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ß-Cell Function Following Human Islet Transplantation for Type 1 Diabetes

¹ Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
² Division of Transplantation, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
³ Monell Chemical Senses Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Islet transplantation can provide metabolic stability for patients with type 1 diabetes; however, more than one donor pancreas is usually required to achieve insulin independence. To evaluate possible mechanistic defects underlying impaired graft function, we studied five subjects at 3 months and four subjects at 12 months following intraportal islet transplantation who had received comparable islet equivalents per kilogram (12,601 ± 1,732 vs. 14,384 ± 2,379, respectively). C-peptide responses, as measures of ß-cell function, were significantly impaired in both transplant groups when compared with healthy control subjects (P < 0.05) after intravenous glucose (0.3 g/kg), an orally consumed meal (600 kcal), and intravenous arginine (5 g), with the greatest impairment to intravenous glucose and a greater impairment seen in the 12-month compared with the 3-month transplant group. A glucose-potentiated arginine test, performed only in insulin-independent transplant subjects (n = 5), demonstrated significant impairments in the glucose-potentiation slope (P < 0.05) and the maximal response to arginine (AR_max; P < 0.05), a measure of ß-cell secretory capacity. Because AR_max provides an estimate of the functional ß-cell mass, these results suggest that a low engrafted ß-cell mass may account for the functional defects observed after islet transplantation.

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