Long-term outcomes of pancreatic islet transplantation alone in type 1 diabetes: a 20-year single-centre study in Italy

Background

Islet transplantation has the potential to cure type 1 diabetes by restoring endogenous insulin production. However, its success relies on balancing improved glycaemic control with the risks of immunosuppressive therapy. This study aimed to evaluate long-term outcomes of islet transplantation alone for type 1 diabetes, focusing on the effects of islet mass and immunosuppressive regimens on graft survival and insulin independence, and weighing glycaemic control benefits against the risks of immunosuppressive therapy.

Methods

This cohort study retrospectively analysed individuals aged 18–67 years with type 1 diabetes who received intraportal islet transplantation alone at IRCCS Ospedale San Raffaele, Milan, Italy. Inclusion criteria comprised adults with type 1 diabetes diagnosed before the age of 55 years with severe recurrent hypoglycaemia or glycaemic instability. Major exclusion criteria included a HbA_1c of more than 12·5%, a BMI of more than 30 kg/m², and insulin requirements exceeding 1·2 IU/kg per day, along with contraindications to immunosuppressive therapy. Participants were recruited from the hospital's islet transplant registry. Follow-up was conducted through regular clinical visits, with data collected retrospectively. Outcomes assessed included patient survival, graft survival, insulin independence, glycaemic control, and adverse events. Data were analysed using an intention-to-treat method, mixed-effects models, Kaplan–Meier estimates, and Cox and logistic regression to identify factors linked to metabolic success and reduced risks.

Findings

79 patients underwent intrahepatic or intraportal islet transplantation alone between Feb 16, 2001, and June 1, 2023, and received a total of 159 islet infusions, with a median total islet mass of 9637 islet equivalents (IEQ) per kg. Complications were infrequent and mostly involved minor bleeding, with only 3% (two of 79) of patients requiring surgical intervention. Glycaemic control improved significantly after infusion, with a reduction of HbA_1c by –10·04 mmol/mol (–13·63 to –6·46), and a decrease in daily insulin requirements by –13·35 units per day (–17·04 to –9·65). The intention-to-treat analysis showed a median graft survival (fasting C peptide ≥0·3 ng/mL) of 3·9 years (95% CI 1·6 to 6·2) and 44% (35/79) insulin independence for a median of 6 years (95% CI 2·88 to 9·08). Patients receiving more than 10 000 IEQ/kg with BAS, FK506, and Rapa therapy had a median graft survival of 9·7 years (3·1–16·0) and 73% (16 of 22) insulin independence. Kaplan–Meier estimates indicated graft survival rates of 86% at 1 year, 65% at 5 years, 47% at 10 years, 47% at 15 years, and 40% at 20 years. Overall survival was 92% (73 of 79) over a median follow-up of 13·1 years, with a 20-year survival probability of 84%. Adverse events related to immunosuppressive therapy were reported in 44% (35 of 79) of patients, with allosensitisation rates increasing from 6% at baseline to 42% after therapy discontinuation.

Interpretation

This analysis of a large islet transplantation alone cohort provides valuable insights into factors influencing outcomes and highlights potential risks, supporting informed clinical decision making and the optimisation of future β-cell replacement strategies.

Funding

None.