Originals

Acta Diabetologica

, Volume 28, Issue 2, pp 151-157

First online:

Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients

Report of six cases
  • C. SocciAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
  • , L. FalquiAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , A. M. DavalliAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , C. RicordiAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
  • , S. BraghiAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , F. BertuzziAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , P. MaffiAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , A. SecchiAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
  • , F. GavazziAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
    • , M. FreschiAffiliated withDepartment of Pathology, Scientific Institute San Raffaele, University of Milan
    • , P. MagistrettiAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
    • , S. SocciAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
    • , A. VignaliAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan
    • , V. Di CarloAffiliated withDepartment of Surgery, Scientific Institute San Raffaele, University of Milan
    • , G. PozzaAffiliated withDepartment of Medicine, Scientific Institute San Raffaele, University of Milan

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Abstract

The aim of this study was to evaluate the feasibility of islet allografts in patients with type 1 diabetes melititus. 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. Patient 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. Patients 5 and 6 received a simultaneous kidney and islet graft and 6 months after transplantation their post-prandial C-peptide secretion peaks were 2.5 and 1.9 ng/ml respectively. Their daily insulin requirement was not significantly modified. In conclusion, these results show that an adequate number of human islets injected intraportally in type 1 diabetic patients can replace the pancreatic endocrine function and can lead to insulin independence.

Key words

Islet allograft Type 1 insulin-dependent diabetes mellitus Human