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

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 1; pp. 100 - 106
• Main Authors: Rickels, Michael R., Schutta, Mark H., Markmann, James F., Barker, Clyde F., Naji, Ali, Teff, Karen L.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2005
• Subjects: Biological and medical sciences; Care and treatment; Complications and side effects; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Medical sciences; Pancreatic beta cell transplantation; Pancreatic beta cells; Transplantation; Type 1 diabetes; United States; Endocrinopathy; Human; Immunopathology; Type 1 diabetes; Langerhans islet; Autoimmune disease; Transplantation; β Cell; Endocrine pancreas
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.1.100

β-Cell Function Following Human Islet Transplantation for Type 1 Diabetes Michael R. Rickels 1 , Mark H. Schutta 1 , James F. Markmann 2 , Clyde F. Barker 2 , Ali Naji 2 and Karen L. Teff 1 3 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 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 (AR max ; P < 0.05), a measure of β-cell secretory capacity. Because AR max 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. AST, arginine stimulation test AUC, area under the curve FPG, fasting plasma glucose GPA, glucose-potentiated arginine HUP, Hospital of the University of Pennsylvania IVGTT, intravenous glucose tolerance test MMT, mixed-nutrient meal test Footnotes Accepted September 29, 2004. Received July 13, 2004. DIABETES