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

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?

SUBMITTER: Liu Z

PROVIDER: S-EPMC4585787 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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

Liu Zhengtao Z Que Shuping S Zhou Lin L Zheng Shusen S

Scientific reports 20150923

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 l ...[more]

PMID: 26395162

Similar Datasets

Changing trajectories of serum uric acid and risk of non-alcoholic fatty liver disease: a prospective cohort study.

Project description:BACKGROUND:It is unclear the role of longitudinal trajectory of serum uric acid (SUA) on the development of non-alcoholic fatty liver disease (NAFLD). We aimed to determine whether longitudinal SUA trajectories are associated with the risk of new-onset NAFLD. METHODS:We explored the relationship between SUA trajectories and NAFLD in a cohort including 3822 participants. Individual's SUA trajectories from 2012 to 2014 were defined using group-based trajectory modeling analysis in four distinct patterns: trajectory 1 (n?=?991, 25.93%), trajectory 2 (n?=?1421, 37.18%), trajectory 3 (n?=?1156, 30.22%), and trajectory 4 (n?=?254, 6.67%). The logistic regression model was used to evaluate the association between SUA changing trajectories and subsequent NAFLD until 2016. Dose-response relationship between SUA changing trajectories and NAFLD risk was evaluated through the testing of trajectory groups as a continuous variable. RESULTS:The 2-year incidence of NAFLD was 13.27%. Compared with trajectory 1, the adjusted odds risk for NAFLD development was in a dose-response relationship as follows: 1.27 (95% CI 0.91-1.78) for trajectory 2, 1.89 (95% CI 1.29-2.75) for trajectory 3, and 2.34 (95% CI 1.43-3.83) for trajectory 4. And this dose-response relationship was not affected by age, sex, and abdominal obesity. CONCLUSIONS:Higher SUA changing trajectory is a risk factor for NAFLD. This finding highlights the importance of paying attention to SUA changing trajectory on the detection and prevention of NAFLD.

| S-EPMC7081554 | biostudies-literature

Serum uric acid and non-alcoholic fatty liver disease in non-diabetic Chinese men.

Project description:Increased serum uric acid (SUA) levels may be involved in the development of non-alcoholic fatty liver disease (NAFLD) in men presenting with metabolic syndrome (MetS) and/or insulin resistance. We aimed to determine the independent relationship between SUA and NAFLD in non-diabetic Chinese male population, and to explore the determinants of SUA levels among indexes of adiposity, lipid, and genotypes pertaining to triglycerides metabolism, inflammation, oxidative stress, and SUA concentrations. A total of 1440 men, classified depending on the presence of ultrasonographically detected NAFLD, underwent a complete healthy checkup program. Genotypes were extracted from our previously established genome-wide association study database. After adjusting for age, smoking, drinking, body mass index, homeostasis model assessment of insulin resistance, C-reactive protein, creatinine, alanine aminotransferase (ALT) and components of metabolic syndrome, the odds ratio for NAFLD, comparing the highest with the lowest SUA quartile, was 2.81 (95% confidence interval 1.66-4.76). A stepwise multivariate linear regression analysis (R(2)?=?0.238, P<0.001) retained age, waist circumference, serum creatinine, triglycerides, the Q141K variant in ABCG2 (rs2231142) and NAFLD as significant predictors of SUA levels (all P<0.001). Besides, ALT and Met196Arg variant in TNFRSF1B (rs1061622) additionally associated with SUA among individuls with NAFLD. Our data suggest that in Chinese men, elevated SUA is significantly associated with NAFLD, independent of insulin resistance and other metabolic disorders, such as central obesity or hypertriglyceridemia. Meanwhile, among subjects with NAFLD, index of liver damage, such as elevated ALT combined with genetic susceptibility to inflammation associated with increased SUA levels.

| S-EPMC3720733 | biostudies-literature

Associations between Serum Uric Acid and the Remission of Non-Alcoholic Fatty Liver Disease in Chinese Males.

Project description:Epidemiological studies suggest that higher serum uric acid (sUA) level is significantly associated with nonalcoholic fatty liver disease (NAFLD) development. However, little information is available on the relationships between sUA and NAFLD remission. In the present study, 841 NAFLD males (30-75 years) were recruited from a Chinese prospective cohort study (PMMJS) and followed up for five years. The baseline sUA levels of participants were categorized into four quartiles: 191 ?mol/L? sUA ? 347 ?mol/L, 347 ?mol/L < sUA ? 392 ?mol/L, 392 ?mol/L < sUA ? 441 ?mol/L and 441 ?mol/L<SUA?676 ?mol/L. As the results show, participants with elevated sUA levels at baseline were significantly associated with the decreased rate of NAFLD remission at the end of study (p<0.0001). After adjustment, RR (95%CI) for remitted NAFLD comparing Q1 to Q3 vs Q4 of sUA were 2.95 (1.49-5.83), 2.40 (1.22-4.73) and 1.39 (0.67-2.86), respectively. Furthermore, the sensitivity analysis showed these significant associations were not affected even after exclusion of participants who had hypertension, diabetes mellitus, MetS and hyperlipidemia. Additionally, the presence of the lowest quartile of sUA levels was still significantly associated with remitted NAFLD when the study population was stratified according to the smoking, and the median values of age, ALT, AST, serum creatinine, HDL-C and LDL-C. Therefore, our present study extended the previous findings and suggested that modulation of sUA levels may attenuate the progression of NAFLD.

| S-EPMC5106003 | biostudies-literature

Paraoxonase-1 Serum Concentration and PON1 Gene Polymorphisms: Relationship with Non-Alcoholic Fatty Liver Disease.

Project description:Non-alcoholic fatty liver disease (NAFLD) is an important cause of chronic liver diseases around the world. Paraoxonase-1 (PON1) is an enzyme produced by the liver with an important antioxidant role. The aim of this study was to evaluate PON1 serum concentration and PON1 gene polymorphisms in patients with NAFLD. We studied a group of 81 patients with NAFLD with persistently elevated aminotransferases and a control group of 81 patients without liver diseases. We collected clinical information and performed routine blood tests. We also measured the serum concentration of PON1 and evaluated the PON1 gene polymorphisms L55M, Q192R, and C-108T. There was a significant difference (p < 0.001) in serum PON1 concentrations among the two groups. The heterozygous and the mutated homozygous variants (LM + MM) of the L55M polymorphism were more frequent in the NAFLD group (p < 0.001). These genotypes were found in a multivariate binary logistic regression to be independently linked to NAFLD (Odds ratio = 3.4; p = 0.04). In a multivariate linear regression model, the presence of NAFLD was associated with low PON1 concentration (p < 0.001). PON1 serum concentrations were diminished in patients with NAFLD, and the presence of NAFLD was linked with low PON1 concentration. The LM + MM genotypes of the PON1 L55M polymorphism were an independent predictor for NAFLD with persistently elevated aminotransferases.

| S-EPMC6947206 | biostudies-literature

High serum uric acid increases the risk for nonalcoholic Fatty liver disease: a prospective observational study.

Project description:Nonalcoholic fatty liver disease (NAFLD) is a common form of chronic liver disease, and serum uric acid is observed to be significantly elevated in NAFLD patients. However, whether this elevation is causal, a bystander, or a consequence of NAFLD remains unclear. We performed a population-based prospective study among the employees of Zhenhai Refining & Chemical Company Ltd., Ningbo, China to investigate whether the elevation of serum uric acid has a casual role for NAFLD. A total of 6890 initially NAFLD-free subjects were followed up for 3 years. Overall, 11.80% (813/6890) subjects developed NAFLD over 3 years of follow-up. The cumulative incidence of NAFLD increased with progressively higher baseline serum uric acid levels (the cumulative incidence was 7.2%, 9.5%, 11.5%, 13.8%, and 17.2% in quintile 1, quintile 2, 3, 4 and 5, respectively; P value for trend <0.001). Cox proportional hazards regression analyses showed that serum uric acid levels were independently and positively associated with the risk for incident NAFLD; the age-, gender- and metabolic syndrome adjusted hazard ratio (95% CI) for the subjects in quintile 2, 3, 4 and 5 versus quintile 1 was 1.18 (0.91-1.54), 1.32 (1.03-1.70), 1.39 (1.09-1.78) and 1.50 (1.18-1.92), respectively. Taken together, our prospective observational study showed that elevation of serum uric acid levels independently predicts increase risk for incident NAFLD.

| S-EPMC2904389 | biostudies-literature

Metabolic drivers of non-alcoholic fatty liver disease.

Project description:BackgroundThe incidence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide parallel to the global obesity epidemic. NAFLD encompasses a range of liver pathologies and most often originates from metabolically driven accumulation of fat in the liver, or non-alcoholic fatty liver (NAFL). In a subset of NAFL patients, the disease can progress to non-alcoholic steatohepatitis (NASH), which is a more severe form of liver disease characterized by hepatocyte injury, inflammation, and fibrosis. Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening.Scope of reviewThe transition from NAFL to NASH likely involves a complex constellation of multiple factors intrinsic and extrinsic to the liver. This review focuses on early metabolic events in the establishment of NAFL and initial stages of NASH. We discuss the association of NAFL with obesity as well as the role of adipose tissue in disease progression and highlight early metabolic drivers implicated in the pathological transition from hepatic fat accumulation to steatohepatitis.Major conclusionsThe close association of NAFL with features of metabolic syndrome highlight plausible mechanistic roles for adipose tissue health and the release of lipotoxic lipids, hepatic de novo lipogenesis (DNL), and disruption of the intestinal barrier in not only the initial establishment of hepatic steatosis, but also in mediating disease progression. Human genetic variants linked to NASH risk to date are heavily biased toward genes involved in the regulation of lipid metabolism, providing compelling support for the hypothesis that NASH is fundamentally a metabolic disease.

| S-EPMC8324696 | biostudies-literature

Sex-Specific Relationship Between Serum Uric Acid and Risk of Stroke: A Dose-Response Meta-Analysis of Prospective Studies.

Project description:Conflicting findings of the association between serum uric acid (UA) and stroke have been reported in both men and women, and it is unclear whether this association was different between men and women. We preformed this meta-analysis to assess the sex-specific effect of serum UA on the risk of stroke and its subtypes.Prospective studies that reported sex-specific association of UA levels with stroke or reported in a certain sex were included. Dose-response relationships were assessed by the generalized least squares trend estimation, and summary effect estimates were evaluated with random-effect models. Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation. Altogether, 13 prospective studies were identified in this study. The summary of relative risks (95% CIs) of stroke for a 1-mg/dL increase in serum UA levels were 1.10 (1.05-1.14) for men and 1.11 (1.09-1.13) for women. There is no significant difference in the effect of UA on future stroke risk between men and women (Pinteraction=0.736). Subgroup analyses showed that the significant associations persisted in most stratifications, and sensitivity analyses according to various inclusion criteria yielded similar results. A nonlinear relationship was observed in men (Pnon-linearity<0.001), with risk increasing significantly from a UA of 6 mg/dL and more steeply at higher UA levels.Elevated serum UA levels were significantly associated with modestly increased risk of stroke in both men and women and have similar adverse effects on development of stroke in both sexes.

| S-EPMC5533011 | biostudies-literature

Metabolic profiling of adolescent non-alcoholic fatty liver disease.

Project description:Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.

| S-EPMC6338132 | biostudies-literature

Relationship between Muscle Mass and Non-Alcoholic Fatty Liver Disease.

Project description:Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05-1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38-1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

| S-EPMC7915258 | biostudies-literature

Elevated serum uric acid levels are associated with non-alcoholic fatty liver disease independently of metabolic syndrome features in the United States: Liver ultrasound data from the National Health and Nutrition Examination Survey.

Project description:ObjectiveExperimental and observational studies suggest a role for uric acid in non-alcoholic fatty liver disease (NAFLD). We examined the association between serum uric acid levels and NAFLD in a large population-based study from the United States.Materials/methodsA cross-sectional analysis of 10,732 nondiabetic adults who participated in the National Health and Nutrition Examination Survey 1988-1994. Sex specific uric acid quartiles were defined: ?5.2, 5.3-6.0, 6.1-6.9, and >6.9mg/dL for men and ?3.7, 3.8-4.5, 4.6-5.3, and >5.3mg/dL for women. NAFLD presence and severity were defined by ultrasonographic detection of steatosis in the absence of other liver diseases. We modeled the probability that more severe NAFLD would be associated with the highest quartiles of uric acid.ResultsCompared to the 1st quartile, the odds ratio for NAFLD was 1.79 (95% C.I. 1.49-2.15, p<0.001) and 3.14 (95% C.I. 2.63-3.75, p<0.001) for the 3rd and 4th quartiles, respectively. After adjusting for demographics, hypertension, waist circumference, triglycerides, high-density lipoprotein-cholesterol, homeostasis model assessment-estimated insulin resistance, estimated glomerular filtration rate, and aspartate aminotransferase, uric acid (4th quartile) was significantly associated with NAFLD (odds ratio 1.43; 95% C.I. 1.16-1.76, p<0.001). Positive parameter estimates suggest increasing uric acid is associated with greater severity of NAFLD.ConclusionsElevated uric acid level is independently associated with ultrasound-diagnosed NAFLD in a nationally representative sample of United States nondiabetic adults. Increasing uric acid is associated with increasing severity of NAFLD on ultrasonography. These findings warrant further studies on the role of uric acid in NAFLD.

| S-EPMC3565047 | biostudies-literature

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