Manifestation eines Typ-1-Diabetes verzögern?

ZUSAMMENFASSUNG

Typ-1-Diabetes hat eine präsymptomatische Phase, die durch den Nachweis von Inselautoantikörpern diagnostiziert werden kann. Dabei werden das Stadium 1 (> 1 Inselautoantikörper ohne Dysglykämie) und Stadium 2 (> 1 Inselautoantikörper mit Dysglykämie) unterschieden. Eine Anti-CD3-Therapie kann den fortschreitenden Verlust der Betazellfunktion nach Manifestation verlangsamen. Kürzlich wurde zudem gezeigt, dass eine 14-tägige Behandlung mit dem monoklonalen Anti-CD3-Antikörper Teplizumab die Manifestation eines Typ-1-Diabetes bei Menschen mit präsymptomatischem Diabetes im Stadium 2 um durchschnittlich fast 3 Jahre verzögern kann. Diese Therapie ist nun bei den zuständigen Behörden eingereicht worden und wir erwarten die erste offiziell zugelassene Therapie zur Prävention eines Typ-1-Diabetes.

Publication History

Article published online:
17 May 2022

• Literatur

• 1 Bonifacio E. Predicting type 1 diabetes using biomarkers. Diabetes Care 2015; 38: 989-996
• 2 Insel RA, Dunne JL, Atkinson MA. 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
• 3 American Diabetes Association Professional Practice Committee Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2022. Diabetes Care 2022; 45 (01) S17-S38
• 4 Lord S, Greenbaum CJ. Disease modifying therapies in type 1 diabetes: Where have we been, and where are we going?. Pharmacol Res 2015; 98: 3-8
• 5 Herold KC, Bundy BN, Long SA. et al An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes [published correction appears in N Engl J Med 2020; 382: 586]. N Engl J Med 2019; 381: 603-613
• 6 Alegre ML, Peterson LJ, Xu D. et al A non-activating „humanized“ anti-CD3 monoclonal antibody retains immunosuppressive properties in vivo. Transplantation 1994; 57: 1537-1543
• 7 Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 2007; 07: 622-632
• 8 Long SA, Thorpe J, DeBerg HA. et al Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol 2016; 01: eaai7793
• 9 Herold KC, Hagopian W, Auger JA. et al Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 2002; 346: 1692-1698
• 10 Herold KC, Gitelman SE, Masharani U. et al A single course of anti-CD3 monoclonal antibody hOKT3γ1(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
• 11 Sherry N, Hagopian W, Ludvigsson J. et al Protégé Trial Investigators Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet 2011; 378: 487-497
• 12 Hagopian W, Ferry Jr RJ, Sherry N. et al Protégé Trial Investigators. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Diabetes 2013; 62: 3901-3908
• 13 Perdigoto AL, Preston-Hurlburt P, Clark P. et al Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis. Diabetologia 2019; 62: 655-664
• 14 Keymeulen B, Vandemeulebroucke E, Ziegler AG. et al Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med 2005; 352: 2598-2608
• 15 Keymeulen B, Walter M, Mathieu C. et al 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 2010; 53: 614-623
• 16 Aronson R, Gottlieb PA, Christiansen JS. et al DEFEND Investigator Group. Low-dose otelixizumab anti-CD3 monoclonal antibody DEFEND-1 study: results of the randomized phase III study in recent-onset human type 1 diabetes. Diabetes Care 2014; 37: 2746-2754
• 17 Sims EK, Bundy BN, Stier K. et al Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 2021; 13: eabc8980
• 18 Sims EK, Cuthbertson D, Herold KC, Sosenko JM. The Deterrence of Rapid Metabolic Decline Within 3 Months After Teplizumab Treatment in Individuals at High Risk for Type 1 Diabetes. Diabetes 2021; 70: 2922-2931
• 19 Rawshani A, Sattar N, Franzén S. et al Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study. Lancet 2018; 392: 477-486