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      Typ-1-Diabetes: Früherkennung und Ansätze zur Prävention : Update 2020 Translated title: Type 1 diabetes: Early diagnosis and preventive approaches : Update 2020

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          Abstract

          Die Inzidenz des Typ-1-Diabetes nimmt zu, besonders bei Kleinkindern. Die Erkrankung kann effektiv bereits im asymptomatischen Frühstadium der Inselautoimmunität erkannt werden. Ein Screening ist nicht nur für Risikofamilien, sondern auch in bevölkerungsweiten Studien wie Fr1da plus in Bayern möglich und sinnvoll. Komplikationen bei der Manifestation kann durch eine frühe Diagnosestellung vorgebeugt werden. Die Teilnahme an experimentellen Interventionen zur Verzögerung der Stadienprogression ist möglich. Unterschiedliche Ansätze zur sekundären Prävention werden verfolgt. Mit dem monoklonalen Antikörper Teplizumab gelang es erstmals, bei Patienten in Stadium 2 den Zeitpunkt der Manifestation hinauszuzögern. Säuglinge mit einem hohen Risiko für die Entwicklung eines Typ-1-Diabetes können durch genetisches Screening identifiziert werden. Bei der Primärprävention wird u. a. das Ziel verfolgt, das Entstehen der Autoimmunreaktion zu verhindern. In der POInT-Studie sollen bei Risikokindern durch frühe orale Exposition zu Insulin die Immuntoleranz verbessert und das Auftreten eines Frühstadiums verzögert oder verhindert werden.

          Anknüpfend an das Leitthemenheft Früherkennung und präventive Behandlung des Typ-1-Diabetes dieser Zeitschrift von 2018 werden in diesem Beitrag ausgewählte Entwicklungen als Update der letzten 2 Jahre vorgestellt.

          Translated abstract

          The incidence of type 1 diabetes is increasing, especially in young children. Early diagnosis is possible in the asymptomatic stage of islet autoimmunity. Screening is offered to high-risk families, but also feasible and useful in the general population, in studies such as Fr1da plus in Bavaria (Germany). Complications at clinical manifestation can be prevented by early diagnosis. Participation in experimental interventions to delay stage progression is possible. Numerous approaches to secondary prevention are being pursued. Treatment with the monoclonal antibody teplizumab successfully delayed progression to clinical diabetes in patients in stage 2. Infants at high risk for developing type 1 diabetes can be identified by genetic screening. Primary prevention pursues, among others, the goal of preventing the onset of the autoimmune reaction. The POInT trial aims to improve immune tolerance to insulin by oral exposure in high-risk children and to delay or prevent the onset of autoimmunity.

          Following up on the focus issue “Early detection and preventive treatment of type 1 diabetes” published in this journal in 2018, this article gives an update on selected developments over the past 2 years.

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          Most cited references31

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          An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes

          Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.
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            Type 1 diabetes—early life origins and changing epidemiology

            Type 1 diabetes is a chronic, immune-mediated disease characterised by the destruction of insulin-producing cells. Standardised registry data show that type 1 diabetes incidence has increased 3–4% over the past three decades, supporting the role of environmental factors. Although several factors have been associated with type 1 diabetes, none of the associations are of a magnitude that could explain the rapid increase in incidence alone. Moreover, evidence of changing prevalence of these exposures over time is insufficient. Multiple factors could simultaneously explain the changing type 1 diabetes incidence, or the magnitude of observed associations could have been underestimated because of exposure measurement error, or the mismodelling of complex exposure-time-response relationships. The identification of environmental factors influencing the risk of type 1 diabetes and increased understanding of the cause at the individual level, regardless of the ability to explain the changing incidence at the population level, is important because of the implications for prevention.
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              Is Open Access

              Teplizumab Preserves C-Peptide in Recent-Onset Type 1 Diabetes

              Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC >0.2 nmol/L, those randomized ≤6 weeks after diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4 units/kg/day, and 8–17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.
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                Author and article information

                Contributors
                benjamin.marcus@helmholtz-muenchen.de
                Journal
                Diabetologe
                Der Diabetologe
                Springer Medizin (Heidelberg )
                1860-9716
                1860-9724
                19 August 2020
                : 1-7
                Affiliations
                [1 ]GRID grid.15474.33, ISNI 0000 0004 0477 2438, Forschergruppe Diabetes der Technischen Universität München, , Klinikum rechts der Isar, ; Heidemannstr. 1, 80939 München, Deutschland
                [2 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, Institut für Diabetesforschung, , Helmholtz Zentrum München, ; München, Deutschland
                [3 ]Deutsches Zentrum für Diabetesforschung (DZD) e. V. München-Neuherberg, Neuherberg, Deutschland
                Article
                668
                10.1007/s11428-020-00668-x
                7437100
                816326e6-02d7-4f7c-83a8-090a1bff5984
                © Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Leitthema

                autoimmundiabetes, verhütung & bekämpfung,genetische veranlagung für eine krankheit,diagnostische screeningprogramme,klinische studien,minderjährige,autoimmune diabetes, prevention & control,genetic predisposition to disease,diagnostic screening programs,clinical studies as topic,minors

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