Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients. Report of six cases.
The aim of this study was to evaluate the feasibility of islet allografts in patients with type 1 diabetes mellitus. Six patients received human islets from either one or two donors via the portal vein, after (n = 4) or simultaneously with (n = 2) a kidney graft. The patients with functioning kidney grafts (nos. 1-4) were already on triple immunosuppressive therapy (cyclosporine A, azathioprine, prednisone). Prednisone was increased to 60 mg/day for 15 days after the islet transplant in patient 1. Patients 2-4 and the patients who underwent a simultaneous kidney-islets graft (nos. 5, 6) also received antilymphocyte globulin. Intravenous insulin was given for the first 15 days to maintain blood glucose concentrations within the normal range. Patient 1 rejected the islets within 15 days of islet transplantation. In patient 2, a 25% reduction in insulin requirement was observed and 12 months after transplantation post-prandial serum C-peptide was 1.5 ng/ml. In patient 3, the insulin requirement decreased from 40 to 8 units/day with a post-prandial serum C-peptide of 4.1 ng/ml 12 months after islet transplantation. In patient 4 the post-prandial secretion of C-peptide increased to 6.4 ng/ml. Six months after the islet infusion, insulin therapy was discontinued and HbA1c, 24-h metabolic profile and oral glucose tolerance test remained within the normal range. He had remained off insulin for 5 months until recently, when foot gangrene paralleled a worsening of post-prandial glycaemic control. Twelve months after transplantation he is receiving 8 units insulin/day.(ABSTRACT TRUNCATED AT 250 WORDS)
Socci
C
C
Department of Surgery, University of Milan, Italy.
Falqui
L
L
Davalli
A M
AM
Ricordi
C
C
Braghi
S
S
Bertuzzi
F
F
Maffi
P
P
Secchi
A
A
Gavazzi
F
F
Freschi
M
M
D000328:Adult; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016572:Cyclosporine / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000601:surgery*; D006650:Histocompatibility Testing; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000502:physiology; D016030:Kidney Transplantation; D008991:Monitoring, Physiologic; D011241:Prednisone / Q000627:therapeutic use; D009927:Tissue and Organ Procurement
D000961:Antilymphocyte Serum; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D016572:Cyclosporine; D001379:Azathioprine; D011241:Prednisone