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Islet transplantation for type 1 diabetes—where should we go?

Nature Clinical Practice Endocrinology & Metabolism volume 3, pages 2–3 (2007)Cite this article

In 2000, investigators from the University of Alberta in Edmonton reported their initial success in rendering 100% (n = 7) of patients with type 1 diabetes insulin-independent for at least 1 year after intrahepatic transplantation of allogeneic human islets.1 Compared with the previous experience of 8% insulin-independence, this result represented a remarkable breakthrough. Success was attributed to improved islet isolation techniques, infusion of large numbers of freshly isolated islets, avoidance of glucocorticoid therapy, reduced dose of tacrolimus (an immunosuppressant that can inhibit insulin secretion), and the addition of sirolimus for immunosuppression. In 2001, the Collaborative Islet Transplant Registry (CITR) was established to collect data on all islet transplants performed, and to facilitate retrospective analysis of islet transplant success and failure.2 As only a limited number of procedures are performed at any single institution, an ongoing analysis of CITR data might also allow investigators to identify prospectively those patients who are likely to benefit from islet transplantation. For example, most centers perform islet transplants in patients with severe hypoglycemic unawareness. Some centers, however, have elected to offer islet transplantation only to patients with hypoglycemic unawareness who also have a renal allograft and are receiving immunosuppressive therapy. Other centers now exclude patients in whom the immunosuppressive regimen might cause harm, such as those with microalbuminuria. In this Viewpoint, we will highlight the key findings of the CITR reports and speculate on the future of islet transplantation as a viable treatment option for type 1 diabetes.

CITR data have largely substantiated the reproducibility of the Edmonton procedure.2,3 In addition, the Edmonton team has published follow-up data with additional patients and extended follow-up periods.4 Of 65 patients who received islet allografts, 44 (68%) achieved insulin-independence at 1 year, which is similar to the rate reported by the CITR of nearly 200 patients at 6 months (50%) and at 12 months (49.4%) after treatment. Unfortunately, complete insulin-independence has not been sustained, and 5 years after transplantation <10% of the Edmonton patients remain insulin-independent; however, 80% of the Edmonton patients have detectable levels of C peptide, which indicates insulin is still being produced.4 Despite patients' need for exogenous insulin, those with residual C peptide had improved glycemic control when compared with patients without detectable C peptide; furthermore, hypoglycemia was markedly improved up to 4 years after islet transplantation. This success might relate to their reduced need for exogenous insulin and/or a protective effect of the small residual mass of β cells on insulin-induced hypoglycemia, as highlighted by a detailed analysis of patients in the Diabetes Control and Complications Trial.5 Importantly, despite chronic immunosuppression, quality-of-life measurements were also improved after islet transplantation, compared with the pretransplant period.3

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Acknowledgements

The contributions and assistance of Drs Paul Harris and Mark A Hardy (Columbia University, New York) are acknowledged and greatly appreciated.

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Authors and Affiliations

  1. and an Assistant Professor in the Department of Surgery, P Witkowski is an Associate Research Scientist at Columbia University, New York, NY, USA, Medical University of Gdansk, Gdansk, Poland;,

    Piotr Witkowski

  2. KC Herold is a Professor in the Section of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.,

    Kevan C Herold

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  1. Piotr Witkowski
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Correspondence to Kevan C Herold.

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K Herold has consulted for TolerRx, Inc. and Macrogenics, Inc. P Witkowski declared he has no competing interests.

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Witkowski, P., Herold, K. Islet transplantation for type 1 diabetes—where should we go?. Nat Rev Endocrinol 3, 2–3 (2007). https://doi.org/10.1038/ncpendmet0369

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