Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
The EMMES Company, LLC, Rockville, MD, USA.
Diabetologia. 2023 Jan;66(1):163-173. doi: 10.1007/s00125-022-05804-4. Epub 2022 Oct 6.
AIMS/HYPOTHESIS: Islet transplantation has been studied in small cohorts of recipients with type 1 diabetes complicated by severe hypoglycaemic events (SHEs). We determined factors associated with favourable outcomes in a large cohort of recipients reported to the Collaborative Islet Transplant Registry (CITR).
In 398 non-uraemic islet transplant alone (ITA) recipients with type 1 diabetes and SHEs, transplanted between 1999 and 2015 and with at least 1 year follow-up, we analysed specified favourable outcomes against each of all available characteristics of pancreas donors, islet grafts, recipients and immunosuppressive regimens, as well as immunosuppression and procedure-related serious adverse events (SAEs).
Four factors were associated with the highest rates of favourable outcomes: recipient age ≥35 years; total infused islets ≥325,000 islet equivalents; induction immunosuppression with T cell depletion and/or TNF-α inhibition; and maintenance with both mechanistic target of rapamycin (mTOR) and calcineurin inhibitors. At 5 years after the last islet infusion, of the recipients meeting these four common favourable factors (4CFF; N=126), 95% were free of SHEs, 76% had HbA <53 mmol/mol (7.0%), 73% had HbA <53 mmol/mol (7.0%) and absence of SHEs, and 53% were insulin independent, significantly higher rates than in the remaining recipients (<4CFF; N=272). The incidence of procedural and immunosuppression-related SAEs per recipient that resulted in sequelae, disability or death was low in both the 4CFF (0.056 per person) and <4CFF (0.074 per person) groups.
CONCLUSIONS/INTERPRETATION: In recipients with type 1 diabetes complicated by SHEs, islet transplantation meeting 4CFF protected 95% from SHEs at 5 years after the last islet infusion and exerted a large and significant benefit on glycaemic control, with an acceptable safety profile for this subgroup of type 1 diabetes.
目的/假设：胰岛移植已在伴有严重低血糖事件（SHEs）的 1 型糖尿病小队列受者中进行了研究。我们在向协作胰岛移植登记处（CITR）报告的大型受者队列中确定了与良好结局相关的因素。
在 1999 年至 2015 年间接受非尿毒症胰岛单独移植（ITA）且伴有 SHEs 的 398 例 1 型糖尿病且至少随访 1 年的患者中，我们针对胰腺供体、胰岛移植物、受者和免疫抑制方案的所有可用特征，以及免疫抑制和程序相关严重不良事件（SAE），分析了特定的良好结局。
有四个因素与最佳结局的发生率最高相关：受者年龄≥35 岁；输注的总胰岛≥325000 胰岛当量；诱导免疫抑制采用 T 细胞耗竭和/或 TNF-α 抑制；以及维持使用雷帕霉素（mTOR）和钙调神经磷酸酶抑制剂。在最后一次胰岛输注后 5 年，符合这四个常见有利因素（4CFF；N=126）的受者中，95%无 SHEs，76%HbA<53mmol/mol（7.0%），73%HbA<53mmol/mol（7.0%）且无 SHEs，53%胰岛素依赖，明显高于其余受者（<4CFF；N=272）。在 4CFF（每人 0.056）和<4CFF（每人 0.074）两组中，导致后遗症、残疾或死亡的程序和免疫抑制相关 SAE 的发生率均较低。
结论/解释：在伴有 SHEs 的 1 型糖尿病受者中，符合 4CFF 的胰岛移植可在最后一次胰岛输注后 5 年内保护 95%的患者免受 SHEs 影响，并对血糖控制产生显著的、重要的益处，对 1 型糖尿病的这一亚组具有可接受的安全性。
