同种异体胰岛移植治疗成人晚期糖尿病早期疗效观察

Early efficacy of islet transplantation in the treatment of adult advanced diabetes

目的探讨同种异体胰岛移植治疗成人晚期糖尿病的安全性和有效性。方法对4例成人受体施行了5例次同种异体胰岛移植。选用同血型成人脑死亡胰腺供体,在GMP实验室制备胰岛,通过门静脉途径将移植胰岛悬液30~60 min内注射移植入受者肝脏内。免疫抑制方案采用巴利昔单抗+他克莫司+吗替麦考酚酯三联,并应用肿瘤坏死因子(TNF)-α单抗抑制移植后炎症反应。术后暂时应用胰岛素控制血糖,并根据血糖情况调整胰岛素用量减量直至停用。结果4例晚期糖尿病患者共施行了5次胰岛移植,其中1例患者施行了2次胰岛移植。手术过程均顺利,术中血糖及门静脉压力稳定。术后继续应用外源性胰岛素控制血糖(4~12 mmol/L),4例次患者(包括2次胰岛移植患者)在第3~4周开始停用胰岛素,另外1例患者未完全停用胰岛素但用量较前减少74%。所有患者胰岛移植术后未再出现低血糖反应。3例患者C肽水平术后2~3周达到正常范围,1例患者(胰岛素未脱离)保持在0.45~0.6μg/L(0.15~0.2 nmol/L)。另外,1例患者在停用胰岛素半年后再次出现血糖升高,遂行第2次胰岛移植,再次移植后10 d停用胰岛素。3例次术后肝脏穿刺口出血,其中2例次即行超声射频消融止血,1例次出血自行停止,未发现其他并发症。结论同种异体胰岛移植治疗晚期糖尿病疗效确切,创伤小、安全性高,值得进一步推广,远期疗效及维护治疗方法尚需进一步观察。

Objective To evaluate the safety and efficacy of islet transplantation for patients with advanced diabetes.Methods Five cases of islet allotransplantation were performed on 4 adult recipients.The same blood type adult brain-dead pancreas donors were selected and the islets were prepared in GMP laboratory.The prepared islet suspension was slowly injected into the liver of the recipients within 30-60 minutes.The immunosuppressive regimen was a combination of basiliximab,tacrolimus and mycophenolate mofetil and TNF-alpha monoclonal antibody was used to reduce the post-transplant inflammatory response.Insulin was temporarily applied to control blood glucose after surgery,and the dosage of insulin was adjusted to decrease according to the blood glucose level until it was discontinued.Results A total of 5 islet transplants were performed in 4 patients,including 1 patient who received the second islet transplantations.All operations were succeed and the blood glucose and portal pressure were stable during the operation.Exogenous insulin was continued to keep blood glucose level stable(4-12 mmol/L)after surgery.Four cases(including the one who received two islet transplantation)started to stop using insulin at the third to fourth week,and the insulin dosage of the other case was 74%lower than that before the operation,and no hypoglycemic reaction occurred in all patients after islet transplantation.The C-peptide level in 3 patients reached the normal range,and the level in one patient with type I diabetes(without insulin release)remained at 0.45-0.6μg/L(0.15-0.2 nmol/L).In addition,one patient showed a rise in blood glucose again and continued to use insulin half a year after insulin discontinuation.Then,he was performed the second islet transplantation which showed good effect and stopped taking insulin in 10 days after surgery.There were 3 cases of liver puncture bleeding after opeation,of which 2 cases were treated with ultrasound radiofrequency ablation to stop bleeding,1 case stopped spontaneously,and no other complications were found.Conclusions Islet transplantation is effective in the treatment of advanced diabetes patients with small trauma and high safety,which is worthy of more promotion.Long-term efficacy and maintenance therapy still need further investigation.