Der Diabetologe

, Volume 7, Issue 8, pp 585–594

Insel(zell)transplantation bei Typ-1-Diabetes-mellitus

Leitthema
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Zusammenfassung

Die funktionellen Ergebnisse der Insel(zell)transplantation (ITx) haben sich seit der ersten klinischen Anwendung kontinuierlich verbessert. Die derzeitige Hauptindikation zur Transplantation besteht bei Patienten mit Typ-1-Diabetes mellitus (ohne signifikante Insulinrestsekretion) mit Hypoglykämiesyndrom bzw. schwerst einstellbarem Diabetes (Brittle Diabetes), grundsätzlich auch mit terminaler Niereninsuffizienz und geplanter simultaner Nierentransplantation oder bereits vorangegangener Nierentransplantation. Durch eine ITx kann das primäre Therapieziel einer guten und stabilen Stoffwechseleinstellung unter Vermeidung schwerer Hypoglykämien in der Mehrzahl der Fälle erreicht werden. Nach Registerdaten beträgt das Insel(zell)transplantatüberleben ein Jahr nach Transplantation 82%, nach 3 Jahren 75% und die Insulinunabhängigkeitsraten zum Einjahreszeitpunkt 50% sowie nach 3 Jahren 35%. Damit gehen eine deutliche Steigerung der Lebensqualität und eine gegenüber der alleinigen intensivierten Insulintherapie verbesserte Progressionshemmung mikrovaskulärer diabetischer Folgekomplikationen einher. Patienten mit einem Typ-1-Diabetes und Transplantationsindikation sollte eine ITx oder eine vaskularisierte Pankreas-Transplantation (PTx) angeboten und dabei die Vor- sowie Nachteile beider Therapieverfahren sorgfältig individuell abgewogen werden. Hierfür erscheint ein Transplantationszentrum vorteilhaft, das beide Verfahren anbietet.

Schlüsselwörter

Langerhans-Insel Pankreas Aufbereitung, Transplantation Hypoglykämie Immunsuppression 

Islet (cell) transplantation for type 1 diabetes mellitus

Abstract

Functional results of islet (cell) transplantation have continuously improved since the first clinical application. The main indication for islet (cell) transplantation is given for patients with type 1 diabetes without significant endogenous insulin secretion and frequent severe hypoglycemic episodes and principally in patients with end-stage nephropathy or previous kidney transplantation. In the majority of cases islet (cell) transplantation achieves the primary therapy goal of graft function and stable glucose control without severe hypoglycemia. According to registry data islet (cell) graft survival after 1 and 3 years is 82% and 75% and insulin independence 50% and 35%, respectively. This is associated with a significant improvement in quality of life and reduced progression of secondary diabetic microvascular complications compared with intensified insulin therapy alone. Patients with type 1 diabetes mellitus and indication for transplantation should be offered either islet (cell) or vascularized pancreas transplantation taking the individual benefits and risks of each treatment option into consideration.

Keywords

Islets of Langerhans Pancreas Conditioning, transplantation Hypoglycemia Immunosuppression 

Literatur

  1. 1.
    Ehehalt S, Blumenstock G, Willasch AM et al (2008) Continuous rise in incidence of childhood type 1 diabetes in Germany. Diabet Med 25:755–757PubMedCrossRefGoogle Scholar
  2. 2.
    Diabetes Control and Complications Trial Research Group (1993) The effect of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986CrossRefGoogle Scholar
  3. 3.
    Hasslacher C, Ritz E, Wahl P et al (1989) Similar risks of nephropathy in patients with type 1 or type 2 diabetes mellitus. Nephrol Dial Transplant 4:859–863PubMedGoogle Scholar
  4. 4.
    Schober-Halstenberg HJ (2002) Jahresbericht 2001 QuaSi-Niere. http://www.quasi-niere.de/deutsch/bericht/01/world.htmlGoogle Scholar
  5. 5.
    Borch-Johnson K, Andersen PK, Deckert T (1985) The effect of proteinuria on relative mortality in type 1 (insulin-dependent) diabetes mellitus. Diabetologia 28:533–547Google Scholar
  6. 6.
    Hostetter TH (2004) Chronic kidney disease predicts cardiovascular disease. N Engl J Med 351:1344–1346PubMedCrossRefGoogle Scholar
  7. 7.
    Bolli G, de Feo P, Compagnucci P et al (1983) Abnormal glucose counterregulation in insulin-dependent diabetes mellitus. Interaction of anti-insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 32:134–141PubMedCrossRefGoogle Scholar
  8. 8.
    Scherbaum W, Ritz E (2005) Prävention und Therapie der diabetischen Nephropathie. Dtsch Arztebl 102:137–143Google Scholar
  9. 9.
    Gerich JE, Mokan M, Veneman T et al (1991) Hypoglycemia unawareness. Endocr Rev 12:356–371PubMedCrossRefGoogle Scholar
  10. 10.
    Sutherland DE, Gores PF, Farney AC et al (1993) Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota. Am J Surg 166:456–491PubMedCrossRefGoogle Scholar
  11. 11.
    Gross CR, Limwattananon C, Matthees BJ (1998) Quality of life after pancreas transplantation: a review. Clin Transplant 12:351–361PubMedGoogle Scholar
  12. 12.
    White SA, Shaw JA, Sutherland DE (2009) Pancreas transplantation. Lancet 373:1808–1817PubMedCrossRefGoogle Scholar
  13. 13.
    Landgraf R (1996) Impact of pancreas transplantation on diabetic secondary complications and quality of life. Diabetologia 39:1415–1424PubMedCrossRefGoogle Scholar
  14. 14.
    Shapiro AM, Lakey JR, Ryan EA et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238PubMedCrossRefGoogle Scholar
  15. 15.
    Shapiro AM, Ricordi C, Hering BJ et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355:1318–1330PubMedCrossRefGoogle Scholar
  16. 16.
    Bretzel RG, Brandhorst D, Brandhorst H et al (1999) Improved survival of intraportal pancreatic islet cell allografts in patients with type 1 diabetes mellitus by refined peritransplant management. J Mol Med 77:140–143PubMedCrossRefGoogle Scholar
  17. 17.
    Brendel MD, Eckhard M, Brandhorst D et al (2003) Inselzelltransplantation – aktueller Stand und Perspektiven. Diabetes Stoffw 12:239–252Google Scholar
  18. 18.
    Alejandro R, Barton FB, Hering BJ et al (2008) Collaborative Islet Transplant Registry Investigators. 2008 Update from the Collaborative Islet Transplant Registry. Transplantation 86:1783–1788PubMedCrossRefGoogle Scholar
  19. 19.
    Lakey JR, Kin T, Warnock GL et al (2007) Long-term graft function after allogeneic islet transplantation. Cell Transplant 16:441–446PubMedGoogle Scholar
  20. 20.
    Ryan EA, Lakey JRT, Paty BW et al (2002) Successful islet transplantation: continued insulin reserve provides long-term glycemic control. Diabetes 51:2148–2157PubMedCrossRefGoogle Scholar
  21. 21.
    Leitao CB, Tharavanij T, Cure P et al (2008) Restoration of hypoglycemia awareness after islet transplantation. Diabetes Care 31:2113–2115PubMedCrossRefGoogle Scholar
  22. 22.
    Steffes MW, Sibley S, Jackson M et al (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26:832–836PubMedCrossRefGoogle Scholar
  23. 23.
    Palmer JP, Fleming GA, Greenbaum CJ et al (2004) C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21–22 October 2001. Diabetes 53:250–264PubMedCrossRefGoogle Scholar
  24. 24.
    Johansson BL, Kernell A, Sjoberg S et al (1993) Influence of combined C-peptide and insulin administration on renal function and metabolic control in diabetes type 1. J Clin Endocrinol Metab 77:976–981PubMedCrossRefGoogle Scholar
  25. 25.
    Johansson BL, Borg K, Fernqvist-Forbes E et al (2000) Beneficial effects of C-peptide on incipient nephropathy and neuropathy in patients with type 1 diabetes mellitus. Diabet Med 17:181–189PubMedCrossRefGoogle Scholar
  26. 26.
    Rigler R, Pramanik A, Jonasson P et al (1999) Specific binding of proinsulin C-peptide to human cell membranes. Proc Natl Acad Sci U S A 96:13318–13323PubMedCrossRefGoogle Scholar
  27. 27.
    Nordquist L, Palm F, Andresen BT (2008) Renal and vascular benefits of C-peptide: molecular mechanisms of C-peptide action. Biologics 2(3):441–452PubMedGoogle Scholar
  28. 28.
    Fiorina P, Folli F, Bertuzzi F et al (2003) Long-term beneficial effect of islet transplantation on diabetic macro-/microangiopathy in type 1 diabetic kidney-transplanted patients. Diabetes Care 26:1129–1136PubMedCrossRefGoogle Scholar
  29. 29.
    Fiorina P, Venturini M, Folli F et al (2005) 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 28:1303–1310PubMedCrossRefGoogle Scholar
  30. 30.
    Luzi L, Perseghin G, Brendel MD et al (2001) Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients. Diabetes 50:277–282PubMedCrossRefGoogle Scholar
  31. 31.
    Luzi L, Hering BJ, Socci C et al (1996) Metabolic effects of successful intraportal islet transplantation in insulin-dependent diabetes mellitus. J Clin Invest 97:2611–2618PubMedCrossRefGoogle Scholar
  32. 32.
    Vantyghem MC, Marcelli-Tourvieille S, Fermon C et al (2009) Intraperitoneal insulin infusion versus islet transplantation: comparative study in patients with type 1 diabetes. Transplantation 87(1):66–71PubMedCrossRefGoogle Scholar
  33. 33.
    Thompson DM, Begg IS, Harris C et al (2008) Reduced progression of diabetic retinopathy after islet cell transplantation compared with intensive medical therapy. Transplantation 85:1400–1405PubMedCrossRefGoogle Scholar
  34. 34.
    Warnock GL, Thompson DM, Meloche RM et al (2008) A multi-year analysis of islet transplantation compared with intensive medical therapy on progression of complications in type 1 diabetes. Transplantation 86:1762–1766PubMedCrossRefGoogle Scholar
  35. 35.
    Thompson DM, Meloche M, Ao Z et al (2011) Reduced progression of diabetic microvascular complications with islet cell transplantation compared with intensive medical therapy. Transplantation 91(3):373–378PubMedCrossRefGoogle Scholar
  36. 36.
    Gerber PA, Pavlicek V, Demartines N et al (2008) Simultaneous islet-kidney vs pancreas-kidney transplantation in type 1 diabetes mellitus: a 5 year single center follow-up. Diabetologia 51:110–119PubMedCrossRefGoogle Scholar
  37. 37.
    Ludwig B, Ziegler CG, Schally AV et al (2010) Agonist of growth hormone-releasing hormone as a potential effector for survival and proliferation of pancreatic islets. Proc Natl Acad Sci U S A 107(28):12623–12628PubMedCrossRefGoogle Scholar
  38. 38.
    Schmid J, Ludwig B, Schally AV et al (2011) Modulation of pancreatic islets-stress axis by hypothalamic releasing hormones and 11β-hydroxysteroid dehydrogenase. Proc Natl Acad Sci U S A 108(33):13722–13727PubMedCrossRefGoogle Scholar
  39. 39.
    Ludwig B, Zimerman B, Steffen A et al (2010) A novel device for islet transplantation providing immune protection and oxygen supply. Horm Metab Res 42(13):918–922PubMedCrossRefGoogle Scholar
  40. 40.
    Bretzel RG, Eckhard M, Jahr H, Brendel MD (2006) Inselzelltransplantation, Stammzelltherapie und regenerative Therapie bei Diabetes mellitus. Dtsch Med Wochenschr 131:903–936PubMedCrossRefGoogle Scholar
  41. 41.
    Bretzel RG, Jahr H, Eckhard M et al (2007) Islet cell transplantation today. Langenbecks Arch Surg 392:239–243PubMedCrossRefGoogle Scholar
  42. 42.
    Valdes-Gonzalez RA, Dorantes LM, Garibay GN et al (2005) Xenotransplantation of porcine neonatal islets of Langerhans and Sertoli cells: a 4-year study. Eur J Endocrinol 153:419–427PubMedCrossRefGoogle Scholar
  43. 43.
    Elliott RB (2011) Towards xenotransplantation of pig islets in the clinic. Curr Opin Organ Transplant 16(2):195–200PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl-Gustav CarusPaul-Langerhans-Institut Dresden (PLID), Deutsches Zentrum für Diabetesforschung e. V. (DZD)DresdenDeutschland
  2. 2.Center for Regenerative Therapies Dresden (CRTD)DresdenDeutschland

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