This study investigated the association between the low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio and carotid plaque risk in patients with first-ever ischemic stroke (IS). We focused on analyzing the differences in this association across different Glucose Metabolic Conditions, preliminarily explored the roles of glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) in this association, and thereby provided a basis for future prospective studies and risk assessment of IS events.

This retrospective study included 12,166 patients hospitalized for first-time IS at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 1, 2013, to May 1, 2023. The LDL-C/HDL-C-carotid plaque risk association across glucose metabolism statuses was assessed employing logistic regression, stratified analysis, and exploratory mediation analyses.

Of 12,166 participants, 9,469 (77.8%) had carotid plaque. Univariate logistic regression showed that LDL-C/HDL-C had a stronger association with the risk of carotid plaque formation than other lipid parameters (LDL-C, total cholesterol, and triglycerides). Multivariate analysis confirmed a significant positive association. Stratified analyses revealed that the association between LDL-C/HDL-C and plaque risk was relatively stronger in the Pre-DM cohort (odds ratio [OR]: 1.233, 95% confidence interval [CI]: 1.093-1.391), followed by patients with diabetes mellitus (OR: 1.178, 95% CI: 1.074-1.293); no significant association appeared in individuals with normal glucose regulation. Exploratory mediation analysis showed HbA1c and FPG accounted for 11.5% and 10.5% of the LDL-C/HDL-C-carotid plaque risk association, respectively.

The findings of this study present that elevated LDL-C/HDL-C was significantly associated with carotid atherosclerosis in patients with IS, and this association was particularly stronger in the Pre-DM cohort. HbA1c and FPG had a certain moderating effect on this association, suggesting that the Pre-DM stage is a potential intervention window for focusing on LDL-C/HDL-C. LDL-C/HDL-C may serve as a reference indicator for clinically assessing the synergistic risk of "lipid-glucose co-morbidity," which holds significant value for the secondary prevention of IS events.

Diabetic kidney disease (DKD) remains a leading cause of end-stage kidney disease despite advances with renin-angiotensin system blockade, sodium-glucose cotransporter 2 inhibitors, finerenone, and glucagon-like peptide-1 receptor agonists. Therapeutic monoclonal antibodies may offer a targeted strategy to modulate inflammatory, fibrotic, metabolic, and vascular pathways involved in DKD. This review summarizes the mechanistic rationale, clinical evidence, translational barriers, and future prospects of antibody-based therapies for DKD.

We conducted a narrative literature review using PubMed, the Cochrane Library, and ClinicalTrials.gov from database inception to March 31, 2026. We prioritized peer-reviewed preclinical studies, clinical trials, and high-quality reviews addressing mAb-based strategies targeting DKD-related pathways, including TGF-β1, VEGF-B, CTGF, suPAR, integrin αvβ8, signal regulatory protein α, and PCSK9.

Phase II studies of anti-TGF-β1 and anti-VEGF-B antibodies failed to show meaningful renal benefit, highlighting challenges such as pathway redundancy, delayed intervention, insufficient intrarenal target engagement, and off-kidney toxicity. Anti-CTGF therapy showed an early signal of albuminuria, whereas anti-suPAR remains under clinical evaluation. Emerging preclinical targets, including integrin αvβ8 and signal regulatory protein α, may provide more kidney-focused modulation of fibrotic and inflammatory pathways. PCSK9 monoclonal antibodies, particularly evolocumab and alirocumab, appear promising because they may confer renal benefit through lipid lowering and kidney-intrinsic effects on lipotoxicity, oxidative stress, AMPK signaling, and profibrotic pathways.

Monoclonal antibodies represent a biologically compelling but clinically underdeveloped strategy for DKD. Future progress will require earlier biomarker-informed patient selection, confirmation of intrarenal target engagement, appropriate renal endpoints, and rational combination with established kidney-protective therapies.

To evaluate the effect of intravitreal faricimab injections on retinal venous diameter in proliferative diabetic retinopathy (PDR) patients with diabetic macular edema (DME).

This single-center, retrospective cohort study included 46 PDR patients (46 eyes) with DME, treated between August 2024 and January 2025. All participants received intravitreal faricimab combined with panretinal photocoagulation (PRP). Best-corrected visual acuity (BCVA, logMAR), central foveal thickness (CFT, μm), microaneurysm (MA) count, hard exudates (HE), neovascularization (NV) area, and retinal venous diameter were assessed at baseline and at 1, 3, and 6 months post-treatment.

Significant improvements in BCVA were observed at 1, 3, and 6 months (0.52 ± 0.16, 0.48 ± 0.18, 0.40 ± 0.15 vs. baseline 0.66 ± 0.18; all P < 0.05). CFT showed a significant reduction at all time points (381.35 ± 40.75, 327.30 ± 43.40, 297.56 ± 35.81 μm vs. baseline 472.34 ± 47.23 μm; all P < 0.05). The MA count showed no significant reduction at 1 month (P > 0.05) but decreased significantly thereafter (72.71 ± 20.53 and 63.06 ± 17.08 at 3 and 6 months, respectively; both P < 0.05). Reductions in HE area were not significant at 1 or 3 months (in 2 and 6 patients, respectively; both P > 0.05). At 6 months, a significant reduction in HE area was observed in 14 patients (P < 0.05). The NV area was significantly reduced at 1, 3, and 6 months compared to baseline (0.17 ± 0.10 mm², 0.17 ± 0.09 mm², and 0.17 ± 0.08 mm² vs. 0.98 ± 0.17 mm²; all P<0.05). Retinal venous diameter showed no significant change at 1 and 3 months compared with baseline (both P > 0.05) but was significantly reduced at 6 months (299.40 ± 19.56 μm; P < 0.05).

Intravitreal faricimab was safe and effective for PDR patients with DME. A trend toward morphological reversal of retinal venous diameter was demonstrated at 6 months, suggesting that faricimab may influence retinal microvascular remodeling through dual inhibition of the VEGF-A and Ang-2 pathways.

Diabetes is a well-established risk factor for cognitive decline and dementia; however, the extent to which diabetes is documented as a contributing cause on death certificates among decedents with dementia remains poorly characterized. This study aimed to evaluate temporal trends and demographic disparities in diabetes as a contributing condition among dementia-related deaths in older adults in the United States.

We analyzed multiple-cause-of-death data from the CDC WONDER database for adults aged ≥ 65 years with dementia listed as an underlying or contributing cause of death between 1999 and 2020. Diabetes was identified using ICD-10 codes E10-E14. We calculated age-adjusted mortality rates (AAMR), crude death rates (CDR), annual percentage changes (APC) using Joinpoint regression, and the proportion of dementia deaths with coexisting diabetes. Analyses were stratified by age, sex, race, and state.

Among 3,818,272 dementia-related deaths, 234,793 (6.2%) had diabetes documented as a contributing condition. The AAMR for dementia with diabetes increased from 8.7 per 100,000 in 1999 to 36.1 per 100,000 in 2020. Joinpoint regression identified a sharp increase from 1999 to 2009 (APC: +13.09%, 95% CI: 11.47-14.94, p < 0.001), followed by a stable trend from 2009 to 2020 (APC: +0.84%, 95% CI: -0.55-2.11, p = 0.187). Both dementia alone and dementia with diabetes demonstrated a sharp spike in 2020. The proportion of dementia deaths with coexisting diabetes was highest among decedents aged 65-74 years (8.5%) and decreased with age (85+ years: 5.3%). By race, American Indian/Alaska Native decedents had the highest proportion (10.4%), followed by Asian/Pacific Islander (9.2%), Black/African American (9.0%), and White (5.8%). Substantial state-level variation was observed across the United States.

The burden of diabetes, documented as a contributing condition among dementia-related deaths, increased substantially from 1999 to 2009 and remained relatively stable thereafter. Significant racial, age, and geographic disparities exist, with American Indian/Alaska Native decedents showing the highest proportion of coexisting diabetes. These findings highlight the burden of metabolic comorbidity among older adults with dementia and underscore the importance of continued surveillance and targeted public health strategies.

Prior studies have suggested that serum total bilirubin (TBil) may be linked to diabetic nephropathy (DN); however, its potential relationship with structural renal injury in histopathology has not been well defined.

The objective of the study is to explore whether physiological levels of TBil are associated with the severity of renal pathological changes in individuals with Type 2 diabetes mellitus (T2DM) and biopsy-confirmed DN.

A cross-sectional cohort of 401 individuals with T2DM and biopsy-confirmed DN was included. DN severity was determined according to the Renal Pathology Society classification and categorized as early-stage DN (Classes I-II) or advanced DN (Classes III-IV). Multivariable logistic regression was used to evaluate the association between TBil and advanced DN. TBil quartiles, restricted cubic spline modeling, subgroup and sensitivity analyses, and receiver operating characteristic curve analysis were also performed.

Among 401 biopsy-confirmed DN patients, 258 (64.3%) were classified as having advanced DN. In multivariable models, higher TBil levels were independently associated with lower odds of advanced DN after full adjustment (OR = 0.882, 95% CI 0.827-0.941; p < 0.001). When TBil was analyzed by quartiles, individuals in the highest quartile exhibited significantly lower odds of advanced-stage disease relative to those in the lowest quartile in the fully adjusted model (OR = 0.331, 95% CI 0.153-0.718; p = 0.005), with a notable dose-response pattern across quartiles (p for trend = 0.003). Restricted cubic spline analyses confirmed an inverse association between TBil levels and advanced DN. Receiver operating characteristic curve analysis identified a TBil cutoff of 9.9 μmol/L for discriminating advanced DN, with an area under the curve of 0.684. The results were broadly consistent across subgroup and sensitivity analyses.

Higher physiological TBil levels were linked to lower histopathological severity of DN in patients with Type 2 diabetes.

The comparative effects of non-insulin glucose-lowering therapies on coronary plaque progression in type 2 diabetes (T2DM) remain unclear. This study aimed to evaluate the impact of five major classes of non-insulin therapies on the progression of coronary atherosclerosis using serial coronary computed tomography angiography (CCTA).

This was a retrospective, registry-based cohort study analyzing 880 serial CCTA scans from patients with T2DM enrolled in the TOCCATA (Tomography of Coronary Artery Plaque and Treatment) registry. Patients were stratified based on their prescribed therapy: metformin (n = 357), dipeptidyl peptidase-4 (DPP-4) inhibitors (n = 97), glucagon-like peptide-1 receptor agonists (GLP-1 RAs, n = 88), sodium-glucose cotransporter-2 inhibitors (SGLT2i, n = 258), and thiazolidinediones (TZDs, n = 80). The primary endpoints were vessel-level stenosis progression and changes in patient-level plaque scores, including the Maximum coronary stenosis score (MAXS), segment involvement score (SIS), and segment stenosis score (SSS). Multivariable Cox regression models, adjusted for relevant covariates, were used for the analysis.

GLP-1 RAs were associated with the most significant reduction in vessel-level stenosis progression (adjusted Hazard Ratio [HR] 0.68, 95% Confidence Interval [CI]: 0.49-0.95, p = 0.024). This therapy class also consistently inhibited patient-level plaque progression across all scores (MAXS: HR 0.34, p = 0.002; SIS: HR 0.34, p < 0.001; SSS: HR 0.41, p < 0.001).In contrast, SGLT2i showed no significant effect on stenosis progression (HR 0.99, 95% CI: 0.82-1.19, p = 0.90) or SSS progression (HR 1.23, 95% CI: 1.00-1.52, p = 0.055). DPP-4 inhibitors showed a trend toward increased stenosis progression (HR 1.31, 95% CI: 1.01-1.69, p = 0.039). Metformin and TZDs had neutral effects on plaque progression.

In this real-world cohort of patients with type 2 diabetes, GLP-1 receptor agonists were associated with significantly slower coronary plaque progression compared to other glucose-lowering therapies. Other therapies, including SGLT2i, demonstrated no similar protective effects. These findings suggest that GLP-1 receptor agonists may offer particular benefits for patients with advanced atherosclerosis and underscore the potential value of CCTA in informing personalized therapeutic decisions in type 2 diabetes management.

Diabetic foot ulcers (DFUs) pose significant therapeutic challenges owing to their intricate microenvironment. Conventional biomaterials often target only a single pathological factor, rendering them inadequate for halting the progressive deterioration of DFUs. To address this limitation, we developed a multifunctional drug delivery platform based on amine-yne click chemistry. The system was constructed using quaternized chitosan (QCS) and tetra-arm polyethylene glycol propiolate (4A-PEG-PA), incorporating metal-polyphenol nanoparticles (MPNs) formed by epigallocatechin gallate (EGCG) and magnesium ions (Mg²⁺) as the drug-loading component. This platform not only fills ulcer cavities to eliminate dead space but also adheres firmly to irregular wound surfaces, minimizing physical disruption. Additionally, the drug delivery system exhibits pH-responsive behavior, along with potent antioxidant and hypoglycemic effects, effectively lowering reactive oxygen species (ROS) and glucose levels in the wound microenvironment by modulating pH, thereby promoting healing. In vitro studies revealed that the material safeguards mitochondrial function and integrity by counteracting oxidative stress. In vivo evaluations further demonstrated its antimicrobial, anti-inflammatory, pro-angiogenic, and re-epithelialization properties. Collectively, this hydrogel-based platform integrates multiple bioactive functions, presenting a promising strategy for the clinical management of DFUs.

Early detection of diabetic atherosclerosis (DAS) remains challenging, and the mechanisms underlying endothelial barrier dysfunction in this condition are not fully understood. Extracellular Hsp90α (eHsp90α) and the ER stress marker GRP78 have been implicated in vascular injury; however, their roles in DAS remain unclear. Therefore, this study aimed to investigate the association of eHsp90α and GRP78 with DAS and explore the underlying mechanisms.

We recruited patients with diabetes mellitus (DM) and patients with DAS. We then compared the levels and potential efficacies of serum eHsp90α and the ER stress marker GRP78 between the two groups. We subsequently conducted cytological experiments and experiments with ApoE^-/- mice to further explore the underlying mechanisms involved.

The serological analysis revealed that the levels of serum eHsp90α and the ER stress marker GRP78 were significantly higher in the DAS group than in the DM group and that the eHsp90α level was correlated with GRP78 level. The association and preliminary discriminative performance of the combination of eHsp90α and GRP78 levels were appeared higher than that of either marker alone. In addition, GRP78 plays a mediating role in the relationship between eHsp90α and DAS. Furthermore, the expression of GRP78 was higher in both diabetic ApoE^-/- mice and DAS patients than in control ApoE^-/- mice and AS patients. Cytological experiments revealed that eHsp90α induced endothelial barrier dysfunction mediated by ER stress via the LRP1 receptor.

Our findings suggest that eHsp90α and GRP78 are associated with diabetic atherosclerosis and may be associated biomarkers with potential discriminative value, although further validation is required. The eHsp90α-LRP1-ER stress pathway may contribute to endothelial barrier dysfunction. However, further large-scale and longitudinal studies are required to validate these findings.

Coronopus didymus (Brassicaceae) is a medicinal herb valued for its anti-inflammatory and hyperlipidemic properties; however, its antidiabetic potential remains entirely unexplored. Furthermore, despite the known therapeutic benefits of Azadirachta indica and the bioflavonoid quercetin, their evaluation in combination with C. didymus has never been investigated. To address this knowledge gap, this study pioneers the evaluation of C. didymus, A. indica, and quercetin-individually and as a novel combined formulation for the management of type 2 diabetes mellitus (T2DM). We employed an integrated approach utilizing in silico network pharmacology and molecular docking (targeting NOS3, AKT1, and PPARG), in vitro bioassays (antioxidant, α-amylase inhibition, hemolytic, and anticancer), and in vivo evaluation in streptozotocin-nicotinamide (STZ-NA)-induced diabetic mice. Network screening identified 100 overlapping targets between the quercetin and T2DM, prioritizing 15 key hub targets via protein-protein interaction and KEGG pathway enrichment analyses. Molecular docking confirmed strong binding affinities of the lead compounds to NOS3, AKT1, and PPARG. In vitro assays validated robust antioxidant, α-amylase inhibitory, and anticancer activities, while maintaining a safe hemolytic profile. In vivo trials demonstrated that while individual treatments effectively lowered blood glucose, the combined formulation exhibited superior hepatoprotective efficacy, profoundly reducing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (p < 0.0001) toward baseline control levels compared to individual plant extracts, alongside enhancing serum antioxidants and ameliorating histopathological damage in hepatic and intestinal tissues. In conclusion, this study bridges a critical gap in ethnopharmacology by identifying the antidiabetic potential of C. didymus and demonstrating that its combination with A. indica and quercetin offers a potent, distinct hepatoprotective advantage, highlighting its potential as a targeted nutraceutical approach for managing T2DM and its associated hepatic complications.

Delayed coronary stent-related inflammatory complications following percutaneous coronary intervention (PCI) are exceptionally rare, and chronic cutaneous fistulization years after stent implantation has only rarely been described. Such indolent presentations may mimic superficial chest wall infections, making diagnosis challenging. Multimodality imaging is essential for accurate diagnosis and surgical planning.

A 53-year-old man with type 2 diabetes mellitus and ischemic heart disease underwent right coronary artery (RCA) stenting in 2018. He presented with recurrent intermittent fever and a persistent draining xiphisternal sinus for seven months following incision and drainage of a presumed chest wall abscess. Ultrasonography demonstrated a localized subcutaneous collection. Contrast-enhanced computed tomography and CT coronary angiography (CTCA) revealed a fractured, chronically occluded RCA stent with extensive peri-stent inflammatory soft tissue extending into the pericardium, diaphragm, and subdiaphragmatic region. Cardiac magnetic resonance imaging confirmed transdiaphragmatic inflammatory extension and a fistulous tract communicating with the overlying skin. Transesophageal echocardiography was not performed because transthoracic echocardiography and cross-sectional imaging adequately delineated the lesion and showed no evidence of endocarditis. Following preoperative and perioperative antibiotic therapy, the patient underwent surgical excision of the fractured stent, chronic fibro-inflammatory tissue, and sinus tract. Intraoperative cultures and GeneXpert testing were negative, possibly reflecting prior prolonged antibiotic therapy. The postoperative course was uneventful, with complete wound healing, resolution of fever, and follow-up transthoracic echocardiography demonstrating no pericardial collection or valvular vegetations.

This case highlights an exceptionally rare delayed culture-negative chronic peri-stent inflammatory fistulizing process associated with RCA stent fracture presenting nearly seven years after PCI. It emphasizes the importance of maintaining a high index of suspicion in patients with persistent chest wall sinuses after coronary intervention and demonstrates the complementary role of CTCA and cardiac magnetic resonance imaging in defining disease extent and guiding successful surgical management.