Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by biallelic loss of function variants in the SLC19A2 gene. It typically presents with a triad of megaloblastic anemia, diabetes mellitus, and sensorineural deafness. In this work, we analyzed ten children with suspected TRMA: nine exhibited the full triad and one, a younger sibling of a patient with full triad, did not develop hearing loss by the age of 18 months. All patients became transfusion-independent on high-dose thiamine therapy. Whole-genome sequencing identified homozygosity for the canonical splice variant SLC19A2 c.1223+1G>A in eight patients. One patient was homozygous for a known SLC19A2 c.196G>T variant, and the other was compound heterozygous for two novel variants, c.120C>G and c.584T>C. All patients with the SLC19A2 c.1223+1G>A variant were ethnic Ingush. In the reference Ingush cohort, 9/328 unrelated adults were c.1223+1G>A carriers (heterozygous carrier frequency 2.7%; carrier frequency ≈ 1/36), and shared a 2.3 Mb ATP1B1-FMO2 haplotype on chromosome 1, demonstrating a strong founder effect. These findings identify Ingushetia as a new TRMA-endemic region and support targeted SLC19A2 screening and early thiamine therapy in patients with macrocytic anemia and diabetes of unclear origin in this population.

Routinely tested biochemical and haematological molecules in the management of diabetes control, including glycated haemoglobin (HbA1c) evaluation, are related to estimated whole blood viscosity (eWBV), which is an indicator of diabetic rheology pathology. Examination of the molecules control could establish their value for clinical laboratory-based cardiovascular risk assessment. The study investigated changes in full blood count (FBC) parameters and lipid profiles with eWBV and HbA1c. The predictiveness of FBC parameters for eWBV and HbA1c is explored. This was a laboratory-based observational study that used mixed-methods analyses. Cross-sectional, longitudinal, descriptive, correlation, and regression approaches were applied to archived clinical pathology data from two health facilities, including a dataset of N = 21,026. Results: Lipid profile molecules significantly change with the level of HbA1c (p < 0.001). The levels of eWBV and its determinant molecules also change with HbA1c, and with seasonal variations (p < 0.001). Considering the predictiveness of FBC parameters for HbA1c and eWBV levels, red blood cells (RBC) and their indices, i.e., haemoglobin molecules, show statistical significance. For instance, RBC most strongly predicted HbA1c (r = 0.30) and was highest for eWBV (r = 0.54), while mean cell volume (MCV) showed strongest inverse correlation with HbA1c (r = -0.47). Conclusion: This study demonstrates that routine FBC parameters, RBC and its indices, offer a practical, low-cost approach to both monitoring and prediction of HbA1c with blood flow issues. This broadens the understanding of blood rheology in diabetes. Future research should move beyond de-identified laboratory datasets and involve patients' primary data collection to include medication and clinical information that are unavailable in pathology records.

Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic targets, but rather as the clinical expression of persistent molecular activity involving multiple interconnected organs and pathways. Insulin resistance, metaflammation, oxidative stress, mitochondrial dysfunction, lipotoxicity, endothelial impairment, hepatic metabolic dysregulation, renal inflammation, fibrotic remodeling, and metabolic memory interact within a dynamic network linking adipose tissue, liver, kidney, immune cells, and vasculature. In this review, we discuss the biochemical and molecular drivers of cardiometabolic residual risk in T2D, with particular emphasis on impaired insulin receptor substrate/PI3K/Akt signaling, stress-kinase activation, NLRP3 inflammasome priming and assembly, MASLD-related lipotoxicity and fibrogenesis, podocyte and tubular injury, endothelial nitric oxide synthase uncoupling, AGE-RAGE signaling, and thrombo-inflammatory vascular injury. These pathways explain why biological vulnerability may persist even when conventional clinical parameters appear adequately controlled. We also examine the role of translational biomarkers and simple clinical indices, including TyG-derived indices, adiposity markers, hepatic steatosis and fibrosis scores, albuminuria, eGFR, and lipid-related markers, as accessible windows into active biological pathways. Finally, we review how contemporary therapeutic strategies may modulate selected components of this residual-risk network. A pathway-centered interpretation of T2D may support more precise residual-risk phenotyping and help move cardiometabolic care beyond isolated target control toward mechanism-based prevention. This review further links these mechanisms to the contemporary cardiovascular-kidney-metabolic (CKM) framework, as defined by the 2026 AHA/ACC/ADA/ASN CKM Guideline, and disaggregates the underlying molecular network into organ-specific pathway cascades that make the causal relationships between metabolic, inflammatory, hepatic, renal, and vascular injury more explicit.

Gestational diabetes mellitus (GDM) is characterized by metabolic disturbances in which oxidative stress may play an important role. Most existing studies have examined individual biomarkers rather than their interrelationships. The present study evaluated selected oxidative stress, metabolic, and antioxidant markers, as well as their associations, in women with GDM compared with healthy pregnant controls. A total of 160 pregnant women (87 with GDM and 73 controls) were included. Biomarkers were measured, and their associations were assessed using correlation and interaction analyses. Women with GDM demonstrated higher levels of malondialdehyde (p < 0.001), leptin (p = 0.007), and ferric reducing antioxidant power (p < 0.001). The difference in the correlation between catalase activity and uric acid remained statistically significant after false discovery rate correction (q = 0.006), with a negative association in women with GDM and a positive association in controls. Interaction analysis further supported a group-dependent relationship between uric acid and catalase activity (p = 0.007; FDR-adjusted q = 0.007). These findings suggest that GDM may be associated not only with changes in individual biomarkers but also with alterations in selected redox-related relationships, indicating differences in redox regulation in GDM.

Background/Objectives: The clinical profile of serum Maresin-1 (MaR1) in relation to diabetic retinopathy phenotypes and proteinuria in type 2 diabetes mellitus (T2DM) remains unclear. We evaluated serum MaR1 across healthy controls and patients with T2DM without diabetic retinopathy (DR), non-proliferative DR (NPDR), or proliferative DR (PDR), and examined the relationship between MaR1 and the urine protein-to-creatinine ratio (UPCR). Methods: This single-center cross-sectional study included 93 participants. Serum MaR1 was measured by ELISA. Group differences were assessed with the Kruskal-Wallis test and Holm-adjusted post hoc tests. DR phenotypes were analyzed among patients with T2DM. The MaR1-UPCR relationship was examined using correlation and adjusted regression models. Results: MaR1 differed across groups (H = 49.36, p < 0.001, epsilon² = 0.521). The median MaR1 was 89.8 (82.8-97.2) pg/mL in controls and 34.3 (33.0-36.0), 35.8 (34.4-36.7), and 34.0 (33.1-35.7) pg/mL in T2DM without DR, NPDR, and PDR, respectively. MaR1 was higher in controls than in all T2DM groups, whereas T2DM groups did not differ. Within T2DM, MaR1 was not associated with DR stage (H = 4.44, p = 0.109; rho = -0.001, p = 0.996). MaR1 was inversely related to the UPCR overall (rho = -0.272, p = 0.008), but not within T2DM (rho = -0.057, p = 0.634) or in adjusted models. Conclusions: MaR1 was markedly lower in T2DM than in controls. This reduction was not explained by DR stage or proteinuria. These findings indicate that MaR1 should be interpreted as a T2DM-associated systemic alteration rather than as a marker of retinopathy stage or proteinuria.

Type 1 diabetes mellitus (T1DM) in primary school children presents unique challenges due to developmental dependence on adults, limited self-care abilities, and the need for continuous medical supervision. These factors may adversely affect health-related quality of life (HRQoL), particularly in early educational settings. Although diabetes-specific HRQoL assessment is essential for comprehensive pediatric diabetes care, no validated Croatian language instrument has previously been available. This preliminary study aimed to evaluate the initial validity, reliability, and factor structure of the Croatian version of the Pediatric Quality of Life Inventory (PedsQL) 3.2 Diabetes Module.

This cross-sectional preliminary study was conducted in a clinical pediatric diabetes care setting in Croatia and included 70 children with T1DM, aged 7-14 years, and their parents or caregivers, recruited using convenience sampling. HRQoL was assessed using the Croatian versions of the PedsQL 4.0 Generic Core Scales and the PedsQL 3.2 Diabetes Module, which was translated using a forward-backward translation procedure. Reliability was evaluated using Cronbach's α and test-retest reliability using the intraclass correlation coefficient (ICC). Construct validity was examined using Spearman's correlation analysis and exploratory factor analysis.

Children with T1DM reported higher overall HRQoL than parent proxy reports, except for the Diabetes symptoms scale of the PedsQL 3.2 Diabetes Module and the School functioning scale of the PedsQL 4.0 Generic Core Scales. Internal consistency was satisfactory across all scales (Cronbach's α = 0.71-0.85). Spearman's correlations between subscales and total scores were strong (ρ = 0.61-0.92). Test-retest reliability was excellent (ICC = 0.982-0.996). Exploratory factor analysis supported construct validity: Bartlett's test of sphericity was significant for both child (χ² = 1398.57, p < 0.001) and parent reports (χ² = 1302.74, p < 0.001), and the Kaiser-Meyer-Olkin measure indicated acceptable sampling adequacy (child = 0.65; parent = 0.68). Extracted factors explained 66.30% of the variance in child reports and 61.80% in parent reports, with factor loadings ranging from 0.41 to 0.89 and 0.41 to 0.85, respectively.

The Croatian version of the PedsQL 3.2 Diabetes Module is an initial valid, reliable, and feasible instrument for assessing diabetes-specific HRQoL in Croatian primary school children with T1DM. Its use may support systematic HRQoL monitoring and improve family-centered pediatric diabetes care.

Leptin is the oldest studied adipokine, and its mechanism of action in the regulation of energy metabolism remains a hot topic of current research. In this paper, we systematically review the progress of clinical and basic research on leptin and energy metabolism from 1994 to 2026. It is shown that leptin can regulate the energy metabolism homeostasis through autocrine, paracrine and neurohumoral pathways (e.g., hypothalamic-leptin-melanocortin axis). In addition, the effects of mainstream weight loss strategies such as dietary control, pharmacological interventions and exercise on leptin levels, and their underlying mechanisms were investigated in this paper, with the aim of providing a theoretical basis for the clinical application of leptin in metabolic diseases (e.g., obesity, diabetes mellitus). Future studies need to further clarify the molecular mechanisms of leptin resistance and explore precise intervention strategies based on the leptin signaling pathway.

To codesign a preclinic Diabetes Priorities Questionnaire (DPQ) tool for people with type 2 diabetes and healthcare professionals to identify patient needs in advance and enable efficient, patient-centred consultations for diabetes management.

Participatory approach using codesign focus groups to explore perspectives and develop solutions.

This study was conducted in Western Sydney, Australia, an area with high socioeconomic disadvantage and cultural diversity.

10 adults with type 2 diabetes and 8 healthcare providers including specialists, diabetes educators, general practitioners, dietitians and pharmacists were recruited from a public hospital-based outpatient diabetes service and community-based providers in Western Sydney.

The codesign process was employed to iteratively develop and refine the DPQ. Focus groups were conducted in a hybrid format including in person and online, using semistructured discussions on four key topics: (1) understanding the purpose of the tool, (2) usability of the tool, (3) perceived benefits of completing the tool and (4) asking the right questions (content). Participants were invited to review and provide feedback on the initial set of questions, with the aim of identifying key challenges and potential solutions to enhance the content and uptake of the tool. Feedback was collected through audio recordings and field notes. These insights informed successive revisions of the DPQ following each round of focus groups.

Five focus groups involving 18 participants identified opportunities to improve the initial questions by restructuring their order, simplifying the content and incorporating concerns about diabetes complications, including mental health. Participants highlighted the importance of holistic care and the need for both digital and paper-based formats to enhance accessibility.

The final DPQ was digitised within a patient care portal and integrated with tailored diabetes educational content. By enabling preconsultation screening, the codesigned DPQ supports multidisciplinary teams in delivering patient-centred care. Further research is needed to assess the tool's impact on clinical outcomes, patient satisfaction and healthcare efficiency.

Telemedicine has been increasingly adopted post-COVID-19 to optimise chronic disease management, improving patient outcomes. The multi-component OPTIMUM (Optimising care of Patients via Telemedicine In Monitoring and aUgmenting their control of diabetes Mellitus) tele-monitoring (TM) system yielded favourable health outcomes and was introduced in primary care nationwide in Singapore. This study aims to understand the factors associated with its implementation during the randomised controlled trial (RCT).

A qualitative study was conducted using individual semi-structured interviews. Data were transcribed, audited, coded and analysed using thematic analysis. The CFIR (Consolidated Framework for Implementation Research) framework, consisting of five domains (Intervention characteristic, Outer setting, Inner setting, Characteristics of individuals and Process), was adopted as the underpinning framework.

Primary care setting in Singapore.

Healthcare professionals involved in the care provided to patients enrolled in the OPTIMUM RCT.

TM facilitated behavioural change in patients, and its robust treatment algorithm allowed continuous monitoring and personalised advice. The associated external factors were manpower, costing and data security. Measures to mitigate internal risks included managing additional healthcare professionals' burden, reducing potential adverse events and addressing medicolegal risks related to TM. While TM enhanced provider satisfaction and the patient-healthcare professional relationship, strategies to enhance user experience and streamline the TM processes are required to improve its acceptance and adoption.

The CFIR served as a useful framework to identify factors associated with successful implementation of an intervention in a real-world setting. Understanding these factors enables healthcare leaders to address the challenges before scaling up the intervention in routine clinical services.

α-Glucosidase (α-Glu) inhibitors are important therapeutic agents for the treatment of type 2 diabetes mellitus. However, the rapid discovery of such bioactive compounds from natural products remains challenging.

In this study, a MOF-818@Pt nanozyme-based colorimetric screening strategy was developed for the efficient discovery of α-Glu inhibitors from natural sources. The MOF-818@Pt composite, synthesized via an in-situ reduction-deposition method, exhibited excellent peroxidase-like activity and was thoroughly characterized. Using α-arbutin as the substrate, the proposed nanozyme-based system enabled sensitive detection of α-Glu activity, exhibiting a good linear relationship within the concentration range of 0.05-120 U/L (R² = 0.991), along with strong anti-interference ability, satisfactory reproducibility, and long-term stability. This method was successfully applied to the bioactivity-guided fractionation of Myrciaria cauliflora, leading to the enrichment of ten subfractions (GH1-GH10) with significant α-Glu inhibitory activity. Feature-based molecular networking analysis revealed that these subfractions are predominantly composed of phloroglucinols, terpenoids, polyketides, and meroterpenoids. Molecular docking studies demonstrated that representative compounds from each class could bind within the active site of α-Glu, forming hydrogen bonds with key residues including Arg213, Asp215, Glu277, Gln279, and Asp352.

This work establishes a rapid, simple, and high-throughput strategy for screening α-Glu inhibitors from complex natural product matrices, providing a promising technological platform for natural product-based drug discovery.