Gestational diabetes mellitus (GDM) is a major public health challenge characterized by placental immunometabolic dysregulation. This study aimed to identify molecular signatures associated with GDM-related placental pathology and evaluate their diagnostic and therapeutic implications.

Two bulk placental transcriptomic datasets (GSE70493 and GSE263483) and one single-cell dataset (GSE173193) were analyzed. Differential expression analysis, WGCNA, and machine-learning feature selection (LASSO and SVM-RFE) were used to identify candidate gene signatures. A two-gene logistic regression model was constructed and externally validated. Immune-cell correlation rewiring and single-cell in silicoperturbation analysis explored immune-network alterations and regulatory roles of identified genes. A drug-prioritization framework was used for therapeutic screening.

Intersecting WGCNA modules with differentially expressed genes identified 29 candidates enriched in antigen presentation and mononuclear phagocyte functions. Dual-algorithm selection converged on HLA-DQA2 and FGL2. The two-gene model achieved an AUC of 0.786 in the discovery cohort and 0.813 in the external validation cohort. Immune rewiring analysis indicated a shift toward M1 macrophage polarization. Single-cell perturbation analysis supported regulatory roles of HLA-DQA2 and FGL2 within the macrophage lineage. Drug analysis reaffirmed insulin, metformin, and glyburide as stable therapeutic anchors.

The HLA-DQA2/FGL2 signature captures key aspects of placental immunometabolic dysregulation in GDM, including altered antigen presentation and macrophage-associated immune rewiring. This integrated framework provides candidate biomarkers for GDM risk stratification and generates computational hypotheses for future mechanistic and therapeutic studies.

Objectives. Atherosclerosis contributes to higher mortality and morbidity in people with diabetes. Preventing future complications largely depends on the early detection of imminent atherosclerosis. This study aimed to explore the relationship between the subclinical atherosclerosis measured by carotid intima-media thickness (CIMT), ankle-brachial index (ABI), and circulating levels of adipocyte fatty acid-binding protein (AFABP) in individuals with type 2 diabetes mellitus (T2DM). Methods. A total of 80 participants evenly divided into two groups: 40 newly diagnosed patients with T2DM and 40 healthy controls. Patients with T2DM had no prior history or clinical signs of macrovascular complications, such as coronary artery disease, cerebrovascular stroke or peripheral artery disease. Serum total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were measured. Plasma AFABP levels were determined using a human enzyme-linked immunosorbent assay (ELISA) kit. ABI was assessed using a sphygmomanometer with a cuff that fits the limb's circumference and a portable Doppler device. Doppler ultrasound of the carotid artery was used to measure CIMT. Results. In patients with T2DM, circulating AFABP levels were significantly higher than those in healthy subjects (p=0.007). Multivariate regression analysis indicated that AFABP is the only independent factor influencing the maximum CIMT (β=0.004, 95% CI: 0.001-0.007, p=0.017). Conclusion. Plasma AFABP level could serve as a biomarker for early diagnosis of atherosclerosis in patients with T2DM.

Male obesity-associated secondary hypogonadism (MOSH) is common in men with obesity and can improve following metabolic bariatric surgery (MBS). However, the quantitative relationship between postoperative weight loss and biochemical remission of MOSH remains unclear. This study aimed to characterize the nonlinear association between percentage total weight loss (TWL%) and MOSH remission after laparoscopic sleeve gastrectomy (LSG), and to identify clinically relevant weight-loss thresholds.

This retrospective study included MOSH patients undergoing LSG with one-year follow-up. Restricted cubic spline (RCS) modeling evaluated the nonlinear relationship between TWL% and remission. Patients were grouped by RCS-derived thresholds, and logistic regression with interaction analyses examined the association and effect modification.

Among 230 patients, mean TWL% was 31.60% and remission rate was 82.17% at one year after LSG. RCS revealed a nonlinear association (P = 0.041) with an exploratory effect-initiation threshold at 21.8% TWL% and a suggested plateau period at 36.0% TWL%. Corresponding remission rates were 47.1% (< 21.8% TWL%), 88.9% (21.8-36.0% TWL%), and 87.1% (≥ 36.0% TWL%). Both higher TWL% groups had significantly greater odds of remission compared with the lowest group (adjusted odds ratio [aOR]: 10.61 and 10.64, respectively). Age, preoperative body mass index (BMI), and type 2 diabetes mellitus (T2DM) did not modify the relationship.

Achieving 21.8% TWL% may represent an exploratory lower threshold for high remission probability, while 36.0% TWL% may indicate the onset of a plateau period. These findings provide preliminary reference points that require prospective validation before being considered for clinical guidance.

• 21.8% TWL% may represent an exploratory minimum threshold for high MOSH remission probability after LSG. • 36.0% TWL% may indicate a plateau; further weight loss appears to yield no additional remission benefit. • These exploratory thresholds showed consistency across age, preoperative BMI, and T2DM subgroups in this cohort.

Pulmonary mucormycosis (PM) imaging has been characterised primarily in patients with hematologic malignancies. Imaging patterns may differ in diabetes mellitus-associated PM (DAPM), the most common risk factor globally, due to different immunologic profiles and disease progression. The impact of glycemic control on CT findings in DAPM is unknown.

We retrospectively analysed chest CT scans of patients with PM, compared DAPM with PM in other risk factors (PMOR), and evaluated imaging features across glycated haemoglobin (HbA1c) categories. The secondary objective was to determine associations between imaging features and mortality in DAPM. Imaging patterns recorded by two radiologists were compared between study groups, and multivariable logistic regression analysis of mortality was performed.

Among 193 patients (161 DAPM, 32 PMOR), consolidation (97%) and cavitation (84%) were the most frequent. DAPM presented significantly later (median 30 vs. 7 days; P < 0.001) and showed distinct features: smaller nodules (62%, <10 mm) with centrilobular distribution (37.4%), while PMOR had larger nodules (10-30 mm, 55.0%) with random distribution (75.0%). Lymphadenopathy was more common in DAPM (26.0% vs. 9.4%, P = 0.043). Among DAPM, Bird's nest sign increased with HbA1c severity: 7.7% (HbA1c ≤7%), 33.3% (HbA1c 7-9%), and 43.3% (HbA1c>9%), P = 0.030. Overall, 12-week mortality was 47.9%. Although the reversed halo sign and bird's nest sign were associated with mortality on univariable analysis, neither was significant after adjusting for clinical factors.

DAPM presents later and exhibits distinct imaging features compared to PMOR. Bird's nest sign is more frequent with HbA1c >9%. No imaging features were independently associated with mortality.

Diabetic foot (DF) disease, including ulcerations, amputations, and infections, represents a major cause of morbidity and mortality in individuals with diabetes mellitus (DM). Despite their substantial clinical, social, and economic burden, robust global epidemiological estimates remain limited due to fragmented evidence and heterogeneous methodologies. This systematic review and meta-analysis aimed to provide reliable pooled estimates of incidence and prevalence of DF disease, to explore geographic and demographic variations, and to assess the types of data sources available for epidemiological research.

Following PRISMA guidelines (PROSPERO registration CRD42025640944), PubMed, Embase, CINAHL Plus, and Cochrane Library were systematically searched from inception to December 21, 2024, for observational studies in adults (≥ 18 years) with DM reporting epidemiological measures of DF disease. Data extraction and quality appraisal (Joanna Briggs Institute checklists) were independently performed by four reviewers. Random-effects meta-analyses were conducted using generalised linear mixed-effects models to calculate pooled complication-specific prevalence and incidence rates among patients with diabetes. Heterogeneity among study estimates was assessed using Cochran's Q test, I² statistic, and the between-study variance (τ²). To identify sources of heterogeneity, meta-regression analyses were performed considering study-level covariates (modifiers).

Eighty-nine studies were included (18 prospective cohorts, 33 retrospective cohorts, 38 cross-sectional), enrolling between 92 and 29,650,811 participants, with data from Europe (N = 29, 32.6%), Asia (N = 25, 28.1%), Africa (N = 16, 18.0%), America (N = 16, 18.0%), and Oceania (N = 3, 3.4%). Pooled global incidence rates were 10.93 cases/1000 person-years (95% CI, 6.67-17.91) for ulcerations, 3.58 (95% CI, 1.93-6.63) for amputations, and 19.11 (95% CI, 4.81-75.97) for infections. Pooled prevalence estimates were 54.57 cases/1000 persons (95% CI, 37.63-78.52) for active ulcerations, 72.63 (95% CI, 48.21-108.02) for past ulcerations, 14.75 (95% CI, 9.52-22.77) for amputations, and 39.17 (95% CI, 6.81-195.07) for infections. Substantial heterogeneity (I² > 90%) was observed, with significant modifiers including geographical region, diabetic foot identification method, data source, study setting, age, diabetes duration, and length of follow-up. Rates in America and Africa were generally above the global pooled average, whereas those in Europe, Asia, and Oceania were below.

Globally, DF disease is common and severe, with incidence and prevalence rates underscoring its important public health impact. Heterogeneity across studies highlighted the influence of geography, methodology, and data sources. These findings may support future clinical and pharmacoepidemiological studies that evaluate new interventions and monitor temporal trends using large-scale data.

Nonalcoholic fatty liver disease (NAFLD), now largely encompassed by the newer metabolic dysfunction-associated steatotic liver disease (MASLD) nomenclature, is increasingly recognized as a marker of systemic metabolic dysfunction. This systematic review synthesized longitudinal evidence from adults examining NAFLD and related steatotic liver disease definitions in relation to incident type 2 diabetes mellitus. PubMed/MEDLINE and Scopus were searched from inception, the supplementary search was repeated to capture recently published studies. Eligible longitudinal reports excluded participants with diabetes at baseline or clearly identified new-onset diabetes during follow-up. Because the included cohorts differed in liver disease definitions, diabetes ascertainment, populations, follow-up structures, and reported effect measures, the findings were synthesized narratively. The protocol was prepared before screening but was not prospectively registered. A total of 61 reports were included. Risk of bias was generally low to moderate where adequately assessed, while reports with incomplete domain-level information were interpreted cautiously. NAFLD or MASLD was generally associated with higher estimates of incident diabetes risk, although the magnitude varied and was attenuated after adjustment for metabolic factors in some studies. Persistent or newly developed steatosis and a greater liver fat or fibrosis burden were associated with higher estimates of future diabetes occurrence, whereas the resolution or reduction of liver fat was associated with lower estimates. Reported subgroup differences arose largely from individual or overlapping cohorts and were not sufficiently consistent to establish uniform effect modification. Overall, the evidence supports NAFLD or MASLD as a clinical risk marker rather than a stand-alone individualized prediction tool and supports standardized longitudinal assessments in future studies.

Diabetic foot ulcers and other chronic diabetic skin lesions persist because vascular insufficiency, neuropathy, infection, oxidative stress, dysregulated inflammation, and impaired stromal and epithelial repair act concurrently. Extracellular vesicles (EVs), including exosome-enriched preparations, can deliver proteins, lipids, and regulatory RNAs to multiple wound-resident cell types and therefore offer a cell-free strategy for this multifactorial pathology. This review examines recent evidence for EV-based therapy across inflammatory resolution, angiogenesis, fibroblast and keratinocyte recovery, extracellular matrix remodeling, redox and mitochondrial homeostasis, and protection from ferroptosis and neutrophil extracellular trap-associated injury. It also evaluates source selection, cargo and surface engineering, and local delivery systems such as hydrogels, dressings, and microneedles. Preclinical studies consistently report improved wound closure and tissue repair, whereas human evidence remains limited to early clinical and biomarker studies. Translation is constrained by product heterogeneity, donor and culture effects, isolation-dependent composition, inconsistent dose metrics, uncertain potency assays, storage and scale-up requirements, and incomplete regulatory alignment. Progress will require phenotype-matched products, MISEV-aligned characterization, GMP-compatible manufacturing, mechanism-linked release assays, and trials that test EVs as adjuncts to high-quality standard care using durable closure and recurrence as clinically meaningful outcomes.

Metabolic disorders, including diabetes mellitus, obesity, dyslipidemia, and metabolic syndrome, represent a growing global health challenge due to their increasing prevalence, multifactorial etiology, and complex pathophysiological mechanisms. Conventional pharmacological interventions, while effective to some extent, are often associated with limitations, such as adverse effects, high costs, and the inability to provide multi-targeted therapeutic outcomes. In this context, phytochemicals derived from medicinal plants have emerged as attractive alternatives owing to their diverse biological activities, including antioxidant, anti-inflammatory, hypoglycemic, and metabolic regulatory effects. However, their clinical translation remains significantly restricted due to inherent drawbacks, such as poor aqueous solubility, limited gastrointestinal absorption, rapid metabolism, and low systemic bioavailability. To overcome these challenges, phytosome technology has gained increasing attention as a novel lipid-based drug delivery platform. In phytosomes, bioactive plant constituents form complexes with suitable phospholipids, thereby improving physicochemical stability, permeability, and targeted delivery. This approach not only enhances pharmacokinetic and pharmacodynamic properties but also ensures sustained therapeutic efficacy with improved patient compliance. Recent preclinical and clinical investigations have demonstrated the potential of phytosome- based formulations to modulate metabolic dysfunctions, regulate lipid and glucose homeostasis, and attenuate oxidative and inflammatory cascades associated with metabolic disorders. Moreover, emerging advancements, such as nanophytosomes, stimuli-responsive delivery systems, and synergistic phytosome-drug combinations, are further broadening the therapeutic scope. These innovative approaches hold promise for maximizing clinical outcomes, minimizing side effects, and offering cost-effective strategies in the management of chronic metabolic diseases. Collectively, phytosome technology represents a promising frontier in developing safe, effective, and translational plant-based therapeutics for addressing the global burden of metabolic disorders.

To evaluate the effects of MCC950, a selective NLRP3 inflammasome inhibitor, on glycemic control, lipid profiles, and sympathetic dysfunction in a streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) rat model.

Male Wistar rats were rendered diabetic by intraperitoneal injection of STZ (50 mg/kg). T1DM induction was confirmed by persistent hyperglycemia, reduced serum C-peptide, and pancreatic histopathological changes. Diabetic cardiac autonomic neuropathy was established by elevated serum noradrenaline (NA) before treatment. Diabetic rats subsequently received MCC950, insulin, or normal saline for four weeks. Fasting blood glucose, serum lipid profiles, C-peptide, pancreatic histology, and serum NA were evaluated before and after treatment.

MCC950-treated rats showed significantly reduced fasting blood glucose, total cholesterol, triglycerides, and LDL-cholesterol (all P<0.0001) levels compared with untreated diabetic rats, while HDL levels remained unchanged, which suggests an improvement in diabetes-associated dyslipidemia. MCC950 treatment also partially restored C-peptide concentrations, improved pancreatic histology, and reduced serum NA levels.

These findings suggest that NLRP3 inflammasome inhibition may improve metabolic disturbances associated with experimental T1DM. Further studies incorporating direct functional assessments of cardiac autonomic function are required to determine its role in diabetic cardiac autonomic neuropathy.