Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta-Analysis of Prospective Studies

Yuan, Huiping; Yu, Chenglong; Li, Xinghui; Sun, Liang; Zhu, Xiaoquan; Zhao, Chengxiao; Zhang, Zheng; Yang, Ze

doi:10.1210/jc.2015-2527

Cited by 193 publications

(150 citation statements)

References 40 publications

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“…Since increased SUA has been consistently shown to be associated with insulin resistance, components of MetS, CVD and renal diseases5619 and all these conditions are also independently associated with NAFLD, interests to explore the association between SUA and NAFLD have grown. Lonardo et al .…”

Section: Discussionmentioning

confidence: 99%

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Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults

Liu

Cai²,

Chen

et al. 2016

Sci Rep

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The present study aimed to explore the independent association and potential pathways between serum uric acid (SUA) and nonalcoholic fatty liver disease (NAFLD). 1365 community-living obese Chinese adults who received hepatic ultrasonography scanning were included. The prevalence rates of NAFLD were 71.5% for men and 53.8% for women. Compared with controls, NAFLD subjects showed significantly increased SUA levels (333.3 ± 84.9 v.s. 383.4 ± 93.7 μmol/L) and prevalence rate of hyperuricemia (HUA) (25.7% v.s. 47.3%, p < 0.001). After adjustment for insulin resistance (IR), components of metabolic syndrome (MetS) and other potential confounders, elevated SUA is independently associated with increased risk of NAFLD, with the adjusted OR of 1.528–2.031 (p < 0.001). By using multivariable fractional polynomial (MFP) modeling, the best FP transformation model shows that SUA was independently and linearly associated with risk of NAFLD. The one-pathway model by using structural equation modeling (SEM) about the relationships among SUA, IR, components of metabolic syndrome and NAFLD fits well (χ2 = 57.367, p < 0.001; CFI = 0.998; TLI = 0.992; and RMSEA = 0.048) and shows SUA might increase the risk of NAFLD directly besides of the indirect effects through increasing fasting insulin, blood pressure, triglyceride and decreasing HDL-C levels. Our results imply that elevated SUA may play an important role in NAFLD pathogenesis.

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Section: Discussionmentioning

confidence: 99%

“…SUA has been consistently shown to be associated with hypertension, insulin resistance, abdominal obesity and dyslipidemia, a cluster of metabolic disorders that is identified as metabolic syndrome (MetS)56. Since NAFLD has also been regarded as a hepatic manifestation of MetS, growing interests have focused on the relationship between SUA and NAFLD.…”

mentioning

confidence: 99%

Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults

Liu

Cai²,

Chen

et al. 2016

Sci Rep

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“…Hyperuricemia was reportedly found to be related to insulin resistance in several clinical analyses [146–152]. In addition, several meta-analyses have suggested the UA level to be positively associated with the development of type 2 diabetes mellitus (DM) [153–156], although Mendelian randomization studies did not support circulating UA as being among the causes of DM development [157, 158].…”

Section: Ua Metabolism and Chronic Renal Disease Atherosclerosismentioning

confidence: 99%

Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis

Kushiyama

Nakatsu

Matsunaga

et al. 2016

Mediators of Inflammation

112

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Uric acid (UA) is the end product of purine metabolism and can reportedly act as an antioxidant. However, recently, numerous clinical and basic research approaches have revealed close associations of hyperuricemia with several disorders, particularly those comprising the metabolic syndrome. In this review, we first outline the two molecular mechanisms underlying inflammation occurrence in relation to UA metabolism; one is inflammasome activation by UA crystallization and the other involves superoxide free radicals generated by xanthine oxidase (XO). Importantly, recent studies have demonstrated the therapeutic or preventive effects of XO inhibitors against atherosclerosis and nonalcoholic steatohepatitis, which were not previously considered to be related, at least not directly, to hyperuricemia. Such beneficial effects of XO inhibitors have been reported for other organs including the kidneys and the heart. Thus, a major portion of this review focuses on the relationships between UA metabolism and the development of atherosclerosis, nonalcoholic steatohepatitis, and related disorders. Although further studies are necessary, XO inhibitors are a potentially novel strategy for reducing the risk of many forms of organ failure characteristic of the metabolic syndrome.

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“…The RR of each 5 μg/ml adiponectin level increment was calculated for studies that provided enough raw data to quantify the association between adiponectin level and risk of stroke using GLST (generalized least-squares trend estimation) and VWLS (variance-weighted least square regression model) for the dose-response analysis, as proposed by Greenland, Longnecker, Orsini et al . The detailed methods of the dose-response meta-analysis have been described before18.…”

Section: Methodsmentioning

confidence: 99%

Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

Yuan

Sun

et al. 2016

Sci Rep

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Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03–1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00–1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk.

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Serum Uric Acid Levels and Risk of Metabolic Syndrome: A Dose-Response Meta-Analysis of Prospective Studies

Abstract: This meta-analysis suggests that higher SUA levels led to an increased risk of MS regardless of the study characteristics, and were consistent with a linear dose-response relationship. In addition, SUA was also a causal factor for the NAFLD risk.

Cited by 193 publications

References 40 publications

Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults

Serum uric acid is independently and linearly associated with risk of nonalcoholic fatty liver disease in obese Chinese adults

Role of Uric Acid Metabolism-Related Inflammation in the Pathogenesis of Metabolic Syndrome Components Such as Atherosclerosis and Nonalcoholic Steatohepatitis

Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

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