Improvement in outcomes of clinical islet transplantation: 1999–2010
Open accessAbstract
OBJECTIVE: To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS: A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999–2002), mid (2003–2006), or recent (2007–2010) transplant era based on annual follow-up to 5 years. RESULTS: Insulin independence at 3 years after transplant improved from 27% in the early era (1999–2002, n = 214) to 37% in the mid (2003–2006, n = 255) and to 44% in the most recent era (2007–2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA1c and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007–2010 vs. 60–65% in 1999–2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001). CONCLUSIONS: The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.
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Both whole organ pancreas and pancreatic islet transplantation can effectively prevent hypoglycemia, restore normoglycemia, and possibly stabilize the progression of complications of type 1 diabetes.
“Both therapeutic options can effectively prevent hypoglycemia, restore normoglycemia, and possibly stabilize the progression of complications of type 1 diabetes (223-227).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [224]
The Results (page not provided) report that more than 90% of islet recipients with available data remained free of severe hypoglycemic events, and that HbA1c and fasting blood glucose improved. The Conclusions (page not provided) describe whole-pancreas transplantation as a β-cell replacement option and report insulin-independence rates for both procedures. The paper does not establish that both procedures restore normoglycemia or stabilize the progression of type 1 diabetes complications. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCareful patient selection and protocol optimization have led to substantial clinical improvements in islet transplantation.
“Careful patient selection and protocol optimization have led to substantial clinical improvements (224).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [224]
The Results describe changes in recipient selection and transplantation protocols, and the Conclusions report better outcomes in 2007–2010 than in 1999–2006. The paper does not establish that those changes caused the improvements: its Statistics section says comparisons across eras were not randomized, and the Conclusions describe the potential benefit of newer immunosuppression strategies as a possibility. (LLM, conf=0.84)
Experimental — accuracy not yet measuredEven without insulin independence, a small amount of islet graft function can prevent severe life-threatening hypoglycaemia.
“Even if insulin independence is not achieved, severe life-threatening hypoglycaemia can be prevented with minimal islet transplant function.162,163”
From Type 1 diabetes (2018) · cites this paper as [163]
Subsequent transplantation studies showed improved patient outcomes, with islet transplantation approaching the success of whole pancreas transplantation without the corresponding surgical risk.
“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 [18]
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Self-citation
- Authors
- 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., Pattou, F., Berney, T., Secchi, A., Messinger, S., Senior, P. A., Maffi, P., Posselt, A., Stock, P. G., Kaufman, D. B., Luo, X., Kandeel, F., Cagliero, E., Turgeon, N. A., Witkowski, P., Naji, A., O’Connell, P. J., Greenbaum, C., Kudva, Y. C., Brayman, K. L., Aull, M. J., Larsen, C., Kay, T. W. H., Fernandez, L. A., Vantyghem, M.-C., Bellin, M., & Shapiro, A. M. J.
- Affiliations
- Emmes (United States) (US)
- University of Pennsylvania (US)
- University of Miami (US)
- University of Minnesota (US)
- Baylor University Medical Center (US)
- Department of Surgery, Division of Transplant Surgery, University of Illinois at Chicago, Chicago, Illinois
- University of Wisconsin–Madison (US)
- Southern Illinois University Carbondale (US)
- The University of Texas Southwestern Medical Center (US)
- Department of General and Endocrine Surgery, Lille University, Lille, France
- University Hospital of Geneva (CH)
- Vita-Salute San Raffaele University (IT)
- University of Alberta (CA)
- University of California, San Francisco (US)
- Northwestern University (US)
- City Of Hope National Medical Center (US)
- Harvard University (US)
- Emory University (US)
- University of Chicago (US)
- Westmead Hospital (AU)
- Virginia Mason Medical Center (US)
- Mayo Clinic (US)
- University of Virginia (US)
- Weill Cornell Medicine (US)
- Department of Medicine, St. Vincent’s Institute, Fitzroy, Victoria, Australia
- Université de Lille (FR)
- Corresponding author
- Barton, Franca B.
- ORCID
- Barton, Franca B.
- Rickels, Michael R.
- Alejandro, Rodolfo
- Hering, Bernhard J.
- Naziruddin, Bashoo
- Odorico, Jon S.
- Levy, Marlon
- Berney, Thierry
- Secchi, Antonio
- Messinger, Shari
- Senior, Peter A.
- Maffi, Paola
- Posselt, Andrew
- Stock, Peter G.
- Kaufman, Dixon B.
- Luo, Xunrong
- Kandeel, Fouad
- Turgeon, Nicole A.
- Witkowski, Piotr
- Naji, Ali
- O’Connell, Philip J.
- Greenbaum, Carla
- Kudva, Yogish C.
- Brayman, Kenneth L.
- Aull, Meredith J.
- Larsen, Christian
- Fernandez, Luis A.
- Vantyghem, Marie-Christine
- Bellin, Melena
- Shapiro, A.M. James
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2012-06-12
- Volume
- 35
- Issue
- 7
- Pages
- 1436-1445
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3379615
- OpenAlex
- W2040605985
- Cited by
- 725
- References
- 18
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 20 · 2023: 38 · 2022: 33 · 2021: 43 · 2020: 47 · 2019: 61 · 2018: 68 · 2017: 64 · 2016: 89 · 2015: 67 · 2014: 74 · 2013: 78 · 2012: 11
- FWCI
- 74.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- American Diabetes Association
- Juvenile Diabetes Research Foundation United States of America
- National Institutes of Health (UL1TR000150)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK084315)
- National Center for Research Resources (UL1RR025741)
- National Center for Advancing Translational Sciences
- 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, severe hypoglycemia, C-peptide, islet graft function, HbA1c, fasting blood glucose, adverse events
- MeSH terms
- Adolescent, Adult, Aged, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Glycated Hemoglobin, Humans, Middle Aged, Registries, Islets of Langerhans Transplantation, Treatment Outcome
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