title: Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus.
abstract: Purified human islets and a kidney from the same donor were transplanted into four patients with Type 1 (insulin-dependent) diabetes mellitus. Two of the patients received additional islets that were isolated from multiple donors, cryopreserved, and stored in a tissue bank. The islets were embolized into the liver via the portal vein. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine, prednisone and cyclosporine. In the first two patients, fasting serum C-peptide rose to levels of 0.5-2.0 ng/ml during the first 4-8 weeks and mixed meal feeding elicited increases to 2-3 ng/ml. C-peptide secretion persisted for 8 months, but at progressively lower levels and insulin therapy could not be withdrawn. In the next two patients who received cryopreserved islets in addition to fresh islets, serum C-peptide levels (fasting/post-meal) rose to 4-7 ng/ml and serum glucose was more stable, allowing withdrawal of insulin therapy after 69 days in one patient, and reduced insulin doses in the other. The insulin-independent patient has maintained normal fasting glucose, glycosylated haemoglobin, and oral glucose tolerance at 1 year following cessation of daily insulin therapy. Episodes of renal graft rejection occurred in three patients, including the insulin-independent patient. High-dose steroid therapy reversed the rejection in all instances, with apparent preservation of C-peptide secretion. These data show that transplantation of purified freshly-prepared and cryopreserved islets into Type 1 diabetic patients results in prolonged insulin secretion, and that sufficient function could be provided in one patient to sustain euglycaemia in the absence of insulin therapy at 1 year of follow-up.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Canada.
authors.forename: G L
authors.initials: GL
authors.lastname: Warnock
authors.forename: N M
authors.initials: NM
authors.lastname: Kneteman
authors.forename: E A
authors.initials: EA
authors.lastname: Ryan
authors.forename: A
authors.initials: A
authors.lastname: Rabinovitch
authors.forename: R V
authors.initials: RV
authors.lastname: Rajotte
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin