利拉鲁肽对糖尿病肾病患者的治疗效果及预后分析

Therapeutic effect and prognosis of linalutide in diabetic nephropathy

目的探讨利拉鲁肽对糖尿病肾病(DN)患者脂肪细胞因子、血糖指标及肾功能指标的影响及预后效果。方法回顾性选取2018年1月至2019年6月在成都市第二人民医院及成都市锦江区春熙社区卫生服务中心和书院社区卫生服务中心诊治的DN患者100例,根据患者治疗方案的不同分为二甲双胍组(48例)和联合组(52例)。二甲双胍组患者给予二甲双胍治疗,联合组患者在二甲双胍治疗的基础上给予利拉鲁肽治疗,两组均连续治疗12周。比较两组的疗效及治疗前后脂肪细胞因子脂联素(ADPN)、分泌型卷曲相关蛋白-5(SFRP5)、人网膜素-1(Omentin-1)和血糖指标空腹血糖(FBG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)及肾功能指标尿蛋白排泄量(UAER)、白蛋白/肌酐比值(ACR)、尿肝型脂肪酸结合蛋白(L-FABP)水平的差异,并分析预后情况。结果广义估计方程分析结果表明,联合组治疗4、8、12周总有效率均高于二甲双胍组,并且治疗时间越长,患者治疗总有效率越高,差异有统计学意义(χ^(2)组别=4.61,χ^(2)时点=78.57,P<0.05)。两组患者治疗前血清FBG、2 h PBG、HbA1c、FINS、HOMA-IR、ADPN、SFRP5、Omentin-1和尿液UAER、ACR及L-FABP水平比较差异均无统计学意义(P>0.05);联合组治疗12周血清FBG、2 h PBG、HbA1c、FINS、HOMA-IR和尿液UAER、ACR及L-FABP水平均低于二甲双胍组[(7.17±1.62)mmol/L比(8.75±2.11)mmol/L、(5.54±1.11)mmol/L比(6.56±1.08)mmol/L、(6.63±0.92)%比(7.95±0.89)%、(7.12±1.17)mU/L比(8.72±1.58)mU/L、3.52±0.88比4.04±0.70、(28.65±3.22)mg/24 h比(65.42±6.85)mg/24 h、(56.24±7.68)μg/mg比(92.68±9.29)μg/mg、(8.62±1.08)μg/(g·Cr)比(14.62±1.85)μg/(g·Cr)](P<0.05),ADPN、SFRP5、Omentin-1水平均高于二甲双胍组[(14.53±2.43)mg/L比(10.21±2.12)mg/L、(12.81±2.31)μg/L比(8.75±2.18)μg/L、(48.49±5.28)μg/L比(36.57±4.32)μg/L],差异有统计学意义(P<0.05)。联合组治疗后终点事件发生率低于二甲双胍组[7.69%(4/52)比22.92%(11/48)],差异有统计学意义(χ^(2)=4.57,P<0.05)。生存分析显示,观察组患者治疗后生存时间及中位生存时间均高于对照组,差异有统计学意义(P<0.05)。结论利拉鲁肽可有效改善DN患者血糖水平及肾功能,且对脂肪细胞因子分泌调节作用明显,有利于改善预后。

Objective To investigate the effect of linalutide on adipocytokine,blood glucose and renal function in diabetic nephropathy(DN)patients.Methods One hundred DN patients diagnosed and treated by Chengdu Second People′s Hospital and Chunxi Community Health Service Center of Jinjiang District and Shuyuan Community Health Service Center of Jinjiang District from January 2018 to June 2019 were selected and divided into metformin group(48 cases)and combined group(52 cases)according to different treatment regimens.Metformin group was treated with metformin,the combined group was treated with linalutide on the basis of metformin group,and both groups were treated for 12 weeks.The therapeutic efficacy,adipocytokine index adiponectin(ADPN),secretory-type curl-related proteins-5(SFRP5),omentin-1;blood glucose index fasting blood glucose(FBG),2 h postprandial blood glucose(2hPBG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),insulin resistance index(HOMA-IR),and renal function index urinary albumin excretion rate(UAER),albumin creatinine ratio(ACR),liver-type fatty acid binding protein(L-FABP)were compared between the two groups and the prognosis was analyzed.Results The total effective rate in the combined group at 4,8 and 12 weeks were higher than those in the metformin group and the longer treatment,the higher total effective,there were statistical differences(χ^(2) group=4.61,χ^(2) time point=78.57,P<0.05).Before treatment,there were no significant differences in serum FBG,2hPBG,HbA1c,FINS,HOMA-IR,ADPN,SFRP5,omentin-1,urine UAER,ACR and L-FABP between the two groups(P>0.05).After treatment,the levels of serum FBG,2hPBG,HbA1c,FINS,HOMA-IR,urine UAER,ACR and L-FABP in the combined group were lower than those in the metformin group:(7.17±1.62)mmol/L vs.(8.75±2.11)mmol/L,(5.54±1.11)mmol/L vs.(6.56±1.08)mmol/L,(6.63±0.92)%vs.(7.95±0.89)%,(7.12±1.17)mU/L vs.(8.72±1.58)mU/L,3.52±0.88 vs.4.04±0.70,(28.65±3.22)mg/24 h vs.(65.42±6.85)mg/24 h,(56.24±7.68)μg/mg vs.(92.68±9.29)μg/mg,(8.62±1.08)μg/(g·Cr)vs.(14.62±1.85)μg/(g·Cr);the levels of ADPN,SFRP5 and omentin-1 were higher than those in the metformin group:(14.53±2.43)mg/L vs.(10.21±2.12)mg/L,(12.81±2.31)μg/L vs.(8.75±2.18)μg/L,(48.49±5.28)μg/L vs.(36.57±4.32)μg/L,there were statistical differences(P<0.05).After treatment,the incidence of end-point events in the combined group was 7.69%(4/52),which was lower than that in the metformin group 22.92%(11/48),and there was statistical differences(χ^(2)=4.57,P<0.05).The survival analysis showed that the survival time and median survival time after treatment in the combined group were higher than those in the metformin group(P<0.05).Conclusions Linalutid can effectively improve blood glucose level and renal function in DN patients,and has obvious effect on adipocykine secretion,which is conducive to improve prognosis.