Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus.

The enzymatic dissociation of human solid tissues is a critical process for disaggregating extracellular matrix and the isolation of individual cells for various applications, including the immortalizing primary cells, creating novel cell lines, and performing flow cytometry and its specialized type, FACS, as well as conducting scRNA-seq studies. Tissue dissociation procedures should yield intact, highly viable single cells that preserve morphology and cell surface markers. However, endocrine tissues, such as adrenal gland tumors, thyroid carcinomas, and pituitary neuroendocrine tumors, present unique challenges due to their complex tissue organization and morphological features. Our study conducted a morphological examination of these tissues, highlighting the intricate structures and secondary degenerative changes that complicate the dissociation process. We investigated the effects of various dissociation parameters, including the types of enzymes, incubation duration, and post-dissociation purification procedures, such as debris removal and nontarget blood cell lysis, on the viability of cells derived from different tumor types. The findings emphasize the importance of optimizing tissue digestion protocols to preserve cell viability and integrity, ensuring reliable outcomes for downstream analyses.

Autoimmune diabetes encompasses rapidly progressive type 1 diabetes mellitus (T1D) and indolent latent autoimmune diabetes in adults (LADA), which represent distinct inflammatory set points along a shared autoimmune spectrum. Yet, the immunological mechanisms that determine these divergent inflammatory states remain unresolved. We performed single-cell RNA sequencing with paired T and B cell receptor profiling on over 400,000 PBMCs from patients with LADA, newly diagnosed T1D, and individuals acting as healthy controls. PBMC composition was comparable across cohorts, indicating that qualitative rather than quantitative immune differences underlie disease heterogeneity. In T1D, pan-lineage activation of NF-κB, EGFR, MAPK, and hypoxia pathways, coupled with a TNF-centered communication hub, enhanced MHC signaling, disrupted adhesion, and promoted systemic inflammation. LADA, by contrast, exhibited global suppression of NF-κB/EGFR activity, retention of moderate JAK/STAT tone, reinforced NK cell inhibitory checkpoints via HLA-C–KIR2DL3/3DL1 interaction, and stabilized CD8 ⁺ T cell synapses through HLA-C–CD8 binding, collectively restraining effector activation. Single-cell V(D)J analysis revealed multiclonal, patient-unique adaptive repertoires, emphasizing the primacy of signaling context over receptor convergence. These findings define autoimmune diabetes as an inflammatory-inhibitory set-point continuum, positioning the NF-κB/EGFR–JAK/STAT gradient and HLA-C–KIR axis as potential therapeutic targets to preserve residual β cell function.

Background: The rarity and variability of MEN1-related primary hyperparathyroidism (mPHPT) has led to contradictory data regarding the bone phenotype in this patient population. Methods: A single-center retrospective study was conducted among young age- and sex-matched patients with mPHPT and sporadic hyperparathyroidism (sPHPT). The main parameters of calcium–phosphorus metabolism, bone remodeling markers, and bone mineral density (BMD) measurements were obtained during the active phase of hyperparathyroidism before parathyroidectomy (PTE) and 1 year after. Trabecular Bone Score (TBS) and 3D-DXA analysis of the proximal femur were used to evaluate the differences in bone architecture disruption between groups. Results: Patients with mPHPT had significant lower preoperative BMD compared to sPHPT at lumbar spine—LS (p = 0.002); femur neck—FN (p = 0.001); and total hip—TH (p = 0.002). 3D-DXA analysis showed the prevalence of cortical rather than trabecular bone damage in mPHPT compared to sPHPT: cortical thickness (p < 0.001); cortical surface BMD (p = 0.001); cortical volumetric BMD (p = 0.007); and trabecular volumetric BMD (p = 0.029). One year after, PTE DXA and 3D-DXA parameters were similar between groups, while 3D-visualisation showed more extensive regeneration in cortical sBMD and cortical thickness in mPHPT. Conclusions: mPHPT is associated with lower preoperative BMD values with predominant architecture disruption in the cortical bone. The absence of differences in DXA and 3D-DXA parameters 1 year after PTE between mPHPT/sPHPT combined with significantly lower BMD in mPHPT at the initial stage may indicate faster bone recovery after surgery in mPHPT than in sPHPT.

Neurofibromatosis type 1 is a hereditary disease that has a multisystem character of organism damage, a wide variability of clinical manifestations, up to the almost complete absence of typical symptoms. Phenotypic manifestations, their expressiveness and heaviness can be varied even among members of the same family with identical mutations. One of the possible clinical manifestations of this pathology is pheochromocytoma, the development of which is associated with a high risk of developing life-threatening conditions. Timely diagnosis of the disease, the choice of treatment tactics for the patient, genetic testing of blood relatives can significantly improve the survival rate and prognosis of the disease. In this article, on the presented clinical examples of patients with a typical and atypical course of type 1 neurofibromatosis in combination with pheochromocytoma, the issues of managing patients with this pathology are outlined.

Endogenous Cushing’s syndrome (CS) is a rare neuroendocrine disorder characterized by either secondary cortisol increases due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor (Cushing’s disease (CD)), an ACTH-secreting neuroendocrine tumor (NET) of non-pituitary origin (ectopic ACTH syndrome (EAS)), or by the primarily adrenal autonomous overproduction of cortisol