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Current Diabetes Reports

, 11:355 | Cite as

Impact of Islet Transplantation on Diabetes Complications and Quality of Life

  • Roberto Bassi
  • Paolo Fiorina
Article

Abstract

Insulin represents a life-saving therapy for patients with type 1 diabetes but, despite appropriate treatment, it prevents only partially long-term diabetic complications, while generating fatal hypoglycemic episodes. Islet transplantation gained attention because of its safety, effectiveness, and minimal invasiveness; however it remains a procedure reserved for a selected group of patients. The introduction of the Edmonton Protocol in 2000, based on a newly designed steroid-free immunosuppressive protocol, revamped the course of islet transplantation. The main goal of islet transplantation remains insulin independence, although the effect of islet transplantation can be more comprehensively evaluated in terms of frequency of hypoglycemic episodes and impact on diabetic complications and quality of life. Islet transplantation was shown to have positive consequences on cardiovascular, renal, neurologic, and ocular diabetic complications. The proof of concept for cellular replacement therapy in diabetes has been established with islet transplantation, it only needs to be improved and rendered widely available.

Keywords

Islet transplantation Quality of life Diabetes complications 

Notes

Acknowledgments

Paolo Fiorina is the recipient of a JDRF and ASN Career Development Award and of a MIUR grant: (“Staminali” RF-FSR-2008-1213704).

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Bloomgarden ZT. Diabetes complications. Diabetes Care. 2004;27:1506–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Kemp CB, Knight MJ, Scharp DW, Ballinger WF, Lacy PE. Effect of transplantation site on the results of pancreatic islet isografts in diabetic rats. Diabetologia. 1973;9:486–91.PubMedCrossRefGoogle Scholar
  3. 3.
    Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC. Human islet transplantation: a preliminary report. Transplant Proc. 1977;9:233–6.PubMedGoogle Scholar
  4. 4.
    Largiader F, Kolb E, Binswanger U, Illig R. Successful allotransplantation of an island of Langerhans. Schweiz Med Wochenschr. 1979;109:1733–6.PubMedGoogle Scholar
  5. 5.
    Scharp DW, Lacy PE, Santiago JV, et al. Insulin independence after islet transplantation into type I diabetic patient. Diabetes. 1990;39:515–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Pileggi A, Ricordi C, Kenyon NS, et al. Twenty years of clinical islet transplantation at the Diabetes Research Institute—University of Miami. Clin Transpl. 2004:177–204.Google Scholar
  7. 7.
    Pyzdrowski KL, Kendall DM, Halter JB, Nakhleh RE, Sutherland DE, Robertson RP. Preserved insulin secretion and insulin independence in recipients of islet autografts. N Engl J Med. 1992;327:220–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Tzakis AG, Ricordi C, Alejandro R, et al. Pancreatic islet transplantation after upper abdominal exenteration and liver replacement. Lancet. 1990;336:402–5.PubMedCrossRefGoogle Scholar
  9. 9.
    Ricordi C, Tzakis AG, Carroll PB, et al. Human islet isolation and allotransplantation in 22 consecutive cases. Transplantation. 1992;53:407–14.PubMedCrossRefGoogle Scholar
  10. 10.
    Brendel M. International islet transplant registry newsletter No.9. Volume 8. Number 1. 2001.Google Scholar
  11. 11.
    Oberholzer J, Triponez F, Mage R, et al. Human islet transplantation: lessons from 13 autologous and 13 allogeneic transplantations. Transplantation. 2000;69:1115–23.PubMedCrossRefGoogle Scholar
  12. 12.
    Oberholzer J, Toso C, Triponez F, et al. Human islet allotransplantation with Basiliximab in type I diabetic patients with end-stage renal failure. Transplant Proc. 2002;34:823–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Benhamou PY, Oberholzer J, Toso C, et al. Human islet transplantation network for the treatment of Type I diabetes: first data from the Swiss-French GRAGIL consortium (1999–2000). Groupe de Recherche Rhin Rhjne Alpes Geneve pour la transplantation d’Ilots de Langerhans. Diabetologia. 2001;44:859–64.PubMedCrossRefGoogle Scholar
  14. 14.
    Hering BJ, Bretzel RG, Hopt UT, et al. New protocol toward prevention of early human islet allograft failure. Transplant Proc. 1994;26:570–1.PubMedGoogle Scholar
  15. 15.
    Bretzel RG, Brandhorst D, Brandhorst H, et al. Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management. J Mol Med. 1999;77:140–3.PubMedCrossRefGoogle Scholar
  16. 16.
    Secchi A, Socci C, Maffi P, et al. Islet transplantation in IDDM patients. Diabetologia. 1997;40:225–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Shapiro AM, Lakey JR, Ryan EA, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343:230–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006;355:1318–30.PubMedCrossRefGoogle Scholar
  19. 19.
    Ryan EA, Paty BW, Senior PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes. 2005;54:2060–9.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee TC, Barshes NR, Brunicardi FC, et al. Procurement of the human pancreas for pancreatic islet transplantation. Transplantation. 2004;78:481–3.PubMedCrossRefGoogle Scholar
  21. 21.
    Venturini M, Angeli E, Maffi P, et al. Technique, complications, and therapeutic efficacy of percutaneous transplantation of human pancreatic islet cells in type 1 diabetes: the role of US. Radiology. 2005;234:617–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Robertson RP. Islet transplantation a decade later and strategies for filling a half-full glass. Diabetes. 2010;59:1285–91.PubMedCrossRefGoogle Scholar
  23. 23.
    Hafiz MM, Faradji RN, Froud T, et al. Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation. Transplantation. 2005;80:1718–28.PubMedCrossRefGoogle Scholar
  24. 24.
    Lakey JR, Mirbolooki M, Shapiro AM. Current status of clinical islet cell transplantation. Methods Mol Biol. 2006;333:47–104.PubMedGoogle Scholar
  25. 25.
    Berney T, Toso C. Monitoring of the islet graft. Diabetes Metab. 2006;32:503–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Vantyghem MC, Kerr-Conte J, Arnalsteen L, et al. Primary graft function, metabolic control, and graft survival after islet transplantation. Diabetes Care. 2009;32:1473–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Naftanel MA, Harlan DM. Pancreatic islet transplantation. PLoS Med. 2004;1:e58; quiz e75.Google Scholar
  28. 28.
    The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977–86.Google Scholar
  29. 29.
    • Fiorina P, Shapiro AM, Ricordi C, Secchi A. The clinical impact of islet transplantation. Am J Transplant. 2008;8:1990–7. This work comprehensively reviews the state of the art of islet transplantation, immunosuppression, outcomes, and their impact on patients’ survival and long-term diabetic complications. PubMedCrossRefGoogle Scholar
  30. 30.
    Hering BJ, Browatzki CC, Schultz A, Bretzel RG, Federlin KF. Clinical islet transplantation–registry report, accomplishments in the past and future research needs. Cell Transplant. 1993;2:269–82. discussion 83–305.PubMedGoogle Scholar
  31. 31.
    Gaston RS, Basadonna G, Cosio FG, et al. Transplantation in the diabetic patient with advanced chronic kidney disease: a task force report. Am J Kidney Dis. 2004;44:529–42.PubMedGoogle Scholar
  32. 32.
    Robertson RP. Update on transplanting beta cells for reversing type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39:655–67.PubMedCrossRefGoogle Scholar
  33. 33.
    Maffi P, Bertuzzi F, De Taddeo F, et al. Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy. Diabetes Care. 2007;30:1150–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Robertson RP. Islet transplantation as a treatment for diabetes—a work in progress. N Engl J Med. 2004;350:694–705.PubMedCrossRefGoogle Scholar
  35. 35.
    Nir T, Melton DA, Dor Y. Recovery from diabetes in mice by beta cell regeneration. J Clin Invest. 2007;117:2553–61.PubMedCrossRefGoogle Scholar
  36. 36.
    Brunicardi FC, Atiya A, Stock P, et al. Clinical islet transplantation experience of the University of California Islet Transplant Consortium. Surgery. 1995;118:967–71. discussion 71–2.PubMedCrossRefGoogle Scholar
  37. 37.
    Goss JA, Goodpastor SE, Brunicardi FC, et al. Development of a human pancreatic islet-transplant program through a collaborative relationship with a remote islet-isolation center. Transplantation. 2004;77:462–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Shapiro AM, Ricordi C, Hering B. Edmonton’s islet success has indeed been replicated elsewhere. Lancet. 2003;362:1242.PubMedCrossRefGoogle Scholar
  39. 39.
    Toso C, Baertschiger R, Morel P, et al. Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol. Am J Transplant: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2006;6:1049–58.Google Scholar
  40. 40.
    Gerber PA, Pavlicek V, Demartines N, et al. Simultaneous islet-kidney vs pancreas-kidney transplantation in type 1 diabetes mellitus: a 5 year single centre follow-up. Diabetologia. 2008;51:110–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Froud T, Ricordi C, Baidal DA, et al. Islet transplantation in type 1 diabetes mellitus using cultured islets and steroid-free immunosuppression: Miami experience. Am J Transplant: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2005;5:2037–46.Google Scholar
  42. 42.
    Hering BJ, Kandaswamy R, Harmon JV, et al. Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody. Am J Transplant: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2004;4:390–401.Google Scholar
  43. 43.
    Bellin MD, Kandaswamy R, Parkey J, et al. Prolonged insulin independence after islet allotransplants in recipients with type 1 diabetes. Am J Transplant. 2008;8:2463–70.PubMedCrossRefGoogle Scholar
  44. 44.
    Gangemi A, Salehi P, Hatipoglu B, et al. Islet transplantation for brittle type 1 diabetes: the UIC protocol. Am J Transplant. 2008;8:1250–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Skyler JS, Greenbaum CJ, Lachin JM, et al. Type 1 Diabetes TrialNet–an international collaborative clinical trials network. Ann N Y Acad Sci. 2008;1150:14–24.PubMedCrossRefGoogle Scholar
  46. 46.
    Oberholzer J, Kinzer K, Fiorina P. The anti-LFA-1 trial in islet transplantation. Am J Transplant. 2010;10:1725–6.PubMedCrossRefGoogle Scholar
  47. 47.
    •• Alejandro R, Barton FB, Hering BJ, Wease S. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation 2008;86:1783–8. This paper summarizes the most recent update from the CITR and represents the most complete collection of information on islet transplantation. PubMedCrossRefGoogle Scholar
  48. 48.
    Davalli AM, Maffi P, Socci C, et al. Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient. J Clin Endocrinol Metab. 2000;85:3847–52.PubMedCrossRefGoogle Scholar
  49. 49.
    Berney T, Ferrari-Lacraz S, Buhler L, et al. Long-term insulin-independence after allogeneic islet transplantation for type 1 diabetes: over the 10-year mark. Am J Transplant. 2009;9:419–23.PubMedCrossRefGoogle Scholar
  50. 50.
    Alejandro R, Lehmann R, Ricordi C, et al. Long-term function (6 years) of islet allografts in type 1 diabetes. Diabetes. 1997;46:1983–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Luzi L, Perseghin G, Brendel MD, et al. Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients. Diabetes. 2001;50:277–82.PubMedCrossRefGoogle Scholar
  52. 52.
    Rickels MR, Schutta MH, Markmann JF, Barker CF, Naji A, Teff KL. {beta}-Cell function following human islet transplantation for type 1 diabetes. Diabetes. 2005;54:100–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Poggioli R, Faradji RN, Ponte G, et al. Quality of life after islet transplantation. Am J Transplant: official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2006;6:371–8.Google Scholar
  54. 54.
    Geiger MC, Ferreira JV, Hafiz MM, et al. Evaluation of metabolic control using a continuous subcutaneous glucose monitoring system in patients with type 1 diabetes mellitus who achieved insulin independence after islet cell transplantation. Cell Transplant. 2005;14:77–84.PubMedCrossRefGoogle Scholar
  55. 55.
    Ryan EA, Shandro T, Green K, et al. Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation. Diabetes. 2004;53:955–62.PubMedCrossRefGoogle Scholar
  56. 56.
    Poggioli R, Faradji RN, Ponte G, et al. Quality of life after islet transplantation. Am J Transplant. 2006;6:371–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Barshes NR, Vanatta JM, Mote A, et al. Health-related quality of life after pancreatic islet transplantation: a longitudinal study. Transplantation. 2005;79:1727–30.PubMedCrossRefGoogle Scholar
  58. 58.
    Johnson JA, Kotovych M, Ryan EA, Shapiro AM. Reduced fear of hypoglycemia in successful islet transplantation. Diabetes Care. 2004;27:624–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Endicott J, Nee J, Harrison W, Blumenthal R. Quality of life enjoyment and satisfaction questionnaire: a new measure. Psychopharmacol Bull. 1993;29:321–6.PubMedGoogle Scholar
  60. 60.
    Teran-Escandon D, Teran-Ortiz L, Ormsby-Jenkins C, Evia-Viscarra ML, White DJ, Valdes-Gonzalez-Salas R. Psychosocial aspects of xenotransplantation: survey in adolescent recipients of porcine islet cells. Transplant Proc. 2005;37:521–4.PubMedCrossRefGoogle Scholar
  61. 61.
    Reliability and validity of a diabetes quality-of-life measure for the diabetes control and complications trial (DCCT). The DCCT Research Group. Diabetes Care 1988;11:725–32.Google Scholar
  62. 62.
    Toso C, Shapiro AM, Bowker S, et al. Quality of life after islet transplant: impact of the number of islet infusions and metabolic outcome. Transplantation. 2007;84:664–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Cure P, Pileggi A, Froud T, et al. Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation. 2008;85:801–12.PubMedCrossRefGoogle Scholar
  64. 64.
    Tharavanij T, Betancourt A, Messinger S, et al. Improved long-term health-related quality of life after islet transplantation. Transplantation. 2008;86:1161–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Melton 3rd LJ, Macken KM, Palumbo PJ, Elveback LR. Incidence and prevalence of clinical peripheral vascular disease in a population-based cohort of diabetic patients. Diabetes Care. 1980;3:650–4.PubMedCrossRefGoogle Scholar
  66. 66.
    Fiorina P, Gremizzi C, Maffi P, et al. Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients. Diabetes Care. 2005;28:1358–65.PubMedCrossRefGoogle Scholar
  67. 67.
    Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med. 1993;328:1676–85.PubMedCrossRefGoogle Scholar
  68. 68.
    Fiorina P, Folli F, D’Angelo A, et al. Normalization of multiple hemostatic abnormalities in uremic type 1 diabetic patients after kidney-pancreas transplantation. Diabetes. 2004;53:2291–300.PubMedCrossRefGoogle Scholar
  69. 69.
    Fiorina P, Folli F, Zerbini G, et al. Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants. J Am Soc Nephrol. 2003;14:2150–8.PubMedCrossRefGoogle Scholar
  70. 70.
    Fiorina P, Venturini M, Folli F, et al. Natural history of kidney graft survival, hypertrophy, and vascular function in end-stage renal disease type 1 diabetic kidney-transplanted patients: beneficial impact of pancreas and successful islet cotransplantation. Diabetes Care. 2005;28:1303–10.PubMedCrossRefGoogle Scholar
  71. 71.
    Fung MA, Warnock GL, Ao Z, et al. The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report. Transplantation. 2007;84:17–22.PubMedCrossRefGoogle Scholar
  72. 72.
    Leitao CB, Cure P, Messinger S, et al. Stable renal function after islet transplantation: importance of patient selection and aggressive clinical management. Transplantation. 2009;87:681–8.PubMedCrossRefGoogle Scholar
  73. 73.
    Senior PA, Zeman M, Paty BW, Ryan EA, Shapiro AM. Changes in renal function after clinical islet transplantation: four-year observational study. Am J Transplant. 2007;7:91–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia. 2000;43:957–73.PubMedCrossRefGoogle Scholar
  75. 75.
    Lee TC, Barshes NR, O’Mahony CA, et al. The effect of pancreatic islet transplantation on progression of diabetic retinopathy and neuropathy. Transplant Proc. 2005;37:2263–5.PubMedCrossRefGoogle Scholar
  76. 76.
    Del Carro U, Fiorina P, Amadio S, et al. Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis. Diabetes Care. 2007;30:3063–9.PubMedCrossRefGoogle Scholar
  77. 77.
    McCall AL. Diabetes mellitus and the central nervous system. Int Rev Neurobiol. 2002;51:415–53.PubMedCrossRefGoogle Scholar
  78. 78.
    Franceschi M, Cecchetto R, Minicucci F, Smizne S, Baio G, Canal N. Cognitive processes in insulin-dependent diabetes. Diabetes Care. 1984;7:228–31.PubMedCrossRefGoogle Scholar
  79. 79.
    Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010;376:124–36.PubMedCrossRefGoogle Scholar
  80. 80.
    Venturini M, Fiorina P, Maffi P, et al. Early increase of retinal arterial and venous blood flow velocities at color Doppler imaging in brittle type 1 diabetes after islet transplant alone. Transplantation. 2006;81:1274–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Transplantation Research Center, Nephrology DivisionChildren’s Hospital/Harvard Medical SchoolBostonUSA
  2. 2.Università del Salento, DiSTeBALecceItaly
  3. 3.Medicine, San Raffaele Scientific InstituteMilanItaly

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