Insulin independence after islet transplantation into type I diabetic patient.
Effective clinical trials of islet transplantation have been limited by the inability to transplant enough viable human islets into patients with type I (insulin-dependent) diabetes mellitus to eliminate their exogenous insulin requirement. We report the first type I diabetic patient with an established kidney transplant on basal cyclosporin immunosuppression who was able to eliminate the insulin requirement after human islet transplantation into the portal vein. We successfully isolated approximately 800,000 islets that were 95% pure from 1.4 cadaver pancreases containing 121 U of insulin. Islets were proven viable by in vitro insulin response to glucose challenge. After 7 days of 24 degrees C culture, the islets were transplanted into the portal vein under local anesthesia. Seven days of Minnesota antilymphoblast globulin (20 mg/kg) administration followed the islet transplantation, with maintenance of the cyclosporin. Blood glucose was kept under strict control via intravenous insulin for 10 days posttransplantation, when all insulin therapy was stopped. Off insulin, the average 24-h blood glucose level remained less than 150 mg/dl, with the fasting glucose level at 115 +/- 6 mg/dl and the 2-h postprandial level at 141 +/- 8 mg/dl for 22 days posttransplantation (the time of this study). The C-peptide values post-Sustacal testing, although initially rising slower, exceeded the normal range, with peak values of 1.0-1.8 pmol/ml. This preliminary result represents the first essential step required to determine the feasibility of islet transplantation by future clinical trials.
Scharp
D W
DW
Human Islet Transplant Center, Washington University Medical Center, Barnes Hospital, St. Louis, Missouri.
Lacy
P E
PE
Santiago
J V
JV
McCullough
C S
CS
Weide
L G
LG
Falqui
L
L
Marchetti
P
P
Gingerich
R L
RL
Jaffe
A S
AS
Cryer
P E
PE
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000601:surgery*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007328:Insulin / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D016030:Kidney Transplantation; D014184:Transplantation, Homologous
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin