摘要
目的探讨达格列净联合二甲双胍治疗对早期2型糖尿病肾病患者的肾小管损伤相关标志物以及血清Klotho、TGF-β的影响。方法选取于2020年9月至2021年12月在深圳市龙岗中心医院内分泌科诊治的合并微量白蛋白尿的2型糖尿病患者共120例,采用随机数字表法分为实验组60例和对照组60例,实验组采用达格列净联合二甲双胍治疗,对照组采用格列齐特缓释片联合二甲双胍治疗,连续治疗随访12周,收集并比较两组患者治疗前后的临床资料、血清学数据以及尿肾小管损伤标志物、血清Klotho、TGF-β水平。结果治疗后实验组的总有效率为91.7%,显著高于对照组70.0%,差异有统计学意义(P=0.003)。治疗12周后,实验组的BMI显著低于治疗前,且低于对照组,差异有统计学意义(P<0.05);治疗前后两组患者收缩压(SBP)、舒张压(DBP)、血肌酐(Scr)、尿素氮(BUN)、估算肾小球滤过率(eGFR)差异无统计学意义(P>0.05);两组患者的空腹血糖(FBG)、糖化血红蛋白(HbA1c)均较治疗前下降,差异有统计学意义(P<0.05);治疗后两组间的FBG、HbA1c对比差异无统计学意义(P>0.05);治疗后两组患者的尿微量白蛋白/肌酐比值(UACR)、尿N-乙酰-β-D-氨基葡萄糖酶(NAG)、尿β2微球蛋白(β2-MG)、尿视黄醇结合蛋白(RBP)均较治疗前下降,且治疗后实验组UACR、尿NAG、尿β2-MG、尿RBP水平低于对照组,差异有统计学意义(P<0.05)。两组患者治疗后的血清Klotho水平较治疗前上升,而TGF-β水平均较治疗前下降,差异均有统计学意义(P<0.05);治疗后实验组血清Klotho高于对照组,血清TGF-β低于对照组,差异有统计学意义(P<0.05)。Pearson相关分析显示,患者治疗前后血清Klotho蛋白变化值与BMI、UACR、尿NAG、尿β2-MG、尿RBP、TGF-β变化值呈负相关(P<0.05)。两组总不良反应发生率差异无统计学意义(实验组3.3%vs.对照组4.2%,P>0.05)。结论达格列净联合二甲双胍治疗可有效降低早期2型糖尿病肾病患者体重指数及血糖水平,改善肾小球和肾小管损伤,并且可以上调血清Klotho、降低血清TGF-β表达水平。
Objective To investigate the effect of dapagliflozin plus metformin on tubular injury biomarkers,serum Klotho and TGF-βin type 2 diabetes mellitus patients with early stage of nephropathy.Methods 120 hospitalized type 2 diabetic patients having microalbuminuria in Longgang Central Hospital between September 2020 and December 2021 were selected.According to the random number table method,the patients were divided into the observation group and the control group with 60 cases in each group.The observation group received dapagliflozin plus metformin,while the control group received gliclazide plus metformin.Both groups were treated for 12 weeks continually.The changes of clinical data,serum indexes,urinary markers of tubular injury,serum Klotho and TGF-βwere compared between two groups before and after treatment.Results The total effective rate of observation group was 91.7%,which was significantly higher than that of control group(70.0%)(P=0.003).After 12 weeks of treatment,BMI was significantly lower in the the observation group after treatment,and lower than the control group(P<0.05).No significant differences were observed in the levels of SBP,DBP,Scr,BUN and eGFR before and after treatment in both groups(P>0.05).The levels of FBG,HbA1c in both groups were significantly decreased compared with baseline(P<0.05),but no differences were observed after treatment between the two groups.The levels of UACR,urine NAG,urineβ2-MG and urine RBP in both groups after treatment were significantly decreased compared with baseline(P<0.05),UACR,urine NAG,urineβ2-MG and urine RBP in observation group after treatment were lower than in control group,with statistically significance differences(P<0.05).The levels of serum Klotho after treatment in both groups were significantly increased compared with baseline,and the levels of TGF-βin both groups were significantly decreased compared with baseline(P<0.05).The levels of serum Klotho in observation group was statistically higher than in control group,and TGF-βin observation group was statistically lower than in control group after 12 weeks of treatment(P<0.05).Pearson correlation analysis showed that the changes of serum Klotho were negatively correlated with the changes of BMI,UACR,urine NAG,urineβ2-MG,urine RBP and TGF-βbefore and after treatment(P<0.05).The rates of adverse reaction of two groups were not significantly different(3.3%in observation group vs.4.2%in control group,P>0.05).Conclusions The combination therapy with dapagliflozin and metformin can effectively lower BMI,glucose,improve glomerular and tubular injury,increase serum Klotho and decrease TGF-βin type 2 diabetic patients with early stage of nephropathy.
作者
何圣清
袁唯唯
孟莞瑞
符青松
郑晓斌
武红梅
He Shengqing;Yuan Weiwei;Meng Wanrui;Fu Qingsong;Zheng Xiaobing;Wu Hongmei(Department of Endocrinology,Longgang Central Hospital of Shenzhen,Shenzhen 518116,China;Department of Laboratory Medicine,Longgang Central Hospital of Shenzhen,Shenzhen 518116,China)
出处
《中华肥胖与代谢病电子杂志》
2022年第4期236-242,共7页
Chinese Journal Of Obesity and Metabolic Diseases：Electronic Edition
基金
深圳市龙岗区医疗卫生科技计划项目(LGKCYLWS2020032)
