Typ-1-Diabetes: Screening, Prävention und neue Therapien

ZUSAMMENFASSUNG

Typ-1-Diabetes entsteht durch eine immunvermittelte Zerstörung der Betazellen in den Langerhans-Inseln der Bauchspeicheldrüse. Dieser Autoimmunprozess führt zu einer chronischen Stoffwechselerkrankung mit lebenslangem absolutem Insulinmangel. Der Fokus der Behandlung liegt aktuell auf der Korrektur der Hyperglykämie mittels Insulintherapie. Zudem hat das Verständnis der zugrundeliegenden Immunpathogenese der Erkrankung die Entwicklung von neuen präventiven und therapeutischen Ansätzen vorangetrieben. Diese zielen darauf ab, das Entstehen bzw. die Progression des Autoimmunprozesses zu verhindern oder zu verzögern, um Betazellfunktion zu erhalten. In den USA wurde im November 2022 erstmals ein Immuntherapeutikum, der anti-CD3-Antikörper Teplizumab, zur Anwendung vor klinischer Manifestation der Stoffwechselerkrankung zugelassen – ein Meilenstein in der Therapie des Typ-1-Diabetes.

Publication History

Article published online:
26 June 2023

• Literatur

• 1 Atkinson MA. et al Type 1 diabetes. Lancet 2014; 383: 69-82
• 2 IDF Diabetes Atlas. 9th. International Diabetes Federation (IDF); 2019 20.04.2020
• 3 Patterson CC. et al Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Research and Clinical Practice 2019; 157: 107842
• 4 Harjutsalo V. et al Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008; 371: 1777-1782
• 5 Ziegler AG, Bonifacio E. BABYDIAB-BABYDIET Study Group. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012; 55: 1937-1943
• 6 Parikka V. et al Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia 2012; 55: 1926-1936
• 7 Krischer JP. et al The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015; 58: 980-987
• 8 Bonifacio E, Achenbach P. Birth and coming of age of islet autoantibodies. Clin Exp Immunol 2019; 198: 294-305
• 9 Ziegler AG. et al Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013; 309: 2473-2479
• 10 Insel RA. et al Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care 2015; 38: 1964-1974
• 11 ElSayed NA. et al 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46: S19-S40
• 12 Rewers A. et al Incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado youth, 1998–2012. JAMA 2015; 313: 1570-1572
• 13 Karges B. et al Frequency and influencing factors of ketoacidosis at diabetes onset in children and adolescents – a long-term study between 1995 and 2009. Klinische Pädiatrie 2011; 223: 70-73
• 14 Alonso GT. et al Diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado children, 2010–2017. Diabetes Care 2020; 43: 117-121
• 15 Kovacs M. et al Initial Psychologic Responses of Parents to the Diagnosis of Insulin-dependent Diabetes Mellitus in Their Children. Diabetes Care 1985; 08: 568-575
• 16 Hauenstein EJ. et al Stress in Parents of Children With Diabetes Mellitus. Diabetes Care 1989; 12: 18-23
• 17 Viner R. et al Family stress and metabolic control in diabetes. Arch Dis Child 1996; 74: 418-421
• 18 Cameron FJ. et al Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. Diabetes Care 2014; 37: 1554-1562
• 19 Fredheim S. et al Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels. Diabetologia 2013; 56: 995-1003
• 20 Duca LM. et al Diabetic ketoacidosis at diagnosis of type 1 diabetes predicts poor long-term glycemic control. Diabetes Care 2017; 40: 1249-1255
• 21 Livingstone SJ. et al Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008–2010. JAMA 2015; 313: 37-44
• 22 Raab J. et al Capillary blood islet autoantibody screening for identifying pre-type 1 diabetes in the general population: Design and initial results of the Fr1da study. BMJ Open 2016; 06: e011144
• 23 Ziegler A-G. et al Yield of a Public Health Screening of Children for Islet Autoantibodies in Bavaria, Germany. JAMA 2020; 323: 339-351
• 24 Weiss A. et al Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening. Diabetologia 2022; 65: 2121-2131
• 25 Achenbach P. et al Mature high-affinity immune responses to (pro)insulin anticipitate the autoimmune cascade that leads to type 1 diabetes. J Clin Invest 2004; 114: 589-597
• 26 Skyler JS. et al Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial – Type 1. Diabetes Care 2005; 28: 1068-1076
• 27 Krischer JP. et al Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes: A Randomized Clinical Trial. JAMA 2017; 318: 1891-1902
• 28 Bonifacio E. et al Effects of high dose oral insulin on immune responses in children at high risk for type 1 diabetes: the Pre-POINT randomized clinical trial. JAMA 2015; 313: 1541-1549
• 29 Kick K. et al Recruiting young pre-symptomatic children for a clinical trial in type 1 diabetes: Insights from the Fr1da insulin intervention study. Contemp Clin Trials Commun 2018; 11: 170-173
• 30 Ziegler AG. et al Type 1 Diabetes Primary Prevention Trial – The GPPAD-POInT study design. BMJ Open 2019; 09: e028578
• 31 Long SA. et al Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol 2016; 01: eaai7793
• 32 Long SA. et al Remodeling T cell compartments during anti-CD3 immunotherapy of type 1 diabetes. Cell Immunol 2017; 319: 3-9
• 33 Perdigoto AL. et al Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2019; 62: 655-664
• 34 Herold KC. et al An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med 2019; 381: 603-613
• 35 Sims EK. et al Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 2021; 13: eabc8980
• 36 Teichgräber FJ, Ziegler AG.. Der Beginn einer neuen Therapieära. Deutsche Apotheker Zeitung 6/2023 https://www.deutsche-apotheker-zeitung.de/daz-az/2023/daz-6-2023/der-beginn-einer-neuen-therapieaera
• 37 Forlenza GP. et al Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial. JAMA 2023; 329: 990-999