Factors Associated with Favourable 5 Year Outcomes in Islet Transplant Alone Recipients with Type 1 Diabetes Complicated By Severe Hypoglycaemia In The Collaborative Islet Transplant Registry
2023 Jan
Journal Article
Authors:
Hering, B.J.;
Ballou, C.M.;
Bellin, M.D.;
Payne, E.H.;
Kandeel, F.;
Witkowski, P.;
Alejandro, R.;
Rickels, M.R.;
Barton, F.B.
Secondary:
Diabetologia
Volume:
66
Pagination:
163-173
Issue:
1
PMID:
36201044
URL:
https://pubmed.ncbi.nlm.nih.gov/36201044/
DOI:
10.1007/s00125-022-05804-4
Keywords:
Adult; Diabetes Mellitus, Type 1; Humans; Islets of Langerhans Transplantation
Abstract:
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).METHODS: 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).RESULTS: 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.
