Ont Health Technol Assess Ser. 2003;3(4):1-45. Epub 2003 Oct 1.
The Medical Advisory Secretariat undertook a review of the evidence on the effectiveness and cost-effectiveness of islet transplantation alone (ITA) in non-uremic patients with type 1 DM who have severe hypoglycemia and uncontrolled diabetes (brittle diabetics).
In a health technology assessment from Alberta, Guo et al. (2003) stated that limited evidence from the Edmonton series suggested that islet cell transplantation (ITA) (using the Edmonton Protocol) is effective in 1) controlling labile diabetes and 2) protecting against unrecognized hypoglycemia in highly selected patients in the short term. This conclusion by Guo et al. (2003) was based on the results of 11/17 insulin independent patients who were followed up for a median of 20.4 months in the trial by Ryan et al. (2002). In contrast, Paty et al. (2002) concluded that glucagon and epinephrine responses and hypoglycemic symptom recognition were not improved by islet transplantation in patients receiving the procedure in Edmonton, despite prolonged insulin independence and near-normal glycemic control. Paty et al. (2002) (a member of the Edmonton team) examined 7 ITA recipients, 7 type 1 DM patients (nonITA), and 7 nondiabetic control patients.The follow-up for most studies was short. It was suggested that the modifications to the conventional ITA approaches, including the steroid free immunosuppressive regimen, islet preparation in xenoproteins free media and transplantation of fresh islets from multiple donors were associated with improved success.The effects of ITA on beta cell function (secretion of insulin) look promising, however, the effects of ITA on pancreatic alpha cell function (secretion of counter-regulatory hormones such as glucagon and epinephrine) in long standing type 1 diabetes remain unclear.The most important barriers to more widespread islet transplantation using the Edmonton protocol are the availability of sufficient donor organs and the uncertainty of long term steroid free immunosuppressive therapy.Because the number of cadaveric pancreas donors is inadequate to the treat the increasing numbers of individuals on organ transplant waiting lists, isolated islet transplantation is unlikely to become practical for treatment of diabetes if each recipient requires islets from several (2-4) donors (Markmann et al., 2003). Therefore, it is important that the experience of the Edmonton investigators be validated by other centres not only in terms of effectiveness of the new immunosuppressive protocol, but also in the need for multiple transplants (Markmann et al., 2003).Preliminary results from a multinational trial indicate wide variation in the success of ITA between different sites. This raises concern about the reproducibility of the results.
The current evidence on the use of ITA for non-uremic type 1 diabetic patients is limited since it is based on studies with weak methodological design (Level 4). The assessment of ITA is based on several small case series studies or small clinical studies studies (Ryan et al., 2002; Goss et al., 2002; Meyer et al., 1998; Paty et al., 2002). The results from these studies were mixed since the objectives and the protocols differed at each centre. In particular, many jurisdictions have, to date, been unable to reproduce results achieved in Edmonton (success rate of 23% versus 90%) - this is the focus of an ongoing multicentre study.Ryan et al. (2002) reported that the median follow-up time for the 17 patients undergoing the Edmonton Protocol was 20.4 months from the first transplant. As of January, 2002, 11/17 patients remained insulin independent. Three of the 11 insulin independent patients had negative C-peptide secretion, indicative of impaired islet function.The effect of ITA on restoring hormonal responses to hypoglycemia is inconclusive.ITA in non-uremic type 1 diabetic patients with hypoglycemia unawareness or uncontrolled diabetes is an evolving procedure with promising preliminary, but inconclusive final results.
医学咨询秘书处对单独进行胰岛移植（ITA）在患有严重低血糖症和糖尿病控制不佳（脆性糖尿病）的非尿毒症1型糖尿病患者中的有效性和成本效益证据进行了审查。
在艾伯塔省的一项卫生技术评估中，Guo等人（2003年）指出，来自埃德蒙顿系列的有限证据表明，胰岛细胞移植（ITA）（采用埃德蒙顿方案）在短期内对以下方面有效：1）控制不稳定型糖尿病；2）在经过高度筛选的患者中预防未被识别的低血糖症。Guo等人（2003年）的这一结论是基于Ryan等人（2002年）试验中11/17例不依赖胰岛素患者的结果，这些患者的中位随访时间为20.4个月。相比之下，Paty等人（2002年）得出结论，在埃德蒙顿接受该手术的患者中，胰岛移植并未改善胰高血糖素和肾上腺素反应以及低血糖症状识别，尽管实现了长期不依赖胰岛素和接近正常的血糖控制。Paty等人（2002年）（埃德蒙顿团队成员）检查了7例ITA受者、7例1型糖尿病患者（非ITA）和7例非糖尿病对照患者。大多数研究的随访时间较短。有人提出，对传统ITA方法的改进，包括无类固醇免疫抑制方案、在无异种蛋白培养基中制备胰岛以及移植来自多个供体的新鲜胰岛，与提高成功率相关。ITA对β细胞功能（胰岛素分泌）的影响看起来很有前景，然而，ITA对长期1型糖尿病患者胰腺α细胞功能（如胰高血糖素和肾上腺素等反调节激素的分泌）的影响仍不清楚。使用埃德蒙顿方案进行更广泛胰岛移植的最重要障碍是足够供体器官的可用性以及长期无类固醇免疫抑制治疗的不确定性。由于尸体胰腺供体数量不足以满足器官移植等待名单上不断增加的个体需求，如果每个接受者需要来自几个（2 - 4个）供体的胰岛，孤立胰岛移植不太可能成为治疗糖尿病的实用方法（Markmann等人，2003年）。因此，重要的是，埃德蒙顿研究人员的经验不仅要在新免疫抑制方案的有效性方面，而且要在多次移植的必要性方面，得到其他中心的验证（Markmann等人，2003年）。一项跨国试验的初步结果表明，不同地点的ITA成功率差异很大。这引发了对结果可重复性的担忧。
目前关于将ITA用于非尿毒症1型糖尿病患者的证据有限，因为它基于方法学设计薄弱的研究（4级）。对ITA的评估基于几个小病例系列研究或小型临床研究（Ryan等人，2002年；Goss等人，2002年；Meyer等人，1998年；Paty等人，2002年）。这些研究的结果参差不齐，因为每个中心的目标和方案不同。特别是，迄今为止，许多司法管辖区无法重现在埃德蒙顿取得的结果（成功率分别为23%和90%）——这是一项正在进行的多中心研究的重点。Ryan等人（2002年）报告说，接受埃德蒙顿方案的17例患者从首次移植起的中位随访时间为20.4个月。截至2002年1月，11/17例患者仍不依赖胰岛素。11例不依赖胰岛素的患者中有3例C肽分泌为阴性，表明胰岛功能受损。ITA对恢复低血糖激素反应的效果尚无定论。对于低血糖意识缺失或糖尿病控制不佳的非尿毒症1型糖尿病患者，ITA是一个不断发展的手术，初步结果有前景，但最终结果尚无定论。
