Pathogenesis of Type 1 Diabetes: Established Facts and New Insights

Abstract

Type 1 diabetes (T1D) is an autoimmune disease characterized by the T-cell-mediated destruction of insulin-producing β-cells in pancreatic islets. It generally occurs in genetically susceptible individuals, and genetics plays a major role in the development of islet autoimmunity. Furthermore, these processes are heterogeneous among individuals; hence, different endotypes have been proposed. In this review, we highlight the interplay between genetic predisposition and other non-genetic factors, such as viral infections, diet, and gut biome, which all potentially contribute to the aetiology of T1D. We also discuss a possible active role for β-cells in initiating the pathological processes. Another component in T1D predisposition is epigenetic influences, which represent a link between genetic susceptibility and environmental factors and may account for some of the disease heterogeneity. Accordingly, a shift towards personalized therapies may improve the treatment results and, therefore, result in better outcomes for individuals in the long-run. There is also a clear need for a better understanding of the preclinical phases of T1D and finding new predictive biomarkers for earlier diagnosis and therapy, with the final goal of reverting or even preventing the development of the disease.

Two putative glutamate decarboxylases of Streptococcus pneumoniae as possible antigens for the production of anti-GAD65 antibodies leading to type 1 diabetes mellitus

“…From these, 1182 isolates could be assigned to 16 different GPSCs and represent 123 STs and 20 serotypes (Table 1). The vast majority (92.4%) of isolates belong to GPSCs6 (424), GPSC8 (363), GPSC38 (110), GPSC53 (100), and GPSC43 (95). Notably, only one member (BioSample: SAMEA3233202) of GPSC9 -a dominant cluster -harbored a gadB Spn gene.…”

Oral delivery of bi-autoantigens by bacterium-like particles (BLPs) against autoimmune diabetes in NOD mice

“…Thus, it may be suggested that inflammatory reactions around pancreatic islets have occurred in PBS and BLPs group at this time (21-week-old), and therefore a decline of the glucose sensitivity of β cells was induced (Siewko et al., 2014 ). The interplay of various pathogenic factors contributes to the initiation of these inflammatory reactions on pancreatic β cells during T1DM development, and β-cell dysfunction may exist years before T1DM diagnosis (Zajec et al., 2022 ; Evans-Molina et al., 2018 ). Therefore, theoretically, interventions such as immunomodulatory therapies should be applied as early as possible to maintain β-cell function and prolong β-cell insulin production (Mastrandrea & Quattrin, 2022 ).…”

“…In T1DM, insulin-producing pancreatic β cells are recognized and destroyed by the self-reactive immune responses, resulting in insulin deficiency, and therefore, T1DM patients require lifelong therapy with exogenous insulin (Katsarou et al., 2017 ). The etiology of T1DM is complicated and multifactorial, including genetic, immunological, epigenetic, environmental, physical, and social factors, resulting in the breakdown of autoimmune tolerance (Zajec et al., 2022 ; Chwalba et al., 2021 ; Bluestone et al., 2010 ; Bauer et al., 2021 ). However, the detailed underlying mechanisms have not been fully elucidated and remain to be further explored.…”

Thyroid Autoantibodies in Type -1 Diabetic Mellitus Patients and their Correlation with Thyroid function and Tumor Necrotic Factor-Alpha

“…Through interactions with immune cells, pancreatic cells also seem crucial in starting pathogenic processes. β-Cells appear to be more active participants in the disease's development than previously thought and are not merely passive targets (Li et al, 2021, Zajec et al, 2022. The present work aimed to investigate serum levels of thyroid autoantibodies and their correlation with thyroid function and tumor necrosis factor-alpha (TNF-α) in T1DM patients compared to randomly selected healthy individuals.…”