Shed Light on Molecular Immunogenetic Pathophysiology of Type 1 Diabetes to Improve Advanced Treatment Strategies Publisher Pubmed



A Moosavi AZAM ; Za Tabrizi Zahra AZIMZADEH ; Z Eghbali ZAHRA ; A Barzegari ABOLFAZL ; Sm Hejazian Seyyedeh MINA ; S Kheiri SEMIRA ; S Seyedmadani SANA
Source: Diabetes Research and Clinical Practice Published:2025

Abstract

Type 1 diabetes (T1D) is widely recognized as a chronic autoimmune disease characterized by insufficient insulin production and persistent high blood sugar levels. Generally, the onset of T1D results from a complex network of factors that disrupt β-cell function. These contributing elements are broadly divided into intrinsic factors, such as genetic susceptibility, immune irregularities, and extrinsic triggers, including viral infections, drug toxicities, immune checkpoint inhibitors, and insufficient vitamin D levels. This article aims to provide a comprehensive understanding of the multifaceted mechanisms driving T1D, which often act directly or indirectly by influencing the immune system. This occurs due to a mix of genetic predispositions and immune system malfunctions. The article explores how genetic markers, including HLA-DR3/DR4, PTPN22, and TYK2 variants, influence and modulate immune tolerance. It also discusses emerging treatments, such as Teplizumab-mediated immune modulation, CRISPR-based gene editing, and stem cell-derived β-cell replacement, as well as their efficacy in preserving β-cell function to delay disease progression. By integrating recent therapeutic advancements with a deeper understanding of the molecular aspects of the disease, this article highlights next-generation treatments’ potential to significantly improve the management of T1D. Future investigations should focus on precision medicine approaches to achieve greater success in long-term treatments. © 2025 Elsevier B.V., All rights reserved.