title: Clinical islet transplantation in type 1 diabetes mellitus: results of Australia's first trial.
abstract: OBJECTIVE
  To determine whether pancreatic islet transplantation can control diabetes and prevent severe life-threatening hypoglycaemia.
  
  
  METHODS
  A single-arm observation study of six patients undergoing islet transplantation. All patients had had type 1 diabetes mellitus for over 5 years and documented episodes of repeated severe hypoglycaemia. Islets were isolated from donor pancreases digested by Liberase. Separated islets were infused into the recipient's liver via the portal vein. Patients were immunosuppressed with daclizumab, sirolimus and tacrolimus. The transplants were performed at Westmead Hospital, NSW, between October 2002 and February 2005.
  
  
  METHODS
  Normal blood glucose control without administration of exogenous insulin; demonstration of islet function and abolition of hypoglycaemia.
  
  
  RESULTS
  Five of the patients received two islet infusions, and the sixth was withdrawn after one infusion following a portal vein thrombosis. Three patients became insulin-independent, with excellent glycaemic control. Two had islet function with circulating C-peptide, improved glycaemic control, reduced insulin requirement and abolition of severe hypoglycaemia. However, over a 2-year period, graft function deteriorated. Recipients who were initially insulin free remained C-peptide positive but required supplemental insulin. Complications included one postoperative bleed, two portal vein thromboses (which resolved completely), presumed recurrence of tuberculosis in one patient, and deterioration in renal function in one patient.
  
  
  CONCLUSIONS
  Islet transplantation is effective at improving glycaemic control and hypoglycaemia unawareness in the short to medium term. However, problems with long-term safety of immunosuppression, islet-induced thrombosis and early detection of loss of islet function remain to be addressed.
authors.affiliation: National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, Darcy Road, Westmead, NSW 2145, Australia. philip_oconnell@wsahs.nsw.gov.au
authors.forename: Philip J
authors.initials: PJ
authors.lastname: O'Connell
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Hawthorne
authors.forename: D Jane
authors.initials: DJ
authors.lastname: Holmes-Walker
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nankivell
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gunton
authors.forename: Anita T
authors.initials: AT
authors.lastname: Patel
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Walters
authors.forename: Henry C C
authors.initials: HC
authors.lastname: Pleass
authors.forename: Richard D M
authors.initials: RD
authors.lastname: Allen
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
mesh_terms: D000328:Adult; D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001315:Australia; D001786:Blood Glucose / Q000032:analysis; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005500:Follow-Up Studies; D006085:Graft Survival; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D008875:Middle Aged; D011183:Postoperative Complications; D020123:Sirolimus / Q000627:therapeutic use; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D020123:Sirolimus; D016559:Tacrolimus