The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada
Open accessAbstract
Background Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation. Methods This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide >0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (<90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival. Findings Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbA 1c concentrations were similar (8·2% [7·5-9·0] vs 8·5% [7·8-9·2]; p=0·23). 201 (79%) recipients had insulin independence, with a Kaplan-Meier estimate of 61% (95% CI 54-67) at 1 year, 32% (25-39) at 5 years, 20% (14-27) at 10 years, 11% (6-18) at 15 years, and 8% (2-17) at 20 years. Patients with sustained graft survival had significantly higher rates of insulin independence (160 [90%] of 178 vs 41 [53%] of 77; p<0·0001) and sustained improvements in glycaemic control mixed-main-effects model group effect, p<0·0001) compared with those with non-sustained graft survival. Multivariate analyses identified the combined use of anakinra plus etanercept (adjusted odds ratio 7·5 [95% CI 2·7-21·0], p<0·0001) and the BETA-2 score of 15 or higher (4·1 [1·5-11·4], p=0·0066) as factors associated with sustained graft survival. In recipients with sustained graft survival, the incidence of procedural complications was lower (23 [5%] of 443 infusions vs 17 [10%] of 167 infusions; p=0·027), whereas the incidence of cancer was higher (29 of [16%] of 178 vs four [5%] of 77; p=0·015) than in those with non-sustained graft survival; most were skin cancers (22 [67%] of 33). End-stage renal disease and severe infections were similar between groups. Interpretation We present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice. Funding None.
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“Subsequent transplantation studies continued to show improved patient outcomes, with islet transplantation approaching the success of whole pancreas transplantation without the corresponding surgical risk.18–23”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [20]
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“Controlled trials 62,63 and followup of recipients 64,65 in major centres showed that high rates of insulin independence can be reached, and long duration of graft function is also seen; however,”
From The future of type 1 diabetes therapy (2025) · cites this paper as [65]
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“In particular, graft success increases when a high number of islets are transplanted, often resulting in the need for multiple donor pancreases. 15,20,24”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [20]
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Cited by
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Items 101–154 of 154
An unmet need: Pancreatic beta cell replacement
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“While solid-organ transplantation has traditionally been reserved for end-stage organ failure, it may hold promise as a potential ‘cure’ for DM. [13] However, there are challenges to consider, including surgical risks, graft failure, the economic burden, chronic immunosuppression, and limited organ…”
BackgroundThe current state of clinical islet transplantation.
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“Pancreas and islet cell transplantation can replenish damaged islet cells, but due to the deficiency in donor sources and post-transplant immunological rejection issues, their large-scale application is limited 5 .”
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Exogenous vs Endogenous Insulin Delivery: 2025
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“Long term follow up studies have demonstrated decreasing islet graft function over time with 4.8%− 28% insulin independence at 10 years andy 8% at 20 years[74, 79–81].”
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“3,4 Transplantation offers a largely permanent solution by replacing the damaged pancreas with an unaffected organ from a deceased donor.”
Anti-TNFα as an Adjunctive Therapy in Pancreas and Kidney Transplantation
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“29 However, for both islet and liver transplantation, tacrolimus and mycophenolate mofetil are the fi rst choice, 30,31 in consideration of its powerful immunosuppressive effect.”
Targeting Protein Kinases to Protect Beta-Cell Function and Survival in Diabetes
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“Islet transplantation is now recognized as an effective treatment for some patients with T1D [19,20].”
BackgroundPsychological care of patients during the pancreas transplantation process: issues and prospects
Galani, V., Villard, O., Olivier, V., Peloso, A., Compagnon, P., Haidar, F., & Prada, P. (2023) · Frontiers in Clinical Diabetes and Healthcare · doi:10.3389/fcdhc.2023.1205964 · Cited by 1
“stated that 16% of post islet transplantation recipients’ deaths in their cohort were due to suicide (39).”
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Pancreas Transplant Training in the United States: Trends and Implications
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“…to improve and are now associated with single digit risk of early pancreas graft loss, with excellent patient survival and long term pancreas graft function (nearly 15 years) making it by far the most durable escape from diabetes and the associated chronic microvascular injury [5, 7, 12, 13].”
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“Its lack of antigen speci fi city and long-term burden limit broad use; it may remain appropriate for selected people with recurrent severe hypoglycaemia despite optimised care, or for recipients already receiving immunosuppression for another organ transplant (6, 8).”
InfluentialAntonov, D., Loguinova, M. Y., Fan, H., Sazonova, E. V., Sosnovtseva, A. O., Karpov, D. S., Molchanov, A. D., Nikolenko, V. N., Chekhonin, V. P., & Mokrysheva, N. G. (2026) · Cells · doi:10.3390/cells15201902
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Eilandjestransplantatie bij type 1-diabetes: van donoreilandjes naar stamceleilandjes?
van Eyk, H. V., Nijhoff, M., & de Koning, E. D. (2026) · Nederlands Tijdschrift voor Diabetologie · doi:10.1007/s12467-026-1629-z
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“…human (hu) C-peptide response to plasma levels > 6 ng/mL. 2 The associated decrease in mouse (mo) C-peptide response to undetectable levels ( 0.5ng/mL) indicated that human beta cells had taken over glucose control, but this only became evident from post-transplant week 20 onwards.”
Engineering the future of advanced therapy medicinal products: a bioengineering call to action
Nieri, G., Spiller, A., Stella, F., Aiuti, A., & Piemonti, L. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1868007 · Cited by 2
Beam, C. A., DiMeglio, L. A., Speake, C., Boest-Bjerg, K., Pearce, O., Almutairi, B., Evans-Molina, C., Wong, F. S., Long, A. E., Gillespie, K. M., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9328145/v1
“Some studies have suggested that Aab measurement could be used to both select patients suitable for transplantation and for monitoring resultant auto-and alloimmunity after surgery[12,13].”
Cuesta-Gomez, N., Kumar, P., Kuppan, P., Paramor, J., Saleh, A., Korbutt, G. S., & Pepper, A. R. (2026) · Transplantation Direct · doi:10.1097/txd.0000000000001945
Development of Nanoflare Nanosensors for Monitoring Cellular Insulin mRNA in Beta Cells and Islets
Hu, Y., Zhang, Q., Tianli, H. U., Liu, J., Fu, H., Zhao, X., Yang, Z., & Xu, C. (2026) · Advanced Materials Technologies · doi:10.1002/admt.202501702
“Clinical practices show that islet transplantation remains an ideal option for the treatment of type 1 diabetes [ 3 ].”
Aggarwal, S., Cuesta-Gomez, N., Paramor, J., Kelly, S., Polishevska, K., Seeberger, K., Worton, J., Kuppan, P., & Pepper, A. R. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08728-8
“Islet transplantation (ITx) improves glycemic control in type 1 diabetes, yet long-term insulin independence remains low, dropping to 20% at 10 years and 8% at 20 years [1].”
Rao, J. S., Barra, J. M., Parmentier, C., Chaudhry, A., Doherty, D. T., Komatsu, H., Mitsugashira, H., Citro, A., Nijhoff, M. F., Piemonti, L., et al. (2026) · Transplantation · doi:10.1097/tp.0000000000005710 · Cited by 1
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Chen, X., Lee, Z.-O., Wu, J.-R., Iwanaga, K., Alexander, A., & Chan, F. (2025) · Current Physical Medicine and Rehabilitation Reports · doi:10.1007/s40141-025-00509-2
“For example, qualitative research has shown that African American breast cancer survivors experience intersecting challenges related to race, gender, class, and disability that affect their quality of life during survivorship [27].”
Liang, M., Wu, P., Zhao, Z., Li, Y., Ye, X., Cui, C., Chen, S., Yang, Y.-W., & Gao, H.-J. (2025) · Cell Transplantation · doi:10.1177/09636897251385284
Kenchadze, G., Abiatari, I., Pileggi, A., Kenyon, N. S., Berman, D., Molano, R., Gogichaishvili, K., Otarashvili, R., Tchavtchavadze, A., Midelashvili, T., et al. (2025) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2024.0400
“…of this approach is compromised by substantial islet loss, attributed to several limiting factors such as instant blood-mediated inflammatory reaction (IBMIR), oxidative stress, loss of extracellular matrix support, and insufficient vascularization during the post-transplantation periods [4].”
Korol, R., Even‐Ram, S., Molakandov, K., Puchinsky, D., Hemed, M., Mizrahi, N., Toledo, I., Lazar, D., Chebath, J., Tritel, M., et al. (2025) · Hormone and Metabolic Research · doi:10.1055/a-2734-1983
Self-citationPerceptions of the Benefits and Risks of Novel Therapies for Type 1 Diabetes: A Qualitative Study
Karpen, S. R., Mellor, R., DiMeglio, L. A., Senior, P. A., Sherr, J. L., Bussberg, C., Mansfield, C. A., Marinac, M., & Myers, K. (2025) · Diabetes Therapy · doi:10.1007/s13300-025-01783-y · Cited by 2
“The infused islet cells from cell replacement therapies, through the action of beta cells, can produce enough insulin to mitigate the need to take exogenous insulin, at least for a period of time, and can provide insulin independence while eliminating hypoglycemia [23, 24].”
Self-citationEilandjestransplantatie nu en in de toekomst
Hauck, R., de Vos, W., Engelse, M., Huurman, V., Nijhoff, M., & de Koning, E. D. (2025) · Nederlands Tijdschrift voor Diabetologie · doi:10.1007/s12467-025-1598-7
Risk of Allosensitization for Islet Recipients and Impact on Access To Renal Transplant
Czarnecka, Z., & Shapiro, A. M. J. (2025) · Current Transplantation Reports · doi:10.1007/s40472-025-00484-6
“Both within our total study population of 255 patients and the 178 patients with sustained graft survival, patients required on average two islet cell infusions with 2% of patients requiring up to five infusions [ 4 ].”
InfluentialSelf-citationCarr, A. L. J., Shah, R., Marfil‐Garza, B. A., Lam, A. P., Dajani, K. Z., Anderson, B. L., Owen, R. J., O’Gorman, D., Kin, T., Bigam, D. L., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0329074
“If insulin independence wanes over time, as seen in ITx with deceased-donor islets [4,17], supplementary infusions of stem cell derived islets may be required periodically to maintain normoglycemia (e.g., every 5–10 years).”
Self-citationChauhan, I., Llore, N. P., Hirakata, A., Ishikawa, Y., Vallabhajosyula, P., Weiner, J., Yamada, K., Sachs, D., & Griesemer, A. (2025) · Transplantation · doi:10.1097/tp.0000000000005447
Pharmacotherapy of type 1 diabetes - part 2 Today
Rendell, M. S. (2025) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2025.2479598
“Then, in 2000, investigators in Edmonton succeeded in achieving insulin independence for seven patients [58].”
Lu, W., Xie, L., Zhang, Y., Gao, H. Z., Geng, D., Xie, C., Liu, M., & Wang, G. (2025) · Diabetes Obesity and Metabolism · doi:10.1111/dom.16197
“24,25 To mitigate the impact of immunosuppression, recent advances have explored the use of alginate gel encapsulation of islets, allowing for treatment without long-term immunosuppression, as an alternative to traditional islet transplantation.”
Photiadis, S., Mai, Q. N., Montanez, G., Nguyen, C., Kramer, T., Photiadis, D., Sylvia, C., Spangler, T., & Nguyen, K. H. (2024) · American Journal of Transplantation · doi:10.1016/j.ajt.2024.11.012
In Vivo Imaging of Immune Rejection of MIN6 Cells Transplanted in C3H Mice
Juang, J.-H., Chen, C.-L., Kao, C.-W., Wu, S.-T., & Shen, C.-R. (2024) · Cells · doi:10.3390/cells13121044
“While most recipients achieve insulin independence shortly after transplantation [4,5], sustained insulin independence is uncommon [5–7].”
BackgroundQuelle place pour la greffe d’îlots à l’ère de la boucle fermée ?
Benhamou, P. (2024) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2024.04.009
Porter, L. T., Adin, C. A., Crews, C. D., Mott, J., & Gilor, C. (2024) · Frontiers in Veterinary Science · doi:10.3389/fvets.2024.1365611
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Greffe d’îlots de Langerhans dans le diabète insulinoprive
Defrance, F., Chetboun, M., Maanaoui, M., Mapihan, K. L., Jannin, A., Kerr-Conte, J., Pattou, F., & Vantyghem, M. (2023) · EMC - Endocrinologie - Nutrition · doi:10.1016/s1155-1941(22)71442-4
Rossi, E., & Pantanowitz, L. (2023) · The Lancet Diabetes and Endocrinology · doi:10.1016/s2213-8587(23)00089-x
Luo, X.-R. (2023) · Transplantation · doi:10.1097/tp.0000000000004547
Kuppan, P., Wong, J., Kelly, S., Lin, J.-X., Worton, J., Castro, C., Paramor, J., Seeberger, K., Anderson, C., Korbutt, G., et al. (2023) · bioRxiv · doi:10.1101/2023.02.14.528345
“1 nmol/L), was 48% at 20 years after the first transplantation (2).”
BackgroundSustained hypoglycaemia improvement 15 years after islet transplantation for type 1 diabetes
Donaldson, L. E., McAuley, S. A., Goodman, D., Howe, K., Loudovaris, T., MacIsaac, R., Kay, T., & Ward, G. (2023) · Internal medicine journal (Print) · doi:10.1111/imj.16017
Gao, Q.-M., & Luo, X.-R. (2022) · Transplantation · doi:10.1097/tp.0000000000004308
Metadata
- Authors
- Marfil-Garza, B. A., Imes, S., Verhoeff, K., Hefler, J., Lam, A., Dajani, K., Anderson, B., O'Gorman, D., Kin, T., Bigam, D., Senior, P. A., & Shapiro, A. M. J.
- Affiliations
- University of Alberta (CA)
- Corresponding author
- Shapiro, A M James
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 10
- Issue
- 7
- Pages
- 519-532
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W4280558719
- Cited by
- 205
- References
- 0
- Citations by year
- 2026: 42 · 2025: 52 · 2024: 51 · 2023: 43 · 2022: 17
- FWCI
- 38.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 174 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- The Lancet Diabetes & Endocrinology (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- Immune Tolerance Network
- University of Alberta
- National Institute of Diabetes and Digestive and Kidney Diseases
- Canada Research Chairs
- Juvenile Diabetes Research Foundation Canada
- Alberta Diabetes Foundation
- Diabetes Canada
- Government of Alberta
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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, graft survival, insulin independence, C-peptide, long-term outcomes, hypoglycemia, glycemic control, patient survival, islet graft failure
- MeSH terms
- Etanercept, Diabetes Mellitus, Type 1, Female, Graft Survival, Humans, Insulin, Male, Retrospective Studies, Cohort Studies, Islets of Langerhans Transplantation, Treatment Outcome, Interleukin 1 Receptor Antagonist Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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