Successful Islet Transplantation
Continued Insulin Reserve Provides Long-Term Glycemic Control
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 (AIRg) and area under the curve for insulin (AUCi), but the AIRg and AUCi were more closely related to glycemic control. The AUCi 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.
Footnotes
Address correspondence and reprint requests to Edmond A. Ryan, Clinical Islet Transplant Program, 2000 College Plaza, 8215 112th St., Edmonton, AB, Canada T6G 2C8. E-mail: edmond.ryan{at}ualberta.ca.
Received for publication 11 February 2002 and accepted in revised form 4 April 2002.
N.M.K. served as a consultant for Wyeth on structuring clinical trials with Sirolimus in liver transplantation.
AIRarg, acute insulin response to arginine; AIRg, acute insulin response to glucose; AUC, area under the curve; AUCC-p, area under the curve for C-peptide; AUCi, area under the curve for insulin; CBC, complete blood count; CMV, cytomegalovirus; GAD, glutamic acid decarboxylase; HOMA, homeostasis model assessment; ICA, islet cell antigen; IE, islet equivalents; IVGTT, intravenous glucose tolerance test; KG, glucose disposal; LFT, liver function test; MAGE, mean amplitude of glycemic excursion; OGTT, oral glucose tolerance test; PTLD, posttransplant lymphoproliferative disorder; WBC, white blood cell count.
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