While exposure to individual non-essential metals (NEMs) links to abdominal obesity (AOB), the NEM mixture effects and mechanisms remain unclear, particularly in vulnerable aging populations. We included 3795 community-dwelling Chinese older adults (age ≥ 60 years), measured 6 urine NEMs [gallium (Ga), arsenic (As), cesium (Cs), barium (Ba), thallium (Tl), and uranium (U)] via ICP-MS, defined AOB by sex-specific waist circumference, assessed insulin resistance (IR) via triglyceride-glucose (TyG) index, and determined vitamin D status by serum 25-hydroxyvitamin D [25(OH)D]. Multivariable logistic regression, mixture models [weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR)], mediation and moderation analyses, and network toxicology analyses were performed. Multivariable logistic regression showed a positive association between urinary Tl and AOB (OR = 1.18, 95% CI: 1.05-1.32). Mixture analyses consistently revealed a significant overall effect of NEMs on AOB, with Tl identified as the primary contributor (WQS weight = 0.481; QGC weight = 0.428; conditional PIP = 0.918). The TyG index was identified as a potential mediator, accounting for 10.18-7.84% of the associations between Tl and AOB and the NEM mixture and AOB, respectively. Vitamin D sufficiency [serum 25(OH)D ≥ 75 nmol/L] significantly attenuated TyG index-AOB association. Network toxicology identified the AGE-RAGE signaling pathway and several hub genes as candidate biological pathways for future investigation of the association between NEM exposure and AOB. These findings highlight the metabolic implications of NEMs, particularly Tl, and suggest that Vitamin D sufficiency may influence metabolic responses associated with AOB, offering novel insights into AOB prevention in the context of NEMs exposure.

The incidence of diabetes mellitus (DM) and its complications is continuously increasing, which imposes a heavy burden on patients and healthcare systems. However, traditional DM diagnosis and monitoring methods are inconvenient to operate and it is difficult to achieve continuous real-time monitoring, which makes them unable to meet the requirements of modern precision medicine. Hence, the development of efficient and convenient intelligent diagnosis and monitoring technologies is of vital importance for breaking through the current bottlenecks in DM management and improving patient prognosis. Polysaccharide derivative intelligent hydrogels (PDIHs) have shown great potential in the field of DM monitoring due to their excellent biocompatibility, intelligent responsiveness, and tunable functional properties. A thorough exploration of the research progress of PDIHs in the field of diabetes management is beneficial for promoting the development and clinical application of intelligent and personalized diabetes management devices. PDIHs with different types and properties play diverse roles in the diagnosis and monitoring of DM. Hence, this paper systematically reviews stimulus-responsive types (pH, light, temperature, magnetic field, ) of PDIHs. Moreover, this review comprehensively analyzes the key properties (mechanical, self-healing, adhesive, anti-swelling, and biocompatibility properties) of PDIHs. Furthermore, this article specifically introduces the latest advancements of PDIHs in continuous glucose monitoring and management of DM complications.

Ultrasound biofeedback served as a clinically valuable adjunct for post-operative muscle retraining, particularly in this medically complex case involving a highly motivated patient with strong psychosocial support. This case supports its broader application in musculoskeletal rehabilitation and underscores the need for further controlled studies with larger samples.

BACKGROUND: The coronary slow flow phenomenon (CSFP) is delayed contrast progression through the epicardial coronary arteries in the absence of significant stenosis. The stress hyperglycemia ratio (SHR) normalizes admission glucose to the estimated average glucose derived from HbA1c, separating acute glycemic excursion from chronic hyperglycemia. Whether the SHR is independently associated with CSFP in patients with type 2 diabetes mellitus (T2DM) is not known. METHODS: This retrospective case-control study enrolled 235 consecutive patients with T2DM who underwent coronary angiography between January 2022 and January 2025. Patients with epicardial stenosis exceeding 40% in any vessel, prior revascularization, or acute coronary syndrome within 30 days were excluded. Among the remaining patients, those with a corrected TIMI frame count (CTFC) above 27 in any epicardial vessel were classified as CSFP (n=112) and the rest as normal coronary flow (NCF) (n=123). The SHR was calculated as admission blood glucose (mmol/L) divided by (1.59 × HbA1c% - 2.59). RESULTS: The SHR was higher in the CSFP group than in the NCF group (1.42 ± 0.31 vs. 1.08 ± 0.24, p<0.001). After multivariate adjustment, it remained independently associated with CSFP (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.92-4.21, p<0.001). On receiver operating characteristic analysis the area under the curve (AUC) was 0.819 (95% CI 0.760-0.876); a cutoff of 1.21 gave 78.6% sensitivity and 74.0% specificity. The SHR correlated with mean CTFC (r=0.621, p<0.001) and outperformed admission glucose alone (AUC 0.724, p=0.003). CONCLUSION: In this cohort, the SHR was independently associated with CSFP and discriminated it better than admission glucose alone. Because it is calculated from two values routinely available at catheterization, admission glucose and HbA1c, the SHR is a practical candidate marker that warrants prospective validation for risk stratification in patients with T2DM undergoing coronary evaluation.

BACKGROUND: Diabetes markedly increases the risk of heart failure, yet the molecular signals connecting metabolic stress, myocardial fibrosis, and impaired cardiac repair remain incompletely understood. METHODS: We integrated bulk transcriptomic data from postischemic hearts (GSE26887), fibrosis-related genes from the CTD database, protein-protein interaction (PPI) analysis, and pathway enrichment (GO, KEGG, GSEA, and GSVA) to identify candidate mediators in diabetic versus nondiabetic heart failure. Single-cell RNA-sequencing datasets were analyzed with Seurat to map the cellular distribution of key genes. Pan-cancer analyses using TCGA cohorts were performed to evaluate prognostic, immune, and tumor mutation burden (TMB) correlations. Mechanistic validation was conducted in human cardiac progenitor cells (CPCs) exposed to normoglycemia or high glucose with S100A9 knockdown or overexpression, recombinant S100A8/A9, and a neutralizing S100A9 antibody. Cell viability (CCK-8); qPCR panels for fibrosis, inflammation, and metabolic genes; ROS production (DCF-DA and MitoSOX); and mitochondrial respiration were quantified. RESULTS: Differential expression and PPI network analyses identified S100A8 as a fibrosis-related hub specifically enriched in diabetic heart failure. Single-cell mapping revealed predominant S100A8 expression in CPCs rather than mature cardiomyocytes. Pathway analyses linked S100A8 to collagen fibril organization, ECM-receptor interaction, oxidative phosphorylation, and fatty acid -oxidation. Functionally, high glucose upregulated S100A8/S100A9 and profibrotic and proinflammatory genes in CPCs, increased total and mitochondrial ROS, and reduced basal, ATP-linked, and maximal respiration and spare capacity. S100A9 knockdown partially restored CPC proliferation, redox balance, and mitochondrial function, whereas S100A9 overexpression or recombinant S100A8/A9 further exacerbated oxidative stress and bioenergetic failure; S100A9 neutralization attenuated these effects. Pan-cancer analyses showed that high S100A8 expression was associated with adverse prognosis, altered immune infiltration, and increased TMB in several TCGA cohorts. CONCLUSIONS: S100A8/S100A9 emerges as a central mediator linking hyperglycemia-induced oxidative stress, metabolic inflexibility, and fibrotic reprogramming of CPCs, thereby promoting diabetic heart failure. S100A8/S100A9 may serve as a biomarker and therapeutic target at the interface of immunometabolism, cardiac regeneration, and cardio-oncology.

Iatrogenic subretinal injection of dexamethasone implants is rare and has been reported in eyes without retinal detachment. We describe the surgical management and successful perfluorocarbon-assisted retrieval of a subretinal dexamethasone implant in the setting of retinal detachment. A 63-year-old man with type 2 diabetes mellitus, proliferative diabetic retinopathy, and diabetic macular edema with prior dexamethasone implants presented with a rhegmatogenous retinal detachment in the left eye. Preoperative examination identified a dexamethasone implant in the subretinal space. During pars plana vitrectomy, the implant migrated into the vitreous cavity and was removed using a perfluorocarbon-assisted bimanual technique, followed by standard retinal detachment repair with gas tamponade. The implant was successfully removed, and retinal reattachment was achieved. Subretinal migration of a dexamethasone implant is a rare complication associated with retinal detachment and intraoperative challenges. Perfluorocarbon-assisted bimanual removal is effective, and careful preinjection retinal evaluation with meticulous injection technique is essential to minimize risk.

BACKGROUND: Older adults with type 2 diabetes are often subjected to intensive glucose-lowering therapies with a high likelihood of hypoglycaemia, falls, functional decline, and treatment burden. While international recommendations advocate for individualised glycaemic targets, they provide little clarification on when, or how, to de-intensify therapies as health status changes. METHODS: We undertook a targeted evidence synthesis of randomised controlled trials, observational cohort studies, target trial emulation studies, and international clinical guidelines focusing on glucose-lowering agents for the treatment of diabetes mellitus in patients aged 65 years and older. Evidence was synthesised and prioritised based on relevance for the important outcomes in later life, including hypoglycaemia, hospitalisation, functional decline, quality of life, and mortality. From this evidence and the principles of geriatric medicine, we constructed a pragmatic, frailty-informed clinical decision framework for the purposes of guiding deprescribing and the de-intensification of glucose-lowering therapy. RESULTS: Older adults in a variety of care continuum settings, particularly with frailty, multimorbidity, cognitive impairment, or a limited life expectancy, tend to stay on intensive glucose-lowering therapies for very little, if any, benefit. Target trial emulation studies and observational studies most often show that hypoglycaemia and treatment burden are lowered by de-intensifying high-risk medications, particularly insulin and sulfonylureas, without any clinically important deterioration in glycaemic control. Even with the evidence, existing guidance lacks a practical operational framework to implement such evidence in everyday clinical practice. CONCLUSION: We suggest a frailty-informed clinical decision framework that integrates functional status, physiologic vulnerability, treatment-related risks, and patient preferences in making glucose-lowering treatment decisions in older adults with type 2 diabetes. This framework shifts the focus to patient safety and functional outcomes, instead of HbA1c targets, to provide a practical approach to deprescribing and de-intensifying treatment to minimise iatrogenic harm and, most importantly, to align care with the preferences of older adults.

PURPOSE: Microalbuminuria and urine albumin-to-creatinine ratio (UACR) are important markers for early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Aspirin (acetylsalicylic acid; ASP) has been associated with anti-inflammatory and metabolic effects in patients with T2DM. This study investigated the association between low-dose ASP use and renal injury markers in patients with T2DM. METHODS: A retrospective matched cohort study was conducted in 60 Taiwanese patients with T2DM. Patients receiving low-dose ASP (100 mg/day) were matched 1:1 with controls according to sex, age, height, weight, body mass index, and duration of diabetes. Metabolic outcomes and renal injury markers, including serum creatinine, urine microalbumin, and urine albumin-to-creatinine ratio (UACR), were evaluated during follow-up. RESULTS: Compared with the DM group, the ASP group demonstrated lower HbA1c and total cholesterol levels during follow-up. In renal outcome analysis, urine microalbumin levels were significantly lower in the ASP group than in the DM group at follow-up (p = 0.039). A trend toward improved UACR was also observed in the ASP group. CONCLUSION: Low-dose ASP use was associated with favorable changes in glycemic control and early renal injury markers in patients with T2DM. Lower urine microalbumin levels and a trend toward improved UACR were observed in the ASP group during follow-up. Although microalbuminuria may be influenced by multiple metabolic and cardiovascular factors, the present findings suggest that low-dose ASP therapy may have potential metabolic and renal associations in patients with T2DM. Further prospective studies are warranted to validate these findings and to explore the underlying mechanisms and their clinical relevance.

BACKGROUND: Adverse drug events are common in psychiatric inpatient care because polypharmacy is frequent and metabolic comorbidities such as diabetes mellitus are prevalent. When nonspecific symptoms and reduced food intake are not promptly managed, clinically significant metabolic deterioration may be missed. We report a medicolegal autopsy case in which a review of nursing records, a postmortem investigation, and toxicology helped reconstruct a medication-related adverse event trajectory in a psychiatric inpatient with diabetes. CASE PRESENTATION: A 47-year-old Japanese woman of Asian ethnicity with bipolar disorder, insomnia, and a 12-year history of type 2 diabetes mellitus was hospitalized in a psychiatric ward where medications were centrally managed. No blood tests were performed during hospitalization. From 8 days before death, nursing records documented frequent nonspecific symptoms and recurrent hypoglycemia. Her oral intake decreased from the evening of 2 days before death and became minimal after breakfast 1 day before death. She was found unresponsive and was pronounced dead, and the cause of death could not be determined clinically, including after postmortem computed tomography at another hospital. A medicolegal autopsy showed food material in the airway and bronchioles, with congested and edematous lungs, suggesting aspiration-related asphyxia. A femoral venous blood sample showed a metformin concentration of 46 mg/L and trihexyphenidyl concentration of 0.45 mg/L. The vitreous glucose concentration was markedly low at 0.33 mmol/L (6 mg/dL) in the left eye and 0.39 mmol/L (7 mg/dL) in the right eye. These findings suggested a complex medication-related adverse event trajectory involving reduced food intake, recurrent hypoglycemia, ongoing antidiabetic therapy, and possible contribution of metformin exposure before terminal aspiration-related death. CONCLUSIONS: This case illustrates that clinically important metabolic deterioration may be overlooked in psychiatric inpatients when nonspecific symptoms and reduced food intake are not promptly managed. Our findings suggest that a medicolegal autopsy and postmortem toxicology can help reconstruct clinically relevant adverse event pathways when an inpatient death remains unexplained.

BACKGROUND: Oxidative stress is a central feature of the metabolic disturbances observed in diabetes, often leading to cellular and molecular damage. Advanced oxidation protein products (AOPPs), formed during oxidative modification of plasma proteins, have been proposed as biomarkers of systemic oxidative stress. Despite increasing interest, the relationship between these markers and diabetes remains inconclusive. This study aimed to systematically evaluate and quantify differences in circulating AOPPs levels in diabetes. METHODS: A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Searches were conducted across PubMed, Scopus, Embase and Web of Science databases up to March 2025 to identify relevant observational studies involving adults aged 18 years or older. Studies were included if they reported circulating levels of AOPPs in individuals with type 1 diabetes (T1DM), type 2 diabetes (T2DM), or impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), compared to non-diabetic controls. Data extraction and quality assessment were conducted independently by two reviewers, and a random-effects model was used for meta-analysis. RESULTS: Sixteen eligible articles with twenty individual studies were identified, encompassing diverse populations and diabetes subtypes. The meta-analysis demonstrated significantly elevated circulating AOPPs in both TDM (WMD ≈ 17.5 µmol/L) and TDM (WMD ≈ 24.68 µmol/L) compared with controls, though heterogeneity was high. Subgroup analyses confirmed the consistent direction of effect, with stronger associations in younger populations, studies with higher baseline AOPPs, and certain designs or regions. Meta-regression showed that examined moderators (continent, study design, baseline AOPPs, age, sample size, gender, study quality, presence of overweight/ obesity, hypertension, smoking and abnormal serum lipids) explained little to none of the variability. Sensitivity analyses indicated that results were robust. Publication bias assessment revealed funnel plot asymmetry for type 2 diabetes, but trim-and-fill analysis did not materially alter the pooled estimates, supporting the stability of the findings. CONCLUSION: Elevated levels of AOPPs appear to be associated with diabetes, supporting the role of oxidative stress in its pathophysiology. Although pooled analyses demonstrated significantly higher circulating AOPP concentrations in patients with diabetes mellitus, substantial between-study heterogeneity and wide prediction intervals suggest that the magnitude and consistency of this association may vary across different populations and study settings. Also, the observational design of included studies limits the strength and generalizability of the pooled estimates. Therefore, causal inferences cannot be drawn, and further well-designed prospective research is warranted to clarify whether these biomarkers can reliably predict the onset or progression of diabetes. PROSPERO REGISTRATION NUMBER: CRD420251275798.

BACKGROUND: healthcare inequalities have been widely documented, yet the COVID-19 pandemic may have altered their magnitude and direction. This study aimed to analyse the dynamics of healthcare inequalities in patients with type 2 diabetes mellitus (T2DM) before and after the pandemic using a real-world data approach. METHODS: we conducted a real-world observational study including T2DM patients aged ≥ 45 from the CARhES cohort, a population-based dataset integrating clinical and administrative information from Aragón (Spain), between 2017 and 2022. Healthcare utilisation was assessed at two levels: Primary Care and specialist care. Socioeconomic, clinical, and healthcare variables were retrieved from electronic health records. We described healthcare utilisation patterns and trends across the study period and estimated adjusted prevalence ratios (PRs) for inequality axes (age, gender, migrant status, socioeconomic level, and rurality) using Poisson regression models at three time points (2017, 2020, 2022), adjusting for multimorbidity. RESULTS: A total of 86,407 T2DM patients were included. Almost all patients consulted a general practitioner (GP) each year and increased over time, while specialist consultations declined during the pandemic and had not recovered by 2022. Socioeconomic inequalities persisted or widened across most axes. After the pandemic, patients aged ≥ 80 were less likely to visit GP than younger patients, reversing pre-pandemic trends. Women continued to show higher GP use than men but fewer consulted with specialist, although the magnitude of the observed difference was small. Immigrants' access to specialists decreased relative to natives in 2022. active people with low socioeconomic status showed the lowest specialist consultations, while mutualists had the highest during the pandemic. Rural residents maintained greater reliance on Primary Care but fewer specialist visits post-pandemic. The explanatory power of socioeconomic variables declined in GP models, whereas multimorbidity gained influence during and after COVID-19. CONCLUSIONS: Healthcare inequalities among T2DM patients persisted and some patterns shifted after 2020. Although GP utilisation increased, nursing and specialist follow-up did not recover to pre-pandemic levels. These patterns underscore the need for targeted interventions to optimise care for older adults, women, migrants, rural residents, and low-income populations, with a focus on promoting digital inclusion and developing tailored healthcare pathways to advance health equity.

BACKGROUND: Cholesterol metabolic reprogramming plays a key role in pancreatic cancer progression by regulating the tumor immune microenvironment (TIME) and influencing responses to immunotherapy. Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), a malignancy that commonly occurs in individuals with high BMI and type 2 diabetes mellitus (T2DM). Key metabolic markers (SOAT1 and SREBP2), the tumor suppressor P53, and the immune marker CD8 are implicated in PanIN initiation, PDAC progression, and subsequent metastasis, but their associations-particularly for those that are potentially targetable-remain poorly defined. METHODS: Using publicly available PDAC datasets from the GEO database, we conducted in silico analyses to investigate the genes of interest. Additionally, we used laser capture microdissection to isolate specific cells from pancreatic cancer tissues obtained from patients. We performed translational research using 17 tumor samples, as well as 17 microdissected PanIN lesions and matched normal tissues. Protein expression analysis was further conducted on a larger cohort, including 65 PanIN lesions and 157 tumor tissues from PDAC patients. RESULTS: Our data identify a dual-direction expression pattern in obese and diabetic patients, with elevated levels of SOAT1, SREBP2, and P53, and reduced CD8 expression, suggesting a coordinated metabolic and immunological alteration in pancreatic cancer. High BMI and T2DM, recognized as independent risk factors for PDAC, are significantly associated with dysregulation of key markers involved in the mevalonate pathway and the TIME, potentially contributing to PanIN and PDAC progression. CONCLUSION: These findings warrant further longitudinal and mechanistic studies to clarify whether metabolic modulation may influence PDAC risk or clinical outcomes.

BACKGROUND: While metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently associated with increased cardiovascular risk in the general population, its association with cardiovascular disease (CVD) mortality in adults with established cardiometabolic risk factor (including obesity, hypertension, diabetes mellitus, or dyslipidemia) remains inconsistent. We aimed to determine whether frailty confounds the MASLD-CVD mortality association. METHODS: We analyzed 10,413 US NHANES III adults with ≥ 1 cardiometabolic risk factor. Frailty was quantified using a 49-item frailty index (FI, ranging from 0 [maximal robustness] to 1 [severe frailty]) and categorized into quartiles. Associations between MASLD and CVD mortality were assessed using multivariable Cox proportional hazards models with and without frailty adjustment. Interaction and mediation analyses were also performed. RESULTS: Over a mean follow-up of 23.36 years, 1,375 (13.20%) CVD deaths occurred. Frailty was significantly associated with both MASLD and CVD mortality. There was no evidence of interaction between MASLD and frailty, and mediation analysis showed no indirect effect of MASLD on CVD mortality through frailty. In absence of frailty adjustment, MASLD was not associated with CVD mortality (HR = 0.92, 95% CI: 0.78-1.10). After adjustment for frailty, MASLD was independently associated with higher CVD mortality (HR = 1.19, 95% CI: 1.07-1.32). Stratified by FI quartiles, significant associations were observed only in the higher frailty quartiles (Q3: HR = 1.35, 95% CI: 1.03-1.77; Q4: HR = 1.70, 95% CI: 1.07-2.69). The population attributable fraction of MASLD for CVD mortality was 10.1-12.5% after frailty adjustment. CONCLUSIONS: Frailty may confound the MASLD-CVD mortality relationship in people with cardiometabolic risk factors. The association between MASLD and CVD mortality is detected only when frailty is adjusted for.

BACKGROUND: High lipoprotein(a) [Lp(a)] levels and insulin resistance (IR) are both established risk factors for atherosclerosis. Nevertheless, the interrelationship between these two factors and their combined effects on atherosclerosis remain poorly understood. This research aimed to explore the distribution characteristics of Lp(a) across individuals at varying IR degrees and to evaluate the combined ability of Lp(a) levels and the IR surrogate marker, estimated glucose disposal rate (eGDR), in predicting atherosclerosis. METHODS: This retrospective study involved data from 10,753 participants who received health examinations at the Third Xiangya Hospital (2017-2025). Carotid ultrasound was employed to diagnose atherosclerotic plaques. Logistic regression and restricted cubic spline (RCS) analysis were used across eGDR quartiles to examine the relationship between Lp(a) and plaque risk. The incremental benefits of incorporating both Lp(a) and eGDR in predicting atherosclerosis were further assessed via machine learning-based analyses. RESULTS: In this study, the median Lp(a) concentration of the participants was 12.4 mg/dL, with 14.4% exhibiting values greater than 30 mg/dL. RCS analysis identified a significant nonlinear (U-shaped) relationship of Lp(a) with eGDR, whereas peak Lp(a) levels were observed within the uppermost eGDR quartile (Q4). Lp(a) levels demonstrated an independent positive link to atherosclerotic plaque risk; notably, this association remained significant in both the lowest and highest eGDR quartiles. Furthermore, machine learning analyses indicated that the incorporation of Lp(a) and eGDR conferred a modest gain in the model's discriminative capacity when forecasting atherosclerotic plaque, with the AUROC value increasing slightly from 0.7810 to 0.7820. CONCLUSIONS: Lp(a) levels exhibited a positive linear association with atherosclerotic plaques in the overall population, which varied across eGDR strata. Furthermore, the interaction between Lp(a) and eGDR was significantly relevant for the prediction of this condition. The integration of Lp(a) levels and the eGDR into machine learning models modestly improved the identification of high-risk individuals. This strategy supports more precise clinical interventions, ultimately contributing to improved cardiovascular health outcomes.

BACKGROUND: Carotid artery calcification (CAC) detected on panoramic radiographs can serve as an early indicator of systemic atherosclerotic disease. This study aimed to determine the prevalence of CAC in digital panoramic radiographs of dental implant patients and to evaluate its association with systemic diseases in a sample of the Turkish population. METHODS: This retrospective cross-sectional study included 254 implant patients who attended follow-up visits between December 2022 and January 2024. Age, gender, number of implants, presence of CAC, and systemic disease status (hypertension, diabetes mellitus, hyperlipidemia, atherosclerosis, cardiovascular disease) were analyzed. All panoramic radiographs were assessed by one experienced oral and maxillofacial surgeon in two separate sessions with a 2-week interval to evaluate intra-observer consistency. Cohen's kappa (κ = 0.86) confirmed excellent agreement. Logistic regression was performed to determine associations between systemic variables and CAC. RESULTS: CAC was detected in 60 of 254 patients (23.6%). Hypertension was the most prevalent systemic condition associated with CAC (46.7% of affected patients). Logistic regression revealed significant associations between CAC and several systemic diseases: hypertension (OR = 48.04), diabetes mellitus (OR = 43.57), cardiovascular disease (OR = 40.92), hyperlipidemia (OR = 33.20), and atherosclerosis (OR = 26.38) (p < 0.05). CONCLUSION: Significant associations were observed between CAC and systemic diseases; however, the magnitude of these associations should be interpreted with caution. On the other hand, panoramic radiographs in dental clinics can incidentally reveal carotid artery calcifications (CAC), which reflect underlying systemic atherosclerosis. Therefore, dentists play a crucial role in the early prevention of stroke and cardiovascular events by identifying carotid artery calcification and referring patients for medical evaluation.

BACKGROUND: Henagliflozin has demonstrated favorable glycemic and metabolic effects in phase III trials. However, real-world evidence regarding its impact on cardiac structure-particularly left ventricular mass index (LVMI)-in patients with type 2 diabetes mellitus (T2DM) and concomitant hypertension remains lacking. METHODS: In this single-center, retrospective cohort study, 183 patients with T2DM and hypertension were enrolled. After 1:1 propensity score matching, 132 patients (henagliflozin group, n = 66; control group, n = 66) were included in the primary analysis. The henagliflozin group received henagliflozin 10 mg once daily added to standard-of-care therapy, whereas the control group received standard therapy alone. The primary outcome was the change in LVMI from baseline to 6 months. Secondary outcomes included changes in other echocardiographic parameters (LVEF, E/e', left atrial diameter, LVEDd, IVSd, LVPWT), glycemic indices (FPG, HbA1c), blood pressure, body mass index (BMI), inflammatory markers, and renal function. RESULTS: At 6 months, LVMI decreased in the henagliflozin group (from 87.90 ± 18.32 to 85.28 ± 18.20 g/m; mean change - 2.62 ± 13.00 g/m) but increased in the control group (from 83.46 ± 18.22 to 87.81 ± 16.53 g/m; mean change + 4.35 ± 15.88 g/m; between-group P = 0.007). Additionally, henagliflozin treatment was associated with significant reductions in left atrial diameter (between-group P = 0.035), E/e' ratio (P = 0.044), interventricular septal thickness (P = 0.030), and left ventricular posterior wall thickness (P = 0.018), as well as a modest increase in LVEF (P = 0.045). Compared with the control group, the henagliflozin group also exhibited greater reductions in fasting plasma glucose (- 0.97 vs. + 0.16 mmol/L; P = 0.037), HbA1c (- 0.42% vs. + 0.04%; P = 0.021), systolic blood pressure (- 9.45 vs. - 1.95 mmHg; P = 0.023), diastolic blood pressure (- 3.38 vs. 0.68 mmHg; P = 0.029), and BMI (- 0.45 vs. 0.00 kg/m; P = 0.023). CONCLUSIONS: In patients with T2DM and hypertension, the addition of henagliflozin to standard therapy over 6 months was associated with significant attenuation of adverse ventricular remodeling-as evidenced by reductions in LVMI, left atrial diameter, and diastolic filling indices-alongside clinically meaningful improvements in glycemic control, blood pressure, and body weight.

BACKGROUND: Aging and diabetes mellitus are associated with structural and biochemical changes in dentin, including altered collagen organization, dentinal sclerosis, tubule occlusion, mineral changes, and, in some contexts, increased non-enzymatic collagen glycation. These substrate changes may influence the performance and durability of adhesive restorative materials. However, the extent to which bonding outcomes can be directly attributed to advanced glycation end products (AGEs) remains uncertain, as AGE levels are rarely measured in adhesive studies. METHODS: This scoping review followed the Joanna Briggs Institute methodology and was reported in accordance with the PRISMA-ScR guidelines. PubMed, Scopus, Web of Science, and Embase databases were searched from inception to December 1, 2025. Eligible studies evaluated bond strength, interfacial morphology, microleakage, mineral content, or remineralization in dentin affected by aging, diabetes, or experimental glycation. Study selection and data charting were independently conducted by two reviewers. RESULTS: Of the 2615 records identified, 16 primary experimental studies met the inclusion criteria, most of which were in vitro investigations using extracted human teeth. Fifteen studies reported bond strength outcomes, and two assessed microleakage. Only four of the included studies directly evaluated diabetic dentin, and these studies generally reported reduced bond strength, particularly in type 1 diabetes. Most of the included studies evaluated age-related dentin, and the findings were heterogeneous, with many contemporary adhesives showing minimal differences between young and aged dentin. None of the included studies directly quantified AGE levels in dentin before adhesive testing. CONCLUSION: Dentin alterations associated with aging and diabetes may influence adhesive performance; however, the available evidence is heterogeneous and does not allow these effects to be directly attributed to AGE accumulation. Therefore, aging and diabetes should be interpreted as distinct dentin-modifying contexts rather than equivalent AGE-mediated substrates. Further studies incorporating biochemical assessment of dentin, participant-level clinical variables, and standardized durability testing are needed. SCOPING REVIEW REGISTRATION: The protocol for this scoping review was registered on the Open Science Framework (OSF) on 16th January 2026 (https://doi.org/10.17605/OSF.IO/JWA6H).

BACKGROUND: Patients with early-onset type 2 diabetes mellitus (T2DM) face a significantly elevated risk of developing diabetic kidney disease (DKD) in the early stages, attributable to their prolonged disease duration. The urinary albumin-to-creatinine ratio (UACR) serves as a critical marker for screening incipient renal injury. While insulin resistance (IR) is a pivotal driver of this pathological progression, the triglyceride-glucose (TyG) index, a simple and effective surrogate marker for IR, has not been thoroughly investigated in this specific population. The association between TyG index and UACR, along with its potential discriminatory ability for early renal damage in patients with early-onset T2DM, remained unclear. OBJECTIVE: This study aimed to explore the correlation between the TyG index and UACR in patients with early-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: A dual-center, retrospective cross-sectional study was conducted. Clinical data from a total of 596 adult patients (aged 18-40 years) with early-onset type 2 diabetes mellitus, admitted to the First Medical Center of the Chinese PLA General Hospital and Hainan Hospital of the Chinese PLA General Hospital between January 2012 and December 2022, were collected and retrospectively analyzed. Participants were stratified into three groups based on the tertiles of the TyG index: Q1 (< 7.67), Q2 (7.67-8.33), and Q3 (> 8.33). They were also categorized into two groups according to UACR levels: <30 mg/g and ≥ 30 mg/g. The association between TyG index, traditional glucose/lipid parameters, and elevated UACR (≥ 30 mg/g) was assessed using correlation analysis and binary logistic regression models. Receiver operating characteristic (ROC) curves were plotted to evaluate the discriminatory ability of these indicators for elevated UACR. Subgroup analyses were further performed based on gender, blood pressure status, and estimated glomerular filtration rate (eGFR). RESULTS: The mean age of the 596 participants was 31.78 ± 9.99 years. A significant positive correlation was observed between the TyG index and UACR (r = 0.250, P < 0.001). Binary logistic regression analysis revealed that after adjustment for multiple confounding factors, patients in the highest TyG tertile (Q3) had a 1.366-fold increased risk of elevated UACR (≥ 30 mg/g) compared to those in the lowest tertile (Q1) (OR: 1.366, 95% CI: 1.015-1.838, P = 0.039). The discriminatory ability of TyG index for elevated UACR was evaluated using the receiver operating characteristic curve, yielding an area under the curve of 0.649 (95% CI: 0.609-0.687). At the optimal cut-off value of 8.18, the sensitivity and specificity were 69.47% and 61.08%, respectively. Notably, the TyG index demonstrated superior discriminatory efficacy compared to traditional lipid parameters, including triglycerides, total cholesterol, LDL-C, and HDL-C. CONCLUSION: In patients with early-onset type 2 diabetes, an elevated TyG index was independently associated with increased UACR levels and served as a potential indicator for early diabetic kidney injury. Specifically, for individuals aged 18-40 years, a TyG index exceeding 8.18 was associated with an elevated association of developing diabetic kidney disease. CLINICAL TRIAL REGISTRATION: Not applicable.

OBJECTIVE: This study aimed to identify clinically interpretable DKD sub-phenotypes for personalized prognosis and intervention. METHODS: We enrolled participants with type 2 diabetes mellitus (T2DM) from three hospitals in China. Clinically interpretable sub-phenotypes were identified using two complementary clustering frameworks: a static model (k-means clustering) capturing the metabolic-renal profile at DKD diagnosis, and a dynamic model (group-based multi-trajectory model, GBMTM) reconstructing longitudinal trajectories preceding diagnosis. Associations between DKD clusters and post-diagnosis DKD progression were estimated using cox regression. RESULTS: A total of 1520 participants were included for the analysis of static clustering, 32.53% were females with a mean age of 54.4 ± 12.1 years. The static clustering method classified DKD patients into four clusters: BALANCE, YOUTH, TYPICAL and NATURAL. Compared with the participants in YOUTH, the hazard ratios (HRs) of progressing to higher stage of CKD (G3b-G5) in BALANCE, TYPICAL and NATURAL are 1.68 (95%CI:0.81-3.49), 7.85 (95%CI:4.25-14.51), 6.58 (95%CI:3.54-12.24), respectively. GBMTM identified three longitudinal trajectories. The HRs (95%CI) of progressing to higher stage of CKD (G3b-G5) was 2.48 (95%CI:1.50-4.09) in Trajectory 1 compared with Trajectory 2. In addition, the clustering results obtained from the validation cohort were consistent with the derivation cohort. CONCLUSIONS: By integrating static and dynamic clustering approaches, this study identifies novel DKD sub-phenotypes, and evaluated the risk of DKD progression in each cluster.

In this cross-sectional study, we aimed to explore the correlation between body composition and bone mineral density (BMD) in young and middle-aged people with different gender and different BMI groups. We selected 1,295 young and middle-aged people (20 to 50 years old) who underwent physical examination at the Health Management Center of the International Medical Service (Xidan Branch) of Peking Union Medical College Hospital from January 2020 to June 2024 as the study subjects, and demographic characteristics, laboratory examinations, body composition(assessed by bioelectrical impedance analysis, including measurements of skeletal muscle mass, skeletal muscle index, body fat mass, percent body fat, fat-free mass, and visceral Fat Area), and dual-energy X-ray bone absorptiometry (DXA) results were collected. Based on gender and body mass index (BMI), the study participants were categorized into three groups: normal weight (18.5 kg/m² ≤ BMI < 24 kg/m²), overweight (24 kg/m² ≤ BMI < 28 kg/m²), and obese (BMI ≥ 28 kg/m²). One-way ANOVA was employed to assess differences among the three groups. The relationship between BMI and BMD was analyzed using multiple regression models along with natural cubic spline models. Additionally, multiple regression models were used to examine the association between body composition and BMD. There were 774 males (216 in the normal body composition group, 380 in the overweight group, and 178 in the obese group) and 521 females (386 in the normal body composition group, 99 in the overweight group, and 36 in the obese group), and there was a significant difference in the laboratory results, body composition, and BMD among the three groups of males and females (all P < 0.05). Multiple regression analysis, after adjusting for age, smoking and alcohol consumption history, hypertension, and diabetes mellitus, revealed a significant positive correlation between BMI and BMD at all skeletal sites (all P < 0.05). The obese group exhibited a more pronounced increase in BMD compared to the overweight group (lumbar spine BMD: β = 0.04, 95% CI 0.02-0.07; femoral neck BMD: β = 0.09, 95% CI 0.07-0.11; total hip BMD: β = 0.11, 95% CI 0.09-0.13; all P < 0.05). Further analysis of the nonlinear relationship between BMI and BMD demonstrated that in women, BMD at all sites increased with higher BMI. In contrast, men exhibited an inverted U-shaped nonlinear association, with a decline in BMD observed in the high BMI range (BMI ≥ 30 kg/m²). The correlation between body composition and BMD, skeletal muscle mass (SMM), skeletal muscle index (SMI), and fat free mass (FFM) were significantly positively correlated with BMD at all sites in both males and females (P < 0.05), and percent body fat (PBF) was negatively correlated with BMD at all sites in the obese group of males, the overweight groups of males and females (P < 0.05). Among young and middle-aged individuals, men show a decline in BMD when BMI reaches 30 or above, whereas women continue to experience a gradual increase in BMD with rising BMI. Additionally, elevated PBF is negatively correlated with BMD. This suggests that maintaining an appropriate BMI and PBF may be beneficial for bone health in this age group.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) undergoing delivery face a significantly higher risk of healthcare-associated infections (HAIs) due to metabolic disorders and impaired immune function compared with healthy pregnant women, making them a key population of concern in HAI prevention and control. However, effective early warning tools specifically tailored to this population are still lacking in clinical practice. Therefore, this study aimed to develop a risk prediction model for HAIs in women with GDM undergoing delivery, with the goal of identifying high-risk individuals and facilitating early intervention. METHODS: Model development and validation were conducted using a sequential approach. In the development phase, a 10‑repeated 5‑fold cross‑validation was performed on the training set (n = 690; January 2022 - December 2024). To address severe class imbalance, the random over‑sampling examples method was applied within each training fold, followed by random forest (RF) modeling. This procedure was repeated 10 times with different random seeds, yielding 50 performance estimates. Candidate variables selected in at least 70% of the 50 folds were retained as stable predictors. Using this selected feature set, both logistic regression (LR) and RF models were developed. Model performance was then evaluated on an independent temporal validation set (n = 294; January - December 2025), which was completely withheld from the model development process. RESULTS: A 10‑repeated 5‑fold cross‑validation on the training set identified five stable predictors selected in ≥ 70% of the 50 model fits: mode of delivery, Group B Streptococcus colonization, artificial rupture of membranes, misoprostol administration, and balloon catheter for cervical ripening. Using these predictors, both RF and LR models were developed. In the temporal validation set (n = 294; positive rate 5.78%), the RF model achieved a PR‑AUC of 0.407 (95% CI: 0.145-0.632) and an ROC‑AUC of 0.789 (95% CI: 0.646-0.911). The LR model yielded a PR‑AUC of 0.345 (95% CI: 0.124-0.563) and an ROC‑AUC of 0.803 (95% CI: 0.665-0.920). The Brier score was 0.0472 for LR and 0.1134 for RF. CONCLUSION: The RF model demonstrated superior performance in identifying positive cases and exhibited greater stability, whereas LR achieved better probability calibration. Given the clinical priority of minimizing false negatives, RF may be preferable when sensitivity is prioritized, while LR may be more suitable when well-calibrated probabilities are required. Both models showed moderate discriminative ability and require further external validation before clinical implementation. Decision curve analyses supported their potential clinical utility. CLINICAL TRIAL NUMBER: Not applicable.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a primary cause of chronic liver disease, affecting over half of individuals with Type 2 Diabetes Mellitus (T2DM). Although uric acid (UA) is linked to metabolic risk factors, its independent association with MASLD presence and advanced liver fibrosis risk within European T2DM populations remains to be fully clarified. This study investigated the relationship between serum UA levels, MASLD prevalence and non-invasive advanced fibrosis risk strata. We cross-sectionally evaluated 768 Caucasian T2DM patients (473 males and 295 females) from the Catanzaro Metabolic Risk Factors Study (CATAMERIS). MASLD was diagnosed via standardized ultrasonography (n = 522). Advanced liver fibrosis risk was stratified using the age-adjusted FIB-4 index into low risk (Grade 0), indeterminate risk (Grade 1), and high risk (Grade 2). Multivariable logistic regression analyses and a stringent sensitivity model adjusting for all major concomitant medications (glucose-lowering, lipid-lowering, and antihypertensive regimens) were performed. The MASLD group exhibited significantly higher UA, BMI, lipid profiles, and HbA1c levels. Across the fibrosis strata (Grade 0 to Grade 2), a stepwise upward trend in serum UA was observed (5.6 ± 1.5 vs. 6.0 ± 1.6 vs. 6.1 ± 1.7 mg/dL; univariable p = 0.067). In the final fully adjusted models, after accounting for demographic, metabolic and therapeutic covariates, elevated serum UA remained robustly and independently associated with an increased likelihood of both MASLD (OR = 1.565, 95% CI = 1.079-2.270, p = 0.018) and high advanced liver fibrosis risk (Grade 2) (OR = 1.344, 95% CI = 1.056-1.710, p = 0.016). These findings demonstrate that serum UA is strongly snd independently associated with MASLD prevalence and high advanced fibrosis risk in patients with T2DM, suggesting its utility as a reliable, non-redundant biomarker for stratified metabolic liver evaluation.

In an attempt to identify novel α‑glucosidase inhibitors, a new series of substituted imidazo[1,2‑a]pyridine derivatives (10a-10ab) was designed, synthesized, and evaluated for their inhibitory activities. All compounds exhibited potent inhibition, with IC values ranging from 12.01 to 93.01 µM, significantly better than acarbose IC = 750.02 µM). SAR analysis highlighted the critical role of para‑substitution on the benzamide ring, especially methoxy groups. The most potent compound, 10s (IC = 12.01 µM), acted as a competitive inhibitor (K = 21 µM) with no α‑amylase inhibition, indicating high selectivity. It was non‑cytotoxic up to 100 µM. Circular dichroism, fluorescence spectroscopy, and thermodynamic analysis revealed strong ligand-enzyme interactions mainly driven by hydrophobic forces. Molecular docking and 200 ns MD simulations, including MM‑GBSA calculations, supported stable binding of 10s within the active site. Collectively, these results introduce imidazo[1,2-a]pyridine derivative 10s as a promising lead compound for the development of novel α-glucosidase inhibitors in further studies.

The increasing incidence of type 2 diabetes mellitus (T2DM) globally necessitates alternative therapeutic strategies. Evidence suggests that intestinal microbiota significantly influences T2DM development, leading to the proposal of probiotics as potential treatments. However, challenges such as strain selectivity and low survival rates limit probiotics' effectiveness. Combining probiotics with prebiotics, known as synbiotics, offers a promising approach for managing T2DM. The development of synbiotic-based functional foods also provides effective interventions for T2DM. This article synthesizes the recent advancements of synbiotics and synbiotic functional foods in managing T2DM, covering 40 studies, of which 29 studies employed synbiotics, and 11 studies employed synbiotic functional foods. In the 21 human studies, 17 focused on T2DM treatment and another 4 on the prevention of prediabetes from developing to T2DM. As for probiotics, 20 studies used single-strain probiotics, while others employed multiple strains, with 5 focusing on the synbiotics combined with hypoglycemic substances. Overall, synbiotics and synbiotic functional foods offer therapeutic benefits by reducing inflammation and oxidative stress, regulating gut microbiota, enhancing short-chain fatty acids, and improving intestinal barrier function. Further research is crucial to determine optimal formulations, dosages, and long-term safety, along with developing new synbiotic functional foods for effective diabetes interventions.

The metabolic score for insulin resistance (METS-IR) is a non-insulin-based surrogate marker of insulin resistance. However, its utility for identifying gestational diabetes mellitus (GDM) risk in early pregnancy remains unclear. This study included 585 singleton pregnant women from a prospective cohort study in South Korea. METS-IR was assessed at 10-14 weeks of gestation. Multivariable logistic regression was used to examine the association between METS-IR and subsequent GDM. Subgroup and sensitivity analyses were performed to evaluate the robustness of the findings, and receiver operating characteristic curve analysis was used to assess the predictive performance of METS-IR. Among 585 participants, 36 women developed GDM. In the fully adjusted model, METS-IR remained positively associated with GDM when analyzed as a continuous variable (OR = 1.18, 95% CI: 1.10-1.26, P < 0.001). Compared with women in the lowest METS-IR tertile, those in the highest tertile had a higher risk of GDM (OR = 5.50, 95% CI: 1.43-21.06, P = 0.013). The association was consistent in subgroup and sensitivity analyses. METS-IR showed good discriminative ability for GDM, with an area under the curve of 0.808 (95% CI: 0.726-0.890). The optimal cutoff value was 34.5, with a sensitivity of 66.7% and specificity of 86.9%. Higher METS-IR at 10-14 weeks of gestation was independently associated with an increased risk of GDM. METS-IR may serve as a simple early-pregnancy marker to help identify women at high risk for GDM.