采用Edmonton免疫抑制方案的成人胰岛移植治疗1型糖尿病八例

Transplantation of human islets in 8 diabetic patients with Edmonton immanosuppressive protocol

目的探讨成人胰岛移植治疗1型糖尿病的临床效果。方法为8例1型糖尿病患者施行胰岛移植,供胰来自于成人尸体,消化、分离获得的胰岛培养过夜,然后经动脉插管输注至肝固有动脉,每例输注胰岛数为(8415±757)胰岛当量/kg。其中3例接受1个供者的胰岛移植,5例接受2个供者的胰岛移植(分2次进行)。8例患者中,除1例供、受者的ABO血型不同外,其余供、受者的ABO血型均相同。本组病例未行HLA配型。术后免疫抑制治疗采用Edmonton方案中的免疫抑制剂使用方法,即不使用类固醇激素,采用西罗莫司和他克莫司联用,并辅以5剂达利珠单抗。术后观察外源性胰岛素的使用量、血糖及血清C-肽的变化。结果移植后平均随访7.7个月,2例完全停用胰岛素,5例的胰岛素用量减少47%～90%,1例效果不明显,胰岛素用量仅减少21%。8例血糖从移植前的(10.6土3.9)mmol/L降至(6.6±1.3)mmol/L,控制更为平稳;糖化血红蛋白A_1从(11.9±1.6)%降至(5.9±1.2)%。移植有效者的血清C-肽基础值及葡萄糖刺激后C-肽水平分别由移植前的(0.054±0.076)nmol/L和(0.075±0.045)nmol/L升高至(0.620±0.080)nmol/L和(1.580±0.770)nmol/L。免疫抑制剂相关的并发症主要为白细胞减少(6例),减少或停用免疫抑制剂后白细胞可回升至正常,无大出血、门静脉栓塞或门静脉高压等并发症发生。结论经肝动脉输注成人胰岛治疗1型糖尿病具有一定的临床效果,采用Edmonton免疫抑制方案安全、有效。

Objective To investigate the clinical effect of adult human islet transplantation in the treatment of patients with type 1 diabetes mellitus. Methods Eight patients with type 1 diabetes were transplanted with adult human islets from 1 or 2 cadaveric donors. The islets were digested, separated and cultured overnight, then transfused into the hepatic artery of each recipient through artery intubatton. The amount of islets for each recipient was （841.5 ± 757） IEQ/kg. Three recipients received 1 donor pancreas, and other 5 recipients received 2 donor pancreases （by 2 times of transplantations）. In the 8 recipients, A/30 blood type between the recipients and the donors were corresponded to each other except 1 recipient. The 8 recipients did not accept pretransplant human leukocyte antigen （HLA） crossmatch. The Edmonton＇s immunosuppressive protocol was used after the transplantations. The dosage of insulin injection, the level of serum C-peptide and blood glucose after operation were examined. Results The median duration of follow-up after initial transplantation was 7.7 months. Two patients were insulin-independent after 2 transplantation procedures. Five recipients have achieved 47 %-90 % reduction of exogenous insulin dosage. In one recipient after two islets transplantations, the dosage reduction of insulin injection just was 21%. The levels of blood glucose in 8 recipients were decreased markedly from （ 10. 6 ± 3.9） mmol/L to （6. 6 ± 1.3） mmol/L （P〈 0.05）. HbAlc levels were reduced from （11.9 ± 1.6） % to （5.9 ±1.2） % （P〈0. 01 ）. Fasting and glucose tolerance-stimulated serum C-peptide was increased significantly from （0. 054 ± 0. 076） nmol/ L and （0. 075 ± 0. 045） nrnol/L to （0. 620 ± 0. 080） nrnol/L and （ 1. 580 ±0. 770） nrnol/L （P〈0. 01 ）. Complication related to immunosuppressants was hypoleukemia （6 cases）, which was cured after reduction and withdrawal of immunosuppressants. No complications such as massive haemorrhage, portal vein embolism, or portal hypertension happened. Conclusion It is effective for islet transplantation through the hepatic artery in the treatment of the patients with type 1 diabetes mellitus. The Edmonton＇s immunosuppressive protocol is safe and effective.