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Insights from a Successful Case of Intrahepatic Islet Transplantation into a Type 1 Diabetic Patient

Cattedra di Clinica Medica, Università Vita-Salute, Ospedale San Raffaele (A.M.D., P.M., L.F., G.P.); Departments of Pathology (F.S., M.F.) and Surgery (C.S., F.B., V.D.C.), Istituto Scientifico San Raffaele; and University of Milan (A.S.), 20132 Milan, Italy

Address all correspondence and requests for reprints to: Dr. Alberto M. Davalli, Cattedra di Clinica Medica, Università Vita-Salute, Hospital San Raffaele, Via Olgettina 60, 20132 Milan, Italy. E-mail: alberto.davalli{at}hsr.it

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 The exogenous insulin requirement decreased progressively after transplantation, and insulin treatment was withdrawn at 6 months.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 ß-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 ß-cell loss as the cause of graft functional deterioration.

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