hyperuricemia and the metabolic syndrome

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    Asia Pac J Clin Nutr 2009:18 (1): 81-87 81

    Original ArticleHyperuricemia and the metabolic syndrome in Hangzhou

    henzhen Cai MSc'", Xiaofeng Xu MD^,Xiangming Wu MD ^,Ciqin Zhou BSc', Duo LiPhD 1.5Department of Food Science andNutrition Zhejiang University Hangzhou, ChinaDepartment of Food Biotechnology and Food Process Engineering, Berlin University of Technology, Berlin,GermanyConvalescentHospital Hangzhou, China NUOTE Nutrition Center, Hangzhou, China IAES Zhejiang University.Hangzhou, China

    The aim of this study was to investigate prevalences of hyperuricemia and the metabolic syndrome (MS) in theHangzhou population, and the relationship between serum uric acid and the MS. A cross-sectional study wasconducted among 4155 subjects (2614 men and 1541 women) aged 20-80 years, recruited through a health checkprogram in Hangzhou, China. Biochemical and haematological parameters were measured by standard methods.The diagnosis of the MS is made when three or four of the following criteria are met: )body mess index (BMI)> 25; 2) systolic blood pressure > 140 mmHg or diastoHc blood pressure > 90 mmHg; 3) fasting triacyglycerol >1.7 mmol/L (150 mg/dL). high density lipoprotein cholesterol (HDL-C) < 0.9 mmol/L (35 mg/dL) in men and 6.1 mmol/L (109 mg/dL). Hyperuricemia is defined bycut-off values of > 420 nmol/L for men and > 360 jimoI/L for women. Prevalences were 16.9% (N=702) for hy-peruricemia and 8.4% {N=349) for the MS. Serum uric acid concentration was significantly higher in males thanin females ( / K O . O O O I ) . , and significantly higher in subjects with obesity, dyslipidemia and hypertension com-pared with those without. In the partial correlation analysis, after controlling for gender, age and creatinine. se-rum uric acid concentration was significantly positively correlated with BMl (r=0.301./)

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    82 Hyperuricemia and the metabolic syndrome

    Centre, Hangzhou Convalescent Hospital, China, in themorning following an overnight fast. Subjects were al-lowed to sit relaxed for 10 min, and then venous bloodwas taken into vacutainers. Serum and plasma sampleswere prepared by centrifugation, aliquoted into separatetubes and stored at -2C until analyses were performed.None of the participants of the study had thyroid, renal,

    hepatic gastrointestinal, or oncology disease or were re-ceiving drugs for hypoglycemia, antioxidant vitamin sup-plementation, or drugs known to affect lipoprotein me-tabolism or uric acid metabolism. The study was ap-proved by the Research Ethics Committee, School of Bio-system Engineering and Food Science. Zhejiang Univer-sity, and all subjects gave written informed consent.According to the Chinese Diabetes Society (CDS),'the diagnosis of the MS is made when three or four of thefollowing criteria are met: 1 )obesity, as body mess index(BMI) > 25; 2) high blood pressure, as systolic bloodpressure > 140 mmHg or diastolic blood pressure > 90mmHg; 3) dysHpidemia, as fasting triacyglycerol > 1.7mmol/L (150 mg/dL), high density lipoprotein cholesterol(HDL-C) < 0.9 mmol/L (35 mg/dL) in men and 6.1 mmol/L 109 mg /dL).Hyperuricemia is defmed by cut-off values of > 420(imol/L for men and > 360 ^m ol/L for women.^~

    lood collectionOvernight fasting blood specimens were collected formeasurement of serum uric acid, lipids and plasma glu-cose . All particip ants fasted for at lease 10 h before bloodcollection. Serum and plasma samples were prepared dur-ing the two hours after blood was drawn, and stored at-20 C until laboratory assays.Parameters measurementsAnthropomtrie and haematological parameters weremeasured by standard methods. Serum uric acid, triacyl-glycerol (TG) and total cholesterol (TC) concentrationswere detenmned by standard enzymatic dipyridamolemethods. High density lipoprotein cholesterol and lowdensity lipoprotein cholesterol (LDL-C) were measuredby differential antibody methods, and blood glucose wasmeasured by hexokinase methods on an auto-biochemical

    analyzer (Olympus AV400, Japan). Lipid, lipoprotein anblood glucose concentrations were reported as mmol/Lwhile uric acid and creatinine concentrations asStatistical analysesStatistical analyses were performed using the SPSS software package version 15.0 for Windows (SPSS Inc., Chicago, IL, USA). Descriptive statistics were initially performed, given as mean and 95% confidence intervalS trata-specific differences were assessed using o ne-waAnalysis of Variance (ANOVA). Prevalences of hyperuricemia, the MS and components of the MS were calculated by cross-tabulation and compared by Chi-square tesfor 2x2 tables for each pair. Bivariate correlation wainitially employed to determine the relationship betweeserum uric acid concentrations and features of the MSPartial correlation analyses were perfonned to assess associations between uric acid and features of the MS afteadjustment for confounding factors (gender, age and serum creatinine concentration). The values were reportedas meanistandard deviation. Two-tailed /j-values werregarded as significant when/7

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    Cai . X Xu. X Wu. C Zhou and D Li

    Table 1.Prevalenceof the metabolic syndrome and individual components ofmetabolicsyndrome (%)"

    A ll subjectsMalesFemales values (Males vs. Females)

    Obesity32.6 N=I354)42.5 N=I11O)15,8 N=244)

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    84 Hyperuricemia and the metabolic syndrome

    Table 5 Prevalence of the metabolic syndrome by quartiles of serum uric acid concentration

    Uric acid (nmol/L)Quartile (4l6)Total

    Males N201523

    260318

    %3.02.33.539.912.2

    Uric acid ((itnol/L)Quartilc (287)Total

    FemalesN1232531

    %0.30.50.86.32,0

    Metabolic syndrome was diagnosed based on Chinese Diabetes Society (CDS) definition.'

    Table 6 Proportion of those with hypemricemia withand without the metabolic syndrome' and vice versa.MetabolicSyndrome MetabolicSyndrome All

    Hyperuricetnia (+) 278Hyperuricem ia^ (-) 71All 349

    42 433823806

    70234534155

    Metabolic syndrome was diagnosed based on Chinese DiabetesSociety (CDS) definition.''Hyperuricemia is diftned by cut-off values of > 420 |imol/L formen and > 360 ^mol/L for women.'^

    with MS, obesity, dyslipidemia and hypertension than insubjects without these conditions.As shown in Table 5, the prevalence of MS increasedacross successive quartiles of serum uric acid concentra-tions (0,3%. 0.5%, 0.8% and 6.3% for successive quar-

    tiles) in women. However, no linear gradient of increasedprevalence of MS across increasing quartiles of uric acidwas observed in men from quartile to quartile 3 (3,0%,2.3% and 3.5% for the first three successive quartiles).There was a sharp increase in the prevalence of MS fromquartile 3 to quartile 4. both in men (from 3.5% lo 39.9% )and women (frotn 0.8% to 6.3%).

    Some 39.6% of those with hyperuricemia (n ^ 702)have the M S (n - 278 ); vice versa, 80% of those with theM S (n = 349) have hyperuricemia (n - 278) (Table 6).DISCUSSIONOverall, the prevalence of hyperuricemia In the presentstudy population was 23.7% in men and 5.3% in women,respectively. In men, prevalence of hyperuricemia washigher than in the Thai population (18.4%),''' Beijing ur-ban population (15.4%) and Beijing rural population(11.3%). ^ However, in women, they were lower than inthe Thai population (7.8%),'^ Beijing urban (11.0%) andrural populations (8.4%). ^ Higher serum uric acid con-centration and higher prevalence of hyperuricemia in menthan in women were consistent with a previous study inthe Hangzhou popu lation,' and from studies of variouspopulations.'''*'''''* Hyperuricemia is consistently morecommon in men than in women.Prevalence ofMSfor this study population (8.4%) was

    to 2002. *' With regard to the lower prevalence of MS andhyeniricemia in women than in men, it is thought thaestrogen's protective effects allow for a lower incidencof MS and hyperuricemia in women. This is further confirmed by the knowledge that some features of MS andcardiovascular diseases can be prevented or alleviatedwith soy or its traditional products, which provides source of phyto-estrogens.The frequency of components of MS varies among different populations. In this study, obesity (prevalenc32,6%) and dyslipidemia (28.0%) were the main components of MS, followed by hypertension (17,7%) and diabetes (7.7%). ln contrast, in Yang's study of the Taiwapopulation, the order is: diabetes (15.5%), dyslipidemi(11.0% ), hypertension (10.0%) then obesity (6.2%),-' anin Gu's study of the general Chinese population, hypertension (41.2%), dyslipidemia (33.9%), obesity (28.9%then diabe tes (12.7%). *'The positive correlation between serum uric acid an

    BMI, systolic blood pressure, diastolie blood pressureserum concentrations of creatinine, total cholesterol, antriacyglycerol in the partial correlation analysis were generally similar to those reported by other investigators. Ithis study, serum uric acid levels were significantlhigher in subjects with the MS than that in healthy subjects. These findings are consistent with those in othepopu lations.'^ Additionally, obesity, dyslipidemia anhypertension contribute in both gender groups to the development of hyperuricemia. Not only is serum uric acicorrelated with individual cardiovascular disease and Mrisk factors such as obesity, hypertension, and dyslipidemia, but hyperuricemia tends to cluster with these risfac tor s. ' Although we were not able to evaluate threlation between serttm uric acid and the incidence ocardiovascular disease, we found positive associationbetween the MS severity and quartiles of serum uric aciconcentrations in men and women. Apart from adultpositive correlations between serum uric acid concentration and the MS have been found in both children anelderly Taiwanese.^^ ^ *

    Many recent epidemiological, cross-sectional ancase-control studies have found that increased serum uracid level is a risk factor for the M S . ' The presenstudy compared serum uric acid levels in subjects witand without the MS using a criteria for the Chinese population. The positive correlation between serum uric aci

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    Cai , X Xu, X Wu, C Zhou and D Li 85

    or LDL-C. A posi t ive correlat ion between serum uric acidand se rum LDL-C concen t ra t ions was repo r ted in Tha ipopu lat ions . ' and a negat ive correlat ion betwee n serumuric acid and serum HDL-C concentrat ions was found int h e Ta i w a n e s e .

    Female subjects with d iabetes had higher concentra-tions of serum uric acid, but this was not the case in men.Serum uric acid has been found elevated in the non-diabet ic range of fas t ing plasma glucose d is tr ibut ion, andredu ced after Ihe onset of diab etes . Serum uric acid leveldecreases in d iabet ic subjects , part icularly in d iabet icmen. ' Normally , uric acid is to tal ly f i l tered in the renalglome nil i and is a lmost com pletely reabsorbe d in theproximal tubule, whi le g lucose competi t ively inhibi ts uricacid reabsorpt ion and enhances i ts excret ion at the sameana tomic pos i t ion , g iven no rmal rena l func t ion .

    Hyperu r icemia can be the consequence o f increaseduric acid product ion or decreased excret ion. ' ' The mecha-nism by which uric acid causes metabolic d iseases mayinvolve a reduct ion in the concentrat ions of endothel ia ln i t r ic oxide (eNO). Uric acid potent ly reduces the concen-trations of endothelial nitric oxide in vitro and in vivo inexperimental animals . In tum, a reduct ion in endothel ia ln i t r ic oxide predisposes animals to develop features of themetabo l i c syndrome. Hyperu r icemia in humans i s a l sostrongly associated with endothel ia l dysfunct ion.^^ Sev-eral potent ia l mechanisms may explain how an impairedproduct ion of endothel ia l n i t r ic oxide resul ts in featuresof the metabolic syndrome. The endothel ium is an elegantsymphony responsible for the synthesis and secret ion ofseveral b io logical ly act ive molecules . I l i s responsible forregulat ion of vascular tone, inflammation, l ip id metabo-l ism, vessel growth, arteria l vessel wall , and modulat ionof coagulat ion and fibrinolysis . The heal thy endothel iumis a net producer of endotbel ia l n i t r ic oxide {eNO). Theact ivated , dysfunct ional endothel ium is a net producer ofSuperoxide (O:) associated with the MS, type 2 d iabetes ,and a therosc le ropa thy . ' ' '

    In conclusions , the present s tudy indicates that an in-creased serum uric acid concentrat ion is associated with acluster of the MS components . Serum uric acid is s ignifi -cant ly correlated with the components of the MS exceptfor hyperglycaemia. Higher serum uric acid concentrat ionis associated w ith tbe MS in the Han gzho u populat ion .A U TH O R D IS C LO S U R ESZhenzhen Cai, Xiaofeng Xu, Xiangming Wu, Ciqin Zhou, DiioLi ,have no conflicts of interest.R E F E R E N C E SI. He Y, Jiang B, Wang J, Feng K, Chang Q, Fan L, Li XY. Hu

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    Cai,XXu,XWu,CZhouand D Li 87

    Original ArticleHyperuricemiaand themetabolic syndrom einHangzhouZhenzhenCaiMSc' ^,XiaofengXuMD'\ Xiangm ingWuMD *,Ciqin Zhou BSc',Duo LiP h D ' - 'Departmen t o f Food Science and Nutrition, Zhejiang University, Hang zhou, ChinaDepartment of Food B iotechnology and Food Process Engineering, Berlin University of Techn ology, Berlin.GermanyConvalescent Hospital,Hangzhou, China NUOTE Nutrition Center.Hang zhou. ChinaIAES,Zhejiang University, Hangzho u, Ch ina

    i t 41552614^M'mv15414Jf ^

    iim-^^i : 1) ^At i^ i^>25 ; 2)mmHg ^if5lJI^>90 mmHg; 3)^S-^;S|>1.7 mmol/L(150 mg/dL) '^^^Jm:mmm^^ l]) ' ftilt^^ii^ -:/ 4^ 8.4%(349 H) o n'l^^^m '4^^ (;?

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