Long-Term Immunosuppression After Solitary Islet Transplantation Is Associated With Preserved C-Peptide Secretion for More Than a Decade

被引:17
作者
Blau, J. E. [1 ]
Abegg, M. R. [1 ]
Flegel, W. A. [2 ]
Zhao, X. [1 ]
Harlan, D. M. [3 ]
Rother, K. I. [1 ]
机构
[1] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA
[2] NIH, Dept Transfus Med, NIH Clin Ctr, Bethesda, MD 20892 USA
[3] Univ Massachusetts, Sch Med, Dept Internal Med, Div Diabet Endocrinol & Nutr,Diabet Ctr Excellenc, North Worcester, MA USA
关键词
INTENSIVE MEDICAL THERAPY; 5-YEAR FOLLOW-UP; QUALITY-OF-LIFE; INSULIN-INDEPENDENCE; CELL TRANSPLANTATION; HLA ANTIBODIES; TYPE-1; PROGRESSION; RECIPIENTS;
D O I
10.1111/ajt.13383
中图分类号
R61 [外科手术学];
学科分类号
100210 [外科学];
摘要
We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30000 measurements per patient) and cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.
引用
收藏
页码:2995 / 3001
页数:7
相关论文
共 24 条
[1]
Magnitude and mechanisms of glucose counterregulation following islet transplantation in patients with type 1 diabetes suffering from severe hypoglycaemic episodes [J].
Ang, Meidjie ;
Meyer, Christian ;
Brendel, Mathias D. ;
Bretzel, Reinhard G. ;
Linn, Thomas .
DIABETOLOGIA, 2014, 57 (03) :623-632
[2]
Improvement in Outcomes of Clinical Islet Transplantation: 1999-2010 [J].
Barton, Franca B. ;
Rickels, Michael R. ;
Alejandro, Rodolfo ;
Hering, Bernhard J. ;
Wease, Stephen ;
Naziruddin, Bashoo ;
Oberholzer, Jose ;
Odorico, Jon S. ;
Garfinkel, Marc R. ;
Levy, Marlon ;
Pattou, Francois ;
Berney, Thierry ;
Secchi, Antonio ;
Messinger, Shari ;
Senior, Peter A. ;
Maffi, Paola ;
Posselt, Andrew ;
Stock, Peter G. ;
Kaufman, Dixon B. ;
Luo, Xunrong ;
Kandeel, Fouad ;
Cagliero, Enrico ;
Turgeon, Nicole A. ;
Witkowski, Piotr ;
Naji, Ali ;
O'Connell, Philip J. ;
Greenbaum, Carla ;
Kudva, Yogish C. ;
Brayman, Kenneth L. ;
Aull, Meredith J. ;
Larsen, Christian ;
Kay, Tom W. H. ;
Fernandez, Luis A. ;
Vantyghem, Marie-Christine ;
Bellin, Melena ;
Shapiro, A. M. James .
DIABETES CARE, 2012, 35 (07) :1436-1445
[3]
Potent Induction Immunotherapy Promotes Long-Term Insulin Independence After Islet Transplantation in Type 1 Diabetes [J].
Bellin, M. D. ;
Barton, F. B. ;
Heitman, A. ;
Harmon, J. V. ;
Kandaswamy, R. ;
Balamurugan, A. N. ;
Sutherland, D. E. R. ;
Alejandro, R. ;
Hering, B. J. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (06) :1576-1583
[4]
Long-Term Insulin-Independence After Allogeneic Islet Transplantation for Type 1 Diabetes: Over the 10-Year Mark [J].
Berney, T. ;
Ferrari-Lacraz, S. ;
Buehler, L. ;
Oberholzer, J. ;
Marangon, N. ;
Philippe, J. ;
Villard, J. ;
Morel, P. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2009, 9 (02) :419-423
[5]
Organ procurement organization (OPO), best practices [J].
Bollinger, RR ;
Heinrichs, DR ;
Seem, DL ;
Rosendale, JD ;
Johnson, KS ;
Metzger, RA .
CLINICAL TRANSPLANTATION, 2001, 15 :16-21
[7]
Improved metabolic control and quality of life in seven patients with type I diabetes following islet after kidney transplantation [J].
Cure, Pablo ;
Pileggi, Antonello ;
Froud, Tatiana ;
Messinger, Shari ;
Faradji, Raquel N. ;
Baidal, David A. ;
Cardani, Roberta ;
Curry, Andrea ;
Poggioli, Raffaella ;
Pugliese, Alberto ;
Betancourt, Arthur ;
Esquenazi, Violet ;
Ciancio, Gaetano ;
Selvaggi, Gennaro ;
Burke, George W., III ;
Ricordi, Camillo ;
Alejandro, Rodolfo .
TRANSPLANTATION, 2008, 85 (06) :801-812
[8]
Sirolimus-induced interstitial pneumonitis in an islet transplant recipient [J].
Digon, BJ ;
Rother, KI ;
Hirshberg, B ;
Harlan, DM .
DIABETES CARE, 2003, 26 (11) :3191-3191
[9]
Persistence of recipient human leucocyte antigen (HLA) antibodies and production of donor HLA antibodies following reduced intensity allogeneic haematopoietic stem cell transplantation [J].
Fasano, Ross M. ;
Mamcarz, Ewelina ;
Adams, Sharon ;
Jerussi, Theresa Donohue ;
Sugimoto, Kyoko ;
Tian, Xin ;
Flegel, Willy A. ;
Childs, Richard W. .
BRITISH JOURNAL OF HAEMATOLOGY, 2014, 166 (03) :425-434
[10]
Predictive Factors of Allosensitization After Immunosuppressant Withdrawal in Recipients of Long-Term Cultured Islet Cell Grafts [J].
Hilbrands, Robert ;
Gillard, Pieter ;
Van der Torren, Cornelis R. ;
Ling, Zhidong ;
Verheyden, Sonja ;
Jacobs-Tulleneers-Thevissen, Daniel ;
Roep, Bart O. ;
Claas, Frans H. J. ;
Demanet, Christian ;
Gorus, Frans K. ;
Pipeleers, Daniel ;
Keymeulen, Bart .
TRANSPLANTATION, 2013, 96 (02) :162-169