Low Beta-Cell Engraftment Is To Blame for Deficit After Islet Transplantation

Poor islet isolation techniques and ineffective immunosuppressive drug regimens are the cause.

Following islet transplantation, patients with type 1 diabetes usually experience functional deficits and, therefore, require more than one donor pancreas to achieve insulin independence. New research suggests that a low engrafted beta-cell mass is responsible for these deficits.

The findings, stem from a study of nine patients who underwent tests of beta-cell function 3 or 12 months after their last islet transplantation. To gauge beta-cell function, Dr. Michael R. Rickels and colleagues, from the University of Pennsylvania School of Medicine in Philadelphia, assessed the C-peptide responses to intravenous glucose, an orally consumed meal, and intravenous arginine.

Compared with healthy control subjects, the transplant recipients showed significantly impaired C-peptide responses to all three interventions (p < 0.05). The impairment was most pronounced in patients who were 12 months out from transplantation in response to intravenous glucose.

Further testing in five insulin-independent patients revealed evidence of a drop in beta-cell secretory capacity, the investigators state.

"These studies demonstrate impaired beta-cell responsiveness of transplanted islets consistent with both an insufficient beta-cell mass and a functional defect in glucose-mediated insulin secretion," the authors conclude.

"Advances in islet isolation techniques and immunosuppressive drug regimens should be considered in order to improve the engraftment and survival of transplanted islets," they recommend.
Diabetes 2005;54:100-106