Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient.
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 The exogenous insulin requirement decreased progressively after transplantation, and insulin treatment was withdrawn at 6 months.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.
Davalli
A M
AM
Cattedra di Clinica Medica, Università Vita-Salute, Ospedale San Raffaele, Milan, Italy. alberto.davalli@hsr.it
Maffi
P
P
Socci
C
C
Sanvito
F
F
Freschi
M
M
Bertuzzi
F
F
Falqui
L
L
Di Carlo
V
V
Pozza
G
G
Secchi
A
A
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D017690:Cell Transplantation / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D008099:Liver / Q000473:pathology; D011384:Proinsulin / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin