A1 Refereed original research article in a scientific journal
Multi-omics analysis reveals drivers of loss of β-cell function after newly diagnosed autoimmune type 1 diabetes : An INNODIA multicenter study
Authors: Armenteros, Jose Juan Almagro; Brorsson, Caroline; Johansen, Christian Holm; Banasik, Karina; Mazzoni, Gianluca; Moulder, Robert; Hirvonen, Karoliina; Suomi, Tomi; Rasool, Omid; Bruggraber, Sylvaine F. A.; Marcovecchio, M. Loredana; Hendricks, Emile; Al-Sari, Naba; Mattila, Ismo; Legido-Quigley, Cristina; Suvitaival, Tommi; Chmura, Piotr J.; Knip, Mikael; Schulte, Anke M.; Lee, Jeong Heon; Sebastiani, Guido; Grieco, Giuseppina Emanuela; Elo, Laura L.; Kaur, Simranjeet; Pociot, Flemming; Dotta, Francesco; Tree, Tim; Lahesmaa, Riitta; Overbergh, Lut; Mathieu, Chantal; Peakman, Mark; Brunak, Søren; INNODIA investigators
Publisher: John Wiley & Sons
Publication year: 2024
Journal: Diabetes/Metabolism Research and Reviews
Journal name in source: Diabetes/metabolism research and reviews
Journal acronym: Diabetes Metab Res Rev
Article number: e3833
Volume: 40
Issue: 5
ISSN: 1520-7552
eISSN: 1520-7560
DOI: https://doi.org/10.1002/dmrr.3833
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/457130925
Aims: Heterogeneity in the rate of β-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of baseline multi-omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis.
Methods: We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in β-cell mass measured as fasting C-peptide.
Results: Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signalling events that were inversely associated with a rapid decline in β-cell function. The second signature was related to translation and viral infection was inversely associated with change in β-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β-cell decline.
Conclusions: Features that differ between individuals with slow and rapid decline in β-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect.
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Funding information in the publication:
Financial compensation for these activities has been received by KU Leuven. S.Br. reports having received funding from INNODIA (grant agreement No 115797), having ownerships in Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S, ALK A/S and managing board memberships in Proscion A/S and Intomics A/S. MK reports ownership and managing board membership in Vactech Oy. CLQ serves on advisory boards of Fondation Alzheimer's and Institute Pasteur, and has an affiliation with Novo Nordisk. LO reports having received funding from INNODIA and INNODIA Harvest. CHJ reports having received funding from INNODIA (grant agreement No 115797).
