Promising trial showed safe restoration of near-normoglycemia in type 1 diabetes….
Islet transplantation is a well-established therapeutic treatment for a subset of patients with difficult to control type 1 diabetes mellitus. Before the Edmonton Protocol, only 9% of the 267 islet transplant recipients since 1999 were insulin independent for more than a year. In 2000, the Edmonton group reported on seven consecutive patients, which in a collaborative team effort propagated expansion of clinical islet transplantation centers worldwide. Despite marked clinical success, donor availability, donor selection, engraftment, and side effects of immunosuppression remain impediments to be addressed to further improve Islet transplantation.
According to Bernhard J. Hering, MD and his colleagues, insulin use fell and C-peptide as a marker of endogenous insulin production rose over the first year and remained stable out to 2 years.
The primary purpose of the trial is to bring glycemic control to an HbA1c under 7.0% at 1 year and freedom from severe hypoglycemia to that point. The trial included 48 adult type 1 diabetes patients with one or more episodes of severe hypoglycemia in the previous year, documented hypoglycemic unawareness of such events or marked glycemic lability and no stimulated C-peptide. All participants got up to three intraportal infusions of purified human pancreatic islets from deceased donors over an 8-month period along with an immunosuppression regimen of sirolimus (Rapamune), tacrolimus (Prograf), and etanercept (Enbrel).
The results showed that the proportion of patients independent of insulin rose from about one-quarter at 2.5 months to 50% at 1 year. There was a marked insulin usage drop about 0.5 units/kg per day at baseline to 0.0 units/kg at 1 year. C-peptide release level to a mixed meal tolerance test rose from none at baseline to 4 ng/mL at 60 minutes at one year of treatment. From the time of treatment glucose range increased between 54 and 180 mg/dL rose to 90% to 95% at 1 year. Significant improvements also occurred in the hypoglycemia score, glycemic lability index scores, and mean amplitude of glycemic excursions score (all P<0.0002) at 1 year in the NIH-funded CIT-07 trial.
In conclusion, the researchers noted that Islet cell transplantation is still in its primitive stages. According to Drexler, “We’re now seeing the kind of slow, steady progress we’ve seen in the past, for example, with pancreas transplant, which is what we should expect from research.”
- Islet cell transplantation can safely restore euglycemic level in complex type 1 diabetics.
- Within a year of treatment, there was rise in insulin and C-peptide level.
- Though promising, Islet cell transplantation is not yet ready for wide use in general population.
Hering BJ, et al “Phase 3 trial of transplantation of human islets in type 1 diabetes (T1D) complicated by severe hypoglycemia” ADA 2014; Abstract 388-OR.