Volume 21, Issue 2, June 2005

Table of Contents 21-2

Islet Cell Transplantation in T1DM

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Islet cell transplantation has succeeded in restoring insulin independence in type 1 diabetes (T1DM) patients. However, islet allografts from 2 to 4 donors have been required to transplant an appropriate cell mass. This paper described the safety and efficacy of a single-donor, marginal-dose islet transplant protocol in 8 women with T1DM, nocturnal hypoglycemia, and advanced secondary complications. Each patient received a small dose of islet cell allotransplants from a single cadaver donor pancreas after antithymocyte globulin, daclizumab, and etanercept, and were immunosuppressed with mycophenolate mofetil, sirolimus, and no- or low-dose tacrolimus. All 8 patients achieved insulin independence and freedom from hypoglycemia; 5 remained insulin-independent for longer than 1 year. Graft failure occurred in 3 patients preceded by sub-therapeutic sirolimus trough levels (<9 ng/mL) in the absence of tacrolimus trough levels (<9 ng/mL). The authors concluded that improved islet cell engraftment was secondary to the peritransplant administration of antithymocyte globulin and etanercept.

Hering B J, Kanadaswamy R, Ansite JD, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA. 2005; 293:830-835.

Editor’s Comment: Transplanting insulin producing cells from fresh cadavers into T1DM patients is known to reverse the disease, but the procedure has been too costly and fraught with difficulties for widespread use. The authors of this study showed that their protocol was effective, safe, and less costly, as a single donor cadaver was sufficient to produce an appropriate dose of islet cells for transplantation. These allografts took residence in the liver of the patients and started producing insulin. Although 3 patients rejected the transplant, they achieved insulin-independence and freedom from hypoglycemia for 127, 76, and 7 days. In previous trials there was a need to utilize 2 to 4 cadavers, and each infusion of cells cost about $75 000, including follow-up treatments. In the new trial there was a cost saving, since only one pancreas was needed and there was a need for less diabetogenic immunosuppressants. These findings are of interest and may have implications for a not very distant day when this type of therapy will be routine in clinical care of T1DM patients.

Fima Lifshitz, MD

Reference - (linked to )

1. Ahima RS. N Engl J Med 2004;351:10:959-62.

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