Comparative profiling of neurological and biomarker status in type 1 diabetes and multiple sclerosis: A cross-sectional observational study

Background and objectives: Type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) are considered chronic organ-specific autoimmune diseases. Their high prevalence, progressive nature, impact on daily life, the need for lifelong management, and increased co-occurrence have attracted research interest. However, the comparative evaluation of neurological and cognitive status in these diseases and their impact on multimodal neurodegenerative biomarkers remains underexplored. Methods: This cross-sectional observational study included 76 participants, including 18 patients with newly diagnosed T1DM, 26 patients with relapsing-remitting MS, and 20 healthy controls (HCs). Additionally, 12 patients with long-duration T1DM were included in exploratory analyses to investigate the effects of prolonged disease exposure. Comprehensive assessments included clinical and neuropsychological evaluations, cellular immune profiles testing, alongside advanced neuroimaging techniques, such as whole-brain and regional grey matter (GM) volumetry and optical coherence tomography, for retinal nerve fibre layer (RNFL) thickness. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP) levels were measured. Results: Patients with newly diagnosed MS and T1DM exhibited cognitive and mood disturbances, elevated sNfL levels, and distinct immunological and biochemical profiles compared with HCs. Patients with MS showed significant thalamic volume reduction and RNFL thinning, whereas those with T1DM did not exhibit significant GM volume loss or RNFL thinning. However, patients with advanced T1DM presented with increased sNfL concentrations and a trend towards retinal thinning. Partial correlations, controlling for age, schooling, or intracranial volume, revealed that impaired cognitive processing speed was significantly associated with higher sNfL levels, increased retinal thinning, and a smaller left thalamus volume. Discussion: Our findings emphasize the shared and distinct mechanisms of neurodegeneration underlying cognitive dysfunction in patients with newly diagnosed MS and T1DM, suggesting that both diseases involve overlapping mechanisms of immune-mediated damage and neurodegenerative processes that can contribute to the future development of neurological disability.