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Felton, J.L.* ; Griffin, K.J.* ; Oram, R.A.* ; Speake, C.* ; Long, S.A.* ; Onengut-Gumuscu, S.* ; Rich, S.S.* ; Monaco, G.S.F.* ; Evans-Molina, C.* ; Dimeglio, L.A.* ; Ismail, H.M.* ; Steck, A.K.* ; Dabelea, D.* ; Johnson, R.K.* ; Urazbayeva, M.* ; Gitelman, S.E.* ; Wentworth, J.M.* ; Redondo, M.J.* ; Sims, E.K.* ; ADA/EASD PMDI (Stefan, N.)

Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: A systematic review.

Commun. Med. 3:130 (2023)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. METHODS: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. RESULTS: We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. CONCLUSIONS: While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2730-664X
e-ISSN 2730-664X
Quellenangaben Band: 3, Heft: 1, Seiten: , Artikelnummer: 130 Supplement: ,
Verlag Springer
Begutachtungsstatus Peer reviewed
POF Topic(s) 90000 - German Center for Diabetes Research
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-502400-001
PubMed ID 37794169
Erfassungsdatum 2024-03-19