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

Bernhard J Hering; Cassandra M Ballou; Melena D Bellin; Elizabeth H Payne; Fouad Kandeel; Piotr Witkowski; Rodolfo Alejandro; Michael R Rickels; Franca B Barton

doi:10.1007/s00125-022-05804-4

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

Diabetologia. 2023 Jan;66(1):163-173. doi: 10.1007/s00125-022-05804-4. Epub 2022 Oct 6.

Authors

Bernhard J Hering¹, Cassandra M Ballou², Melena D Bellin³, Elizabeth H Payne⁴, Fouad Kandeel⁵, Piotr Witkowski⁶, Rodolfo Alejandro⁷, Michael R Rickels⁸, Franca B Barton⁴

Affiliations

¹ Schulze Diabetes Institute and Department of Surgery, University of Minnesota, Minneapolis, MN, USA. bhering@umn.edu.
² The EMMES Company, LLC, Rockville, MD, USA. cballou@emmes.com.
³ Schulze Diabetes Institute and Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁴ The EMMES Company, LLC, Rockville, MD, USA.
⁵ Department of Clinical Diabetes, Endocrinology & Metabolism, City of Hope, Duarte, CA, USA.
⁶ Pancreatic and Islet Transplant Program, Transplantation Institute, University of Chicago, Chicago, IL, USA.
⁷ Diabetes Research Institute and Department of Medicine, University of Miami, Miami, FL, USA.
⁸ Institute for Diabetes, Obesity & Metabolism and Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

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_1c <53 mmol/mol (7.0%), 73% had HbA_1c <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.

Keywords: Clinical islet transplantation; Favourable factors; Severe hypoglycaemia; Type 1 diabetes.

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

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