利拉鲁肽联合人脐带间充质干细胞治疗对2型糖尿病患者糖代谢及胰岛β细胞功能的作用  

The effect of liraglutide in combination with human umbilical cord mesenchymal stem cells treatment on glucose metabolism and β cell function in type 2 diabetes mellitus

作　　者：陈频[1] 黄勤[2] 徐向进[1] 邵珠林 黄梁浒[3] 杨熙章[4] 郭雯[1] 李春梅[1] 陈晨[1] 

机构地区：[1]南京军区福州总医院内分泌科,350025 [2]第二军医大学长海医院内分泌科 [3]南京军区福州总医院干细胞中心,350025 [4]南京军区福州总医院放射影像科,350025

出　　处：《中华内科杂志》2016年第5期349-354,共6页Chinese Journal of Internal Medicine

基　　金：福建省自然科学基金（2012J01403）;福建省科技计划重点项目（2011Y0047）;全军医学科学技术研究＂十二五＂计划（CWSIIJ254）

摘　　要：目的 探讨利拉鲁肽（LIRA）联合人脐带间充质干细胞（hUC-MSCs）治疗对2型糖尿病（T2DM）患者糖代谢及胰岛β细胞功能的作用.方法 筛选12例合格受试者：确诊T2DM病程大于10年,已应用促泌剂、二甲双胍和胰岛素治疗不达标并加用LIRA至少6个月,但仍未达标[糖化血红蛋白（HbAlc）7％ ～ 10％].受试者随机分为A组（LIRA联合hUC-MSCs假移植组）和B组（LIRA联合hUC-MSCs移植组）.每组6例.其中B组第1天行介入下经胰腺动脉输注hUC-MSCs,第8、15和22天行外周静脉输注hUC-MSCs（每次细胞量为1×106/kg）;A组同期同方式输注等体积生理盐水.两组继续应用LIRA干预24周.观察患者一般情况、空腹血糖（FPG）、餐后2h血糖（2hPG）和HbA1c;行75 g口服葡萄糖耐量试验及C肽释放试验评价早相C肽分泌功能（ΔCP30/ΔG30）、C肽分泌总量（AUCCP180）和稳态模型法评估的胰岛素抵抗指数（HOMA-IR）.结果 （1）两组患者基线时FPG、2hPG、HbAlc、ΔCP30/ΔG30、AUCCP180及HOMA-IR具有可比性（P＞0.05）.（2）干预24周末,B组FPG（6.64±0.79） mmol/L、2hPG（8.65±1.12） mmol/L和HbAlc （6.82±0.53）％明显低于A组[（8.33±0.99） mmol/L、（13.85 ±0.86） mmoL/L、（7.82±0.31）％,P＜0.05].（3）干预24周末,B组ΔCP30/ΔG30（0.70±0.38）和AUCCP180 （21.16±3.17）均明显高于A组（分别为0.22 ±0.13、12.52±5.30,P ＜0.05）,而HOMA-IR明显低于A组（4.30±2.68比9.46±4.88,P＜0.05）.结论 对T2DM患者联合LIRA和hUC-MSCs治疗可以起到更好地改善糖代谢和胰岛功能的作用.Objective To observe the effect of liraglutide （LIRA） in combination of umbilical cord mesenchymal stem cells （hUC-MSCs） in treating type 2 diabetes mellitus.Methods Eligibility criteria for subjects includes： type 2 diabetes mellitus with more than 10 years duration;having been treated with secretagogues, metformin and insulin in combination with LIRA for at least 6 months;poor glycemic control [glycosylated hemoglobin A1 c （HbA1 c） 7 ％-10％].Totally, twelve patients were enrolled and randomly divided into two groups ： the group A （LIRA group, n =6） and the group B （LIRA ＋ hUC-MSCs group, n =6）.The hUC-MSCs were transplanted through infusing of 1 × l06 cells/kg via pancreatic artery directed by interventional radiology on the first day, and followed by infusing 1 × 106 cells/kg through peripheral vein on the eighth, the fifteenth and the twenty-second day sequentially.The control subjects were infused with saline.Both groups were treated with LIRA for 24 weeks at the same period.Fasting plasma glucose（FPG）, 2h postprandial plasma glucose （2hPG） and HbAlc were measured.A 75 g oral glucose tolerance test （OGTr）was performed.The early phase of C peptide （CP） secretion function（ΔCP30/ΔG3o）, the total amount of C peptide secretion function （AUCCp180） and Homeostasis model assessment of insulin resistance （HOMA-IR） were calculated.Results （1） The baseline FPG, 2hPG, HbAlc, ΔCP30/ΔG30, AUCcP180 and HOMA-IR were comparable between the two groups（P ＞0.05）.（2） Compared with subjects in group A, FPG,2hPG and HbAlc levels were significantly decreased in subjects in group B [（8.33 ± 0.99） mmol/L vs （6.64 ± 0.79） mmol/L, （13.85 ± 0.86） mmol/L vs （8.65 ± 1.12） mmol/L, （7.82 ± 0.31）％ vs （6.82 ± 0.53）％, P ＜ 0.05].（3） Compared with group A, ΔCP30/ΔG30 and AUCcP180 were significantly increased, and HOMA-IR was significantly decreased in group B（0.22 ±0.13 vs 0.70 ±0.38, 12.52±5.30vs21.16±3.17,9.46±4.88vs4.3

关 键 词：糖尿病 2型 利拉鲁肽 脐带间充质干细胞 糖代谢 胰岛Β细胞功能 

分 类 号：R587.1[医药卫生—内分泌]