BACKGROUND: Latent autoimmune diabetes in adults (LADA) is considered an intermediate form between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying its unique clinical and pathogenetic features remain insufficiently studied. Identifying differentially expressed genes (DEGs) in LADA compared to T1DM is essential for developing more personalized diagnostic and therapeutic approaches.OBJECTIVE: To identify DEGs in peripheral blood mononuclear cells (PBMCs) of patients with LADA compared to those with T1DM, and to evaluate differences in DEGs between these patient groups and healthy volunteers.MATERIALS AND METHODS: The study included 60 participants (23 T1DM patients with disease duration of up to 1 year, 15 LADA patients with disease duration of up to 5 years, and 22 healthy volunteers). The median age of LADA patients was 40 [34; 45] years, and for T1DM patients, 26 [21; 31] years. This was a single-center, cross-sectional observational study. PBMCs were isolated from all participants, and single-cell RNA sequencing (scRNA-seq) was performed. Differential gene expression analysis was conducted using a pseudo-bulk approach (pyDEseq2, p<0.05 adjusted for multiple comparisons, |log2FoldChange| ≥0.5). Statistical analyses employed nonparametric tests (Kruskal–Wallis, Mann–Whitney).RESULTS: In LADA patients, reduced expression of HLA-G, SPARC, and C20orf204 and increased expression of AC002460.2 were observed compared to healthy volunteers (p<0.05) in CD4+ Naive T-cells. In the T1DM group, the most significant differences were identified in CD4+ Central memory T-cells (IFIT1, CASP3, LAMP3, HIST1H2BN). When comparing LADA to T1DM, only one transcript, C20orf204, showed statistically significant differential expression (p<0.05) in CD4+ Naive T-cells.CONCLUSION: The findings indicate that LADA and T1DM share similar molecular patterns, with LADA exhibiting moderate changes in the expression of genes associated with immune regulation and inflammation. The minimal differences between these forms of diabetes highlight their pathogenetic similarity.

Background. Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in inflammatory processes by recruiting monocytes and macrophages to sites of inflammation. Inflammation is closely linked to poor control of diabetes mellitus (DM), characterized by significant glycemic fluctuations and prolonged hyperglycemia, as well as subclinical, low-grade inflammation of adipose tissue in type 2 DM. Elevated levels of MCP-1 have been associated with both type 1 and type 2 DM; however, data on its role in the pathogenesis of latent autoimmune diabetes in adults (LADA) are extremely limited. Aim. To evaluate MCP-1 levels and their association with glycemic control parameters in patients with different types of DM (type 1 DM, type 2 DM, and LADA). Materials and methods. Between February and November 2023, 80 individuals participated in the study, divided into four groups: patients with type 1 DM (n = 22), type 2 DM (n = 22), LADA (n = 14), and healthy volunteers (n = 22). The median ages were 26 years [21; 32] for type 1 DM, 41 years [33; 51] for type 2 DM, 41 years [33; 46] for LADA, and 33 years [26; 40] for healthy controls. Inclusion criteria were age between 18 and 55 years, body mass index up to 35 kg/m², and a diagnosis of one of the specified forms of DM. Exclusion criteria included other systemic autoimmune diseases, pancreatic diseases, and the use of immunosuppressive therapy. Results. MCP-1 levels were significantly higher in patients with type 1 DM (213 [162; 263] pg/ml) and type 2 DM (228 [168; 294] pg/ml) compared to healthy volunteers (174 [151; 207] pg/ml; p 0.05). Patients with LADA showed a non-significant trend toward elevated MCP-1 levels (218.51 [160; 268] pg/ml; p 0.05). ROC analysis indicated that MCP-1 is not suitable as an additional marker for the differential diagnosis of LADA. Conclusion. Elevated MCP-1 levels in patients with type 1 and type 2 DM suggest its possible involvement in the pathogenesis of these diabetes types. The lack of significant MCP-1 elevation in patients with LADA limits its utility as a diagnostic marker for this condition.

The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent—and at times opposing—roles, attenuating dopaminergic neurotoxicity in Parkinson’s disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms.