Insulin independence has been demonstrated in seven patients with type 1 diabetes following pancreatic islet cell transplantation and glucocorticoid-free immunosuppression.
While many islet cell transplants have taken place over the past 20 years, few have resulted in insulin independence for long periods of time. Of the 267 transplants that have taken place since 1990, only 8 per cent have resulted in insulin independence for longer than a year, say Dr James Shapiro (department of surgery, University of Alberta, Canada) and colleagues.
They say that use of immunosuppressant drugs is a particular problem in islet cell transplantation since many of the current agents, particularly glucocorticoids, can damage beta cells or induce peripheral insulin resistance. Dr Shapiro's team tested a glucocorticoid-free immunosuppressive protocol. A combination of sirolimus, low-dose tacrolimus and daclizumab was used. They report that patients taking the regimen had no diabetogenic or toxic effects and there were no clinically evident episodes of graft rejection. No adverse interaction between sirolimus and tacrolimus was observed and, in fact, a strong synergistic potentiation effect was seen.
Patients included in the trial had uncontrolled diabetes despite compliance with an insulin regimen or had severe hypoglycaemic episodes. Following transplantation, all seven patients remained insulin independent after a median follow-up of 11.9 months (range 4.4 to 14.9 months). Exogenous insulin therapy became unnecessary once a sufficient number of islet cells had been transplanted. Six of the seven patients required a second transplant after a median of 29 days and one required a third. Since transplantation, no further episodes of hypoglycaemia occurred in any patient. The authors conclude that, as a result of transplantation, the patients had "excellent metabolic control".
The islet cells were transplanted to the liver by infusion into the portal vein (New England Journal of Medicine 2000;343:230).
In an accompanying editorial, Dr Paul Robertson (Pacific Northwest research institute, Seattle, US) describes the study as a "remarkable preliminary success". He cautions that pancreas availability (from which islet cells are harvested) may be a problem because of a lack of organ donation. If the transplantation success continues, he says, a supply-and-demand issue will determine whether the procedure becomes a readily available therapeutic option for patients with diabetes (ibid, p289).