Mathematical Analysis of Repeated BCG Administration in Type 1 Diabetes: Improved Macrophage Response and Prolonged β-Cell Viability

Mathematical Analysis of Repeated BCG Administration in Type 1 Diabetes: Improved Macrophage Response and Prolonged β-Cell Viability | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Mathematical Analysis of Repeated BCG Administration in Type 1 Diabetes: Improved Macrophage Response and Prolonged β-Cell Viability Haneen Hamam This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8360019/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract This study develops an extended mathematical model to investigate innate immune dynamics in Type 1 Diabetes (T1D), focusing on the interplay between pro-inflammatory M1 macrophages, anti-inflammatory M2 macrophages, and pancreatic β-cells, which was shown in H.Hamam (2023). This model incorporates the immunomodulatory effect of Bacillus Calmette-Guérin (BCG) vaccination by representing each dose as a pulse-like input, implemented through a finite-duration Heaviside function, together with first-order elimination to describe the decay of the vaccine within the system. Simulation results after a single BCG pulse show a temporary decrease in M2 levels, followed by an increase in M2 macrophages, leading to a transient rise in β-cell levels. However, a key mechanism of this study is that repeated BCG doses generate a much clearer and more sustained improvement in β-cell levels compared to a single dose. Multiple-dose protocols produce more sustained reductions in inflammatory pressure, resulting in extended periods of β-cell preservation. Given uncertainties in several parameter values, a local sensitivity analysis was performed. The results show that parameters governing M2-mediated activation of β-cells Health sciences/Diseases Biological sciences/Immunology Innate immunity adaptive immunity M1 and M2 macrophages β-cells T1D BCG vaccine Full Text Additional Declarations No competing interests reported. Supplementary Files snbibliography.bib snHaneenH.tex snHaneenH.tex Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 16 May, 2026 Reviewers agreed at journal 05 May, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers agreed at journal 23 Apr, 2026 Reviewers invited by journal 23 Apr, 2026 Editor assigned by journal 14 Apr, 2026 Editor invited by journal 23 Dec, 2025 Submission checks completed at journal 21 Dec, 2025 First submitted to journal 21 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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