Five-Year Follow-Up After Clinical Islet Transplantation
Abstract
Islet transplantation can restore endogenous beta-cell function to subjects with type 1 diabetes. Sixty-five patients received an islet transplant in Edmonton as of 1 November 2004. Their mean age was 42.9 +/- 1.2 years, their mean duration of diabetes was 27.1 +/- 1.3 years, and 57% were women. The main indication was problematic hypoglycemia. Forty-four patients completed the islet transplant as defined by insulin independence, and three further patients received >16,000 islet equivalents (IE)/kg but remained on insulin and are deemed complete. Those who became insulin independent received a total of 799,912 +/- 30,220 IE (11,910 +/- 469 IE/kg). Five subjects became insulin independent after one transplant. Fifty-two patients had two transplants, and 11 subjects had three transplants. In the completed patients, 5-year follow-up reveals that the majority ( approximately 80%) have C-peptide present post-islet transplant, but only a minority ( approximately 10%) maintain insulin independence. The median duration of insulin independence was 15 months (interquartile range 6.2-25.5). The HbA(1c) (A1C) level was well controlled in those off insulin (6.4% [6.1-6.7]) and in those back on insulin but C-peptide positive (6.7% [5.9-7.5]) and higher in those who lost all graft function (9.0% [6.7-9.3]) (P < 0.05). Those who resumed insulin therapy did not appear more insulin resistant compared with those off insulin and required half their pretransplant daily dose of insulin but had a l…
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The initially promising results of islet transplantation deteriorated so that at 5 years, only 10% of patients remained independent of exogenous insulin.
“the initially promising results deteriorated so that at 5 years, only 10% of patients remained independent of exogenous insulin.150”
From Type 1 diabetes (2014) · cites this paper as [150]
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Successful Islet Transplantation
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. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2148 · Cited by 719 · see citing works
Self-citationMoberg, L., Johansson, H., Lukinius, A., Berne, C., Foss, A., Källen, R., Østraat, Ø., Salmela, K., Tibell, A., Tufveson, G., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)12020-4 · Cited by 568 · cited 2× · see citing works
“Islet transplantation is associated with activation of the coagulation cascade and an increase in serum cross-linked fibrin degradation products (21,22).”
BackgroundInsulin Independence Following Isolated Islet Transplantation and Single Islet Infusions
Markmann, J. F., Deng, S., Huang, X., Desai, N. M., Velidedeoglu, E. H., Lui, C., Frank, A., Markmann, E., Palanjian, M., Brayman, K., et al. (2003) · Annals of Surgery · doi:10.1097/01.sla.0000072110.93780.52 · Cited by 175 · see citing works
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Atkinson, M. A., Eisenbarth, G. S., & Michels, A. W. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60591-7 · Cited by 2,713 · see citing works
International trial of the Edmonton protocol for islet transplantation
Shapiro, A. M. J., Ricordi, C., Hering, B. J., Auchincloss, H., Lindblad, R., Robertson, R. P., Secchi, A., Brendel, M. D., Berney, T., Brennan, D. C., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061267 · Cited by 1,942 · see citing works
Self-citationIslet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044 · see citing works
Improvement in outcomes of clinical islet transplantation: 1999–2010
Barton, F. B., Rickels, M. R., Alejandro, R., Hering, B. J., Wease, S., Naziruddin, B., Oberholzer, J., Odorico, J. S., Garfinkel, M. R., Levy, M., et al. (2012) · Diabetes Care · doi:10.2337/dc12-0063 · Cited by 725 · see citing works
Self-citationMeier, J. J., Butler, A. E., Saisho, Y., Monchamp, T., Galasso, R., Bhushan, A., Rizza, R. A., & Butler, P. C. (2008) · Diabetes · doi:10.2337/db07-1369 · Cited by 689 · see citing works
Recovery from diabetes in mice by β cell regeneration
Nir, T., Melton, D. A., & Dor, Y. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32959 · Cited by 595 · see citing works
Advances in islet encapsulation technologies
Desai, T., & Shea, L. D. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.232 · Cited by 427 · see citing works
MTOR inhibitors in cancer therapy
Xie, J., Wang, X., & Proud, C. G. (2016) · F1000Research · doi:10.12688/f1000research.9207.1 · Cited by 266 · see citing works
“…islet transplantations 52 , yet a follow-up study 5 years later has demonstrated that only approximately 10% of the recipients remained insulin independent 53 , likely owing to the fact that mTOR inhibitors would induce pancreatic β -cell death 54,55 as a result of the inhibition of mTORC2 56 .”
BackgroundMarfil-Garza, B. A., Imes, S., Verhoeff, K., Hefler, J., Lam, A., Dajani, K., Anderson, B., O'Gorman, D., Kin, T., Bigam, D., et al. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00114-0 · Cited by 205 · see citing works
Self-citationLong-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States
Brennan, D. C., Kopetskie, H. A., Sayre, P. H., Alejandro, R., Cagliero, E., Shapiro, A. M. J., Goldstein, J. S., DesMarais, M. R., Booher, S., & Bianchine, P. J. (2016) · American Journal of Transplantation · doi:10.1111/ajt.13458 · Cited by 176 · see citing works
“Two prior studies had followed patients for 5 years (12,13).”
Self-citationThe journey of islet cell transplantation and future development
Gamble, A., Pepper, A. R., Bruni, A., & Shapiro, A. M. J. (2018) · Islets · doi:10.1080/19382014.2018.1428511 · Cited by 171 · see citing works
Self-citationBeta cell mass in diabetes: a realistic therapeutic target?
Meier, J. J. (2008) · Diabetologia · doi:10.1007/s00125-008-0936-9 · Cited by 155 · see citing works
Evidence-based practice guideline for the treatment for diabetes in Japan 2013
Tajima, N., Noda, M., Origasa, H., Noto, H., Yabe, D., Fujita, Y., Goto, A., Fujimoto, K., Sakamoto, M., & Haneda, M. (2015) · Diabetology International · doi:10.1007/s13340-015-0206-2 · Cited by 154 · see citing works
Growth factors and beta cell replication
Vasavada, R. C., Gonzalez-Pertusa, J. A., Fujinaka, Y., Fiaschi-Taesch, N., Cozar-Castellano, I., & Garcia-Ocaña, A. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.08.003 · Cited by 133 · see citing works
The Future of Islet Transplantation Is Now
Bottino, R., Knoll, M. F., Knoll, C. A., Bertera, S., & Trucco, M. M. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00202 · Cited by 93 · see citing works
Immunotherapy via PD-L1–presenting biomaterials leads to long-term islet graft survival
Coronel, M. M., Martin, K. E., Hunckler, M. D., Barber, G., O’Neill, E. B., Medina, J. D., Opri, E., McClain, C. A., Batra, L., Weaver, J. D., et al. (2020) · Science Advances · doi:10.1126/sciadv.aba5573 · Cited by 89 · see citing works
Hilderink, J., Spijker, S., Carlotti, F., Lange, L., Engelse, M., van Blitterswijk, C., de Koning, E., Karperien, M., & van Apeldoorn, A. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12555 · Cited by 83 · see citing works
Besser, R. E. J., Ludvigsson, J., Jones, A. G., McDonald, T. J., Shields, B. M., Knight, B. A., & Hattersley, A. T. (2011) · Diabetes Care · doi:10.2337/dc10-2114 · Cited by 82 · see citing works
Yang, K., O’Cearbhaill, E. D., Liu, S. S., Zhou, A., Chitnis, G. D., Hamilos, A. E., Xu, J., Verma, M. K. S., Giraldo, J. A., Kudo, Y., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2101258118 · Cited by 58 · see citing works
“The majority of patients also experience complications from immunosuppression, including elevated risk of opportunistic infections and cancer (4, 8, 9).”
Human allograft rejection in humanized mice: a historical perspective
Brehm, M. A., & Shultz, L. D. (2012) · Cellular & Molecular Immunology · doi:10.1038/cmi.2011.64 · Cited by 30 · see citing works
Haque, M. R., Jeong, J.-H., & Byun, Y. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.01.039 · Cited by 29 · see citing works
Blau, J. E., Abegg, M. R., Flegel, W. A., Zhao, X., Harlan, D. M., & Rother, K. I. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13383 · Cited by 15 · see citing works
“The Edmonton protocol raised the hope for sustained insulin independence, but 5 years after islet transplantation, only 10% of patients remained insulin free (1).”
- Authors
- Ryan, E. A., Paty, B. W., Senior, P. A., Bigam, D., Alfadhli, E., Kneteman, N. M., Lakey, J. R. T., & Shapiro, A. M. J.
- Affiliations
- University of Alberta (CA)
- ORCID
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-07-01
- Volume
- 54
- Issue
- 7
- Pages
- 2060-2069
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2133186034
- Cited by
- 1,641
- References
- 4
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 26 · 2023: 33 · 2022: 46 · 2021: 45 · 2020: 62 · 2019: 54 · 2018: 70 · 2017: 52 · 2016: 79 · 2015: 76 · 2014: 100 · 2013: 107 · 2012: 129
- FWCI
- 118.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- islet transplantation, type 1 diabetes, insulin independence, C-peptide, graft function, hypoglycemia, HbA1c, insulin dose, immunosuppression complications, retinal complications, microalbuminuria, long-term outcomes, portal vein thrombosis, graft failure, retinopathy, kidney disease
- MeSH terms
- Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Humans, Hypoglycemia, Insulin, Male, Postoperative Complications, Time Factors, Survival Analysis, Islets of Langerhans Transplantation, Treatment Outcome
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