LONG-TERM FOLLOW-UP AFTER TRANSPLANTATION OF INSULIN-PRODUCING PANCREATIC-ISLETS INTO PATIENTS WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS
LONG-TERM FOLLOW-UP AFTER TRANSPLANTATION OF INSULIN-PRODUCING PANCREATIC-ISLETS INTO PATIENTS WITH TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS
复制标题
DOI：
10.1007/bf00400857
复制
发表时间：
1992-01-01
期刊：
影响因子：
8.2
通讯作者：
RAJOTTE, RV
中科院分区：
文献类型：
--
作者：
WARNOCK, GL;KNETEMAN, NM;RAJOTTE, RV
来自同一捐献者的纯化人类胰岛和肾脏被移植到四名 1 型（胰岛素依赖型）糖尿病患者体内。其中两名患者接受了从多个捐赠者分离出来的额外胰岛，冷冻保存并储存在组织库中。胰岛通过门静脉栓塞到肝脏中。用抗淋巴细胞球蛋白诱导免疫抑制，并用硫唑嘌呤、泼尼松和环孢素维持。在前两名患者中，前 4-8 周内空腹血清 C 肽水平升至 0.5-2.0 ng/ml，混合膳食喂养则升高至 2-3 ng/ml。 C肽分泌持续8个月，但水平逐渐降低，且无法撤消胰岛素治疗。接下来的两名患者除了新鲜胰岛外还接受了冷冻胰岛，血清 C 肽水平（空腹/餐后）升至 4-7 ng/ml，血糖更加稳定，一名患者可以在 69 天后停止胰岛素治疗，另一名患者则减少胰岛素剂量。胰岛素非依赖型患者在停止每日胰岛素治疗后 1 年内仍保持正常的空腹血糖、糖化血红蛋白和口服葡萄糖耐量。三名患者出现肾移植排斥反应，其中包括胰岛素非依赖型患者。高剂量类固醇疗法在所有情况下都逆转了排斥反应，并明显保留了 C 肽分泌。这些数据表明，将新鲜制备和冷冻保存的纯化胰岛移植到 1 型糖尿病患者体内会导致胰岛素分泌延长，并且在随访 1 年时，在没有胰岛素治疗的情况下，可以为一名患者提供足够的功能来维持正常血糖。
Purified human islets and a kidney from the same donor were transplanted into four patients with Type 1 (insulin-dependent) diabetes mellitus. Two of the patients received additional islets that were isolated from multiple donors, cryopreserved, and stored in a tissue bank. The islets were embolized into the liver via the portal vein. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine, prednisone and cyclosporine. In the first two patients, fasting serum C-peptide rose to levels of 0.5-2.0 ng/ml during the first 4-8 weeks and mixed meal feeding elicited increases to 2-3 ng/ml. C-peptide secretion persisted for 8 months, but at progressively lower levels and insulin therapy could not be withdrawn. In the next two patients who received cryopreserved islets in addition to fresh islets, serum C-peptide levels (fasting/post-meal) rose to 4-7 ng/ml and serum glucose was more stable, allowing withdrawal of insulin therapy after 69 days in one patient, and reduced insulin doses in the other. The insulin-independent patient has maintained normal fasting glucose, glycosylated haemoglobin, and oral glucose tolerance at 1 year following cessation of daily insulin therapy. Episodes of renal graft rejection occurred in three patients, including the insulin-independent patient. High-dose steroid therapy reversed the rejection in all instances, with apparent preservation of C-peptide secretion. These data show that transplantation of purified freshly-prepared and cryopreserved islets into Type 1 diabetic patients results in prolonged insulin secretion, and that sufficient function could be provided in one patient to sustain euglycaemia in the absence of insulin therapy at 1 year of follow-up.