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Die Diabetologie

Erschienen in:

26.07.2022 | Typ-1-Diabetes | Leitthema

Pankreasinseltransplantation – State of the Art

verfasst von: Prof. Dr. med. Barbara Ludwig, Roger Lehmann

Erschienen in: Die Diabetologie | Ausgabe 7/2022

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Zusammenfassung

Die Inseltransplantation stellt eine wirksame Therapieoption für Patienten mit instabilem Diabetes mellitus dar. Die Hauptindikationen für allogene Inseltransplantationen sind gehäufte Hypoglykämien und schwere metabolische Instabilität trotz optimierter Insulintherapie oder die simultane oder sequenzielle Insel-Nieren-Transplantation bei Patienten mit Diabetes mellitus Typ 1 und terminaler Niereninsuffizienz. Klare Definitionen von funktionellen Endpunkten und Therapieversagen trugen entscheidend zu einer positiven Anerkennung dieser Therapieform unter Diabetologen/Endokrinologen bei. In internationaler Zusammenarbeit haben Forschende eine kontinuierliche Optimierung der Inselprozessierung, des Patientenmanagements und der Entwicklung spezifischer immunsuppressiver Protokolle erreicht und dadurch die Ergebnisse signifikant verbessert. Exzellente metabolische Kontrolle, zuverlässige Vermeidung von Hypoglykämien und positive Effekte auf diabetesassoziierte Komplikationen und Lebensqualität wurden demonstriert. Die Inseltransplantation ist ein sicheres, minimalinvasives Verfahren, das potenziell eine funktionelle Heilung bei Menschen mit Diabetes mellitus Typ 1 bewirken kann. Aufgrund der limitierten Verfügbarkeit von Spenderorganen und der Notwendigkeit einer systemischen Immunsuppression bleibt diese Therapieoption jedoch einer ausgewählten Gruppe kritisch Kranker vorbehalten.

Pellegrini S, Cantarelli E, Sordi V, Nano R, Piemonti L (2016) The state of the art of islet transplantation and cell therapy in type 1 diabetes. Acta Diabetol 53(5):683–691PubMedCrossRef

Najarian JS, Sutherland DE, Matas AJ, Goetz FC (1979) Human islet autotransplantation following pancreatectomy. Transplant Proc 11(1):336–340PubMed

Najarian JS, Sutherland DE, Matas AJ, Steffes MW, Simmons RL, Goetz FC (1977) Human islet transplantation: a preliminary report. Transplant Proc 9(1):233–236PubMed

Piemonti L, Pileggi A (2013) 25 YEARS OF THE RICORDI AUTOMATED METHOD FOR ISLET ISOLATION. CellR4 Repair Replace Regen Reprogram 1(1):e128. PMID: 30505878. PMCID: PMC6267808PubMedPubMedCentral

Pellegrini S, Piemonti L, Sordi V (2018) Pluripotent stem cell replacement approaches to treat type 1 diabetes. Curr Opin Pharmacol 43:20–26PubMedCrossRef

Steffes MW, Sibley S, Jackson M, Thomas W (2003) Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 26(3):832–836PubMedCrossRef

Bjørgaas MR (2012) Cerebral effects of severe hypoglycemia in young people with type 1 diabetes. Pediatr Diabetes 13(1):100–107PubMedCrossRef

Zoungas S, Patel A, Chalmers J et al (2010) Severe hypoglycemia and risks of vascular events and death. N Engl J Med 363(15):1410–1418PubMedCrossRef

10.

Federlin K, Pozza G (1999) Indications for clinical islet transplantation today and in the forseeable future—the diabetologist’s point of view. J Mol Med 77(1):148–152PubMedCrossRef

11.

Choudhary P, Rickels MR, Senior PA et al (2015) Evidence-informed clinical practice recommendations for treatment of type 1 diabetes complicated by problematic hypoglycemia. Diabetes Care 38(6):1016–1029PubMedPubMedCentralCrossRef

12.

Rickels MR, Stock PG, de Koning EJP et al (2018) Defining outcomes for β‑cell replacement therapy in the treatment of diabetes: a consensus report on the Igls criteria from the IPITA/EPITA opinion leaders workshop. Transplantation 102(9):1479–1486PubMedPubMedCentralCrossRef

13.

14.

Alejandro R, Barton FB, Hering BJ, Wease S (2008) 2008 update from the collaborative islet transplant registry. Transplantation 86(12):1783–1788PubMedCrossRef

15.

Barton FB, Rickels MR, Alejandro R et al (2012) Improvement in outcomes of clinical islet transplantation: 1999–2010. Diabetes Care 35(7):1436–1445PubMedPubMedCentralCrossRef

16.

Hering BJ, Clarke WR, Bridges ND et al (2016) Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care 39(7):1230–1240PubMedPubMedCentralCrossRef

17.

Lablanche S, Vantyghem MC, Kessler L et al (2018) Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial. Lancet Diabetes Endocrinol 6(7):527–537PubMedCrossRef

18.

Maffi P, Lundgren T, Tufveson G et al (2020) Targeting CXCR1/2 does not improve insulin secretion after pancreatic islet transplantation: a phase 3, double-blind, randomized, placebo-controlled trial in type 1 diabetes. Diabetes Care 43(4):710–718PubMedPubMedCentralCrossRef

19.

Markmann JF, Rickels MR, Eggerman TL et al (2021) Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes. Am J Transplant 21(4):1477–1492PubMedCrossRef

20.

Johnson JA, Kotovych M, Ryan EA, Shapiro AM (2004) Reduced fear of hypoglycemia in successful islet transplantation. Diabetes Care 27(2):624–625PubMedCrossRef

21.

Leitão CB, Tharavanij T, Cure P et al (2008) Restoration of hypoglycemia awareness after islet transplantation. Diabetes Care 31(11):2113–2115PubMedPubMedCentralCrossRef

22.

Poggioli R, Faradji RN, Ponte G et al (2006) Quality of life after islet transplantation. Am J Transplant 6(2):371–378PubMedCrossRef

23.

Radosevich DM, Jevne R, Bellin M, Kandaswamy R, Sutherland DE, Hering BJ (2013) Comprehensive health assessment and five-yr follow-up of allogeneic islet transplant recipients. Clin Transplant 27(6):E715–724PubMedPubMedCentralCrossRef

24.

Tharavanij T, Betancourt A, Messinger S et al (2008) Improved long-term health-related quality of life after islet transplantation. Transplantation 86(9):1161–1167PubMedPubMedCentralCrossRef

25.

Toso C, Shapiro AM, Bowker S et al (2007) Quality of life after islet transplant: impact of the number of islet infusions and metabolic outcome. Transplantation 84(5):664–666PubMedCrossRef

26.

Vantyghem MC, de Koning EJP, Pattou F, Rickels MR (2019) Advances in β‑cell replacement therapy for the treatment of type 1 diabetes. Lancet 394(10205):1274–1285PubMedPubMedCentralCrossRef

27.

Vantyghem MC, Chetboun M, Gmyr V et al (2019) Ten-year outcome of islet alone or islet after kidney transplantation in type 1 diabetes: a prospective parallel-arm cohort study. Diabetes Care 42(11):2042–2049PubMedCrossRef

28.

Vantyghem MC, Raverdy V, Balavoine AS et al (2012) Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (β-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (β-score greater than 3). J Clin Endocrinol Metab 97(11):E2078–2083PubMedPubMedCentralCrossRef

29.

Reid L, Baxter F, Forbes S (2021) Effects of islet transplantation on microvascular and macrovascular complications in type 1 diabetes. Diabet Med 38(7):e14570PubMedCrossRef

30.

Cure P, Pileggi A, Froud T et al (2008) Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation. Transplantation 85(6):801–812PubMedCrossRef

31.

Fiorina P, Folli F, Zerbini G et al (2003) Islet transplantation is associated with improvement of renal function among uremic patients with type I diabetes mellitus and kidney transplants. J Am Soc Nephrol 14(8):2150–2158PubMedCrossRef

32.

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(6):1303–1310PubMedCrossRef

33.

Fung MA, Warnock GL, Ao Z et al (2007) The effect of medical therapy and islet cell transplantation on diabetic nephropathy: an interim report. Transplantation 84(1):17–22PubMedCrossRef

34.

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 centre follow-up. Diabetologia 51(1):110–119PubMedCrossRef

35.

Gillard P, Rustandi M, Efendi A et al (2014) Early alteration of kidney function in nonuremic type 1 diabetic islet transplant recipients under tacrolimus-mycophenolate therapy. Transplantation 98(4):451–457PubMedCrossRef

36.

Leitão CB, Cure P, Messinger S et al (2009) Stable renal function after islet transplantation: importance of patient selection and aggressive clinical management. Transplantation 87(5):681–688PubMedPubMedCentralCrossRef

37.

Maffi P, Bertuzzi F, De Taddeo F et al (2007) Kidney function after islet transplant alone in type 1 diabetes: impact of immunosuppressive therapy on progression of diabetic nephropathy. Diabetes Care 30(5):1150–1155PubMedCrossRef

38.

Senior PA, Zeman M, Paty BW, Ryan EA, Shapiro AM (2007) Changes in renal function after clinical islet transplantation: four-year observational study. Am J Transplant 7(1):91–98PubMedCrossRef

39.

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):373–378PubMedCrossRef

40.

Toso C, Baertschiger R, Morel P et al (2006) Sequential kidney/islet transplantation: efficacy and safety assessment of a steroid-free immunosuppression protocol. Am J Transplant 6(5 Pt 1:1049–1058CrossRef

41.

Lee TC, Barshes NR, O’Mahony CA et al (2005) The effect of pancreatic islet transplantation on progression of diabetic retinopathy and neuropathy. Transplant Proc 37(5):2263–2265PubMedCrossRef

42.

Venturini M, Fiorina P, Maffi P et al (2006) Early increase of retinal arterial and venous blood flow velocities at color Doppler imaging in brittle type 1 diabetes after islet transplant alone. Transplantation 81(9):1274–1277PubMedCrossRef

43.

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(12):1762–1766PubMedCrossRef

44.

D’Addio F, Maffi P, Vezzulli P et al (2014) Islet transplantation stabilizes hemostatic abnormalities and cerebral metabolism in individuals with type 1 diabetes. Diabetes Care 37(1):267–276PubMedCrossRef

45.

Del Carro U, Fiorina P, Amadio S et al (2007) Evaluation of polyneuropathy markers in type 1 diabetic kidney transplant patients and effects of islet transplantation: neurophysiological and skin biopsy longitudinal analysis. Diabetes Care 30(12):3063–3069PubMedCrossRef

46.

Vantyghem MC, Quintin D, Caiazzo R et al (2014) Improvement of electrophysiological neuropathy after islet transplantation for type 1 diabetes: a 5-year prospective study. Diabetes Care 37(6):e141–142PubMedCrossRef

47.

Danielson KK, Hatipoglu B, Kinzer K et al (2013) Reduction in carotid intima-media thickness after pancreatic islet transplantation in patients with type 1 diabetes. Diabetes Care 36(2):450–456PubMedPubMedCentralCrossRef

48.

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(4):1129–1136PubMedCrossRef

49.

Fiorina P, Folli F, Maffi P et al (2003) Islet transplantation improves vascular diabetic complications in patients with diabetes who underwent kidney transplantation: a comparison between kidney-pancreas and kidney-alone transplantation. Transplantation 75(8):1296–1301PubMedCrossRef

50.

Fiorina P, Gremizzi C, Maffi P et al (2005) Islet transplantation is associated with an improvement of cardiovascular function in type 1 diabetic kidney transplant patients. Diabetes Care 28(6):1358–1365PubMedCrossRef

51.

Lehmann R, Graziano J, Brockmann J et al (2015) Glycemic control in simultaneous islet-kidney versus pancreas-kidney transplantation in type 1 diabetes: a prospective 13-year follow-up. Diabetes Care 38(5):752–759PubMedCrossRef

Titel: Pankreasinseltransplantation – State of the Art
verfasst von: Prof. Dr. med. Barbara Ludwig
Roger Lehmann
Publikationsdatum: 26.07.2022
Verlag: Springer Medizin
Schlagwörter: Typ-1-Diabetes
Hypoglykämie
Nierentransplantation
Insuline
Nierentransplantation
Nierentransplantation
Nierentransplantation
Nierentransplantation
Insuline
Diabetes mellitus
Nierentransplantation
Erschienen in: Die Diabetologie / Ausgabe 7/2022
Print ISSN: 2731-7447
Elektronische ISSN: 2731-7455
DOI: https://doi.org/10.1007/s11428-022-00933-1

Praxisempfehlungen der Deutschen Diabetes Gesellschaft

Kurz, prägnant und aktuell: Die Praxisempfehlungen der Deutschen Diabetes Gesellschaft.

Zu den Praxisempfehlungen

Springer Medizin

Zusammenfassung

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