达格列净对正常白蛋白尿的2型糖尿病患者早期肾功能损伤的影响

Effect of dapagliflozin on early renal function damage in type 2 diabetic patients with normal albuminuria

目的探讨钠-葡萄糖共转运蛋白抑制剂达格列净对正常白蛋白尿的2型糖尿病患者尿系列蛋白和早期肾损伤标志物的影响。方法入选尿白蛋白/肌酐正常但尿β2微球蛋白(β2-MG)或尿N乙酰基-β-D葡萄糖苷酶(NAG)升高的2型糖尿病患者80例,随机分为常规治疗组40例(继续予以常规口服降糖药治疗,R组)和达格列净组(常规治疗基础上加用达格列净10 mg,1次/d,DA组)40例。12周后比较两组患者治疗前后空腹和餐后2 h血糖、糖化血红蛋白、肝肾功能变化,尿β2-MG、尿α1微球蛋白(α1-MG)、尿NAG水平,同时检测尿液中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子-1(KIM-1)、血清晚期糖基化终末产物(AGEs)的变化。结果DA组治疗后空腹和餐后2 h血糖、糖化血红蛋白、尿NAG较治疗前显著下降(P<0.01或P<0.05)。DA组治疗后尿NGAL、KIM-1较治疗前显著降低,同时血清AGEs显著下降(P<0.05);R组治疗后尿NGAL、KIM-1及血清AGEs均无明显改变(P>0.05)。血清AGEs与尿NAG、NGAL、KIM-1呈显著正相关。结论达格列净改善2型糖尿病患者早期肾脏损伤,可能与抑制AGEs产生有关。

Objective To investigate the effect of sodium-glucose co-transporter inhibitor dapagliflozin on urinary proteins and early renal injury markers in type 2 diabetic patients with normal albuminuria.Methods Totally 80 patients with type 2 diabetes were enrolled,who had elevated urinaryβ2 microglobulin(β2-MG)or elevated urinary N-acetyl-β-D glucosidase(NAG)but with normal urine albumin/creatinine.Patients were randomly divided into conventional treatment group(group R)and dapagliflozin group(group DA),40 cases in each group.Group R were given conventional oral hypoglycemic agents,while group DA were given dapagliflozin,10 mg once daily,along with conventional antidiabetic treatment.The fasting and 2 hours postprandial blood glucose,glycated hemoglobin,and hepatic and renal function were recorded after 12 weeks.The levels ofβ2-MG,α1 microglobulin(α1-MG),NAG,neutrophil gelatinase-associated lipocalin(NGAL)and urinary kidney injury molecule-1(KIM-1)in urine and serum advanced glycation end products(AGEs)were detected.Results The levels of fasting and 2 hours postprandial blood glucose,glycosylated hemoglobin,and urinary NAG in DA group were significantly lower than those before treatment(P<0.01 or P<0.05).The urinary NGAL,KIM-1,and serum AGEs in group DA were significantly decreased compared with those before treatment(P<0.05).No significant changes was found in urinary NGAL,KIM-1 or serum AGEs in group R before and after treatment(P>0.05).Serum AGEs were significantly positively correlated with urinary NAG,NGAL and KIM-1.Conclusion Dapagliflozin improves early kidney damage in patients with type 2 diabetes,which may be associated with the inhibition of AGEs production.