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.
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References
Ricordi C, Lacy PE, Finke EH, Olack BJ, Scharp DW, Automated method for human pancreatic islets. Diabetes 37: 413–420, 1988
Sharp DW, Lacy PE, Santiago JV, Mc Cullough CS, Weide LG, Falqui L, Marchetti P, Gingerich RL, Jaffe AS, Cryer PE, Anderson CB, Flye M, Insulin independence after islet transplantation into type I diabetic patient. Diabetes 39: 515–518, 1990
Ricordi C, Lacy PE, Sterbenz K, Davie JM, Low temperature culture of human islets or in vivo treatment with L3T4 antibody produces a marked prolongation of islets human to mouse xenograft survival. Proc Natl Acad Sci USA 84: 8080–8084, 1987
Ricordi C, Kneteman NM, Scharp DW, Lacy PE, Transplantation of cryopreserved human pancreatic islets into diabetic nude mice. World J Surg 12: 861–864, 1988
Scharp D, Lacy P, Ricordi C, Boyle P, Santiago J, Cryer P, Gingerich A, Jaffe A, Anderson C, Flye W, Human islet transplantation in patient with type 1 diabetes. Transplant Proc 21: 2744–2745, 1989
Warnock GL, Kenterman NM, Ryan EA, Evans MG, Seelis REA, Halloran PF, Rabinovitch A, Rajotte RV, Continued function of pancreatic islets after transplantation in type 1 diabetes. Lancet II: 570–572, 1989
Tzakis AG, Ricordi C, Alejandro R, Fung YZJJ, Todo S, Demetris AJ, Mintz DH, Starzl TE, Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet 336: 402–405, 1990
Warnock GL, Kneteman NM, Ryan E, Seelis REA, Rabinivitch A, Rajotte RV, Normoglycemia after transplantation of freshly isolated and cryopreserved pancreatic islets in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 34: 55–58, 1991
Ricordi C, Socci C, Davalli AM, Staudacher C, Baro P, Vertova A, Sassi I, Gavazzi F, Pozza G, DiCarlo V, Isolation of the elusive pig islet. Surgery 107: 688–694, 1990
Ricordi C, Gray DWR, Hering BJ, Kaufman DB, Warnock GL, Kneteman NM, Lake SR, London NJM, Socci C, Alejandro R, Zeng Y, Scharp DW, Viviani G, Falqui L, Tzakis A, Bretzel RG, Federlin K, Pozza G, James RFL, Rajotte RV, DiCarloV, Morris PJ, Sutherland DER, Starzl TE, Mintz DH, Lacy PE, Islet isolation assessment in man and large mammals. Acta Diabetol Lat 27: 185–195, 1990
Latif ZA, Noel J, Alejandro R, A simple method of staining fresh and cultured islets. Transplantation 45: 827–830, 1988
Weir GC, Bonner-Weir S, Leahy JL, Islet mass and function in diabetes and transplantation. Diabetes 39: 401–405, 1990
Bajorunas DR, Dresler CM, Horowitz GD, Mc Dermott K, Jeevanandam M, Fortner JG, Brennan MF, Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance. Diabetes 35: 556–562, 1986
Walsh TJ, Eggleston JC, Cameron JL, Portal hypertension, hepatic infarction, and liver failure complicating pancreatic islet autotransplantation. Surgery 485–487, 1982
Gray DWR, Sutton R, Mc Shane P, Peters M, Morris PJ, Exocrine contamination adversely affects the implantation of rat islets transplanted to the kidney capsule site. Transplant Proc 18: 1823–1824, 1986
Gray DWR, Morris PJ, Developments in isolated pancreatic islet transplantation. Transplantation 43: 321–331, 1987
Lacy PE, Davie JM, Transplantation of pancreatic islets. Annu Rev Immunol 2: 183–198, 1984
Reckard CR, Barker CF, Transplantation of isolated pancreatic islets across strong and weak histocompatibility barriers. Transplant Proc 5: 761–763, 1973
Griffith RC, Scharp DW, Hartman BK, Ballinger WF, Lacy PE, A morphological study of intrahepatic portal vein islet isografts. Diabetes 26: 201, 1977
Davalli AM, Ricordi C, Socci C, Braghi S, Bertuzzi F, Fattor B, DiCarlo V, Pontiroli AE, Pozza G, Abnormal sensitivity to glucose of human islets cultured in a high glucose medium: partial reversibility after an additional culture in a normal glucose medium. J Clin Endocrinol Metab 72: 202–208, 1991
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Socci, C., Falqui, L., Davalli, A.M. et al. Fresh human islet transplantation to replace pancreatic endocrine function in type 1 diabetic patients. Acta Diabetol 28, 151–157 (1991). https://doi.org/10.1007/BF00579718
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DOI: https://doi.org/10.1007/BF00579718