Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada.

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. 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. 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 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. None.

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Declaration of interests BAM-G is a co-inventor for a patent on TNFRSF25-mediated treatments of immune diseases and disorders (PCT/US2020/053085). PAS serves in an independent data monitoring committee overseeing safety of stem cell-derived β-cells for type 1 diabetes (Vertex Pharmaceuticals), as a board chair for Diabetes Canada, and as a co-lead for Diabetes Action Canada's innovations in a type 1 diabetes goal group. AMJS has received grants or contracts from the Juvenile Diabetes Research Foundation, Canadian Stem Cell Network, Diabetes Research Foundation in Canada, ViaCyte, and the US National Institute of Diabetes and Digestive and Kidney Diseases; serves as a consultant to Protokinetix, ViaCyte, Hemostemix, Pelican Therapeutics, Diagon, and Aspect Biosystems; and is a co-inventor for a patent on TNFRSF25-mediated treatments of immune diseases and disorders (PCT/US2020/053085) and for a Cellular Transplant Site- Device-less technology (US 14/863541, CA.286512). All other authors declare no competing interests.