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

  1. Michael R. Rickels1,
  2. Mark H. Schutta1,
  3. James F. Markmann2,
  4. Clyde F. Barker2,
  5. Ali Naji2 and
  6. Karen L. Teff13
  1. 1Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  2. 2Division of Transplantation, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  3. 3Monell Chemical Senses Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  1. Address correspondencereprint requests to Michael R. Rickels, MD, University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes,Metabolism, 778 Clinical Research Building, 415 Curie Blvd., Philadelphia, PA 19104-6149. E-mail: mrrickels{at}aol.com

Abstract

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 β-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 (ARmax; P < 0.05), a measure of β-cell secretory capacity. Because ARmax provides an estimate of the functional β-cell mass, these results suggest that a low engrafted β-cell mass may account for the functional defects observed after islet transplantation.

Footnotes

    • Accepted September 29, 2004.
    • Received July 13, 2004.
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