达格列净对血糖控制不佳的2型糖尿病患者肾脏保护作用的研究

Effect of Dapagliflozin on renal protection in patients with uncontrolled type 2 diabetes mellitus

目的探讨达格列净对血糖控制不佳的T2DM患者肾脏保护作用。方法选取90例既往未使用钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂、血糖控制不佳的T2DM住院患者,其中1例失访,1例因经济原因停用,最终纳入88例患者,分为达格列净治疗组(Dap,n=44),不使用达格列净为对照组(Con,n=44)。治疗12周后,比较治疗前后UACR、24 h UAlb、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、eGFR、血肌酐(Scr)、血胱抑素C(CysC)、血尿酸(SUA)和其他相关代谢指标。结果 Dap组治疗后SBP[(126. 04±9. 72)vs(135. 62±20. 07)mmHg]、DBP[(71. 84±5. 92)vs(81. 53±9. 34)mmHg]、体重[74. 35(68. 10,76. 50)vs 76. 70(69. 50,77. 25)kg]、BMI[26. 04(24. 13,28. 12)vs 26. 81(24. 60,29. 13)kg/m^2]、FBG[(7. 33±1. 36)vs(8. 87±2. 86)mmol/L]、HbA1c[(8. 06±1. 06)vs(9. 26±1. 74)%]、TC[(4. 09±1. 35)vs(4. 94±1. 36)mmol/L]、LDL-C[(2. 49±0. 74)vs(2. 96±0. 90)mmol/L]、UACR[17. 70(9. 70,36. 30)vs 19. 90(9. 50,39. 20)mg/g]、NAG[12. 20(10. 00,14. 90)vs16. 80(11. 30,21. 35)U/L]、CysC[0. 65(0. 51,0. 78)vs 0. 67(0. 56,0. 90)mg/L]和SUA[(312. 29±92. 84)vs(339. 40±97. 55)μmol/L]低于治疗前(P<0. 05或P<0. 01);Dap组UACR[4. 00(3. 05,14. 15)vs 2. 10(0. 20,5. 00)mg/g]、DBP[(9. 69±9. 22)vs(5. 42±7. 48)mmHg]、BMI[(0. 89±1. 04)vs(0. 28±1. 13)kg/m^2]和NAG[2. 70(0. 40,6. 20)vs 1. 60(1. 20,3. 30)U/L]治疗后较治疗前下降幅度大于Con组(P<0. 05或P<0. 01)。结论达格列净可减少血糖控制不佳的T2DM患者蛋白尿,降低肾小管标记物,可能具有肾脏保护作用。

Objective To observe the effect of Dapagliflozin on renal protection in patients with type 2 diabetes mellitus(T2 DM)with poor glycemic control.MethodsNinety hospitalized T2 DM patients who had never used sodium-glucose co-transporter 2(SGLT2)inhibitors with poor glycemic control were included in the study. Among them,one male patient was lost to follow-up and one patient was discontinued due to economic reasons. The final inclusion of 88 patients was divided into Dapagliflozin treatment group(Dap,n=44)and control group(Con,n=44). The levels of UACR,24 h UAlb,urinary N-acetylbeta-glucosaminidase(NAG),e GFR,serum creatinine(Scr),cystatin C(Cys C),serum uric acid(SUA)and other related metabolic indicators were compared before and after 12 weeks of treatment.ResultsAfter12 weeks of Dap treatment,the levels of SBP[(126. 04 ± 9. 72)vs(135. 62 ± 20. 07)mm Hg],DBP[(71. 84±5. 92)vs(81. 53±9. 34)mm Hg],weight[74. 35(68. 10,76. 50)vs 76. 70(69. 50,77. 25)kg],BMI[26. 04(24. 13,28. 12)vs 26. 81(24. 60,29. 13)kg/m^2],FBG[(7. 33±1. 36)vs(8. 87±2. 86)mmol/L],Hb A1 c[(8. 06±1. 06)vs(9. 26±1. 74)%],TC[(4. 09±1. 35)vs(4. 94±1. 36)mmol/L],LDL-C[(2. 49±0. 74)vs(2. 96±0. 90)mmol/L],UACR[17. 70(9. 70,36. 30)vs 19. 90(9. 50,39. 20)mg/g],NAG[12. 20(10. 00,14. 90)vs 16. 80(11. 30,21. 35)U/L],Cys C[0. 65(0. 51,0. 78)vs 0. 67(0. 56,0. 90)mg/L]and SUA[(312. 29±92. 84)vs(339. 40±97. 55)μmol/L]were significantly decreased(P<0. 05 for Cys C and SUA,P<0. 01 for other parameters). Compared with Con group,Dap group had a greater reduction in the levels of DBP[(9. 69 ± 9. 22)vs(5. 42 ± 7. 48)mm Hg],BMI[(0. 89±1. 04)vs(0. 28±1. 13)kg/m^2],UACR[4. 00(3. 05,14. 15)vs 2. 10(0. 20,5. 00)mg/g]and NAG[2. 70(0. 40,6. 20)vs 1. 60(1. 20,3. 30)U/L]after treatment(P<0. 01 for UACR,P<0. 05 for other parameters).ConclusionDapagliflozin can reduce albuminuria and renal tubular markers in patients with uncontrolled T2 DM,suggesting that it may have a renal protective effect on diabetic patients.