Dose-response Relationship of Serum Uric Acid with Metabolic Syndrome and Non-alcoholic Fatty Liver Disease Incidence: A Meta-analysis of Prospective Studies

Zhengtao Liu, Shuping Que, Lin Zhou, Shusen Zheng, Zhengtao Liu, Shuping Que, Lin Zhou, Shusen Zheng

Abstract

Emerging evidence has shown that serum uric acid (SUA) elevation might cause metabolic derangements, including metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD); however, magnitude of the risk has not been quantified. We searched PubMed, EMBASE, and ISI databases for relevant studies through 10 May 2015. Prospective studies reporting the risk of SUA elevation on the incidence of MetS/NAFLD were enrolled. Pooled HR of MetS was 1.55 (95%CI: 1.40-1.70) for the highest versus lowest SUA categories, and 1.05 (95%CI: 1.04-1.07) per incremental increased in SUA of 1 mg/dl. The pooled HR of MetS in younger women was higher than age-matched men and older women (1.17 vs. 1.05 and 1.04, respectively, P < 0.05). Individuals in the highest SUA category had a 40% greater risk of disease NAFLD occurrence. Dose-response increment of NAFLD events was 1.03 (95%CI: 1.02-1.05). A positive relationship with a linear trend for SUA elevation with MetS and NAFLD in different genders was examined by a dose-response meta-analysis (P < 0.001).SUA assay is useful in screening metabolic disorders for linear trend between its elevation and MetS/NAFLD incidence. SUA-lowering therapy is a potential strategy for preventing systemic/hepatic metabolic abnormalities.

Figures

Figure 1. Flow diagram of eligible literature…
Figure 1. Flow diagram of eligible literature selection.
Figure 2. Forest plot of association between…
Figure 2. Forest plot of association between serum uric acid and metabolic syndrome in prospective studies.
(A) Pooled hazard ratios of metabolic syndrome compared between highest and lowest serum uric acid categories; (B) Pooled hazard ratios of metabolic syndrome followed per 1 mg/dL of serum uric acid elevation.
Figure 3. Dose-response relations between serum uric…
Figure 3. Dose-response relations between serum uric acid levels and risk of metabolic syndrome/non-alcoholic fatty liver disease in prospective studies.
(A) Restricted cubic splines and generalized least squares dose-response models on evaluation of association between uric acid and risk of metabolic syndrome in men; (B) Restricted cubic splines and generalized least squares dose-response models on evaluation of association between uric acid and risk of metabolic syndrome in women; (C) Restricted cubic splines and generalized least squares dose-response models on evaluation of association between uric acid and risk of non-alcoholic fatty liver disease. The solid line represents the fitted hazard ratios curve compared to the subgroup with the lowest mean dose of uric acid, and flanked dotted line is 95%CI of this risk by restricted cubic splines model. Middle dotted line represents the weighted regression index compared to subgroup with lowest mean dose of uric acid by generalized least squares model.
Figure 4. Subgroup analysis of factors influencing…
Figure 4. Subgroup analysis of factors influencing the dose-response risk of metabolic syndrome associated with uric acid elevation.
*P-value was calculated by metan between subgroups.
Figure 5. Comparison of dose-response risk of…
Figure 5. Comparison of dose-response risk of metabolic syndrome between age-confined subgroups.
Young men/women represents the first two age tertiles of subjects in enrolled studies, old men/women represents the third tertile of subjects in enrolled studies. P1 represented the heterogeneity within subgroups, P2 represented the heterogeneity between subgroups. P value was calculated between subgroups based on metan calculation.
Figure 6. Forest plot of association between…
Figure 6. Forest plot of association between serum uric acid and non-alcoholic fatty liver disease incidence in prospective studies.
Figure 7. Potential mechanisms between serum uric…
Figure 7. Potential mechanisms between serum uric acid elevation and incident metabolic disorders.

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