Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen
Open accessAbstract
BACKGROUND: Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year. METHODS: Seven consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization. RESULTS: All seven patients quickly attained sustained insulin independence after transplantation of a mean (+/-SD) islet mass of 11,547+/-1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from two donors to achieve sustained insulin independence. The mean glycosylated hemoglobin values were normal after transplantation in all recipients. The mean amplitude of glycemic excursions (a measure of fluctuations in blood glucose concentrations) was significantly decreased after the attainment of insulin independence (from 198+/-32 mg per deciliter [11.1+/-1.8 mmol per liter] before transplantation to 119+/-37 mg per deciliter [6.7+/-2.1 mmol per liter] after the first transplantation and 51+/-30 mg per deciliter [2.8+/-1.7 mmol per liter] after the attainment of insulin independence; P<0.001). There were no further episodes of hypoglycemic coma. Complications were minor, and there were no significant increases in lipid concentrations during follow-up. CONCLUSIONS: Our observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.
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Shapiro and colleagues' steroid-free Edmonton Protocol demonstrated that islet transplantation can produce insulin independence.
“Shapiro and colleagues’ landmark work, by use of a steroid free Edmonton Protocol,160 showed that islet transplantation could achieve insulin independence”
From Type 1 diabetes (2018) · cites this paper as [160]
In 2000, a breakthrough protocol was developed for islet transplantation without the use of glucocorticoids for immune suppression.
“In 2000, a breakthrough protocol was developed for islet transplantation without the use of glucocorticoids for immune suppression;149”
From Type 1 diabetes (2014) · cites this paper as [149]
Transplantation of pancreatic islets alone had limited success until the Edmonton Protocol in 2000 demonstrated that infusion of islets into the liver via the portal vein was sufficient to restore glucose homeostasis.
“Transplantation of pancreatic islets alone to restore β cell mass, however, had limited success until the development of the Edmonton Protocol in 2000, which demonstrated that infusion of islets into the liver via the portal vein was sufficient to restore glucose homeostasis.15,16”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [15]
Graft success increases when a high number of islets are transplanted, often resulting in the need for multiple donor pancreases.
“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 [15]
The Edmonton Protocol initial trial led to insulin independence of all seven patients 1 year after transplantation.
“Their initial trial led to insulin independence of all seven patients 1 year after transplantation, vastly improving previous islet transplantation outcomes due to optimization of their immunosuppression regimen as well as benefiting from improvements in islet isolation techniques.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [15]
Conventional islet transplantation by infusion into the hepatic portal vein suffers from limitations, such as acute graft loss triggered by an instant blood-mediated inflammatory response (IBMIR).
“Because conventional islet transplantation by infusion into the hepatic portal vein suffers from certain limitations, such as acute graft loss triggered by an instant blood-mediated inflammatory response (IBMIR)”
From Transplantation of chemically induced pluripotent stem-cell-derived islets under abdominal anterior rectus sheath in a type 1 diabetes patient. (2024) · cites this paper as [23]
25 years ago, seven consecutive islet transplant recipients in Edmonton, Alberta, Canada had insulin independence.
“25 years ago, islet transplantation made a major advance when seven consecutive islet transplant recipients in Edmonton, Alberta, Canada had insulin independence.59”
From The future of type 1 diabetes therapy (2025) · cites this paper as [59]
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Hope vs hype: where are we in type 1 diabetes?
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Hepatocyte growth factor enhances engraftment and function of nonhuman primate islets
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Antiapoptotic Actions of Exendin-4 against Hypoxia and Cytokines Are Augmented by CREB
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- Authors
- Shapiro, A. M. J., Lakey, J. R. T., Ryan, E. A., Korbutt, G. S., Toth, E., Warnock, G. L., Kneteman, N. M., & Rajotte, R. V.
- Affiliations
- University of Alberta (CA)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2000-07-27
- Volume
- 343
- Issue
- 4
- Pages
- 230-238
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2328786770
- Cited by
- 5,237
- References
- 41
- Citations by year
- 2026: 75 · 2025: 104 · 2024: 122 · 2023: 135 · 2022: 141 · 2021: 168 · 2020: 150 · 2019: 158 · 2018: 175 · 2017: 150 · 2016: 195 · 2015: 185 · 2014: 214 · 2013: 238 · 2012: 255
- FWCI
- 224.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (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 › Surgery › Transplantation: Methods and Outcomes
- Keywords
- islet transplantation, type 1 diabetes, rapamycin, tacrolimus, daclizumab, insulin independence, glycemic excursions, hypoglycemia, islet purification, collagenase perfusion, HbA1c
- MeSH terms
- Daclizumab, Adult, Antibodies, Monoclonal, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Drug Therapy, Combination, Glucose Tolerance Test, Glycated Hemoglobin, Humans, Immunoglobulin G, Immunosuppressive Agents, Insulin, Middle Aged, Islets of Langerhans Transplantation, Tacrolimus, Transplantation Conditioning, Sirolimus, Antibodies, Monoclonal, Humanized
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