糖尿病并高尿酸血症的流行及尿酸排泄与肾功能关系的研究

发布时间：2018-07-06 17:23

本文选题：高尿酸血症 + 糖尿病　；参考：《上海交通大学》2015年硕士论文

【摘要】：研究目的随着我国人民生活水平的不断提高,高尿酸血症的患病率呈逐年上升趋势。高尿酸血症和糖尿病一样,是危害人类健康的一种严重的代谢性疾病。同为代谢性疾病的糖尿病和高尿酸血症,两种疾病之间存在何种联系?目前缺乏对糖尿病合并高尿酸血症的系统流行病学研究。尿酸排泄是影响血尿酸水平的重要因素。既往大多以24 h尿尿酸定量测定来简单区分尿酸生成过多或肾脏排泄减少,但此种方法受饮食、饮水、尿量及血尿酸的影响,现在采用尿酸排泄分数(fraction excertion of uric acid,FEUA)代替24 h尿尿酸定量法,该指标消除了血尿酸波动、尿量等混杂因素的影响,更为准确可靠。糖尿病患者中尿酸排泄与高尿酸血症、肾功能之间存在何种关系,目前尚未见研究报道。计算排泄分数通常收集24 h尿,但由于收集24 h尿标本较为困难,对正常人更是受到一定限制。FEUA与血尿酸、血肌酐、任意点尿尿酸及尿肌酐之间的对应关系目前尚无定论。是否可以用点尿酸的结果替代目前未见有研究报道。此外,在临床工作中血尿酸的检测通常都选择空腹,进食对血尿酸水平究竟有多大的影响?因此本研究的目的为:1、分析糖尿病合并高尿酸血症的流行情况、易患因素及与肾功能的关系;2、分析糖尿病合并高尿酸血症患者的尿酸排泄情况、影响因素及与肾功能的关系;3、分析进餐前后血尿酸水平的变化、24h尿酸排泄与点尿酸之间的相关关系。研究方法受试者均为2011年7月到2014年9月之间来自于上海糖尿病临床中心,另招募了80名健康志愿者作为正常糖耐量无高尿酸血症的对照。向病人采集病史及测量血压、身高、体重,检测肝肾功能、电解质、血脂、尿微量白蛋白和肌酐比值、HbA1c、24h尿尿酸及尿肌酐、点尿尿酸及尿肌酐等临床指标。不同组患者的特征以ANOVA作比较、协方差作分析,对照组和患者组之间连续变量比较使用t检验,分类变量使用卡方检验。相关分析采用Pearson相关检验、多元线性回归分析和偏相关分析。pearson相关分析显示与尿酸呈显著相关(p0.05)的变量进入逐步线性回归分析。多元logistic回归分析尿酸与糖尿病患者肾功能不全及异常蛋白尿发生之间的关系。gfr评估公式与mgfr的一致性用bland-altman作图法分析,各公式对超滤过及肾功能下降的诊断效能采用受试者工作特征曲线(receiver-operatingcharacteristiccurve,roc曲线)分析。研究结果1、糖尿病合并高尿酸血症的流行情况、易患因素及与肾功能关系本研究表明在中国糖尿病患者中,高尿酸血症的患病率为15.87%,在男性中为14.52%,在女性中为17.80%,gfr、空腹c肽、性别、尿微量白蛋白、年龄糖化白蛋白及bmi与血尿酸独立相关。我们的研究显示,49岁以后女性糖尿病患者高尿酸血症患病率显著高于男性,而且女性糖尿病患者随年龄的增加,高尿酸血症的患病率逐渐增加;随着bmi、空腹c肽及使用c肽计算的homa-ir增加,糖尿病患者高尿酸血症的患病率逐渐增加,血尿酸水平与空腹c肽及homa-ir呈显著正相关;随着ga增加,无论男性还是女性,高尿酸血症的患病率逐渐降低;随着gfr水平的下降及尿微量白蛋白水平的增加,高尿酸血症的患病率逐渐增加。糖尿病合并高尿酸血症患者肾功能不全及异常蛋白尿发生的危险度显著增加,超滤过发生危险度显著降低,该相关独立于年龄、性别、bmi、糖尿病病程、hba1c、sbp、dbp、ldl及hdl等其他相关因素。在合并高尿酸血症的糖尿病患者中,血尿酸水平每增加1sd(94μmol/l),肾功能不全发生危险度增加0.8%,异常蛋白尿发生危险度增加0.3%,超滤过发生危险度降低0.5%(model2)。2、糖尿病合并高尿酸血症患者的尿酸排泄情况、影响因素及与肾功能的关系无论1型还是2型糖尿病,未合并高尿酸血症时均已存在尿酸排泄减少及尿酸生成增多的情况,以尿酸生成增多为主;合并高尿酸血症时,以尿酸排泄降低为主。在gfr60ml/min/1.73m2人群,1型糖尿病合并高尿酸血症患者尿酸排泄以尿酸生成增多为主,2型糖尿病以尿酸排泄减少为主,尿酸排泄(feua)与hdl、bmi、年龄、ga、性别、ldl、lnacr及tg独立相关。研究表明,随着年龄的增加,女性尿酸排泄水平无显著变化,男性57岁以上人群feua水显著高于57岁以下人群;在每一年龄组,女性患者的feua水平均显著高于男性的feua水平。随着bmi、ga及蛋白尿水平的增加,feua水平显著增加。糖尿病不伴蛋白尿患者,随着尿酸排泄的增加gfr显著升高;合并蛋白尿患者者不论是高尿酸人群还是非高尿酸人群,随着尿酸排出的增加,尿蛋白逐渐增加的同时gfr逐渐下降。在总体糖尿病人群中,feua每升高1sd(2.64%),肾功能不全发生的危险度增加24.7%,异常蛋白尿发生的危险度增加13.9%(model2);尿酸生成增加人群肾功能不全及蛋白尿发生的危险度显著增加,or值分别为5.187(3.594-7.488,p0.001)和1.875(1.465-2.401,p0.001)。3、进餐前后血尿酸水平的变化、尿酸排泄水平及糖尿病肾功能的评估正常人群、糖耐量异常及糖尿病人群空腹及进餐2小时血尿酸水平无统计学差异。feua与血尿酸、血肌酐及任意点尿尿酸、尿肌酐显著相关,与血尿酸及任意点尿尿酸独立相关,其线性回归方程为:feua=14.02-0.02×sua-0.002×uua(mg/l),r=0.617。对以肌酐为基础的gfr评估公式(cg、mdrd及ckd-epi公式)的比较显示,ckd-epi公式的偏倚最小,15%、30%及50%准确性最高。对mdrd公式、胱抑素c公式及肌酐-胱抑素c公式的比较显示,肌酐-胱抑素c公式的偏倚最小,精确度及15%、30%、50%准确性最好,胱抑素c公式适用性最差。研究结论1、在中国糖尿病患者中,高尿酸血症的患病率为15.87%,在男性中为14.52%,在女性中为17.80%,49岁以后女性糖尿病患者高尿酸血症患病率显著高于男性,而且女性糖尿病患者随年龄的增加,高尿酸血症的患病率逐渐增加;随着bmi、空腹c肽、使用c肽计算的homa-ir及蛋白尿水平的增加及gfr水平的下降,高尿酸血症的患病率逐渐增加;随着ga水平的增加,高尿酸血症的患病率逐渐降低。2、糖尿病合并高尿酸血症患者肾功能不全及蛋白尿发生的危险度显著增加,超滤过发生危险度显著降低。3、无论1型还是2型糖尿病,未合并高尿酸血症时已存在尿酸排泄减少及尿酸生成增多的情况,以尿酸生成增多为主;合并高尿酸血症时,以尿酸排泄降低为主。在肾功能正常(gfr60ml/min/1.73m2)的糖尿病患者中,1型糖尿病合并高尿酸血症患者尿酸排泄以尿酸生成增多为主,2型糖尿病以尿酸排泄减少为主。4、糖尿病不伴蛋白尿患者,随着尿酸排泄的增加gfr显著升高;合并蛋白尿患者者不论是高尿酸人群还是非高尿酸人群,随着尿酸排出的增加,尿蛋白逐渐增加的同时gfr逐渐下降。5、在糖尿病患者中,无论是否合并高尿酸血症,尿酸生成增加人群肾功能不全及蛋白尿发生的危险度显著增加。6、正常人群、糖耐量异常及糖尿病人群空腹及进餐2小时血尿酸水平无统计学差异。7、feua与血尿酸及任意点尿尿酸独立相关,其线性回归方程为:feua=14.02-0.02×SUA-0.002×UUA(mg/L),R=0.617。8、以肌酐为基础的GFR评估公式中,CKD-EPI公式在中国糖尿病人群中的适用性最好;与MDRD公式及胱抑素C公式相比,肌酐-胱抑素C公式在中国糖尿病人群中的适用性更好,该结论同样适用于不同血糖水平的患者。
[Abstract]:With the continuous improvement of the living standard of our people, the prevalence of hyperuricemia is increasing year by year. Like hyperuricemia and diabetes, it is a serious metabolic disease that endangers human health. What is the connection between the two diseases and diabetes and hyperuricemia? A systematic epidemiological study of diabetes with hyperuricemia. Uric acid excretion is an important factor affecting the level of blood uric acid. Most of the past 24 h urine uric acid quantitative determination is used to simply distinguish uric acid formation or renal excretion, but this method is affected by diet, drinking water, urine volume and blood uric acid, and uric acid excretion score is now used. Fraction excertion of uric acid, FEUA) instead of 24 h urine uric acid quantitative method, which eliminates the influence of mixed factors such as uric acid fluctuation and urine volume, is more accurate and reliable. The relationship between uric acid excretion and hyperuricemia and renal function in diabetic patients has not yet been reported. The calculation of excretory score usually collects 24 h urine, However, as it is difficult to collect 24 h urine specimens, there is no definite relationship between the normal people and the relationship between.FEUA and blood uric acid, blood creatinine, urinic urinic acid at any point and urine creatinine. The purpose of this study is to analyze the effect of eating on the level of uric acid? 1, the purpose of this study is to analyze the prevalence of diabetes with hyperuricemia, the risk factors and the relationship with renal function; 2, analyze the relationship between uric acid excretion, influence factors and renal function in diabetic patients with hyperuricemia; 3. The changes in the level of uric acid in the post blood, the relationship between 24h uric acid excretion and point uric acid. The subjects were recruited from July 2011 to September 2014 from the clinical center of diabetes in Shanghai and recruited 80 healthy volunteers as normal glucose tolerance and non hyperuricemia. Weight, detection of liver and kidney function, electrolyte, blood lipid, urine microalbumin and creatinine ratio, HbA1c, 24h uric acid and urine creatinine, urine creatinine, urine creatinine and other clinical indicators. The characteristics of different groups were compared with ANOVA, covariance was analyzed, t test was used for the continuous variables between the control group and the patient group, and the classified variables were checked by chi square test. Correlation analysis used Pearson correlation test, multivariate linear regression analysis and partial correlation analysis.Pearson correlation analysis showed that the variables associated with uric acid (P0.05) entered the stepwise linear regression analysis. Multivariate logistic regression analysis of the relationship between uric acid and diabetic patients with renal dysfunction and ISO albuminuria was.Gfr evaluation formula The consistency of mgfr was analyzed by Bland-Altman mapping. The efficacy of each formula in the diagnosis of ultrafiltration and renal dysfunction was analyzed by the subjects' working characteristic curve (receiver-operatingcharacteristiccurve, ROC curve). Results 1, the flow of diabetes with hyperuricemia, the risk factors and the relationship with the renal function Among Chinese diabetic patients, the prevalence of hyperuricemia was 15.87%, 14.52% in men and 17.80% in women, GFR, fasting C peptide, sex, urine microalbumin, age glycated albumin and BMI were independent of blood uric acid. Our study showed that the incidence of hyperuricemia in women with 49 years old was significantly higher than that of men. Sex, and with the increase of age, the prevalence of hyperuricemia increased gradually. With the increase of BMI, fasting C peptide and the increase of HOMA-IR using C peptide, the prevalence of hyperuricemia in diabetic patients increased gradually. The serum uric acid level was positively correlated with the C peptide and HOMA-IR in the empty stomach; with the increase of GA, both male and female, The prevalence of hyperuricemia gradually decreased, with the decrease of GFR level and the increase of microalbuminuria, the prevalence of hyperuricemia increased gradually. The risk of renal dysfunction and abnormal proteinuria in patients with hyperuricemia was significantly increased, the risk of ultrafiltration decreased significantly, and the correlation was independent of the year. Age, sex, BMI, the course of diabetes, HbA1c, SBP, DBP, LDL and HDL, and other related factors. In patients with hyperuricemia, the level of uric acid increased by each 1sd (94 mu mol/l), the risk of renal dysfunction increased by 0.8%, the risk of abnormal proteinuria increased by 0.3%, the risk of ultrafiltration was reduced by 0.5% (model2).2, diabetes mellitus, and diabetes mellitus. Uric acid excretion in patients with hyperuricemia, the influence factors and the relationship with renal function in type 1 or type 2 diabetes mellitus, the decrease of uric acid excretion and the increase of uric acid production in the absence of hyperuricemia, the increase of uric acid production, and the decrease of uric acid excretion in the case of hyperuricemia in gfr60ml/min/ 1.73m2 population, uric acid excretion in patients with type 1 diabetes combined with hyperuricemia was mainly increased by uric acid production, and type 2 diabetes was mainly induced by uric acid excretion, and uric acid excretion (feua) was independent of HDL, BMI, age, GA, sex, LDL, lnacr and TG. The study showed that the level of uric acid excretion was not significantly changed with the age of age, and the male was over 57 years old. The population of feua was significantly higher than those under 57 years of age. In each age group, the feua level of the female patients was significantly higher than that of the male feua. With the increase of BMI, GA and proteinuria, the level of feua increased significantly. The patients with diabetes without proteinuria increased significantly with the increase of uric acid excretion; the patients with proteinuria were high urine. In the acid population or in the non high uric acid population, with the increase of uric acid excretion, the urinary protein gradually increased and the GFR decreased gradually. In the population of general diabetes, the risk of renal dysfunction increased by 24.7%, the risk of abnormal proteinuria increased by 13.9% (model2) per 1sd (2.64%), and the formation of uric acid increased renal insufficiency in the population. The risk of proteinuria and proteinuria increased significantly. The or values were 5.187 (3.594-7.488, p0.001) and 1.875 (1.465-2.401, p0.001).3, the changes in the level of uric acid before and after the meal, the level of uric acid excretion and the assessment of the renal function in the normal population. There was no statistical difference between the abnormal glucose tolerance and the blood uric acid level of the diabetic group and the 2 hour meal. .feua was significantly related to blood uric acid, serum creatinine and urine creatinine at any point and urine creatinine. It was independent of blood uric acid and urinate at any point. The linear regression equation was feua=14.02-0.02 x sua-0.002 x UUA (mg/l), r=0.617. for GFR evaluation formula based on creatinine (CG, MDRD and CKD-EPI formula), the bias of CKD-EPI formula was the smallest, 15 The accuracy of%, 30% and 50% was the highest. The comparison of the MDRD formula, the cystatin C formula and the creatinine C formula showed that the bias of the creatinine C formula was the least, the accuracy and the accuracy of 15%, 30%, and 50% were the best, and the applicability of the cystatin C formula was the worst. Conclusion 1 in Chinese diabetic patients, the prevalence rate of hyperuricemia was 15.87% in men. The prevalence of hyperuricemia in women with diabetes was significantly higher than that of 14.52% in women and 17.80% in women. The prevalence rate of hyperuricemia in women with diabetes mellitus increased with age, with BMI, C peptide, HOMA-IR and proteinuria, and the decrease of GFR level, and hyperuria. The prevalence of acidemia increased gradually, with the increase of GA level, the prevalence of hyperuricemia gradually decreased.2. The risk of renal dysfunction and proteinuria increased significantly in patients with hyperuricemia, and the risk of ultrafiltration significantly decreased.3, no matter type 1 or type 2 diabetes, there was no hyperuricemia. The decrease of uric acid excretion and the increase of uric acid production are mainly in the increase of uric acid production; in patients with hyperuricemia, uric acid excretion is mainly reduced. In diabetic patients with normal renal function (gfr60ml/min/1.73m2), uric acid excretion is mainly increased in patients with type 1 diabetes and hyperuricemia, and type 2 diabetes mellitus is excreted with uric acid. The decrease in.4 and diabetes without proteinuria increased significantly with the increase of uric acid excretion; in the patients with proteinuria, both high uric acid and non high uric acid population, with the increase of uric acid excretion, the urinary protein gradually increased and GFR gradually decreased.5, in diabetic patients, whether or not hyperuricemia and urine were combined. The risk of renal dysfunction and proteinuria increased significantly by.6. There was no significant difference between normal population, abnormal glucose tolerance and diabetes and 2 hours of diabetes,.7, feua was independent of blood uric acid and urinate at any point. The linear regression equation was feua=14.02-0.02 * SUA-0.002 * UUA (mg/L), R =0.617.8, in the GFR assessment formula based on creatinine, the CKD-EPI formula is the best in the Chinese diabetic population. Compared with the MDRD formula and the cystatin C formula, the creatinine C formula is better in the Chinese diabetic population. This conclusion is also applicable to patients with different blood glucose levels.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1;R589.7

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