title: Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States.
abstract: 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.
authors.affiliation: Washington University School of Medicine in St. Louis, St. Louis, MO.
authors.forename: D C
authors.initials: DC
authors.lastname: Brennan
authors.affiliation: Rho Federal Systems Division, Chapel Hill, NC.
authors.forename: H A
authors.initials: HA
authors.lastname: Kopetskie
authors.affiliation: Immune Tolerance Network, San Francisco, CA.
authors.forename: P H
authors.initials: PH
authors.lastname: Sayre
authors.affiliation: University of Miami Leonard M. Miller School of Medicine, Miami, FL.
authors.forename: R
authors.initials: R
authors.lastname: Alejandro
authors.affiliation: Massachusetts General Hospital/Harvard Medical School, Boston, MA.
authors.forename: E
authors.initials: E
authors.lastname: Cagliero
authors.affiliation: University of Alberta, Edmonton, AB, Canada.
authors.forename: A M J
authors.initials: AM
authors.lastname: Shapiro
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD.
authors.forename: J S
authors.initials: JS
authors.lastname: Goldstein
authors.affiliation: Immune Tolerance Network, San Francisco, CA.
authors.forename: M R
authors.initials: MR
authors.lastname: DesMarais
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD.
authors.forename: S
authors.initials: S
authors.lastname: Booher
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, MD.
authors.forename: P J
authors.initials: PJ
authors.lastname: Bianchine
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006085:Graft Survival; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Discipline: islet transplantation; Focus: clinical trial, immunosuppressive regimens; Scope: clinical research/practice