Der Diabetologe

, Volume 7, Issue 8, pp 576–584

Diabetesprävention bei Kindern

Leitthema
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Zusammenfassung

Der Typ-1-Diabetes stellt mit einer jährlichen Inzidenzsteigerung von 4,4% die häufigste Stoffwechselerkrankung bei Kindern und Jugendlichen dar. Die Manifestation der Erkrankung verschiebt sich immer weiter ins jüngere Lebensalter und bedeutet für die Patienten eine lebenslange s.c.-Insulin-Substitution. Präventionsstudien mit dem Ziel, der Entstehung des Autoimmunprozesses, der zum Typ-1-Diabetes führt, vorzubeugen (primäre Prävention) oder seine Entwicklung (sekundäre und tertiäre Prävention) zu verzögern, müssen daher sehr früh im Kindes- und Jugendalter beginnen. Der vorliegende Übersichtsbeitrag stellt Interventionsstudien vor, die an Kindern und Jugendlichen sowie in altersunabhängigen Kollektiven zurzeit durchgeführt werden oder bereits abgeschlossen sind. Die bisherigen Ergebnisse dieser Studien sowie die Vor- und Nachteile für Betroffene und ihre Familien, die mit einer Studienteilnahme verbunden sind, werden kritisch diskutiert.

Schlüsselwörter

Diabetes mellitus, Typ 1 Autoimmunität Insulin β-Zellen, pankreatisch Humane Leukozytenantigene 

Diabetes prevention in children

Abstract

Type 1 diabetes is the most frequent metabolic disease in children and adolescents with an increasing annual incidence of approximately 4.4%. Patients affected by type 1 diabetes are becoming younger and consequently have to inject insulin subcutaneously for their whole life span. Studies aiming at the prevention (primary prevention) or delay (secondary and tertiary prevention) of the autoimmune process causing type 1 diabetes must therefore be initiated during childhood and adolescence. The present review concentrates on recent or current diabetes prevention studies involving children and adolescents and discusses the pros and cons for study participants and their families.

Keywords

Diabetes mellitus, type 1 Autoimmunity Insulin Beta cells, pancreatic Human leukocyte antigens 

Literatur

  1. 1.
    Ehehalt S, Dietz K, Willasch AM et al (2011) Prediction model for the incidence and prevalence of type 1 diabetes in childhood and adolescence: evidence for a cohort-dependent increase within the next two decades in Germany. Pediatr Diabetes. doi: 10.1111/j.1399-5448.2011.00799.xGoogle Scholar
  2. 2.
    Patterson CC, Dahlquist GG, Gyürüs E et al (2009) Incidence trends for childhood type 1 diabetes in Europe during 1989–2003 and predicted new cases 2005–20: a multicentre prospective registration study. Lancet 373:2027–2033PubMedCrossRefGoogle Scholar
  3. 3.
    Harjutsalo V, Sjöberg L, Tuomilehto J (2008) Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 371:1777–1782PubMedCrossRefGoogle Scholar
  4. 4.
    Rosenbauer J, Stahl A (2010) Häufigkeit des Diabetes mellitus im Kindes- und Jugendalter in Deutschland. Diabetologe 6:177–189CrossRefGoogle Scholar
  5. 5.
    Mandrup-Poulsen T (1998) Diabetes. Br Med J 316:1221–1225CrossRefGoogle Scholar
  6. 6.
    Lenzen S (2011) The beta cell in diabetes. Dtsch Med Wochenschr 136:1123–1127PubMedCrossRefGoogle Scholar
  7. 7.
    Jörns A, Günther A, Hedrich HJ et al (2005) Immune cell infiltration, cytokine expression, and beta-cell apoptosis during the development of type 1 diabetes in the spontaneously diabetic LEW.1AR1/Ztm-iddm rat. Diabetes 54:2041–2052PubMedCrossRefGoogle Scholar
  8. 8.
    Eizirik DL, Colli ML, Ortis F (2009) The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol 5:219–226PubMedCrossRefGoogle Scholar
  9. 9.
    Lenzen S (2008) Oxidative stress: the vulnerable beta-cell. Biochem Soc Trans 36:343–347PubMedCrossRefGoogle Scholar
  10. 10.
    Achenbach P, Krause S, Ziegler A-G (2010) Pathogenese des Diabetes mellitus Typ 1– Update 2010. Diabetologie 5:R29–R46CrossRefGoogle Scholar
  11. 11.
    Knip M, Korhonen S, Kulmala P et al (2010) Prediction of type 1 diabetes in the general population. Diabetes Care 33:1206–1212PubMedCrossRefGoogle Scholar
  12. 12.
    Robles DT, Eisenbarth GS (2001) Type 1A diabetes induced by infection and immunization. J Autoimmun 16:355–362PubMedCrossRefGoogle Scholar
  13. 13.
    Walter M, Albert E, Conrad M et al (2003) IDDM2/insulin VNTR modifies risk conferred by IDDM1/HLA for development of type 1 diabetes and associated autoimmunity. Diabetologia 46:712–720PubMedCrossRefGoogle Scholar
  14. 14.
    Pozzilli P, Di Mario U (2001) Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention. Diabetes Care 24:1460–1467PubMedCrossRefGoogle Scholar
  15. 15.
    Greenbaum CJ, Mandrup-Poulsen T, McGee PF et al (2008) Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care 31:1966–1971PubMedCrossRefGoogle Scholar
  16. 16.
    Akerblom HK, Krischer J, Virtanen SM et al (2011) The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up. Diabetologia 54:627–633PubMedCrossRefGoogle Scholar
  17. 17.
    Norris JM, Barriga K, Klingensmith G et al (2003) Timing of initial cereal exposure in infancy and risk of islet autoimmunity. JAMA 290:1713–1720PubMedCrossRefGoogle Scholar
  18. 18.
    Ziegler AG, Schmid S, Huber D et al (2003) Early infant feeding and risk of developing type 1 diabetes-associated autoantibodies. JAMA 290:1721–1728PubMedCrossRefGoogle Scholar
  19. 19.
    Hummel S, Pflüger M, Hummel M et al (2011) Primary dietary intervention study to reduce the risk of islet autoimmunity in children at increased risk for type 1 diabetes: the BABYDIET study. Diabetes Care 34:1301–1305PubMedCrossRefGoogle Scholar
  20. 20.
    Achenbach P, Barker J, Bonifacio E, Pre-POINT Study Group (2008) Modulating the natural history of type 1 diabetes in children at high genetic risk by mucosal insulin immunization. Curr Diab Rep 8:87–93PubMedCrossRefGoogle Scholar
  21. 21.
    Gale EA, Bingley PJ, Emmett CL et al (2004) European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 363:925–931PubMedCrossRefGoogle Scholar
  22. 22.
    Lampeter EF, Klinghammer A, Scherbaum WA et al (1998) The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS group. Diabetes 47:980–984PubMedCrossRefGoogle Scholar
  23. 23.
    Skyler JS, Krischer JP, Wolfsdorf J et al (2005) Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial – Type 1. Diabetes Care 28:1068–1076PubMedCrossRefGoogle Scholar
  24. 24.
    Diabetes Prevention Trial – Type 1 Diabetes Study Group (2002) Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 346:1685–1691CrossRefGoogle Scholar
  25. 25.
    Näntö-Salonen K, Kupila A, Simell S et al (2008) 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 372:1746–1755PubMedCrossRefGoogle Scholar
  26. 26.
    The Diabetes Control and Complications Trial Research Group (1198) Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med 128:517–523Google Scholar
  27. 27.
    Nathan DM, Cleary PA, Backlund JY et al (2005) Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353:2643–2653PubMedCrossRefGoogle Scholar
  28. 28.
    Ludvigsson J, Faresjö M, Hjorth M et al (2008) GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med 359:1909–1920PubMedCrossRefGoogle Scholar
  29. 29.
    Ludvigsson J, Hjorth M, Chéramy M et al (2011) Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. Diabetologia 54:634–640PubMedCrossRefGoogle Scholar
  30. 30.
    Ludvigsson et al. (2012) # eingereichtGoogle Scholar
  31. 31.
    Wherrett DK, Bundy B, Becker DJ et al (2011) Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial. Lancet 378:319–327PubMedCrossRefGoogle Scholar
  32. 32.
    Wallner M, Thümer L, Hummel M, Ziegler AG (2011) Therapie des Typ-1-Diabetes im Wandel – Neue Möglichkeiten durch Immunintervention? Diabetologie 6:98–103CrossRefGoogle Scholar
  33. 33.
    Chatenaud L (2010) Immune therapy for type 1 diabetes mellitus – what is unique about anti-CD3 antibodies? Nat Rev Endocrinol 6:149–157CrossRefGoogle Scholar
  34. 34.
    Keymeulen B, Walter M, Mathieu C et al (2010) Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia 53:614–623PubMedCrossRefGoogle Scholar
  35. 35.
    Herold KC, Hagopian W, Auger JA et al (2002) Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346:1692–1698PubMedCrossRefGoogle Scholar
  36. 36.
    Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H et al (2009) Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med 361:2143–2152PubMedCrossRefGoogle Scholar
  37. 37.
    Mastrandrea L, Yu J, Behrens T et al (2009) Etanercept treatment in children with new-onset type 1 diabetes: pilot randomized, placebo-controlled, double-blind study. Diabetes Care 32:1244–1249PubMedCrossRefGoogle Scholar
  38. 38.
    Gottlieb PA, Quinlan S, Krause-Steinrauf H et al (2010) Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new-onset type 1 diabetes. Diabetes Care 33:826–832PubMedCrossRefGoogle Scholar
  39. 39.
    Hummel M, Ziegler AG, Roth R (2004) Psychological impact of childhood islet autoantibody testing in families participating in the BABYDIAB study. Diabet Med 21:324–328PubMedCrossRefGoogle Scholar
  40. 40.
    Bennett Johnson S, Baughcum AE, Carmichael SK et al (2004) Maternal anxiety associated with newborn genetic screening for type 1 diabetes. Diabetes Care 27:392–397CrossRefGoogle Scholar
  41. 41.
    Goldstein E, Hermann R, Renfors TJ et al (2009) From genetic risk awareness to overt type 1 diabetes: parental stress in a placebo-controlled prevention trial. Diabetes Care 32:2181–2183PubMedCrossRefGoogle Scholar
  42. 42.
    Barker JM, Goehrig SH, Barriga K et al (2004) Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care 27:1399–1404PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Allgemeine Kinderheilkunde, Diabetologie, Endokrinologie und Klinische Forschung Auf der Bult, Kinder- und JugendkrankenhausHannoverDeutschland

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