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 · kg−1 · 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 HbAlc. 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.
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December 01 1997
Long-Term Function (6 Years) of Islet Allografts in Type 1 Diabetes
Rodolfo Alejandro;
Rodolfo Alejandro
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
Veterans Administration Medical Center
Miami, Florida
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Roger Lehmann;
Roger Lehmann
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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Camillo Ricordi;
Camillo Ricordi
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
Department of Surgery, University of Miami School of Medicine
Miami, Florida
Veterans Administration Medical Center
Miami, Florida
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Norma S Kenyon;
Norma S Kenyon
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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M Clara Angelico;
M Clara Angelico
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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George Burke;
George Burke
Department of Surgery, University of Miami School of Medicine
Miami, Florida
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Violet Esquenazi;
Violet Esquenazi
Department of Surgery, University of Miami School of Medicine
Miami, Florida
Veterans Administration Medical Center
Miami, Florida
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Jose Nery;
Jose Nery
Department of Surgery, University of Miami School of Medicine
Miami, Florida
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Arthur E Betancourt;
Arthur E Betancourt
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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Shen S Kong;
Shen S Kong
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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Joshua Miller;
Joshua Miller
Department of Surgery, University of Miami School of Medicine
Miami, Florida
Veterans Administration Medical Center
Miami, Florida
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Daniel H Mintz
Daniel H Mintz
Diabetes Research Institute, University of Miami School of Medicine
Miami, Florida
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Address correspondence and reprint requests to Dr. R. Alejandro, Diabetes Research Institute (R-134), 1450 NW 10th Ave., Miami, FL 33136. Email: [email protected].
Diabetes 1997;46(12):1983–1989
Article history
Received:
May 15 1997
Revision Received:
September 03 1997
Accepted:
September 03 1997
PubMed:
9392484
Citation
Rodolfo Alejandro, Roger Lehmann, Camillo Ricordi, Norma S Kenyon, M Clara Angelico, George Burke, Violet Esquenazi, Jose Nery, Arthur E Betancourt, Shen S Kong, Joshua Miller, Daniel H Mintz; Long-Term Function (6 Years) of Islet Allografts in Type 1 Diabetes. Diabetes 1 December 1997; 46 (12): 1983–1989. https://doi.org/10.2337/diab.46.12.1983
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