Background

Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation.

Methods

This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival.

Findings

Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4–12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0–9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3–41·7] vs 26·2 years [17·0–35·5]; p=0·0003), median older age (49·4 years [43·5–56·1] vs 44·2 years [35·4–54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45–0·67] vs 0·59 units/kg per day [0·48–0·70]; p=0·032), but median HbA_1c concentrations were similar (8·2% [7·5–9·0] vs 8·5% [7·8–9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54–67) at 1 year, 32% (25–39) at 5 years, 20% (14–27) at 10 years, 11% (6–18) at 15 years, and 8% (2–17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7–21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5–11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups.

Interpretation

We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice.

Funding

None.

中文翻译：

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胰岛移植治疗 1 型糖尿病：来自加拿大单中心队列的 20 年经验

背景

胰岛移植为特定的 1 型糖尿病和难治性低血糖症患者提供了一种有效的治疗方法。然而，长期经验仍然有限。我们报告了胰岛移植后长达 20 年的单中心队列的结果。

方法

这项队列研究包括 1999 年 3 月 11 日至 2019 年 10 月 1 日期间在阿尔伯塔大学医院（加拿大艾伯塔省埃德蒙顿）接受同种异体胰岛移植的 18 岁以上 1 型糖尿病患者。包括接受胰岛后肾移植和单独胰岛移植或在全胰移植前进行胰岛移植的患者（随访在全胰移植时截尾）。报告了患者存活率、移植物存活率（空腹血浆 C 肽 >0·1 nmol/L）、胰岛素独立性、血糖控制和不良事件。为了确定与移植物存活时间延长相关的因素，将移植物持续存活（≥90% 的患者随访时间）的受者与非持续移植物存活（<90% 的随访时间）的受者进行了比较。

发现

1999 年 3 月 11 日至 2019 年 10 月 1 日期间，255 名患者接受了胰岛移植并被纳入分析（149 名 [58%] 为女性，218 名 [85%] 为白人）。在 7·4 年的中位随访期间 (IQR 4·4–12·2)，230 名 (90%) 患者存活下来。中位移植物存活率为 5·9 年 (IQR 3·0–9·5)，91 名 (36%) 患者发生移植物失败。178 名 (70%) 接受者移植物持续存活，77 名 (30%) 接受者移植物未持续存活。在基线时，与移植物非持续存活的患者相比，移植物持续存活的患者中位 1 型糖尿病病程更长（33·5 年 [IQR 24·3–41·7] vs 26·2 年 [17 · 0– 35·5]；p=0·0003），年龄中位数（49·4 岁 [43·5–56·1]比44·2 年 [35·4–54·2]；p=0·0011），胰岛素需求中位数较低（每天 0·53 单位/kg [0·45–0·67] vs每天 0·59 单位/kg [0·48–0·70]；p =0·032），但中位 HbA _1c浓度相似（8·2% [7·5–9·0]对比8·5% [7·8–9·2]；p=0·23）。201 (79%) 接受者有胰岛素独立性，Kaplan-Meier 估计在 1 年时为 61% (95% CI 54-67)，在 5 年时为 32% (25-39)，在 5 年时为 20% (14-27) 10 年，15 年时为 11% (6-18)，20 年时为 8% (2-17)。移植物持续存活的患者具有显着更高的胰岛素非依赖性（160 [90%] of 178 vs77 个中的 41 个 [53%]；p<0·0001) 和血糖控制持续改善混合主效应模型组效应，p<0·0001) 与非持续移植物存活率相比。多变量分析确定了阿那白滞素加依那西普的联合使用（调整后的比值比 7·5 [95% CI 2·7–21·0]，p<0·0001）和 BETA-2 评分为 15 或更高（4·1 [1·5–11·4], p=0·0066) 作为与持续移植物存活相关的因素。在移植物持续存活的接受者中，手术并发症的发生率较低（443 次输注中的 23 [5%]与167 次输注中的 17 [10%]；p=0·027），而癌症的发生率较高（29 [16%] 的 178对比77 个中的四个 [5%]；p=0·015) 比非持续移植物存活的那些；大多数是皮肤癌（33 人中有 22 人 [67%]）。终末期肾病和严重感染在各组之间相似。

解释

我们提出了最大的胰岛移植后长期结果的单中心队列研究。尽管我们的研究仍然存在一些局限性，例如回顾性​​成分、相对较小的样本量以及缺乏非移植对照，但我们发现联合使用阿那白滞素加依那西普和 BETA-2 评分与改善结果相关，因此这些因素可以为临床实践提供信息。

资金

没有任何。