Clinical islet transplantation in type 1 diabetes mellitus: results of Australia's first trial.
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Five of the patients received two islet infusions, and the sixth was withdrawn after one infusion following a portal vein thrombosis.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.
O'Connell
Philip J
PJ
National Pancreas Transplant Unit, University of Sydney at Westmead Hospital, Darcy Road, Westmead, NSW 2145, Australia. philip_oconnell@wsahs.nsw.gov.au
Hawthorne
Wayne J
WJ
Holmes-Walker
D Jane
DJ
Nankivell
Brian J
BJ
Gunton
Jenny E
JE
Patel
Anita T
AT
Walters
Stacey N
SN
Pleass
Henry C C
HC
Allen
Richard D M
RD
Chapman
Jeremy R
JR
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001786:Blood Glucose; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D020123:Sirolimus; D016559:Tacrolimus