Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Pancreas and islet transplantation in diabetes mellitus

INTRODUCTION

The Diabetes Control and Complication Trial (DCCT) demonstrated an approximately 50 percent reduction in eye, nerve, and kidney complications with intensive treatment for hyperglycemia and greatly increased interest in reducing blood glucose concentrations to normal in patients with diabetes [1]. However, no certain and consistently reliable means of achieving this goal are currently available. (See "Glycemic control and vascular complications in type 1 diabetes mellitus".)

This topic will briefly review the history, techniques, and clinical results of pancreas and pancreatic islet transplantation in hyperglycemic patients with long-standing type 1 diabetes mellitus, with a focus upon transplantation of pancreatic tissue alone. Combined pancreas-kidney transplantation is discussed separately. (See "Patient selection for and immunologic issues relating to kidney-pancreas transplantation in diabetes mellitus" and "Benefits and complications associated with kidney-pancreas transplantation in diabetes mellitus".)

PANCREAS TRANSPLANTATION

Pancreas transplantation was first used for the treatment of diabetes in humans in 1966 [2]. The rates of graft and patient survival were low; as a result, very few procedures were performed in the early to mid-1970s.

The subsequent introduction of better immunosuppressive regimens (particularly cyclosporine and anti-T-cell antibodies), new surgical techniques, and the selection of healthier recipients resulted in markedly improved outcomes. As a result, the number of pancreatic transplantations has steadily increased each year [3]. In 2006, approximately 1400 procedures were recorded, 14 percent of which involved the pancreas alone (without a kidney transplanted before or at the same time as the pancreas).

Outcomes — The mortality, morbidity, and results of transplantation vary with operative experience and patient selection. The following overall outcomes are based upon 2006 data [3]:
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2010 UpToDate, Inc.
References Top
  1. Robertson, RP. Seminars in medicine of the Beth Israel Hospital, Boston: Pancreatic and islet transplantation for diabetes--cures or curiosities?. N Engl J Med 1992; 327:1861.
  2. Kelly, WD, Lillehei, RC, Merkel, FK, et al. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy. Surgery 1967; 61:827.
  3. www.ustransplant.org (Accessed 7/6/09).
  4. Venstrom, JM, McBride, MA, Rother, KI, et al. Survival after pancreas transplantation in patients with diabetes and preserved kidney function. JAMA 2003; 290:2817.
  5. Nathan, DM. Isolated pancreas transplantation for type 1 diabetes: a doctor's dilemma. JAMA 2003; 290:2861.
  6. Gruessner, RW, Sutherland, DE, Gruessner, AC. Mortality assessment for pancreas transplants. Am J Transplant 2004; 4:2018.
  7. Pancreas and islet transplantation in type 1 diabetes. Diabetes Care 2006; 29:935.
  8. Sutherland, DE, Gruessner, R, Dunn, D, et al. Pancreas transplants from living-related donors. Transplant Proc 1994; 26:443.
  9. Knight, RJ, Kerman, RH, Zela, S, et al. Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine. Transplantation 2006; 81:1101.
  10. Havrdova, T, Saudek, F, Boucek, P, et al. Metabolic effect of sirolimus versus mycophenolate mofetil on pancreatic graft function in the early posttransplant period. Transplant Proc 2005; 37:3544.
  11. Gautam, A, Morrissey, PE, Gohh, R, et al. Experience with sirolimus for calcineurin minimization/elimination in pancreas-after-kidney transplantation. Transplant Proc 2005; 37:3542.
  12. Rogers, J, Ashcraft, EE, Emovon, OE, et al. Long-term outcome of sirolimus rescue in kidney-pancreas transplantation. Transplantation 2004; 78:619.
  13. Kaufman, DB, Leventhal, JR, Gallon, LG, Parker, MA. Alemtuzumab induction and prednisone-free maintenance immunotherapy in simultaneous pancreas-kidney transplantation comparison with rabbit antithymocyte globulin induction - long-term results. Am J Transplant 2006; 6:331.
  14. Luo, G, Falta, EM, Elster, EA. Steroid-free immunosuppression in organ transplantation. Curr Diab Rep 2005; 5:305.
  15. Mark, W, Berger, N, Lechleitner, M, et al. Impact of steroid withdrawal on metabolic parameters in a series of 112 enteric/systemic-drained pancreatic transplants. Transplant Proc 2005; 37:1821.
  16. Cantarovich, D, Karam, G, Hourmant, M, et al. Steroid avoidance versus steroid withdrawal after simultaneous pancreas-kidney transplantation. Am J Transplant 2005; 5:1332.
  17. Humar, A, Ramcharan, T, Kandaswamy, R, et al. Technical failures after pancreas transplants: why grafts fail and the risk factors--a multivariate analysis. Transplantation 2004; 78:1188.
  18. Drachenberg, CB, Papadimitriou, JC, Farney, A, et al. Pancreas transplantation: the histologic morphology of graft loss and clinical correlations. Transplantation 2001; 71:1784.
  19. Sutherland, DER, Moudry-Munns, K, Gruessner, A. Pancreas transplant results in United Networks for Organ Sharing (UNOS) United States of America (USA) Registry with a comparison to non-USA data in the International Registry. Clinical Transplants, Terasaki, PI, Cecka, JM (Eds) UCLA Tissue Typing Laboratory, Los Angeles 1996.
  20. Gruessner, RW, Sutherland, DE, Najarian, JS, et al. Solitary pancreas transplantation for nonuremic patients with labile insulin-dependent diabetes mellitus. Transplantation 1997; 64:1572.
  21. Gruessner, RWG, Nakhleh, R, Tzardis, P, et al. Rejection patterns after simultaneous pancreaticoduodenal-kidney transplants in pigs. Transplantation 1994; 57:756.
  22. Pirsch, JD, Andrews, C, Hricik, DE, et al. Pancreas transplantation for diabetes mellitus. Am J Kidney Dis 1996; 27:444.
  23. Papadimitriou, JC, Drachenberg, CB, Wiland, A, et al. Histolologic grading of acute allograft rejection in pancreas needle biopsy. Transplantation 1998; 66:1741.
  24. Stiller, CR, Dupre, J, Gent, M, et al. Effects of cyclosporine immunosuppresion in insulin-dependent diabetes of recent onset. Science 1984; 223:1362.
  25. Benedetti, E, Najarian, JS, Gruessner, AC, et al. Correlation between cystoscopic biopsy results and hypoamylasuria in bladder-drained pancreas transplants. Surgery 1995; 118:864.
  26. Kuhr, CS, Davis, CL, Barr, D, et al. Use of ultrasound and cystoscopically guided pancreatic allograft biopsies and transabdominal renal allograft biopsies: Safety and efficacy in kidney-pancreas transplant recipients. J Urol 1995; 153:316.
  27. Pozza, G, Traeger, J, Dubernard, JM, et al. Endocrine responses of type 1 (insulin-dependent) diabetic patients following successful pancreas transplantation. Diabetologia 1983; 24:244.
  28. Katz, H, Homan, M, Velosa, J, et al. Effects of pancreas transplantation on postprandial glucose metabolism. N Engl J Med 1991; 325:1278.
  29. Diem, P, Abid, M, Redmon, JB, et al. Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type 1 diabetic recipients. Diabetes 1990; 39:534.
  30. Osei, K, Henry, ML, O'Dorisio, TM, et al. Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type 1 diabetic pancreas allograft recipients. Diabetes 1990; 39:1235.
  31. Elahi, D, Clark, BA, McAloon-Dyke, M, et al. Islet cell responses to glucose in human transplanted pancreas. Am J Physiol 1991; 261:E800.
  32. Robertson, RP, Diem, P, Sutherland, DER. Time related, cross-sectional and prospective follow-up of pancreatic endocrine function after pancreas allograft transplantation in type 1 (insulin-dependent) diabetic patients. Diabetologia 1991; 34(Suppl 1):S57.
  33. Landgraf, R, Nusser, J, Riepl, RL, et al. Metabolic and hormonal studies of type 1 (insulin-dependent) diabetic patients after successful pancreas and kidney transplantation. Diabetologia 1991; 34(Suppl 1):S61.
  34. Secchi, A, Dubernard, JM, La Rocca, E, et al. Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients — a two-year follow-up. Transplantation 1991; 51:625.
  35. Luzi, L, Secchi, A, Facchini, F, et al. Reduction of insulin resistance by combined kidney-pancreas transplantation in type 1 (insulin-dependent) diabetic patients. Diabetologia 1990; 33:549.
  36. La Rocca, E, Secchi, A, Parlavecchia, M, et al. Lipid metabolism after successful kidney and pancreatic transplantation. Transplant Proc 1991; 23:1672.
  37. Larsen, JL, Stratta, RJ, Ozaki, CF, et al. Lipid status after pancreas-kidney transplantation. Diabetes Care 1992; 15:35.
  38. Katz, HH, Nguyen, TT, Velosa, JA, et al. Effects of systemic delivery of insulin on plasma lipids and lipoprotein concentrations in pancreas transplant recipients. Mayo Clin Proc 1994; 69:231.
  39. Diem, P, Redmon, JB, Abid, M, et al. Glucagon, catecholamine and pancreatic polypeptide secretion in type 1 diabetic recipients of pancreas allografts. J Clin Invest 1990; 86:2008.
  40. Barrou, Z, Seaquist, ER, Robertson, RP. Pancreas transplantation in diabetic humans normalizes hepatic glucose production during hypoglycemia. Diabetes 1994; 43:661.
  41. Kendall, DM, Rooney, D, Smets, YFC, et al. Pancreas transplantation restores epinephrine response and symptom recognition during hypoglycemia in patients with long-standing type I diabetes mellitus and autonomic neuropathy. Diabetes 1997; 46:249.
  42. Cottrell, DA, Henry, ML, O'Dorisio, TM, et al. Hypoglycemia after successful pancreas transplantation in type 1 diabetic patients. Diabetes Care 1991; 14:1111.
  43. Redmon, JB, Teuscher, AU, Robertson, RP. Hypoglycemia after pancreas transplantation. Diabetes Care 1998; 21:1944.
  44. Robertson, RP, Sutherland, DER, Kendall, DM, et al. Metabolic characterization of long-term successful pancreas transplants in type I diabetes. J Investig Med 1996; 44:1.
  45. Robertson, RP, Sutherland, DE, Lanz, KJ. Normoglycemia and preserved insulin secretory reserve in diabetic patients 10-18 years after pancreas transplantation. Diabetes 1999; 48:1737.
  46. Bohman, S-O, Tydén, G, Wilczek, H, et al. Prevention of kidney graft diabetic nephropathy by pancreas transplantation in man. Diabetes 1985; 34:306.
  47. Bilous, RW, Mauer, SM, Sutherland, DE, et al. The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 1989; 321:80.
  48. Fioretto, P, Steffes, MW, Sutherland, DE, et al. Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 1998; 339:69.
  49. Navarro, X, Sutherland, DER, Kennedy, WR. Long-term effects of pancreatic transplantation on diabetic neuropathy. Ann Neurol 1997; 42:725.
  50. Secchi, A, Martinenghi, S, Galardi, G, et al. Effects of pancreatic transplantation on diabetic polyneuropathy. Transplant Proc 1991; 23:1658.
  51. Aridge, D, Reese, J, Niehoff, M, et al. Effect of successful renal and segmental pancreatic transplantation on peripheral and autonomic neuropathy. Transplant Proc 1991; 23:1670.
  52. Allen, RD, Al-Harbi, IS, Morris, JG, et al. Diabetic neuropathy after pancreas transplantation: determinants of recovery. Transplantation 1997; 63:830.
  53. Navarro, X, Kennedy, WR, Sutherland, DE. Autonomic neuropathy and survival in diabetes mellitus: effects of pancreas transplantation. Diabetologia 1991; 34 Suppl 1:S108.
  54. Gaber, AO, Cardoso, S, Pearson, S, et al. Improvement in autonomic function following combined pancreas-kidney transplantation. Transplant Proc 1991; 23:1660.
  55. Navarro, X, Kennedy, WR, Loewenson, RB, Sutherland, DER. Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction, and mortality in diabetes mellitus. Diabetes 1990; 39:802.
  56. Ramsay, RC, Goetz, FC, Sutherland, DER, et al. Progression of diabetic retinopathy after pancreas transplantation for insulin-dependent diabetes mellitus. N Engl J Med 1988; 318:208.
  57. Petersen, MR, Vine, AK, University of Michigan Pancreas Transplant Evaluation Committee. Progression of diabetic retinopathy after pancreas transplantation. Ophthalmology 1990; 97:496.
  58. Scheider, A, Meyer-Schwickerath, E, Nusser, J, et al. Diabetic retinopathy and pancreas transplantation: a 3-year follow-up. Diabetologia 1991; 34 Suppl 1:S95.
  59. Wang, Q, Klein, R, Moss, SE, et al. The influence of combined kidney-pancreas transplantation on the progression of diabetic retinopathy. Ophthalmology 1994; 101:1071.
  60. Koznarova, R, Saudek, F, Sosna, T, et al. Beneficial effect of pancreas and kidney transplantation on advanced diabetic retinopathy. Cell Transplant 2000; 9:903.
  61. Markowski, D, Larsen, JL, McElligott, M, et al. Diet after pancreas transplantation. Diabetes Care 1996; 19:735.
  62. Fiorina, P, La Rocca, E, Venturini, M, et al. Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes. Diabetes 2001; 50:496.
  63. Larsen, JL, Colling, CW, Ratanasuwan, T, et al. Pancreas transplantation improves vascular disease in patients with type 1 diabetes. Diabetes Care 2004; 27:1706.
  64. Jukema, JW, Smets, YF, van der, Pijl JW, et al. Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes. Diabetes Care 2002; 25:906.
  65. Robertson, RP. Islet transplantation as a treatment for diabetes - a work in progress. N Engl J Med 2004; 350:694.
  66. Rother, KI, Harlan, DM. Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus. J Clin Invest 2004; 114:877.
  67. Warnock, GL, Kneteman, NM, Ryan, EA, et al. Long-term follow-up after transplantation of insulin-producing pancreatic islets into patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 1992; 35:89.
  68. 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.
  69. www.citregistry.com (Accessed 7/6/09).
  70. Najarian, JS, Sutherland, DER, Baumgartner, D, et al. Total or near total pancreatectomy and islet autotransplantation for treatment of chronic pancreatitis. Ann Surg 1980; 192:526.
  71. Bellin, MD, Carlson, AM, Kobayashi, T, et al. Outcome after pancreatectomy and islet autotransplantation in a pediatric population. J Pediatr Gastroenterol Nutr 2008; 47:37.
  72. Pyzdrowski, KL, Kendall, DM, Halter, JB, et al. Preserved insulin secretion and insulin independence in recipients of islet autografts. N Engl J Med 1992; 327:220.
  73. Robertson, RP, Lanz, KJ, Sutherland, DE, Kendall, DM. Prevention of diabetes for up to 13 years by autoislet transplantation after pancreatectomy for chronic pancreatitis. Diabetes 2001; 50:47.
  74. Wahoff, DC, Papalois, BE, Najarian, JS, et al. Autologous islet transplantation to prevent diabetes after pancreatic resection. Ann Surg 1995; 222:562.
  75. Robertson, RP. Successful islet transplantation for patients with diabetes--fact or fantasy? [comment] [editorial]. N Engl J Med 2000; 343:289.
  76. Ryan, EA, Paty, BW, Senior, PA, et al. Five-year follow-up after clinical islet transplantation. Diabetes 2005; 54:2060.
  77. Bromberg, JS, LeRoith, D. Diabetes cure--is the glass half full?. N Engl J Med 2006; 355:1372.
  78. Shapiro, AM, Ricordi, C, Hering, BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med 2006; 355:1318.
  79. 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.
  80. Berney, T, Morel, P. Islet transplantation: steeple chase and the next hurdle. Transplantation 2005; 80:1658.
  81. Campbell, PM, Senior, PA, Salam, A, et al. High risk of sensitization after failed islet transplantation. Am J Transplant 2007; 7:2311.
  82. Markmann, JF, Deng, S, Huang, X, et al. Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg 2003; 237:741.
  83. Hirshberg, B, Rother, KI, Digon BJ, 3rd, et al. Benefits and risks of solitary islet transplantation for type 1 diabetes using steroid-sparing immunosuppression: the National Institutes of Health experience. Diabetes Care 2003; 26:3288.
  84. Hering, BJ, Kandaswamy, R, Ansite, JD, et al. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 2005; 293:830.
  85. Ramiya, VK, Maraist, M, Arfors, KE, et al. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 2000; 6:278.
  86. D'Amour, KA, Agulnick, AD, Eliazer, S, et al. Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 2005; 23:1534.
  87. Guo, T, Hebrok, M. Stem cells to pancreatic beta-cells: new sources for diabetes cell therapy. Endocr Rev 2009; 30:214.
  88. Kroon, E, Martinson, LA, Kadoya, K, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol 2008; 26:443.
  89. Stainier, D. No stem cell is an islet (yet). N Engl J Med 2006; 354:521.
  90. Hao, E, Tyrberg, B, Itkin-Ansari, P, et al. Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas. Nat Med 2006; 12:310.
  91. Kodama, S, Kuhtreiber, W, Fujimura, S, et al. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science 2003; 302:1223.
  92. Chong, AS, Shen, J, Tao, J, et al. Reversal of diabetes in non-obese diabetic mice without spleen cell-derived beta cell regeneration. Science 2006; 311:1774.
  93. Nishio, J, Gaglia, JL, Turvey, SE, et al. Islet recovery and reversal of murine type 1 diabetes in the absence of any infused spleen cell contribution. Science 2006; 311:1775.
  94. Suri, A, Calderon, B, Esparza, TJ, et al. Immunological reversal of autoimmune diabetes without hematopoietic replacement of beta cells. Science 2006; 311:1778.
  95. Magliocca, JF, Odorico, JS. Embyonic stem cell-based therapy for the treatment of diabetes mellitus: a work in progress. Current Opinion in Organ Transplantation 2006; 11:88.
  96. Hering, BJ, Wijkstrom, M, Graham, ML, et al. Prolonged diabetes reversal after intraportal xenotransplantation of wild-type porcine islets in immunosuppressed nonhuman primates. Nat Med 2006; 12:301.
  97. Kendall, DM, Teuscher, AU, Robertson, RP. Defective glucagon secretion during sustained hypoglycemia following successful islet allo- and autotransplantation in humans. Diabetes 1997; 46:23.
  98. Gupta, V, Rooney, DP, Kendall, DM, et al. Defective glucagon responses from transplanted intrahepatic pancreatic islets during hypoglycemia is transplantation site-determined. Diabetes 1997; 46:28.
  99. Zhou, H, Zhang, T, Bogdani, M, et al. Intrahepatic glucose flux as a mechanism for defective intrahepatic islet alpha-cell response to hypoglycemia. Diabetes 2008; 57:1567.
  100. Merani, S, Toso, C, Emamaullee, J, Shapiro, AM. Optimal implantation site for pancreatic islet transplantation. Br J Surg 2008; 95:1449.
  101. Calafiore, R, Basta, G, Luca, G, et al. Grafts of microencapsulated pancreatic islet cells for the therapy of diabetes mellitus in non-immunosuppressed animals. Biotechnol Appl Biochem 2004; 39:159.
  102. Calafiore, R, Basta, G, Luca, G, et al. Microencapsulated pancreatic islet allografts into nonimmunosuppressed patients with type 1 diabetes: first two cases. Diabetes Care 2006; 29:137.
  103. Eich, T, Eriksson, O, Lundgren, T. Visualization of early engraftment in clinical islet transplantation by positron-emission tomography. N Engl J Med 2007; 356:2754.
  104. Barnett, BP, Arepally, A, Karmarkar, PV, et al. Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat Med 2007; 13:986.
white circle LOG IN
white circle DEMO