| OBJECTIVE: HUA is one of the components of the metabolic syndrome,which is closely related to obesity,diabetes mellitus,hyperlipidemia and insulin resistance(IR).obesity is an important risk factor for HUA and higher body mass index(BMI)was significantly associated with HUA.However,the potential mechanism of HUA combined with diabetes remains to be fully understood.In this study,we investigate the relationship between BMI and UA in Tianjin of Chinese T2 DM patients.The reason HUA mainly includes increase of UA production and / or reduce of UA excretion.The re-absorption and excretion of UA in kidney need the assistance from many UA transporters,such as urate anion transporter 1(URAT1),glucose transporter 9(GLUT9)and ABCG2.However,few studies have been evaluated the relationship between BMI and URAT1 or GLUT9,ABCG2 in T2 DM patients.Further we explored the potential molecular mechanism of HUA combined with obesity using an insulin-resistant(IR)rat model.METHODS: The first part:A cross-sectional study was carried out in Tianjin between January 2014 to July 2015.A total of 609 unrelated T2 DM patient were recruited for this study,which includes 301 males and 308 females.The age distribution is 54.5±11.5 in men and 58.2±10.3 in women.Uric acid,Hb A1c(glycohemoglobin A1c),blood viscosity,serum lipids,C-reactive protein,24-hour urinary protein,BUN,and creatinine clearance rate were measured with standard techniques.Hyperuricemia was diagnosed as UA ? 420(?mol/L)in male and UA ? 360(?mol/L)in female.According to serum UA concentrations,the patients were divided into the normal UA group and the high UA group,compared the levels of the various parameters between the two groups.BMI categories defined using WHO criteria,as followings: Normal weight =BMI 18.5-24.9;overweight = BMI 25.0-29.9;obese = BMI ? 30.0.Compared the levels of SUA among three BMI groups.Multivariable logistic regression was employed to analyze the relationship between UA(normal UA and high UA)and different clinical variables.The second part: Thirty SD male rats of 6 weeks old were randomly assigned to two treatment groups,which were fed with standard diet(ND)(8% fat,ND group)and high fat diet(HFD)(40% fat,HFD group)for 10 weeks respectively.Subsequently,both groups received adenine adenine 100mg/kg.day by gavage for 2 weeks.The obese with IR rat model established successfully.We detected the expression of URAT1,GLUT9 and ABCG2 in renal tissue of high fat diet rats and normal diet rats at the m RNA level and the protein level,compared the differences between the two groups.RESULTS: 1.In male patients,the HUA prevalence is 12.6% and the HUA patients tended to have high BMI(P=0.031),low blood viscosity(P=0.041),increased 24-hour urinary protein(P=0.002),high BUN level(P=0.002),and decreased creatinine clearance rate(P=0.003).whereas in female patients,the HUA prevalence is 19.5% and the HUA the patients tended to have high BMI(P=0.000),long waist length(P=0.000),high waist-hip-rate(P=0.000),low Hb A1 C level(P=0.015),high VLDL-C level(P=0.006),high triglyceride level(P=0.040),increased 24-hour urinary protein(P=0.000),high BUN level(P=0.000),and decreased creatinine clearance rate(P=0.000).2.The difference between normal group and overweight group,and obese group in male patients(8.4%,11.1%,and 25.24%,respectively.P=0.005),and in female patients(9.89%,15.19%,and 28.57%,respectively.P=0.003)were statistically significant.Moreover,the percents of high UA in obese group were the most largest in both gender compared with those of the other two BMI groups.3.Multivariate analyses showed that in male patients,body mass index(BMI,OR 1.711,P = 0.038),BUN(OR 1.100,P = 0.034),and 24-hour urinary protein(OR 1.004,P = 0.021)were significantly different between normal UA and high UA.In female,BMI(OR 1.169,P=0.001),BUN(OR 1.337,P=0.000),and triglyceride(OR 1.359,P=0.006)were significantly different between normal UA and high UA.4.Though the initial body mass was not different between the HFD rats and ND rats(P>0.05),the significant difference in weight accompanied with elevated blood lipids were observed after 10 weeks of HFD treatment(P<0.05).Though the blood glucose had no significant difference between the two groups(P>0.05),the HFD rats achieved significantly higher plasma glucose concentrations than the ND rats at 30,60,90,and 120 min after glucose intraperitoneal loading,respectively(P<0.05).Moreover,the HOMA-IR index was significantly enhanced in 10-week HFD-treated rats compared with ND rats(P<0.05).The results indicated that the obese with IR rats model established successfully.5.The serum UA levels in obese with IR rats were significantly higher than those in the control rats(P<0.05),though there were no difference between urine UA and urine volume between these two groups.In addition,there seemed to have a increasing tendency both in serum creatinine and BUN in obese with IR rats than those in control rats,though the difference has no statistically significant for these two indexes between these two groups.6.Results of q RT-PCR revealed that expression levels of URAT1 and GLUT9 were significantly increased by more than three-fold for URAT1 and nearly three-fold for GLUT9 in HFD rats than those in control rats.The upregulated expression levels of URAT1 and GLUT9 were confirmed by western blot analysis.However,ABCG2 expression seemed to decreased,but the difference between HFD rats and control rats had no statistic significance neither at m RNA level nor at protein level.CONCLUTION:1.Both in Tianjin of Chinese T2 DM patients,the average of SUA were increased accompanied with elevated BMI,SUA level is positively correlated with BMI.2.BMI is one of the independent risk factor for HUA in T2 DM patients.3.The SUA is increased under IR and overweight condition.4.In obese with IR rat model,the expression of URAT1 and GLUT9 is upregulated,the overexpression of URAT1 and GLUT9 enhanced re-absorption of UA in renal tubules. |
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