title: Successful islet transplantation: continued insulin reserve provides long-term glycemic control.
abstract: Clinical islet transplantation is gaining acceptance as a potential therapy, particularly for subjects who have labile diabetes or problems with hypoglycemic awareness. The risks of the procedure and long-term outcomes are still not fully known. We have performed 54 islet transplantation procedures on 30 subjects and have detailed follow-up in 17 consecutive Edmonton protocol-treated subjects who attained insulin independence after transplantation of adequate numbers of islets. Subjects were assessed pretransplant and followed prospectively posttransplant for immediate and long-term complications related to the procedure or immunosuppressive therapy. The 17 patients all became insulin independent after a minimum of 9,000 islets/kg were transplanted. Of 15 consecutive patients with at least 1 year of follow-up after the initial transplant, 12 (80%) were insulin independent at 1 year. In 14 subjects who have maintained demonstrable C-peptide secretion, glucose control has been stable and glycemic lability and problems with hypoglycemic reactions have been corrected. After 2 of the 54 procedures, some thrombosis was detected in the portal vein circulation. Five subjects had bleeding related to the percutaneous portal vein access procedures: three required transfusion alone, and in one subject, who had a partial thrombosis of the portal vein, an expanding intrahepatic and subscapular hemorrhage occurred while on anticoagulation, requiring transfusion and surgery. Elevated liver function test results were found in 46% of subjects but resolved in all. Complications related to the therapy have been hypercholesterolemia requiring statin therapy in 65%; a rise in creatinine in two patients, both of whom had preexisting renal disease; a rise in protein in four, all of whom had preexisting proteinuria; and antihypertensive therapy increased or started in 53%. Three of the 17 patients have required retinal laser photocoagulation. There have been no cases of posttransplant lymphoproliferative disorder or cytomegalovirus infection, and no deaths. The acute insulin response to arginine correlated better with transplanted islet mass than acute insulin response to glucose (AIR(g)) and area under the curve for insulin (AUC(i)), but the AIR(g) and AUC(i) were more closely related to glycemic control. The AUC(i) directly posttransplant was lower in those who eventually became C-peptide deficient. Our results, with a maximum follow-up of 34 months, indicate that prolonged insulin independence can be achieved after islet transplantation. There are some risks associated acutely with the procedure, and hypercholesterolemia and hypertension are treatable concerns on longer-term follow-up. All patients with persisting C-peptide secretion have had a resolution of both glycemic lability and problems with hypoglycemic reactions. Apart from the rise in serum creatinine in two subjects, no serious consequences of immunosuppressive therapy have been encountered. Islet transplantation is a reasonable option in those with severe problems with glycemic lability or hypoglycemia.
authors.affiliation: Department of Medicine, Clinical Islet Transplant Program, University of Alberta and Capital Health Authority, 2000 College Plaza, 8215 112th Street, Edmonton, Alberta, Canada T6G 2C8. edmond.ryan@ualberta.ca
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: Breay W
authors.initials: BW
authors.lastname: Paty
authors.forename: Sharleen
authors.initials: S
authors.lastname: Imes
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Korbutt
authors.forename: Norman M
authors.initials: NM
authors.lastname: Kneteman
authors.forename: David
authors.initials: D
authors.lastname: Bigam
authors.forename: Ray V
authors.initials: RV
authors.lastname: Rajotte
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D017668:Age of Onset; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology*; D008297:Male; D011169:Portal Vein; D011183:Postoperative Complications / Q000145:classification; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006442:Glycated Hemoglobin; D007328:Insulin