Diabetes, Vol 46, Issue 12 1983-1989, Copyright © 1997 by American Diabetes Association

ARTICLES

Long-term function (6 years) of islet allografts in type 1 diabetes

R Alejandro, R Lehmann, C Ricordi, NS Kenyon, MC Angelico, G Burke, V Esquenazi, J Nery, AE Betancourt, SS Kong, J Miller and DH Mintz
Diabetes Research Institute, Veterans Administration Medical Center, Miami, Florida 33136, USA. ralejandro@mednet.med.miami.edu

Eight type 1 diabetic patients, ages 29-41 years, with mean diabetes duration of 23 years (range 18-29 years) received islet transplants from 1 to 5 donors. Seven patients had stable kidney allografts 1-11 years before the islet transplant, and one patient had a simultaneous islet-kidney allograft. Patients' blood glucose control was poor as reflected by the mean +/- SD HbA1c of 9.1 +/- 1.7% before transplant. Of the first three patients, two (1 and 3) achieved insulin independence for 36 and 38 days, respectively. Two recipients rejected their islet grafts within 1 month (2 and 8) and therefore were excluded from analysis. The HbA1c and insulin requirement of the six remaining patients who had persistent islet function for more than 60 days was significantly reduced from 9.3 +/- 1.9 to 6.4 +/- 1.0% (P = 0.002) and from 0.75 +/- 0.15 to 0.35 +/- 0.12 U x kg(-1) x day(-1) (P < 0.001), respectively. The two patients with the longest graft survival (4 and 6) achieved a normalization or near-normalization of their HbA1c levels during 6 years in the absence of severe episodes of hypoglycemia. As demonstrated by a decline in C-peptide response during Sustacal challenge tests over a 6-year period, there was a diminution of islet allograft function over time, despite persistence of normal or near normal HbA1c. We concluded that transplantation of allogeneic islets with an islet mass comparable with whole or segmental pancreas transplants in type 1 diabetic patients can result in long-term islet allograft function; further, we concluded that, in conjunction with small dosages of exogenous insulin, a functioning islet allograft can result in near-normalization of blood glucose levels and significant improvement in HbA1c. The occurrence of severe hypoglycemic episodes observed for patients in the Diabetes Control and Complications Trial was not observed in recipients with functioning islet transplants, despite the continuous need for exogenous insulin therapy to sustain normal HbA1c over the 6-year follow-up. The significant improvement in metabolic control observed for the patients described in this study, and the potential to significantly decrease or halt the progression of diabetic complications, support the continued application of islet allotransplantation as a treatment modality for type 1 diabetic patients.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Bertuzzi and C. Ricordi Prediction of Clinical Outcome in Islet Allotransplantation Diabetes Care, February 1, 2007; 30(2): 410 - 417. [Full Text] [PDF]

				E. A. Ryan, B. W. Paty, P. A. Senior, D. Bigam, E. Alfadhli, N. M. Kneteman, J. R.T. Lakey, and A.M. J. Shapiro Five-Year Follow-Up After Clinical Islet Transplantation Diabetes, July 1, 2005; 54(7): 2060 - 2069. [Abstract] [Full Text] [PDF]

				M. Venturini, E. Angeli, P. Maffi, P. Fiorina, F. Bertuzzi, M. Salvioni, F. De Cobelli, C. Socci, L. Aldrighetti, C. Losio, et al. Technique, Complications, and Therapeutic Efficacy of Percutaneous Transplantation of Human Pancreatic Islet Cells in Type 1 Diabetes: The Role of US Radiology, February 1, 2005; 234(2): 617 - 624. [Abstract] [Full Text] [PDF]

				R. P. Robertson Islet Transplantation as a Treatment for Diabetes -- A Work in Progress N. Engl. J. Med., February 12, 2004; 350(7): 694 - 705. [Full Text] [PDF]

				C. Ricordi Lilly Lecture 2002: Islet Transplantation: A Brave New World Diabetes, July 1, 2003; 52(7): 1595 - 1603. [Full Text] [PDF]

				R. D. Molano, A. Pileggi, T. Berney, R. Poggioli, E. Zahr, R. Oliver, C. Ricordi, D. M. Rothstein, G. P. Basadonna, and L. Inverardi Prolonged Islet Allograft Survival in Diabetic NOD Mice by Targeting CD45RB and CD154 Diabetes, April 1, 2003; 52(4): 957 - 964. [Abstract] [Full Text] [PDF]

				N. Kumagai, J. C. LaMattina, C. Kamano, P. A. Vagefi, R. N. Barth, J. J. O'Neil, S. Yamamoto, S. G. Moran, R. Utsugi, D. H. Sachs, et al. Vascularized Islet Cell Transplantation in Miniature Swine: Islet-Kidney Allografts Correct the Diabetic Hyperglycemia Induced by Total Pancreatectomy Diabetes, November 1, 2002; 51(11): 3220 - 3228. [Abstract] [Full Text] [PDF]

				J. M. Thomas, J. L. Contreras, C. A. Smyth, A. Lobashevsky, S. Jenkins, W. J. Hubbard, D. E. Eckhoff, S. Stavrou, D. M. Neville Jr., and F. T. Thomas Successful Reversal of Streptozotocin-Induced Diabetes With Stable Allogeneic Islet Function in a Preclinical Model of Type 1 Diabetes Diabetes, June 1, 2001; 50(6): 1227 - 1236. [Abstract] [Full Text]

				R. B. Stevens, S. Matsumoto, and C. L. Marsh Is Islet Transplantation a Realistic Therapy for the Treatment of Type 1 Diabetes in the Near Future? Clin. Diabetes, April 1, 2001; 19(2): 51 - 60. [Abstract] [Full Text] [PDF]

				C. D. Ching, R. C. Harland, B. H. Collins, W. Kendall, H. Hobbs, and E. C. Opara A Reliable Method for Isolation of Viable Porcine Islet Cells Arch Surg, March 1, 2001; 136(3): 276 - 279. [Abstract] [Full Text] [PDF]

				A. M. Davalli, P. Maffi, C. Socci, F. Sanvito, M. Freschi, F. Bertuzzi, L. Falqui, V. Di Carlo, G. Pozza, and A. Secchi Insights from a Successful Case of Intrahepatic Islet Transplantation into a Type 1 Diabetic Patient J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3847 - 3852. [Abstract] [Full Text]

				J. H. Silverstein and A. L. Rosenbloom New Developments in Type 1 (Insulin-Dependent) Diabetes Clinical Pediatrics, May 1, 2000; 39(5): 257 - 266. [Abstract] [PDF]

				D. M. Harlan and A. D. Kirk The Future of Organ and Tissue Transplantation: Can T-Cell Costimulatory Pathway Modifiers Revolutionize the Prevention of Graft Rejection? JAMA, September 15, 1999; 282(11): 1076 - 1082. [Abstract] [Full Text] [PDF]

				N. S. Kenyon, M. Chatzipetrou, M. Masetti, A. Ranuncoli, M. Oliveira, J. L. Wagner, A. D. Kirk, D. M. Harlan, L. C. Burkly, and C. Ricordi Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154 PNAS, July 6, 1999; 96(14): 8132 - 8137. [Abstract] [Full Text] [PDF]