Immunintervention zum Betazellerhalt bei Typ-1-Diabetes

Zusammenfassung

Der Typ 1 Diabetes ist eine chronische immune-mediierte Erkrankung, die zur selektiven Zerstörung der Insulin-produzierenden β-Zellen führt. Die Inzidenz des Typ 1 Diabetes steigt weltweit. In den letzten Jahren wurden eine Vielzahl von Studien durchgeführt, um die Krankheitsprogression nach Diagnose (tertiäre Prävention), bei Risikopersonen mit positivem Nachweisvon Typ 1 Diabetes-assoziierten Inselautoantikörpern (sekundäre Prävention) oder bei genetisch prädisponierten Kindern ohne Inselautoantikörper (primäre Prävention) aufzuhalten. Einige Studien zur Tertiärprävention konnten zeigen, dass mittels anti-entzündlicher, T-Zell gerichteter, Antigen-spezifischer Ansätze oder Stammzelltherapie die Krankheitsprogression verlangsamt, jedoch in den meisten Fällen nicht gestoppt oder zur Remission gebracht werden konnte.

Abstract

Type 1 diabetes is a chronic immune mediated disease leading to selective loss of insulin producing ß-cells. The incidence of type 1 diabetes has been rising. In past years quite a number of studies have been performed that aim to mitigate disease progression after diagnosis (tertiary prevention), in islet-antibody positive subjects at increased diabetes risk (secondary prevention) or in subjects genetically at risk but without autoantibodies (primary prevention). Studies of tertiary prevention are based on anti-inflammatory, T-cell directed, antigen-specific or stem cell approaches. Amelioration of disease course has been seen in a few of these trials, but no therapeutic regimen has so far been developed to cure type 1 diabetes after its clinical manifestation.

Typ-1-Diabetes - Betazellerhalt - Immunmodulation

type 1 diabetes - beta-cell function - immunomodulation

Literatur

• 1 Barker J M, Liu E. Celiac disease: pathophysiology, clinical manifestations, and associated autoimmune conditions.  Adv Pediatr. 2008;  55 349-65
• 2 Bonifacio E, Achenbach P, Pan L, Ziegler A G. Mucosal insulin vaccination for type 1 diabetes prevention.  Exp Clin Endocrinol Diabetes. 2008;  116, Suppl 1 S26-29
• 3 Couri C E, Oliveira M C, Stracieri A B, Moraes D A, Pieroni F, Barros G M, Madeira M I, Malmegrim K C, Foss-Freitas M C, Simões B P, Martinez E Z, Foss M C, Burt R K, Voltarelli J C. Hematopoietic stem cell transplantation in newly diagnosed type 1 diabetes mellitus.  J Am Med Assoc. 2009;  301 1573-1579
• 4 Diabetes prevention trial study grout DPT 1 . Effects of insulin in relatives of patients with type 1 diabetes mellitus.  N Engl J Med. 2002;  346 1685-1691
• 5 Ehehalt S, Blumenstock G, Willasch A M. et al . Continuous rise in incidence of childhood Type 1 diabetes in Germany.  Diabet Med. 2008;  25 755-757
• 6 Eisenbarth G S. Type 1 Diabetes mellitus, A chronic autoimmune disease.  N Engl J Med. 1986;  341 1360-1368
• 7 Eisenbarth G S, Jeffrey J. The natural history of type 1A diabetes.  Arq Bras Endocrinol Metabol. 2008;  52 146-155
• 8 Elias D, Cohen I R. Treatment of autoimmune diabetes and insulitis in NOD mice with heat shock protein 60 peptide p277.  Diabetes. 1995;  44 1132-1138
• 9 EURODIAB ACE Study Group . Variation and trends in incidence of childhood diabetes in Europe.  Lancet. 2000;  355 873-876
• 10 Feltbower R G, Bodansky H J, Patterson C C, Parslow R C, Stephenson C R, Reynolds C, McKinney P A. Acute complications and drug misuse are important causes of death for children and young adults with type 1 diabetes: results from the Yorkshire Register of diabetes in children and young adults.  Diabetes Care. 2008;  31 922-926
• 11 Fourlanos S, Varney M D, Tait B D. et al . The rising incidence of type 1 diabetes is accounted for by cases with lower-risk human leukocyte antigen genotypes.  Diabetes Care. 2008;  31 1546-1549
• 12 Gale E A, Bingley P J, Emmett C L, Collier T. European Nicotinamide Diabetes Intervention Trial (ENDIT) Group . European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes.  Lancet. 2004;  363 925-931
• 13 Gottlieb P A, Eisenbarth G S, Harrsion L, Colman P, Roep B, Quan J, Sovason N, Steinman L, Garren H. BHT-3021 Study Group . Interimresults of a phase I/II clinical trial of a DNA plasmid vaccine (BHT3021) for type 1 diabetes.  Diabetologia. 2009;  52, suppl 1 S83, Abstract 188
• 14 Greenbaum C J, Mandrup-Poulsen T, McGee P F, Battelino T, Haastert B, Ludvigsson J, Pozzilli P, Lachin J M, Kolb H. Type 1 Diabetes Trial Net Research Group; European C-Peptide Trial Study Group (Schloot N) . Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes.  Diabetes Care. 2008;  31 1966-1971
• 15 Haller M J, Wasserfall C H, McGrail K M, Cintron M, Brusko T M, Wingard J R, Kelly S S, Shuster J J, Atkinson M A, Schatz D A. Autologous umbilical cord blood transfusion in very young children with type 1 diabetes.  Diabetes Care. 2009;  32 2138-2139
• 16 Harjutsalo V, Sjoberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study.  Lancet. 2008;  371 1777-1782
• 17 Herold K C, Gitelman S E, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan D M, Bluestone J A. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes.  Diabetes. 2005;  54 1763-1769
• 18 Huurman V A, Decochez K, Mathieu C, Cohen I R, Roep B O. Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients.  Diabetes Metab Res Rev. 2007;  23 269-275
• 19 Jörns A, Akin M, Taivankhuu, Meyer zu Vilsendorf A, Lenzen S. Protection of the beta cell function by treatment with a rat specific CD3 antibody alone or in combination iwht the immunomodulatory agent FTY720 in the IDDM rat, an animal modle of human type 1 diabetes.  Diabetologia. 2009;  52, Suppl 1 S198, Abstract 495
• 20 Kempf K, Manzo G, Hanifi-Moghaddam P, Kappler S, Seissler, Jaeger C, Boehm B, Roden M, Kolb H, Martin S, Schloot N C. for the PRODIAB Study Group . Effect of combined oral proteases and flavonoid treatment in subjects at risk for type 1 diabetes.  (letter) Diabet Med. 2009;  26 1309-1310
• 21 Keymeulen B, Vandemeulebroucke E, Ziegler A G, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin J M, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach J F, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes.  N Engl J Med. 2005;  352 2598-2608
• 22 Lammi N, Blomstedt P A, Moltchanova E. et al . Marked temporal increase in the incidence of type 1 and type 2 diabetes among young adults in Finland.  Diabetologia. 2008;  51 897-899
• 23 Larsen C M, Faulenbach M, Vaag A, Vølund A, Ehses J A, Seifert B, Mandrup-Poulsen T, Donath M Y. Interleukin-1-receptor antagonist in type 2 diabetes mellitus.  N Engl J Med. 2007;  356 1517-1526
• 24 Lazar L, Ofan R, Weintrob N, Avron A, Tamir M, Elias D, Phillip M, Josefsberg Z. Heat-shock protein peptide DiaPep277 treatment in children with newly diagnosed type 1 diabetes: a randomised, double-blind phase II study.  Diabetes Metab Res Rev. 2007;  23 286-291
• 25 Ludvigsson J, Faresjö M, Hjorth M, Axelsson S, Chéramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson N O, Aman J, Ortqvist E, Zerhouni P, Casas R. GAD treatment and insulin secretion in recent-onset type 1 diabetes.  N Engl J Med. 2008;  359 1909-1920
• 26 Martin S, Herder C, Schloot N C, Heise T, Heinemann L, Kolb H. DIATOR study group . .  Preservation of residual beta cell function in newly diagnosed type 1 diabetes by treatment with atorvastatin: the DIATOR trial.. 2009;  52, suppl 1 S199, Abstract 496
• 27 Mastrandrea L, Yu J, Behrens T. et al . Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study.  Diabetes Care. 2009;  32 1244-1249
• 28 Mineo D, Pileggi A, Alejandro R, Ricordi C. Point: steady progress and current challenges in clinical islet transplantation.  Diabetes Care. 2009;  32 1563-1569
• 29 Näntö-Salonen K, Kupila A, Simell S, Siljander H, Salonsaari T, Hekkala A, Korhonen S, Erkkola R, Sipilä J I, Haavisto L, Siltala M, Tuominen J, Hakalax J, Hyöty H, Ilonen J, Veijola R, Simell T, Knip M, Simell O. Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial.  Lancet. 2008;  372 1746-1755
• 30 Pfleger C, Mortensen H B, Hansen L, Herder C, Roep B O, Hoey H, Aanstoot H J, Kocova M, Schloot N C. ON BEHALF OF THE HVIDØRE STUDY GROUP ON CHILDHOOD DIABETES . Association of IL-1ra and adiponectin with C-peptide and remission in patients with type 1 diabetes.  Diabetes. 2008;  57 929-937
• 31 Pickersgill L M, Mandrup-Poulsen T R. on behalf of the AIDA study group . The anti-interleukin-1 in type 1 diabetes action trial – background and rationale.  Diabetes Metab Res Rev. 2009;  25 321-324
• 32 Raz I, Avron A, Tamir M, Metzger M, Symer L, Eldor R, Cohen I R, Elias D. Treatment of new-onset type 1 diabetes with peptide DiaPep277 is safe and associated with preserved beta-cell function.  Diabetes Metab Res Rev. 2007;  23 292-298
• 33 Raz I, Elias D, Avron A, Tamir M, Metzger M, Cohen I R. Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277).  Lancet. 2001;  358 1749-1753
• 34 Rother K I, Brown R J, Morales M M, Wright E, Duan Z, Campbell C, Hardin D S, Popovic J, McEvoy R C, Harlan D M, Orlander P R, Brod S A. Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes.  Diabetes Care. 2009;  32 1250-1255
• 35 Schloot N C, Meierhoff G, Lengyel C, Vandorfi G, Takacs J, Panczel P, Barkai L, Madacsy L, Oroszlan T, Kovacs P, Suto G, Battelino T, Hosszufalusi N, Jermendy G. Effect of heat shock protein peptide DiaPep277 on ß-cell function in paediatric and adult patients with recent-onset diabetes mellitus type 1.  Diabetes Metab Res Rev. 2007;  23 276-285
• 36 Schloot N C, Roep B O. Islet antigen-specific T cell clones in autoimmune diabetes: from mice to men.  Diabetes Metab Rev. 1997;  13 127-138
• 37 Steffes M W, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial.  Diabetes Care. 2003;  26 832-836
• 38 Zipitis C S, Akobeng A K. Vitamin D supplementation in early childhood and risk of type 1 diabetes.  Arch Dis Child. 2008;  93 512-517