Insights from a successful case of intrahepatic islet transplantation intoa type 1 diabetic patient

We report a case of long-term (>4 yr) successful intrahepatic islet transpl antation into a type 1 diabetic patient chronically immunosuppressed for a prior kidney graft. The exogenous insulin requirement decreased progressive ly after transplantation, and insulin treatment was withdrawn at 6 months.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% a nd 6.4%). Fasting C peptide levels remained stable during the entire follow -up, but the proinsulin to insulin ratios increased dramatically at yr 3. G lycemic levels after an oral glucose tolerance test showed a diabetic profi le at 1 yr, a normal profile at 2 yr, and an impaired glucose tolerance pro file at 3 yr. Intravenous glucose tolerance test-induced first phase insuli n release, present at 1 and 2 yr, disappeared at 3 yr. Diabetes-related aut oantibodies (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 d ied of myocardial infarction 50 months after transplantation while she was still in good metabolic control (glycosylated hemoglobin, <6.8%) in the abs ence of exogenous insulin administration. The autoptic Liver showed well gr anulated islets, richly vascularized and without evidence of lympho-mononuc lear 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, follow ed by a slow progressive decline. The absence of allo- and autoreactivities against the transplanted islets points to a nonimmune-mediated beta-cell l oss as the cause of graft functional deterioration.