Inselzelltransplantation bei Diabetes mellitus – ein Prototyp translationaler Forschung

Zusammenfassung

Die Inselzelltransplantation erzielt in ausgewählten Zentren deutlich größere Erfolge und stellt ­inzwischen eine Alternative zur Pankreasorgantransplantation dar. Mögliche Empfänger sind Typ-1-Diabetiker ohne signifikante Insulin-Restsekretion mit Hypoglykämie-Syndrom bzw. schwerst einstellbarem Diabetes (Brittle-Diabetes), mit terminaler Niereninsuffizienz und geplanter simultaner Nierentransplantation, mit bereits vorangegangener Nierentransplantation oder geplanter simultaner bzw. vorangegangener anderweitiger Organtransplantation. Durch eine Inselzelltransplantation wird nach Registerdaten das primäre Therapieziel einer erhaltenen Insel­transplantatfunktion mit sehr guter und stabi­ler Stoffwechseleinstellung sowie Vermeidung schwerer Hypoglykämien in der Mehrzahl der Fälle erreicht. Die gegenwärtigen Erfolgsraten betrag­en 1 Jahr nach Transplantation 82 %, nach 3 Jahren 75 %. Am erfahrensten Zentrum Edmonton, Kanada liegt die Rate nach 8 Jahren bei 67 %. Damit einher geht eine signifikante Verbesserung der Lebensqualität und eine gegenüber intensivierter konventioneller Insulintherapie stärkere Progressionshemmung diabetischer Sekundärkomplikationen. Das Maximalziel einer kom­pletten Insulinunabhängigkeit lässt sich gemäß Registerdaten seltener als nach Pankreasorgantransplantation erreichen. Die Erfolgsraten be­tragen 1 Jahr nach Transplantation 43–50 %, nach 3 Jahren 35 %. Am erfahrensten Zentrum Edmonton, Kanada liegt die Rate nach 8 Jahren bei 13 %. Einzelfälle mit deutlich länger erhaltener Insu­linunabhängigkeit nach Inselzelltransplantation sind aber aus verschiedenen Zentren berichtet. Die gegenwärtig noch ungelösten Probleme – eine lebenslang erforderliche Immunsuppression und ein im Langzeitverlauf häufiger werdendes Inseltransplantatversagen – scheinen prinzipiell lösbar. Eine intensive Forschung mit unterschiedlichen Lösungsstrategien hat eingesetzt. In Deutschland sind ­neben dem langjährig auf diesem Gebiet tätigen und mit 105 inseltransplantierten Patienten erfahrenem Zentrum an der Universität Gießen kürzlich weitere klinische Inselzelltransplantationsprogramme in Dresden, Freiburg und Tübingen gestartet worden mit bisher 5 Patienten in Dresden. Es besteht Konsens, dass den Patienten mit einem Typ-1-Diabetes, bei ­denen sich die Indikation zum biologischen Inselersatz stellt, beide Therapieverfahren angeboten und dabei die Vor- und Nach­teile einer Pankreasorgantransplantation und einer Inselzelltransplantation sorgfältig diskutiert und individuell abgewogen werden sollten.

Abstract

More than 700 patients have been islet-trans­plant­ed in more than 50 centers worldwide dur­ing the last decade. Islet cell transplantation in selected centers achieved significant success and makes this method an alternative to pancreas ­organ transplantation. Candidates for an islet transplant are patients with type 1 diabetes with no residual insulin secretion suffering from hypo­glycemia-associated syndrome and “brittle-diabetes”; with renal end-stage disease waiting for a kidney transplant; with previous kidney graft or waiting for a simultaneous or after previous transplantation of another organ. Based on reg­istry data, the primary goal of persistent islet graft function with optimal and stable metabolic control avoiding severe hypoglycemic episodes has been achieved in the majority of cases. The success rates are 82 % and 75 % after 1 year and 3 years, respectively. The most experienced center of the University of Alberta in Edmonton / Canada reported a success rate of 67 % after 8 years. Successful islet transplantation is accompanied by significantly improved quality of life and a greater halt of progression of diabetic secondary com­plications compared to intensified conventional insulin therapy. Compared to pancreas organ transplantation, the ultimate goal of insulin independence has been achieved to a lesser extent by islet transplantation. The success rates are 43–50 % and 35 % after 1 year and 3 years, respectively. The most experienced center of the University of Alberta in Edmonton / Canada reported a success rate of 13 % after 8 years. The current problems – the need for a life-long immunosuppressive treatment of the recipient and a progressive loss of ­islet graft function – may be solved in the future. Large research activities with different strategies have been started. The German Islet Cell Transplant Center of the Justus-Liebig-University in Gießen has accomplished large experience with 105 islet-transplanted patients over two decades. Recently, new clinical islet transplant programs have been started in Germany at the Universities of Dresden, Freiburg, and Tübingen with 5 islet-transplanted patients at Dresden Center so far. There is consensus, that type 1 diabetic patients elected for a biological islet replacement therapy should be offered both treatment options, pancreas organ and pancreatic islet cell transplantation. It is also recommended that the advantages and disadvantages of each of the methods has to be carefully discussed with the patient in focus and the final decision should be made on an individual basis.

Schlüsselwörter

Inselzelltransplantation - Pankreasorgantransplantation - Typ-1-Diabetes - chronische Niereninsuffizienz - Hypoglykämie-Syndrom - Internationales Inseltransplantationsregister (ITR) - Internationales Pankreastransplantationsregister (IPTR)

Key words

islet cell transplantation - pancreas transplantation - type 1 diabetes - end-stage renal disease - hypoglycemia-associated syndrome - International Islet Transplant Registry (ITR) - International Pancreas Transplant Registry (IPTR)

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