Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.

Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.
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DOI:
10.1056/nejm200007273430401
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发表时间:
2000-07-27
影响因子:
158.5
通讯作者:
Rajotte, RV
Rajotte, RV
中科院分区:
医学1区
文献类型:
--
作者:
Shapiro, AMJ;Lakey, JRT;Rajotte, RV

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背景:接受胰岛移植的1型糖尿病患者的登记数据表明,只有8%的患者在一年内不需要胰岛素治疗。方法:连续7例有严重低血糖和代谢不稳定史的1型糖尿病患者接受胰岛移植,并联合使用无糖皮质激素的免疫抑制方案,包括西罗莫司、他克莫司和daclizumab。胰岛通过冷的、纯化的胶原酶进行导管灌注分离,在无异种蛋白的培养基中消化和纯化,并通过经皮经肝门静脉栓塞术立即移植。结果:所有7例患者在移植胰岛质量平均(+/-SD)为每公斤体重11,547+/-1604胰岛当量(中位随访11.9个月,范围4.4 - 14.9)后,均迅速实现了持续的胰岛素独立性。所有接受者都需要来自两个供体的胰岛,其中一个需要来自两个供体的第三个移植来实现持续的胰岛素独立性。所有受者移植后的平均糖化血红蛋白值均正常。胰岛素独立后,血糖波动的平均幅度(血糖浓度波动的测量指标)显著降低(从移植前的198+/-32 mg / dl [11.1+/-1.8 mmol / l]降至首次移植后的119+/-37 mg / dl [6.7+/-2.1 mmol / l],胰岛素独立后的51+/-30 mg / dl [2.8+/-1.7 mmol / l]
Background: Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year.Methods: Seven consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization.Results: All seven patients quickly attained sustained insulin independence after transplantation of a mean (+/-SD) islet mass of 11,547+/-1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from two donors to achieve sustained insulin independence. The mean glycosylated hemoglobin values were normal after transplantation in all recipients. The mean amplitude of glycemic excursions (a measure of fluctuations in blood glucose concentrations) was significantly decreased after the attainment of insulin independence (from 198+/-32 mg per deciliter [11.1+/-1.8 mmol per liter] before transplantation to 119+/-37 mg per deciliter [6.7+/-2.1 mmol per liter] after the first transplantation and 51+/-30 mg per deciliter [2.8+/-1.7 mmol per liter] after the attainment of insulin independence; P