Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States

• Published in: American journal of transplantation Vol. 16; no. 2; pp. 509 - 517
• Main Authors: Brennan, D.C., Kopetskie, H.A., Sayre, P.H., Alejandro, R., Cagliero, E., Shapiro, A.M.J., Goldstein, J.S., DesMarais, M.R., Booher, S., Bianchine, P.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2016; Elsevier Limited
• Subjects: Adult; Blood Glucose - analysis; C-Peptide - analysis; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 1 - therapy; Discipline: islet transplantation; Female; Focus: clinical trial, immunosuppressive regimens; Follow-Up Studies; Glycated Hemoglobin - analysis; Graft rejection; Graft Survival; Hemoglobin; Humans; Hypoglycemia; Hypoglycemia - prevention & control; Hypoglycemic Agents - therapeutic use; Insulin; Insulin - therapeutic use; Islet cells; Islets of Langerhans Transplantation; Lymphoma; Male; Middle Aged; Opportunist infection; Pancreas; Pancreatic islet transplantation; Peptides; Prognosis; Risk Factors; Scope: clinical research/practice; Transplants & implants; United States > US; GLP-1; MMTT; Scope: clinical research/practice; Discipline: islet transplantation; DPP-4; Focus: clinical trial, immunosuppressive regimens; GAD65; PML; DSA; IEQ; PTLD; CITR; HbA1c
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.13458

We report the long-term follow-up of the efficacy and safety of islet transplantation in seven type 1 diabetic subjects from the United States enrolled in the multicenter international Edmonton Protocol who had persistent islet function after completion of the Edmonton Protocol. Subjects were followed up to 12 years with serial testing for sustained islet allograft function as measured by C-peptide. All seven subjects demonstrated continued islet function longer than a decade from the time of first islet transplantation. One subject remained insulin independent without the need for diabetic medications or supplemental transplants. One subject who was insulin-independent for over 8 years experienced graft failure 10.9 years after the first islet transplant. The remaining six subjects demonstrated continued islet function upon trial completion, although three had received a supplemental islet transplant each. At trial completion, five subjects were receiving insulin and two remained insulin independent, although one was treated with liraglutide. The median hemoglobin A1c was 6.3% (45 mmol/mol). All subjects experienced progressive decline in the C-peptide/glucose ratio. No patients experienced severe hypoglycemia, opportunistic infection, or lymphoma. Thus, although the rate and duration of insulin independence was low, the Edmonton Protocol was safe in the long term. Alternative approaches to islet transplantation are under investigation.