Expectations and strategies regarding islet transplantation: Metabolic data from the GRAGIL 2 trial
Expectations and strategies regarding islet transplantation: Metabolic data from the GRAGIL 2 trial
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DOI：
10.1097/01.tp.0000268511.64428.d8
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发表时间：
2007-07-15
期刊：
影响因子：
6.2
通讯作者：
Berney, Thierry
中科院分区：
文献类型：
--
作者：
Badet, Lionel;Benhamou, Pierre Y.;Berney, Thierry
背景。胰岛移植的目的是恢复胰岛素独立性还是提供足够的代谢控制仍存在争议。 GRAGIL2 试验被设计为 1-2 期研究，主要结局是胰岛素独立率，次要结局是根据基础 C 肽、HbA1c、低血糖事件和外源性胰岛素需求的综合评分定义的成功率。方法。根据瑞士-法国 GRAGIL 多中心网络内的埃德蒙顿方案，患有严重低血糖的 C 肽阴性 I 型脆性糖尿病患者有资格接受最多两次总计 10,000 IE/kg 或以上的胰岛制剂，首次输注的阈值为 5,000 IE/kg。 6 个月和 12 个月的随访后，每 5 名患者进行一次三角检验序贯分析。最大低效率设置为 40%，最小效率设置为 66%。结果。 2003年9月至2005年10月，共纳入10例患者。中位等待时间为 6.7 个月（第一次注射）和 9 周（第二次注射）。除一名患者外，所有患者均接受了 11,089 +/- 505 IE/kg 的移植：其中一名患者接受了 5398 IE/kg 的单次移植。 6 个月时，胰岛素独立性和复合成功率分别为 10 例中的 6 例和 10 例中的 6 例。 12 个月时，10 名患者中有 3 名观察到胰岛素独立性，10 名患者中有 5 名成功。结论。根据我们的序贯分析设置，胰岛移植未能实现主要目标，即胰岛素独立性，但往往成功实现次要目标，即成功的代谢控制。目前它似乎是治疗脆性糖尿病的一种成功的生物闭环血糖控制方法。
Background. Whether islet transplantation should be aimed at restoring insulin independence or providing adequate metabolic control is still debated. The GRAGIL2 trial was designed as a phase 1-2 study where primary outcome was the rate of insulin independence, and secondary outcome was the success rate defined by a composite score based upon basal C-peptide, HbA1c, hypoglycemic events, and exogenous insulin needs.Methods. C-peptide negative type I brittle diabetic patients experiencing severe hypoglycemia were eligible to receive a maximum of two islet preparations totalizing 10,000 IE/kg or more, with a threshold of 5,000 IE/kg for the first infusion, according to the Edmonton protocol, within the Swiss-French GRAGIL multicentric network. A sequential analysis with a triangular test was performed in every five patients after 6- and 12-month follow-up. Maximal inefficiency was set at 40% and minimal efficiency at 66%.Results. From September 2003 to October 2005, 10 patients were included. Median waiting time was 6.7 months (first injection) and 9 weeks (second injection). All but one patient received 11,089 +/- 505 IE/kg: one received a single graft of 5398 IE/kg. At 6 months, insulin independence and composite success rates were 6 of 10 and 6 of 10, respectively. At 12 months, insulin independence was observed in 3 of 10 patients and success in 5 of 10 patients.Conclusion. Based upon our sequential analysis settings, islet transplantation failed to achieve the primary goal, insulin independence, but tended to succeed in reaching the secondary goal, successful metabolic control. Currently it appears to be a successful biological closed-loop glucose control method for brittle diabetes.