title: Long-term immunosuppression after solitary islet transplantation is associated with preserved C-peptide secretion for more than a decade.
abstract: We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33 units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30 000 measurements per patient) and β cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, NIDDK National Institutes of Health, Bethesda, MD.
authors.forename: J E
authors.initials: JE
authors.lastname: Blau
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, NIDDK National Institutes of Health, Bethesda, MD.
authors.forename: M R
authors.initials: MR
authors.lastname: Abegg
authors.affiliation: Department of Transfusion Medicine, NIH Clinical Center National Institutes of Health, Bethesda, MD.
authors.forename: W A
authors.initials: WA
authors.lastname: Flegel
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, NIDDK National Institutes of Health, Bethesda, MD.
authors.forename: X
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Division of Diabetes, Endocrinology, and Nutrition Diabetes Center of Excellence, Department of Internal Medicine, University of Massachusetts Medical School, North Worcester, MA.
authors.forename: D M
authors.initials: DM
authors.lastname: Harlan
authors.affiliation: Diabetes, Endocrinology, and Obesity Branch, NIDDK National Institutes of Health, Bethesda, MD.
authors.forename: K I
authors.initials: KI
authors.lastname: Rother
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis* / Q000523:psychology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D017060:Patient Satisfaction; D011182:Postoperative Care / Q000379:methods; D011788:Quality of Life; D018570:Risk Assessment; D012494:Sampling Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide
keywords: Clinical research/practice; immunosuppressant; islet transplantation; monitoring: physiologic; quality of life (QOL)