Insights From a Successful Case of Intrahepatic Islet Transplantation Into a Type 1 Diabetic Patient

J Clin Endocrinol Metab. 2000 Oct;85(10):3847-52. doi: 10.1210/jcem.85.10.6877.

Abstract

We report a case of long-term (>4 yr) successful intrahepatic islet transplantation into a type 1 diabetic patient chronically immunosuppressed for a prior kidney graft. The exogenous insulin requirement decreased progressively after transplantation, and insulin treatment was withdrawn at 6 months. Glycosylated hemoglobin levels were in the normal range at 1 and 2 yr (5.3%) and increased slightly above the upper normal limit at 3 and 4 yr (6.3% and 6.4%). Fasting C peptide levels remained stable during the entire follow-up, but the proinsulin to insulin ratios increased dramatically at yr 3. Glycemic levels after an oral glucose tolerance test showed a diabetic profile at 1 yr, a normal profile at 2 yr, and an impaired glucose tolerance profile at 3 yr. Intravenous glucose tolerance test-induced first phase insulin release, present at 1 and 2 yr, disappeared at 3 yr. Diabetes-related autoantibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, and tyrosine phosphatase-like protein antibodies) were undetectable before transplantation and remained so during the entire follow-up. The patient died of myocardial infarction 50 months after transplantation while she was still in good metabolic control (glycosylated hemoglobin, <6.8%) in the absence of exogenous insulin administration. The autoptic liver showed well granulated islets, richly vascularized and without evidence of lympho-mononuclear cell infiltration. The morphometrically extrapolated intrahepatic beta-cell mass was 99.9 mg. In conclusion, this successful islet graft showed a bell-shaped clinical effect, maximal at 2 yr after transplantation, followed by a slow progressive decline. The absence of allo- and autoreactivities against the transplanted islets points to a nonimmune-mediated beta-cell loss as the cause of graft functional deterioration.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • C-Peptide / metabolism
  • Cell Transplantation / physiology*
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / physiology*
  • Islets of Langerhans Transplantation / physiology*
  • Liver / pathology
  • Proinsulin / blood
  • Proinsulin / metabolism

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Proinsulin