Association Of Serum Uric Acid With Metabolic Syndrome And Metabolic Risk Factors: A Cross-sectional Study In Chinese Population

Metabolic syndrome (MS) is a series of physiological and metabolicdisorders induced by insulin resistance, ultimately leading to increased risk ofcardiovascular and cerebrovascular diseases. Increasing evidence supports arelationship between hyperuricemia(HUA) and MS or its components. MScomponents such as visceral obesity, hypertension， hyperglycemia andhyperlipidemia are all stronge risk factors for HUA. More than60%patients ofHUA combined with MS and positively correlated with MS components.Recently, several large-scale population surveys indicated the prevalence of MSand HUA were all increasing. However, the study of the relation between MSand HUA in Asia mainly in Japanese and Taiwan area. There are few large-scalepopulation surveys foused on MS and HUA in mainland of China especially theinland areas. Therefore, it is important to study the relationship between MS andHUA in Chinese population.As we know, many studies have focused on the association of serum uric acid(SUA) with indicators of obesity such as weight, body mass index(BMI),waist-to-hip ratio(WHR). But data remains limited on the association betweenmaximum weight and SUA, or regarding weight change from the maximumobesity condition. For the clinical doctors, maximum weight is more attractivefor it is easy to get it. So it is interesting to analysis the relation of them andevaluate whether maximum weight would be an potential indicators to screenHUA population. Moreover，several studies have found family history ofmetabolic disorders could cause various metabolic abnormities. However, fewstudies focused on the relation between family history of metabolic risk factorsand SUA. SUA as a secondary components of MS, whether it likes othermetabolic components or not, has close relation with family history of metabolicdisorders needs us to further study.Objective:To evaluate the relationship between SUA and MS in the adults of northareas Qinling Mountains in Shaanxi Province and the Chinese populaiton fromthe2007-8China National Diabetes and Metabolic Disorders Study.Furthermore to evaluate whether maximum weight and family history ofmetabolic risk factors are risk factors for elevated SUA level in Chinesepopulation. We hope the results of it would confirm the HUA role in the MS andlay the foundations for HUA intervention research.Methods:The multistage, stratified sampling process was uesed to select populationin north areas Qinling Mountains in Shaanxi Province. Total3298adults wereincluded in our database to analyse the relationship between SUA and MS. Also 21,414participants (8,630males and12,784females) selected from2007-8China National Diabetes and Metabolic Disorders Study were included in ourfinal analysis to study the relationship between SUA and MS; the association ofmaximum weight with hyperuricemia risk; and the family history of metabolicrisk factors with hyperuricemia risk.All subjects completed a standardized questionnaire, physical examination,OGTT test. After physical examination, participants were subject to collectedfasting venous blood specimen including SUA, TC, TG, HDL, LDL, Cr andBUN. Biochemical testing had successfully completed at a standardization/certification program. All subjects had been in our previous study signed aninformed consent. EpiData (EpiData Association, Odense, Denmark) establishedthe database, and SPSS16.0for Windows (SPSS Inc, Chicago, IL, USA) wasutilized for statistical analyses. SUA concentration were devided into fourgroups from low to high (Q1-Q4) according to SUA quartile. All variables werepresented either as mean for continuous variables or proportions for categoricalvariables. Comparisons among groups were tested by one-way ANOVA. Thechi-squared test was employed to estimate the difference for categoricalvariables. Multivariate logistic regression models examined the associationbetween SUA and maximum weight, family history or MS. ROC curves wereused to determine the maximum weight for hyperuricemia diagnosis. Allstatistical tests were two-tailed with type I error set at0.05, and P values <0.05considered statistically significant.Results:1. The relaion between MS and SUA in north areas Qinling Mountainsin Shaanxi Province: The prevalence of HUA in north areas Qinling Mountains in Shaanxi Province was6.22%, males were higher than females(9.22%VS3.40%，P<0.001). The prevalence of MS was16.89%, males were lowerer thanfemales(15.84%VS17.65%，P<0.001). With SUA level increasing, the level ofMS components (BMI, BP, TC, TG, LDL, postprandial30-min glucose and120-min glucose) were also increased(P<0.01). Moreover, different degree ofglucose elevation indicated different change trend of SUA. Partial correlationanalysis showed when FBG<7.0mmol/L, there were significantly positivecorrelation among glucose and SUA level（r=0.087，P<0.001）; when FBG≥7.0mmol/L, there were significantly negative correlation among glucose andSUA level (r=-0.255，P<0.001）. A significantly positive correlation was foundbetween postprandial30-min and2h glucose and SUA when glucose<11.1mmol/L（r=0.086，r=0.151，P<0.001）; Postprandial30-min and2h glucosewas negatively correlated with SUA when glucose≥11.1mmol/L（r=-0.132，r=-0.257，P<0.001）. Finally, with accumulation of MS components, theincidence of hyperuricemia increased (P<0.001). Also, the risk of MS showed agraded increase according to SUA level（P<0.001）. Compared with the firstquartile of SUA, multivariate regressions model showed the risk of MS(oddsratio，OR) from second to fourth quartile was1.208（95%CI0.924-1.581）,2.039（95%CI1.561-2.665）,4.280（95%CI3.216-5.696） respectively. Afteradjustment for relevant confounders, the OR values decreased. However it wasstill significantly indicated the higher SUA level the higher relative risk of MS.2. The relaion between MS and SUA in Chinese population: Ourlarge-scale epidemiological investigation in Chinese population showed thelevel of MS components increased with the SUA level increasing（P<0.001）. Inthe highest SUA quartile, glucose and insluin significantly increased（P<0.001）.Compared with the lowest SUA quartile, HOMA-IR in the highest SUA quartile was significantly higher（2.06±1.98VS1.63±1.32，P<0.001）. Moreover, SUAhad close association with CVD. With elevated SUA level, the incidence ofabnormal ECG notably increased, especially the incidence in Q4group was29.03%. Self-reported cardiovascular events had the same tendency. Theincidence of CVD in the highest and lowest SUA quartile were4.64%and1.99%, respectively. By analysis of statistics, there was significant differenceamong four SUA groups（P<0.001）. Finally, the risk of MS showed a gradedincrease according to SUA level, the incidence of MS in the Q4group and Q1group were31.47%and11.18%, respectively. Females had higher incidencethan males（P<0.001）. Also, with accumulation of MS components theincidence of hyperuricemia increased, males were higher than females. Theincidence of HUA in MS5group and MS0group were25.71%and3.46%,respectively (P<0.001). After adjustment for relevant confounders, multivariateregressions model showed the risk of MS in the highest quartile of uric acid was4.319（95%CI3.834-4.865）compared with the first quartile.3. The relaion between maximum weight and SUA in Chinesepopulation: Data showed in highest quartile of SUA, there were higher BMI,WHR，maximum weight，maximum BMI and older age at maximum weight,while weight reduction had the opposite change（P<0.001）. After adjustment forconfounding factors, maximum weight was associated with increased risk ofelevated SUA level. When maximum weight exceeded70kilograms, multiplelogistic regression analysis revealed the OR of elevated SUA level was1.75,2.233, and3.513in the second to fourth SUA quartile compared to the lowestSUA quartile, respectively. Duration of maximum weight was associated withdecreased risk of elevated SUA level. For duration of maximum weightextending beyond3years, compared to the lowest SUA quartile, the OR in the second, third, fourth quartile was0.619,0.498, and0.410, respectively. Therewas an association between time since weight loss and decreased risk ofincreased SUA level. When the time interval was0-5year duration,5-10yearduration and>10year duration，OR in the highest SUA quartile was0.615,0.505, and0.341respectively. Multivariable analysis demonstrated associationbetween increased maximum weight loss and decreased risk for increased SUAlevel. When absolute maximum weight loss exceeded5kilograms, OR in thesecond, third, and fourth quartile was0.682,0.522, and0.407in comparison tothe lowest SUA quartile. Finally, ROC curve analysis revealed area under thecurve was statistically significant for maximum weight association withhyperuricemia（area under the curve was0.661）.4. The relaion between family history of metabolic risk factors andSUA in Chinese population: The results showed SUA level in the groups ofdisorder MS components (abnormal WC, hypertriglyceridemia, lower HDL,hypertension) were all higher both in male and female (P<0.001). Theparticipants whose first-degree relatives had diabetes, hypertension,hyperlipoidemia, obesity had higher SUA level compared with negative familyhistory participants（P<0.001）. Correspondingly, with elavated SUA level theincidence of diabetes, hypertension, hyperlipoidemia, obesity, metabolic riskfactors in first-degree relatives were all increased, the incidence in Q4groupwere14.72%,43.23%,11.91%,20.77%,53.72%, respectively (P<0.001).Moreover, the SUA level was gradually increasing with accumulation offirst-degree relatives who had abnormal metabolic family history. When morethan five first-degree relatives had family history the SUA level wassignificantly increased compared with negative history subjects （294.49umol/LVS269.81umol/L，P<0.001). And the incidence of HUA had the same tendency （P<0.001）. Especially more than five first-degree relatives had family historythe HUA incidence was12.68%. Finally, after adjustment for relevantconfounders, multivariate regressions model showed the OR in the second tofourth SUA quartile was1.130,1.180and1.261, compared with the first quartile（P<0.001）. Family history of metabolic risk factors was associated with SUAelevation significantly, even except for metabolic disease influence. Familyhistory of metabolic risk factors was an independent risk factors for elevatedSUA level.Conclusion:In our large-scale epidemiological investigation we confirmed the closerelation between SUA and MS or its components in Chinese population. Therisk of MS was elevated with the uric acid level increasing. Maximum weightand the family history of metabolic risk factors were strong risk factors forelevated uric acid level. So it is important to concerned about the impact of thesefactors on HUA risk population. Early intervention would bring more benefits toreduce the risk of hyperuricemia.