes for the highest compared with the lowest category of serum uric acid level. No evidence of heterogeneity across studies was found (I² = 0.0%, P = 0.571). The square sizes are proportional to the weight of each study in the meta-analysis; the horizontal lines represent 95% CIs; the diamond represents the overall RR with its 95% CI.