Previously, two trials from the Clinical Islet Transplantation Consortium demonstrated that islet cell transplantation, either alone or after a kidney transplant, was a safe and effective treatment for people with type 1 diabetes experiencing severe hypoglycaemia, with most participants achieving an HbA1c of <53 mmol/mol in the absence of severe hypoglycaemia (Hering et al, 2016; Markmann et al, 2021). The objective of the present study was to determine islet graft function and outcomes over longer-term follow-up, up to 8 years.
Of the 48 islet-alone and 24 islet-after-kidney transplant recipients, 7 and 9, respectively, experienced islet graft failure over the original or long-term follow-up, while 15 and 7 withdrew from long-term follow-up with islet graft function intact. The remaining 15 and 7, respectively, completed long-term follow-up and had intact islet graft function. Actuarial islet graft survival rates at final follow-up were 69% for islet-alone and 49% for islet-after-kidney transplants.
Overall, 57% and 35% of islet-only and islet-after-kidney recipients maintained an HbA1c of <53 mmol/mol at final follow-up, while over 90% of both cohorts were free from severe hypoglycaemia. Of the 53 participants who achieved good glycaemic control without need for exogenous insulin therapy, 54% of islet-alone and 63% of islet-after-kidney recipients remained insulin-independent throughout the duration of follow-up.
Kidney function remained stable in both cohorts over the follow-up, and rates of sensitisation to islet donor human leukocyte antigen were low. Severe adverse events occurred at rates of 0.31 and 0.43 per person-year in the islet-alone and islet-after-kidney cohorts, respectively.
The authors conclude that islet transplantation results in good long-term glycaemic control without severe hypoglycaemia for many recipients with type 1 diabetes and impaired hypoglycaemia awareness. Glycaemic control and islet graft survival may be superior with islet-alone transplantation; however, this must be balanced against the lower added risk of immunosuppression in people who are already receiving it for a kidney transplant.