AIMS: This study aimed to investigate the impact of type 2 diabetes (T2D) on muscle and tendon mechanics by comparing individuals with controlled diabetes to a healthy cohort matched for age, BMI, and physical activity l...AIMS: This study aimed to investigate the impact of type 2 diabetes (T2D) on muscle and tendon mechanics by comparing individuals with controlled diabetes to a healthy cohort matched for age, BMI, and physical activity level. A secondary aim was to investigate the possible association between muscle-tendon proprieties and glycated haemoglobin (HbA1c) or advanced glycated end products (AGE, RAGE) as determined in blood and skin biopsies. METHODS: Twenty-eight patients and eighteen controls were recruited for this study. Achilles tendon stiffness (k), muscle-tendon stiffness (k, in gastrocnemius medialis) and the rate of torque development (RTD) were evaluated by combining dynamometric and ultrasound data. RESULTS: Diabetic patients showed increased tendon stiffness and reduced tendon elongation compared to controls, but similar RTD and k values. No differences in advanced glycation end products (in serum or biopsies) were observed between cohorts, but a significant positive correlation was observed between k and HbA1c (r = 0.610, N = 46, P < 0.001). CONCLUSION: Our data indicate that muscle, but not tendon, properties can be preserved in controlled and physically active diabetic patients and that higher tendon stiffness does not result in a functional deficit (i.e., same explosive capacity between cohorts). Although this study is cross-sectional and has a limited sample size, our data suggest a potential role of HbA1c as a non-invasive biomarker of altered tendon mechanics in people with diabetes. GOV, PROTOCOL NUMBER: NCT05585502.
AIMS: To identify patterns of complication burden among individuals with diabetes mellitus based on sociodemographic, behavioral, and clinical characteristics, and to examine their co-occurrence with diabetes-related com...AIMS: To identify patterns of complication burden among individuals with diabetes mellitus based on sociodemographic, behavioral, and clinical characteristics, and to examine their co-occurrence with diabetes-related comorbidities. METHODS: This cross-sectional study was conducted during a diabetes health campaign in a municipality in southern Bahia, Brazil, involving 1,542 patients. Data were obtained through a standardized questionnaire and ophthalmological examinations. Latent class analysis was applied to identify subgroups with similar clinical characteristics. Models with two to four classes were estimated, with the two-class model presenting the most parsimonious and interpretable solution according to BIC. Associations between classes and comorbidities were estimated using Poisson regression with robust variance, adjusted for age and sex. RESULTS: Two classes were identified. Class 1 (86.6%) showed lower complication burden, with preserved vascular and sensory function. Class 2 (13.4%) was characterized by a higher frequency of ulceration, amputation, absent peripheral pulses, and impaired protective sensation. Individuals in Class 2 presented higher prevalence of cardiovascular disease (PR = 1.47), myocardial infarction (PR = 1.64), neurological disease (PR = 1.67), and retinopathy (PR = 1.63). CONCLUSION: The identified classes primarily reflect differences in peripheral complication burden, with higher co-occurrence of vascular and microvascular conditions in the more affected group. These findings describe patterns of complication clustering within a screening population and may support population-level strategies for identifying individuals with greater healthcare needs.
BACKGROUND: Diabetic cardiomyopathy (DCM) occurs in the context of coronary artery disease or pressure overload heart disease, characterized by alterations in cardiac structure and function. The mechanisms linking metabo...BACKGROUND: Diabetic cardiomyopathy (DCM) occurs in the context of coronary artery disease or pressure overload heart disease, characterized by alterations in cardiac structure and function. The mechanisms linking metabolic memory and METTL1-mediated modifications to DCM progression remain unclear. METHODS: This study integrated multiple public transcriptome datasets to conduct a systematic analysis of gene expression profiles associated with diabetic cardiomyopathy. Potential key characteristic genes were identified through differential expression analysis and machine learning techniques. Their associated biological processes and signaling pathways were assessed using functional enrichment analysis. Additionally, single-cell RNA sequencing data were employed to examine the expression and distribution of key genes across various cardiac cell types, while gene set enrichment analysis (GSEA) was utilized to explore their potential functional networks. RESULTS: The integration of three public transcriptome datasets and subsequent differential expression analysis identified 159 genes associated with diabetic cardiomyopathy, of which 133 were upregulated and 26 downregulated. These differentially expressed genes (DEGs) effectively distinguished between DCM and control samples. Machine learning analyses, including LASSO regression and random forest, identified several key candidate genes, with METTL1 showing a significant association with inflammation, fibrosis, and metabolic disorders. In multiple independent datasets, METTL1 expression was markedly elevated in DCM samples and demonstrated substantial diagnostic potential (ROC AUC = 0.826). Functional enrichment analysis revealed that METTL1-related genes predominantly participated in pathways related to white blood cell migration, inflammatory activation, and extracellular matrix remodeling. Single-cell RNA sequencing further indicated that METTL1 was primarily enriched in the fibroblast population. The proportion of METTL1-positive fibroblasts in DCM samples was significantly increased and was associated with inflammatory and fibrosis-related signaling pathways. A comprehensive analysis suggests that METTL1 may play a role in the pathological progression of DCM by regulating fibroblast activation, amplifying inflammation, and contributing to myocardial remodeling. CONCLUSIONS: This study elucidates the expression characteristics of METTL1 and its potential regulatory functions in diabetic cardiomyopathy. The findings suggest that METTL1 metabolic memory may be influenced by RNA modifications occurring in the context of persistent inflammation and fibrosis.
Rabbone I, Scaramuzza A, Pozzi E
… +20 more, Corti E, Monzani A, Barra FL, Canonico M, Leon LFB, Bassi M, Bonfanti R, Di Candia F, Frontino G, Iafusco D, Lombardo F, Macedoni M, Mancioppi V, Marigliano M, Martino M, Schiaffini R, Tiberi V, Tinti D, Toni S, Cherubini V
AIM: To use high-fidelity simulation to validate the clinical applicability and safety of the recently updated Italian Society for Pediatric Endocrinology and Diabetes (ISPED) recommendations for the management of diabet...AIM: To use high-fidelity simulation to validate the clinical applicability and safety of the recently updated Italian Society for Pediatric Endocrinology and Diabetes (ISPED) recommendations for the management of diabetic ketoacidosis (DKA). METHODS: Expert pediatric diabetologists participated in a full-day simulation session. Teams of four managed three advanced scenarios on a pediatric manikin: severe DKA, DKA with cerebral edema, and DKA with acute kidney injury (AKI). During the scenarios, teams utilized the new guidelines as a paper protocol, a digital application, and an AI chatbot. Each session was followed by a structured debriefing to analyze decisions, protocol adherence, and user experience, with feedback collected via questionnaires and discussion. RESULTS: The simulation confirmed the overall robustness and clinical validity of the new guidelines. Participants appreciated the increased detail on managing complications like cerebral edema and AKI. A key learning point emerged regarding uncertainty in the initial choice of fluids (normal saline vs. Ringer’s lactate). A quantitative analysis of user experience revealed a statistically significant preference for the paper protocol, which outperformed digital versions on key usability metrics, including efficiency and dependability (p < 0.001). The AI chatbot, despite being rated as highly novel, was perceived as impractical and inefficient. CONCLUSION: High-fidelity simulation is an effective methodology for prospectively validating and refining clinical practice guidelines in a controlled environment before official release. We confirm the validity of the new ISPED recommendations while identifying key areas for targeted training and the need for the user-centered design of digital support tools.
OBJECTIVES: Tinnitus is common but challenging to treat. Investigating diabetes-related factors may inform prevention and targeted interventions. This study evaluated associations between diabetes-related factors and tin...OBJECTIVES: Tinnitus is common but challenging to treat. Investigating diabetes-related factors may inform prevention and targeted interventions. This study evaluated associations between diabetes-related factors and tinnitus traits. METHODS: Using UK Biobank data (n = 136,181), we performed cross-sectional logistic regression to evaluate links between diabetes status, HbA1c, medication use, and diabetes duration with tinnitus occurrence, frequency, and severity. Subgroup analyses assessed variations by sex and age. RESULTS: This study systematically identified the associations between diabetes-related factors and the frequency and severity of tinnitus. Patients with type 2 diabetes had higher odds of experiencing current, constant, and upsetting tinnitus (OR: 2., 95% CI: 1.4-2.85, p = 0.001; OR: 2.49, 95% CI: 1.44-4.31, p = 0.0011; OR: 6.36, 95% CI: 2.3-17.54, p = 0.001, respectively). Insulin use was associated with lower odds of developing current, transient, and upsetting tinnitus compared to non-users of hypoglycemic drugs (OR: 0.61, 95% CI: 0.47-0.80; OR: 0.62, 95% CI: 0.43-0.9, p = 0.011; OR: 0.42, 95% CI: 0.25-0.69, p = 0.007, respectively). Subgroup analyses revealed stronger associations in younger females. CONCLUSIONS: Type 2 diabetes increases tinnitus risk, whereas insulin use was associated with a lower prevalence of tinnitus. Notably, diabetes status and HbA1c were significantly associated with tinnitus, mainly in younger females.
AIMS: To quantify the absolute time in months by which the 1-h post-load glucose (1-hPG) criterion advances the diagnosis of type 2 diabetes (T2D). METHODS: We analyzed data from 7,165 adults (≥ 40 years) without T2D at...AIMS: To quantify the absolute time in months by which the 1-h post-load glucose (1-hPG) criterion advances the diagnosis of type 2 diabetes (T2D). METHODS: We analyzed data from 7,165 adults (≥ 40 years) without T2D at baseline in the Korean Genome and Epidemiology Study (KoGES). Participants were categorized into high (≥ 155 mg/dL) and low (< 155 mg/dL) 1-hPG groups and followed for a median of 11.5 years. The primary outcome, incident T2D, was analyzed using Cox proportional hazards models, while differences in time-to-diagnosis were determined through restricted mean survival time (RMST) analysis. RESULTS: High 1hPG was a strong independent predictor for incident T2D (adjusted Hazard Ratio: 2.88; 95% CIs: 2.55 − 3.26). After full adjustment, the high 1-hPG group had a diagnostic lead time of 11.1 months (95% CIs, 9.6 − 12.5) for T2D over a decade compared to the low 1-hPG group. This diagnostic advancement was more notable among individuals with prediabetes, expediting diagnosis by up to 15.9 months, and was consistent across sociodemographic factors and comorbidity subgroups. CONCLUSION: High 1-hPG advances the diagnosis of T2D by approximately 11 months over a decade, providing quantifiable diagnostic lead time in detecting high-risk individuals. These findings highlight the potential of 1-hPG as a supplementary tool to address the limited sensitivity of conventional screening tests. 1-hPG can aid in identifying high-risk individuals, particularly those with prediabetes, for early preventive interventions.
Mavraganis G, Bampatsias D, Konstantaki C
… +10 more, Stankowski K, Athanasopoulos S, Moustou C, Alexandropoulos A, Figliozzi S, Soranides A, Petropoulos I, Klettas D, Stamatelopoulos K, Georgiopoulos G
Acta Diabetol
· 2026 Jun · PMID 41984241
·
Full text
INTRODUCTION: Diabetic cardiomyopathy (DCM) often evades diagnosis before manifestation of clinical symptoms. In this study we explored how cardiometabolic traits influence early cardiac structure and function in asympto...INTRODUCTION: Diabetic cardiomyopathy (DCM) often evades diagnosis before manifestation of clinical symptoms. In this study we explored how cardiometabolic traits influence early cardiac structure and function in asymptomatic people living with diabetes (PwD), using advanced imaging. METHODS: We conducted a cross-sectional study of 88 participants: 57 people living with type 2 diabetes (PwT2D), 16 people living with type 1 diabetes (PwT1D) and 15 controls. All subjects underwent transthoracic echocardiography and/or cardiac magnetic resonance (CMR) imaging. Strain analysis, perfusion indices, and tissue characterization (T1, T2, and extracellular volume) were assessed. Arterial stiffness via pulse wave velocity (PWV), ventricular-arterial coupling (VAC), circulating biomarkers and liver fibrosis indices were evaluated. RESULTS: PwD had lower cardiac index than controls. Global longitudinal strain (GLS) and global radial strain were lower in both diabetes mellitus (DM) groups, while left atrial strain was most impaired in PwT2D (β-coefficient= − 11.77, P= 0.003). DM duration ≥ 10 years was associated with worse GLS (β-coefficient= − 2.18, P= 0.033) and right VAC (β-coefficient= − 0.27, P= 0.027) after multivariable analysis. While tissue characterization and perfusion indices showed no significant group differences, tight glycemic control in PwD correlated with improved myocardial strain parameters. PwT2D exhibited greater arterial stiffness (β-coefficient= 1.52, P= 0.003). In PwD, elevated non-alcoholic fatty liver disease score correlated with increased left ventricular mass (β-coefficient= 6,195, P= 0.022) and decreased left ventricular ejection fraction (LVEF) (β-coefficient= − 3.12, P= 0.017). Higher growth differentiation factor levels were associated with reduced LVEF (β-coefficient= − 0.005, P= 0.029). CONCLUSION: This multimodal imaging study highlights myocardial and vascular changes in asymptomatic PwD. Early comprehensive cardiovascular assessment may help identify dysfunction before overt heart failure develops.
AIMS: Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2DM), yet diagnosis remains challenging. This study investigated whether perirenal structural features on CT offer diagnostic value...AIMS: Chronic kidney disease (CKD) is a major complication of type 2 diabetes mellitus (T2DM), yet diagnosis remains challenging. This study investigated whether perirenal structural features on CT offer diagnostic value for identifying T2DM patients at higher CKD risk. METHODS: 494 T2DM patients who underwent plain abdominal CT were enrolled from 2 institutions. Patients were stratified into lower or higher CKD risk categories per KDIGO 2012 guidelines. The grade of perirenal fat stranding, fascia thickening, perirenal fat thickness, and Mayo adhesive probability were evaluated. Predictors were selected via Lasso and logistic regression to build clinical, imaging, and combined nomogram models. RESULTS: Perirenal fat stranding (grade 2) and fascia thickening constituted the imaging model for higher CKD risk, while systolic blood pressure and haemoglobin formed the clinical model. The nomogram incorporating these 4 factors achieved concordance indices of 0.888 (95% CI: 0.850-0.927), 0.830 (95% CI: 0.731-0.929), and 0.791 (95% CI: 0.681-0.900) in the training, internal, and external validation sets, respectively, for identifying T2DM patients at increased CKD risk. CONCLUSIONS: T2DM patients exhibiting perirenal fat stranding and fascia thickening should be identified as being at higher CKD risk. Further renal function tests are recommended to detect abnormalities early and be integrated promptly into standardised CKD management protocols.
Rheumatoid arthritis (RA) is an inflammatory disease characterized by a higher burden of cardiovascular and metabolic diseases than in the general population. Altered lipid and glucose metabolic pathways are widely obser...Rheumatoid arthritis (RA) is an inflammatory disease characterized by a higher burden of cardiovascular and metabolic diseases than in the general population. Altered lipid and glucose metabolic pathways are widely observed, primarily due to chronic inflammation. However, metabolic dysfunction may also affect RA pathogenesis, further enhancing immune cell activation and joint damage. Glucose and lipid alterations observed in RA help define the comorbidity burden of this disease, significantly affecting disease activity and prognosis. The aim of the present review is to describe the role of metabolic dysfunctions in RA and to examine how disease activity and treatments can influence these conditions. We also summarized the main management strategies based on current literature and developed a cardiometabolic monitoring algorithm across different clinical settings to support daily patient care of these patients.
Succurro E, Cersosimo G, Sarnelli P
… +13 more, Brisinda F, Gattuso I, Mazza V, Fabiano G, Iorio F, Arena R, Mazzitello G, Nicotera R, Capria M, Zaza G, Andreucci M, Mancini R, Andreozzi F
Acta Diabetol
· 2026 Jun · PMID 41984237
·
Full text
AIMS: To describe the main glycemic outcomes and the Quality of Life (QOL) observed in a cohort of people with type 1 (T1D) or type 2 (T2D) insulin-treated diabetes under dialysis who started an Automated Insulin Deliver...AIMS: To describe the main glycemic outcomes and the Quality of Life (QOL) observed in a cohort of people with type 1 (T1D) or type 2 (T2D) insulin-treated diabetes under dialysis who started an Automated Insulin Delivery (AID) system. METHODS: This is a longitudinal retrospective pilot real-world analysis of 14 individuals with T1D and T2D undergoing dialysis who began using an AID system to optimize glycemic control. All subjects used the MiniMed™ 780G system. Glucose metrics were collected at baseline, 3, 6, and 12 months after initiating the SmartGuard™ feature. The WHOQoL-Bref questionnaire was administered at the last follow-up to evaluate the QOL. RESULTS: Out of the 14 people, 8 reached 1-year follow-up. Time in Range (TIR) increased from 63% at baseline to 69% at 12 months, Time Below Range < 70 mg/dL (TBR70) decreased from 0.3% to 0%, and Time Above Range > 250 mg/dL (TAR250) decreased from 6.7% to 3.9%. Seven out of eight subjects who reached a 12-month follow-up achieved all three glycemic targets for this fragile population (TIR > 50%, TBR70 < 1% and TAR250 < 10%). At the last follow-up, 58.3% of the users were satisfied or very satisfied with their health status, versus only 25% with the previous treatment, and 81.7% had a good or very good QOL, whereas only 8.3% had a good QOL, and no one had a very good QOL with the previous treatment. CONCLUSION: This pilot real-world study showed how the use of an AID system is safe and can help to improve the glycemic outcomes and the QOL of people with diabetes in dialysis.
Chico A, Aguilera-Hurtado E, Albareda M
… +10 more, Moreno-Fernández J, Beato-Vibora P, Fernández-Rubio E, Cuesta M, Bartual A, Ampudia-Blasco FJ, Bandrés O, Ares J, Rivero MT, Picón-César MJ
AIMS: Continuous glucose monitoring (CGM) has demonstrated to improve glucose control in people with type 2 diabetes (T2D) especially in those on insulin therapy. Dexcom ONE + is a CGM system with some particular feature...AIMS: Continuous glucose monitoring (CGM) has demonstrated to improve glucose control in people with type 2 diabetes (T2D) especially in those on insulin therapy. Dexcom ONE + is a CGM system with some particular features, however, there is no clinical study conducted with this device. The aim was to determine whether Dexcom ONE + can improve glucose control and patient-reported outcomes in insulin-treated T2D subjects. METHODS: Prospective, multicenter study including T2D on multiple insulin injections (MDI) or basal insulin (BI), without CGM experience and HbA1c > 7% (53 mmol/l). They used blinded Dexcom ONE + for 10 days and in open mode for 12 weeks. HbA1c, CGM-metrics, quality of life, fear and awareness of hypoglycemia were obtained baseline and at 12-weeks, and treatment satisfaction at 12 weeks. RESULTS: 159 subjects completed the study (MDI 75, BI 84). HbA1c decreased in MDI group from 8.18 ± 1.3% (65.9 ± 3.3 mmol/mol) to 7.34 ± 0.8% (56.7 ± 2.1 mmol/mol) and in BI group from 8.13 ± 1.3% (65 ± 3.3 mmol/mol) to 7.32 ± 0.7% (56.5 ± 1.9 mmol/mol) (p < 0.01). TIR increased in MDI group from 52.1 ± 25% to 60.7 ± 22% (p = 0.011) and in BI group from 58.8 ± 22% to 65.8 ± 19% (p = 0.0015). High degree of satisfaction and improvement in quality of life were observed in both groups and lower fear of hypoglycemia in BI group. CONCLUSIONS: In this first clinical study, Dexcom ONE + enhanced glycemic control and improve patient-reported outcomes with high satisfaction.
Diabetes mellitus (DM) is a global metabolic disorder characterised by chronic hyperglycemia resulting from insulin deficiency or resistance. Metformin, a first-line pharmacotherapy for type 2 diabetes mellitus (T2DM), e...Diabetes mellitus (DM) is a global metabolic disorder characterised by chronic hyperglycemia resulting from insulin deficiency or resistance. Metformin, a first-line pharmacotherapy for type 2 diabetes mellitus (T2DM), effectively lowers blood glucose levels and improves insulin sensitivity. However, emerging evidence from studies indicates a significant association between long-term metformin use and vitamin B12 deficiency, with prevalence rates ranging from 6% to 66%. This study is a narrative literature review that summarises and interprets the available evidence on the association between metformin therapy and vitamin B12 deficiency in patients with type 2 diabetes mellitus. The mechanism primarily involves interference with calcium-dependent absorption of the vitamin B12–intrinsic factor complex in the ileum. Prolonged therapy and higher doses of metformin correlate with decreased serum B12 levels, contributing to neuropathy, anemia, and cognitive impairment in diabetic patients. Evidence from North America, Europe, Asia, Africa, and Latin America consistently highlights the need for routine B12 monitoring and supplementation, especially in elderly patients and those on high-dose or long-term therapy. Despite widespread recognition of this risk, clinical monitoring remains suboptimal. Proactive screening and targeted supplementation can prevent irreversible neurological and hematological complications, improving long-term outcomes in metformin-treated diabetic populations.
OBJECTIVE: Endometrial cancer is one of the most common gynecological malignancies with an incidence rising globally in parallel with the increasing prevalence of diabetes mellitus. The objective of the present study was...OBJECTIVE: Endometrial cancer is one of the most common gynecological malignancies with an incidence rising globally in parallel with the increasing prevalence of diabetes mellitus. The objective of the present study was to provide an updated and comprehensive synthesis of the evidence on the association between diabetes and the risk of endometrial cancer, while accounting for study design, methodological quality plus population characteristics. METHODS: A systematic review and meta-analysis was undertaken in accordance with PRISMA 2020 guidelines. PubMed/MEDLINE, Embase, Web of Science, Scopus and Cochrane Library were searched from inception to 15 Aug 2025 alongside; eligible designs were observational studies assessing diabetes mellitus and incident endometrial cancer. Risk of bias was assessed using the Newcastle–Ottawa Scale and ROBINS-I. The most fully adjusted estimate from each study was extracted, transformed to the log-relative risk scale and pooled using a random-effects model with restricted maximum likelihood estimation. Lastly, prespecified subgroup analyses examined differences by geographic region, menopausal status, diabetes type, study base, study design plus study quality. RESULTS: Thirty-five studies met the inclusion criteria and contributed 37 risk estimates to the quantitative synthesis. Diabetes mellitus was found to be associated with a statistically significant higher risk of endometrial cancer incidence; resulting in a pooled relative risk of 1.64 (95% CI 1.50–1.80). Substantial heterogeneity was observed but was partly explained by study base and quality; as hospital-based and lower-quality studies reported stronger associations rather than population-based and higher-quality cohorts. The found association was consistent across continents, menopausal groups and diabetes types, including gestational diabetes. Ultimately, funnel plot asymmetry and results from Egger’s test suggested small-study effects, although sensitivity analyses, leave-one-out and cumulative meta-analysis, demonstrated that the overall association remained robust. CONCLUSION: Diabetes mellitus is associated with a materially increased risk of endometrial cancer, independent of adiposity. Moreover, this relationship has been consistently demonstrated across diverse populations and study designs. These findings underscore the importance of targeted preventive strategies in women with diabetes mellitus and highlight the need for further research addressing diabetes duration, glycemic control alongside treatment effects on cancer risk. TRIAL REGISTRATION: PROSPERO CRD420251142624.
BACKGROUND: Diabetic microvascular complications (DMCs) are a principal driver of blindness, kidney failure, neuropathy, and non-healing ulcers. A shared early lesion across microvascular beds is endothelial barrier brea...BACKGROUND: Diabetic microvascular complications (DMCs) are a principal driver of blindness, kidney failure, neuropathy, and non-healing ulcers. A shared early lesion across microvascular beds is endothelial barrier breakdown with pathological hyperpermeability, which is exacerbated by diabetic metabolic stress and heterogeneous microcirculatory flow. The molecular nodes that connect flow-derived mechanical cues to metabolic remodeling and sustained permeability remain incompletely defined. METHODS: We implemented an integrated multi-omics strategy combining bulk transcriptomics, network biology, and spatially resolved single-cell analyses. Bulk RNA-sequencing datasets from ApoE−/− murine aortas and human carotid/aortic lesion tissues were analyzed using differential expression, weighted gene co-expression network analysis (WGCNA), and pathway enrichment. Single-cell RNA-sequencing (GSE159677) was used to resolve cell-type-specific expression patterns and ANGPTL4-stratified endothelial states. Spatial transcriptomics (GSE241346; Visium) localized ANGPTL4 and RhoA within lesion microenvironments. Finally, protein-compound interaction profiling and AutoDock Vina molecular docking were used to prioritize candidate modulators, focusing on Tanshinol B. RESULTS: Angiopoietin-like 4 (ANGPTL4) was consistently downregulated and occupied central positions in co-expression modules enriched for endothelial barrier regulation, cytoskeletal remodeling, and mitochondrial bioenergetic pathways. Across independent cohorts, reduced ANGPTL4 expression was robustly associated with increased RhoA expression and with transcriptional programs consistent with heightened actomyosin contractility and endothelial permeability, accompanied by signatures of mitochondrial dysfunction and metabolic reprogramming. Single-cell and spatial analyses concentrated ANGPTL4 expression within endothelial compartments and supported a spatial association between ANGPTL4-low regions and RhoA-high transcriptional features. In silico docking predicted that Tanshinol B engages specific residues on both ANGPTL4 and RhoA, suggesting dual-target potential. CONCLUSIONS: These results define a conserved ANGPTL4-RhoA axis coupled to metabolic dysregulation and barrier-relevant cytoskeletal programs. We propose a mechanometabolic model in which reduced ANGPTL4 permissively enhances RhoA-driven contractility and endothelial hyperpermeability-mechanisms that are highly relevant to DMC pathogenesis. Together, our findings highlight ANGPTL4 and its pharmacologic modulation as candidate leverage points to preserve endothelial integrity in diabetes-associated microvascular disease.
BACKGROUND: Gestational diabetes mellitus (GDM) poses a serious threat to maternal and fetal health. OBJECTIVE: To investigate the clinical significance and molecular mechanisms of miR-1180-5p in GDM and evaluate its pot...BACKGROUND: Gestational diabetes mellitus (GDM) poses a serious threat to maternal and fetal health. OBJECTIVE: To investigate the clinical significance and molecular mechanisms of miR-1180-5p in GDM and evaluate its potential as a diagnostic and prognostic biomarker. METHODS: It includes GDM patients and healthy pregnant women in this research. The diagnostic value of miR-1180-5p expression levels for GDM was estimated using ROC curves. Correlation analysis was used to estimate the relationship between miR-1180-5p expression levels and GDM indicators. Multivariate logistic regression analysis was performed to estimate the risks of poor pregnancy outcomes in patients with GDM. RESULTS: miR-1180-5p expression was significantly elevated in GDM patients, and the ROC curve indicated it had moderate diagnostic efficacy. Its expression was closely linked to fasting blood glucose and HOMA-IR. The high-expression group showed increased neonatal and placental weights and a higher incidence of adverse pregnancy outcomes. It was confirmed that it can target and combine to the TXLNA to regulate expression. CONCLUSION: miR-1180-5p is a potential diagnostic and prognostic biomarker for GDM. It participates in the pathological process of GDM through its target regulation mechanism, thus providing new evidence for clinical management.