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Cited by 719Pancreatic function and diabetesDiabetes Management and ResearchDiabetes and associated disorders

Successful Islet Transplantation

Open access
Ryan, Edmond A., Lakey, Jonathan R.T., Paty, Breay W., Imes, Sharleen, Korbutt, Gregory S., Kneteman, Norman M., Bigam, David, Rajotte, Ray V. +1 more·2002·Diabetes
DOI 10.2337/diabetes.51.7.2148
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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.

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  • Assuming a similar dose as with human islets from deceased donors, on the order of 10^9 cells will be required per patient.

    “Assuming a similar dose as with human islets from deceased donors,175,176 on the order of 109 cells will be required per patient.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [176]

    The transplant procedures section says the islets came from deceased donors, and the transplant outcomes section reports a mean dose of 850,035 islet equivalents per patient. The paper does not express that dose as cells or establish that approximately 10^9 cells are required per patient. Page numbers are not provided in our copy. (LLM, conf=0.85)

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Research works printed but not linked: 1

  1. Korc M: Normal function of the endocrine pancreas. In The Pancreas. Go VLW, Dimagno EP, Gardner JD, Lebenthal E, Reber HA, Scheele GA, Eds. New York, Raven Press, 1993, p. 751-758

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Authors
Ryan, E. A., Lakey, J. R. T., Paty, B. W., Imes, S., Korbutt, G. S., Kneteman, N. M., Bigam, D., Rajotte, R. V., & Shapiro, A. M. J.
Affiliations
  • University of Alberta (CA)
  • Capital Health Authority, Edmonton, Alberta, Canada
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2002-07-01
Volume
51
Issue
7
Pages
2148-2157
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.51.7.2148
OpenAlex
W2102915416
Cited by
719
References
35
Citations by year
2026: 3 · 2025: 10 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 10 · 2020: 12 · 2019: 15 · 2018: 22 · 2017: 12 · 2016: 15 · 2015: 16 · 2014: 27 · 2013: 17 · 2012: 27
FWCI
77.16
Type
journal article
Language
en
Open access
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
Juvenile Diabetes Research Foundation International
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
islet transplantation, type 1 diabetes, insulin independence, Edmonton protocol, C-peptide, glycemic control, hypoglycemia, portal vein thrombosis, immunosuppression complications, post-transplant complications, acute insulin response, islet mass, retinal photocoagulation, long-term outcomes, hypercholesterolemia, liver function tests, post-transplant lymphoproliferative disorder
MeSH terms
Insulin Secretion, Adult, Blood Glucose, C-Peptide, Female, Follow-Up Studies, Glucose Tolerance Test, Glycated Hemoglobin, Humans, Insulin, Male, Portal Vein, Postoperative Complications, Time Factors, Islets of Langerhans Transplantation, Treatment Outcome, Age of Onset

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