OBJECTIVES: Children with type 1 diabetes mellitus (T1DM) have an increased risk of developing celiac disease (CD), frequently without typical symptoms. However, the optimal screening strategies and diagnostic threshold for tissue transglutaminase antibody immunoglobulin A (tTG-IgA) remain controversial. This study aimed to assess the performance of CD screening tests and identify optimal serological thresholds in children with T1DM. METHODS: This 12-year retrospective single-center cohort study from Türkiye included 282 newly diagnosed T1DM children without prior CD. Patients with <2 CD screenings performed ≥ 6 months apart or incomplete records were excluded. Among the remaining cohort, 206 patients had longitudinal screening for CD. Of them, only 24 patients who had seropositivity constituted the main analytical sample for assessing the diagnostic performance of tTG-IgA levels using receiver operating characteristic (ROC) analysis. RESULTS: Among the 206 patients with longitudinal CD screening, tTG-IgA positivity was observed in 24 patients (11.6%), either at T1DM diagnosis (70.8%) or during follow-up (29.2%). Biopsy-confirmed CD was diagnosed in 4.8% of the cohort. The remaining patients had fluctuations in tTG-IgA level; 50% became seronegative, but two-thirds became positive again. ROC analysis identified an optimal tTG-IgA threshold of ≥7.3× the upper limit of normal (ULN), yielding an area under the curve of 0.81, sensitivity of 70%, and specificity of 100%. Notably, 8.3% of biopsy-confirmed CD cases had tTG-IgA levels < 3×ULN. CONCLUSION: Although tTG-IgA level ≥7.3×ULN is highly predictive of CD in children with T1DM, lower levels may also be noteworthy. Continuous long-term monitoring and a multi-dimensional approach are crucial for early and accurate CD diagnosis in this high-risk group.

Oral semaglutide, the first oral glucagon-like peptide-1 (GLP-1) receptor agonist therapy approved for the treatment of type 2 diabetes, is now approved for obesity management and cardiovascular risk reduction in adults, demonstrating weight loss comparable to that of subcutaneous GLP-1 therapies, alongside improvements in cardiometabolic risk factors. The availability of oral semaglutide for the treatment of obesity provides healthcare professionals with additional opportunities to individualize therapy based on patient preferences, lifestyle, and clinical circumstances. However, the oral semaglutide formulation requires specific administration conditions to optimize absorption and effectiveness. Notably, oral semaglutide tablets should be taken first thing in the morning on an empty stomach with no more than half a glass of plain water (up to 120 mL or 4 fl oz), followed by 30 min before eating food, drinking additional fluids, or ingesting other oral medications. Person-centered clinical discussions between healthcare professionals (HCPs) and patients prior to treatment initiation are important to ensure patients understand administration requirements and why they are necessary, establish realistic expectations for obesity treatment targets, and cover approaches to maintain adherence. HCP-patient consultations should also include discussion of strategies to help patients minimize, prepare for, and manage adverse events. In this article, we provide practical guidance for incorporating oral semaglutide into obesity management, drawing on evidence from clinical trials, including the OASIS 4 trial, and the authors' clinical insights.

Type 2 diabetes (T2D) is a major global health concern strongly associated with atherosclerosis and subsequent macrovascular complications. These complications are the leading cause of death among T2D patients. Despite a decline in cardiovascular events over the last decade, individuals with T2D still have an approximately doubled risk compared to those without diabetes. This shows an urgent need for therapies targeting biological processes specific to T2D-associated atherosclerosis. Nevertheless, more research is needed to identify exactly which processes can be targeted therapeutically. Current therapies either target lipid metabolism or inflammation, two processes commonly considered important in T2D-associated atherosclerosis. However, more recent human plaque tissue studies show no differences in plaque levels of lipids nor inflammatory markers, possibly reflecting improved clinical treatment strategies. Other distinct differences in plaque tissue composition in T2D have been put forward, including thin fibrous caps and large necrotic cores. Moreover, T2D may influence several biological processes affecting both plaque formation and progression (such as oxidative stress and efferocytosis). These mechanisms could potentially also be targeted to prevent atherosclerotic cardiovascular complications. This review focuses on the shifting epidemiology of T2D-associated cardiovascular complications, as well as biological changes in T2D plaques, and how these changes can guide future clinical approaches to further reduce atherosclerotic complications.

BACKGROUND: Patient-engaged research is essential for ensuring that research prioritizes patients' needs and perspectives. Despite the known value of and need for engaging historically marginalized patient groups in research, there are limited examples of their engagement and across the research continuum. OBJECTIVE: This study describes ways that a Patient Advisory Group (PAG) of African American women with type 2 diabetes were engaged in the design, implementation, and dissemination of a randomized clinical trial (RCT) and the influence of their engagement. METHODS: The PAG was established in 2020 as part of the (Sisters Inspiring Sisters to Engage in Relevant Diabetes Self-Care) SISTER Diabetes Study. A pragmatic, non-systematic approach was used for documenting engagement, including research team review of meeting notes and progress reports. Engagement activities were categorized according to research phase and summarized. RESULTS: The PAG actively contributed across all phases of the research process. During study design, members co-developed recruitment materials and informed the selection of culturally relevant RCT comparator group content. During implementation PAG members supported recruitment through community engagement, co-refining intervention session topics, and guiding development of COVID-19 safety protocols. During dissemination, PAG members contributed to data interpretation and served as manuscript co-authors. CONCLUSION: The PAG's involvement across the research continuum of the SISTER Diabetes Study demonstrated many opportunities to leverage their experience and expertise. The value and level of their engagement demonstrate the importance of patient engagement across different research phases, which is particularly salient for historically marginalized patient groups.

BACKGROUND: The triglyceride-glucose (TyG) index is an accessible marker of insulin resistance and may reflect metabolic susceptibility to kidney stone disease (KSD). This review synthesizes observational evidence on TyG and KSD and examines whether the association varies with increasing TyG. METHODS: PubMed, Embase, Web of Science, Scopus, the Cochrane Library, and ProQuest were searched up to May 22, 2026 according to PRISMA 2020 and a PROSPERO-registered protocol. Eligible studies enrolled adults, assessed TyG as either a continuous or categorical exposure, reported KSD as the outcome, and provided extractable effect estimates. Study quality was evaluated using the Joanna Briggs Institute (JBI) tools. Maximally adjusted odds ratios (ORs) were synthesized using the restricted maximum likelihood (REML) random-effects model. One-stage dose-response meta-analyses using linear and restricted cubic spline models were also conducted, and the certainty of evidence was judged using GRADE. RESULTS: Fourteen studies (total n = 1,066,215; KSD cases = 50,286) met the inclusion criteria. In the continuous analysis, each 1-unit increment in TyG corresponded to higher KSD odds (pooled adjusted OR: 1.33; 95% confidence interval [CI]: 1.15-1.54). Compared with the lowest TyG category, the highest had 52% higher odds of KSD (OR: 1.52; 95% CI: 1.26-1.84). In a one-stage random-effects dose-response meta-analysis, restricted cubic spline models provided the best fit but showed no statistical evidence of non-linearity, supporting a linear association with a 26% increase in odds per 1-unit increase in TyG (OR: 1.26; 95% CI: 1.12-1.42; 95% PI: 0.91-1.75). CONCLUSION: A higher TyG index was associated with greater odds of KSD in a broadly linear manner; however, the marked heterogeneity across studies suggests that TyG should be viewed as a potential metabolic risk marker rather than a routine screening tool. These findings may support broader cardiometabolic risk assessment and standard preventive counseling in patients at risk of KSD.

BACKGROUND: Cardiovascular disease (CVD) remains a major global health challenge. The triglyceride-glucose (TyG) index and its derived indices serve as indicators of insulin resistance (IR) and are closely associated with CVD incidence. This study aimed to compare the predictive value of different TyG-related indices for CVD incidence and assess the impact of the TyG-BMI across various subgroups, including potential interaction effects. METHODS: This study conducted a secondary analysis using data from the China Health and Retirement Longitudinal Study (CHARLS), which included 5,382 participants aged 45 years and older. Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and Cox proportional hazards regression models were employed to evaluate the associations between TyG-related indices and CVD incidence. Subgroup analyses were performed to evaluate the predictive performance of the TyG-BMI across different population categories and assess potential interactions. RESULTS: Cox proportional hazards regression indicated a significantly increased risk of CVD among participants in the highest quartile of the TyG-BMI, with a hazard ratio (HR) of 1.60 (95% CI: 1.33-1.99). Subgroup analyses confirmed this association across multiple demographic and clinical subgroups, including sex, residence, education level, alcohol consumption, smoking history, and history of hypertension, diabetes, stroke, liver disease, and kidney disease. Restricted cubic spline (RCS) analysis revealed a nonlinear relationship between the TyG-BMI and CVD incidence. Interaction analysis revealed a significant positive interaction between kidney disease and the TyG-BMI. CONCLUSIONS: The TyG-BMI demonstrated a modestly higher predictive value than other TyG-related indices in predicting CVD risk, establishing it as a valuable tool for clinicians assessing the incidence of CVD.

BACKGROUND: Growth differentiation factor 15 (GDF-15) is a circulating biomarker reflecting oxidative stress, inflammation, and cellular aging. However, its role in disease risk assessment amongst individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 remains unclear. METHODS: This study included 29,697 UK Biobank participants with CKM stages 0-3 defined in accordance with the American Heart Association criteria. Associations of GDF-15 with metabolic, inflammatory and liver fibrosis markers and CKM stage were examined using linear or multinomial logistic regression models. Fine-Gray competing risk regression models were used to evaluate associations with incident atherosclerotic cardiovascular disease (ASCVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and their comorbidity (coexistence of both conditions). Bidirectional disease transitions were assessed using a multi-state Markov model. The relative importance of GDF-15 was evaluated using SHapley Additive exPlanations (SHAP) and likelihood ratio (LR) statistics. Improvements in risk prediction models were assessed using time-dependent area under the receiver operating characteristic curve, Brier score, integrated discrimination improvement and continuous net reclassification improvement. RESULTS: Amongst 29,697 participants (mean age of 56.16 years; 57.32% female), 2,786 developed ASCVD and 456 developed MASLD during follow-up. Higher GDF-15 levels were associated with poorer CKM health and showed the strongest associations with renal function markers, followed by insulin resistance indices. Each 1-unit increase in GDF-15 (normalised protein expression, log2 scale) was associated with increased risks of ASCVD (HR = 1.25, 95%CI 1.15-1.36, P = 1.35 × 10), MASLD (HR = 1.62, 95%CI 1.41-1.86, P = 2.06 × 10) and their comorbidity (HR = 1.62, 95%CI 1.32-2.18, P = 4.36 × 10) after multivariable adjustment for age, sex, smoking status, body mass index, diabetes mellitus, glycated haemoglobin, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, cystatin C, Townsend deprivation index, physical activity, and CKM stage. These associations remained consistent across subgroup analyses. Multi-state analyses indicated that GDF-15 predicted bidirectional progression between ASCVD and MASLD, with 10-year cumulative incidences of ASCVD and MASLD reaching 15.75% and 2.03%, respectively, among individuals in the top 10% of GDF-15 levels, and further increasing to 20.05% and 2.32% in those in the top 5%. SHAP and LR analyses showed that GDF-15 had high relative importance in predicting ASCVD and MASLD. Incorporating GDF-15 into established risk scores (PREVENT, SCORE2, FLI, FIB-4 and ARPI) showed modest improvements in risk discrimination, reclassification, and prediction error, particularly for ASCVD. In several settings, GDF-15 outperformed established biomarkers, including insulin resistance, systemic inflammation, apolipoprotein A/B, lipoprotein(a), cardiac troponin I, and N-terminal prohormone of brain natriuretic peptide. CONCLUSIONS: GDF-15 may serve as a promising biomarker for cardiovascular-kidney-liver-metabolic syndrome risk stratification and management.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population. METHODS: In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12 months with visits at 1, 3, 6, and 12 months post-procedure. We measured baseline ApoB100 and assessed its ability to predict MACE, MALE, and composite endpoints, adjusting for clinical covariates. RESULTS: Composite events occurred in 49.1% of patients, MACE in 24%, and MALE in 35.3%. ApoB100 levels were significantly higher in event groups (composite: 62.1 vs 38.0 mg/dL, p < 0.01; MACE: 66.1 vs 44.4 mg/dL, p < 0.01; MALE: 61.0 vs 42.4 mg/dL, p < 0.01). Multivariable analyses confirmed ApoB100 as an independent predictor (composite OR 1.14 per mg/dL, 95% CI 1.08-1.20, p < 0.01; MACE OR 1.10, p < 0.01; MALE OR 1.05, p < 0.01). ROC analysis demonstrated excellent predictive accuracy for ApoB100 (AUC 0.86, 95% CI 0.80-0.91), with optimal ROC-derived cut-off of 56.6 mg/dL. Adding baseline ApoB100 to conventional risk factors significantly improved model discrimination (AUC gains 0.08-0.15, all p < 0.01), while Kaplan-Meier curves by cut-off effectively stratified early events (log-rank p < 0.001). CONCLUSIONS: Elevated baseline ApoB100 independently predicted MACE, MALE, and composite events post-LER in T2DM-CLTI patients, substantially improving clinical risk models. Integrating ApoB100 into post-LER management algorithms could refine individualized therapeutic strategies, especially in patients with residual atherogenic risk despite optimal LDL-C control.

BACKGROUND: Diabetes distress drives treatment non-adherence and poor quality of life among Ghanaian adults with type 2 diabetes. Terrain, occupational, and Akan cultural stressors in high-burden peri-urban communities remain underexplored. OBJECTIVE: This study examined lived experiences of stress, sociocultural barriers, and impacts on daily quality of life among adults with type 2 diabetes across agrarian (Mampong Ashanti) and mining (Obuasi) communities in Ghana's Ashanti Region. METHODS: We conducted a descriptive qualitative study with purposive sampling of 92 adults (30-45 and > 45 years) via 16 FGDs (6-10/group) and 12 IDIs with health workers (6/district) in two districts. Bilingual guides explored stress triggers, coping, taboos, and WHOQOL domains (Nov-Dec 2025). NVivo 14 content analysis included triangulation, member checking, and interrater reliability (≥ 85). RESULTS: Five themes emerged with ≥ 85% source convergence across 92 patients and 12 providers: medication poverty, transport barriers, occupational conflicts, fears of complications, and family-related stigma. Medication poverty was reported across all focus groups, while transport barriers were particularly prominent among participants in Mampong. Occupational conflicts were uniquely emphasized by miners in Obuasi. Older adults frequently expressed fears of complications, whereas younger participants highlighted experiences of stigma within family and social contexts. Additionally, Akan cultural taboos were described as restricting shrine access, church participation, and communal feasts during hyperglycaemic episodes. CONCLUSIONS: Diabetes distress in the Ashanti Region is multifactorial, influenced by geography, occupation, generational differences, and cultural norms. Interventions should integrate psychosocial screening, medication affordability, CHPS satellite clinics, culturally sensitive peer support, and engagement with traditional healers to improve adherence and quality of life.

BACKGROUND: The COVID-19 pandemic disrupted healthcare delivery and individual behaviors in individuals with diabetes. Limited data exist on glycemic control during this period. This study aimed to evaluate trends in glycemic control and severe hyperglycemia among U.S. adults with diagnosed diabetes before and during the COVID-19 pandemic. METHODS: We conducted a retrospective cohort analysis of data from the National Health and Nutrition Examination Survey (NHANES) between pre-pandemic (January 2017-March 2020) and pandemic (August 2021-August 2023) periods. Glycemic control (HbA1c < 7%) and severe hyperglycemia (HbA1c > 10%) were assessed overall and by age, race/ethnicity, and socioeconomic status using logistic regression. RESULTS: Among 2528 adults with diabetes, glycemic control remained unchanged between pre- and during the pandemic (59.7% vs. 56.1%, p = 0.29), but severe hyperglycemia increased significantly (5.6% to 8.5%, p = 0.03). Female participants were more likely to achieve glycemic control (adjusted OR [aOR], 1.40; 95% CI, 1.11-1.75), and those with more than high school education had higher glycemic control (aOR, 1.33; 95% CI, 1.06-1.67) and lower severe hyperglycemia (aOR, 0.51; 95% CI, 0.29-0.89). Severe hyperglycemia was least prevalent in adults aged 65 years or older (aOR, 0.27; 95% CI, 0.15-0.50) but more common among Hispanic/Mexican American (aOR, 2.62; 95% CI, 1.53-4.50) and Non-Hispanic Black adults (aOR, 2.80; 95% CI, 1.62-4.84). CONCLUSION: While glycemic control remained stable, severe hyperglycemia increased during the COVID-19 pandemic, particularly among Hispanic/Mexican American and Non-Hispanic Black adults. Higher education and older age were associated with better outcomes, emphasizing the need for targeted interventions to address disparities and prevent hyperglycemia.

BACKGROUND: Early-stage (0-3) cardiovascular-kidney-metabolic (CKM) syndrome populations require urgent cardiovascular disease (CVD) prevention. Chronic inflammation, insulin resistance, and visceral adiposity are three core interactive CVD pathogenic pathways, while current biomarkers fail to integrate all three. This study aimed to explore the association of the novel three-dimensional composite index CTI-CVAI with incident CVD and its predictive value in Chinese adults with CKM stages 0-3. METHODS: This nationwide prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 6728 participants aged ≥ 45 years with CKM stages 0-3. CTI-CVAI was calculated by combining the C-reactive protein-triglyceride-glucose index (CTI) and Chinese visceral adiposity index (CVAI). Cox regression, restricted cubic spline, survival analysis, ROC curves, and reclassification analysis were used to evaluate its value. Subgroup and multiple sensitivity analyses, including competing-risks models, were conducted to assess the robustness of the results. RESULTS: During a median follow-up of 9 years, the overall CVD incidence was 23.83%. CTI-CVAI elevation showed a linear, dose-dependent correlation with increased CVD risk (P < 0.001). After full confounder adjustment, per 1-SD CTI-CVAI increment increased CVD risk by 32% (HR = 1.32, 95% CI 1.26-1.39, P < 0.001), and the highest quartile exhibited 2.07-fold higher risk than the lowest (HR = 2.07, 95% CI 1.77-2.42, P < 0.001). Restricted cubic spline analysis revealed a linear association between CTI-CVAI and incident CVD (P for non-linearity > 0.05). CTI-CVAI demonstrated improved risk reclassification (NRI = 0.0566, P < 0.001) compared with single biomarkers. The association was stable across most subgroups. All sensitivity analyses yielded reliable, robust results. CONCLUSIONS: CTI-CVAI is independently and linearly associated with incident CVD risk in Chinese adults with CKM stage 0-3. As a low-cost, accessible biomarker integrating three key pathological pathways, it optimizes early CVD risk stratification and reclassification, providing a promising tool for targeted CVD prevention in CKM high-risk populations.

BACKGROUND: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes and weight loss, with well known gastrointestinal side effects including nausea, vomiting, and delayed gastric emptying. While mucosal injuries such as Mallory Weiss tears have been reported, full thickness esophageal perforation has not previously been described. We report the first documented case of Boerhaave's syndrome associated with GLP-1 RA use, highlighting the potential for rare but life threatening complications following abrupt reinitiation at high doses. CASE PRESENTATION: A previously healthy woman in her 50s presented with vasopressor dependent shock and respiratory failure requiring intubation following severe nausea, emesis, and acute chest pain. She had restarted semaglutide at the maximum 2.4 mg weekly dose the day prior to symptom onset, after several months off therapy and without dose titration. Imaging revealed pneumomediastinum and bilateral pleural effusions. Esophagram confirmed a contained esophageal perforation. She was managed with endoscopic stent placement, nasojejunal feeding, and chest tube drainage, followed by clinical improvement and discharge. Two months later, she was readmitted with necrotizing pneumonia. Imaging and endoscopy revealed an esophagopleural fistula, abscess, and migrated stent. She underwent left thoracotomy, abscess drainage, decortication, and wedge resection of necrotic lung. The perforation site was reinforced with an intercostal muscle flap, and a PEG tube was placed. Postoperatively, at 10-month follow up she was on a regular diet, PEG tube removed, and esophagus was healed on EGD. She was advised to permanently discontinue GLP-1 RAs. CONCLUSIONS: This case underscores a previously unreported but serious complication of GLP-1 RA therapy, transmural esophageal rupture, likely precipitated by drug induced gastroparesis and forceful emesis. Restarting semaglutide at a high dose without titration after a prolonged interruption likely increased vulnerability to injury. Clinicians should maintain a high index of suspicion for esophageal complications in patients presenting with chest pain and vomiting during GLP-1 RA initiation or reinitiation. Early multidisciplinary management is crucial to optimizing outcomes in this rare but life-threatening scenario.

OBJECTIVE: The mechanisms by which type II diabetes mellitus (T2DM) impairs tooth supraeruption following tooth loss remain incompletely understood, with evidence suggesting disruption of alveolar bone remodeling. This study aimed to investigate the effects of T2DM on apical alveolar bone remodeling during tooth supraeruption in a mouse model. METHODS: A T2DM mouse model with unopposed mandibular molars was established, including a control group (n = 70) and an experimental T2DM group (n = 70). We systematically analyzed periapical alveolar bone volume, periodontal ligament morphology, supraeruption distance, and histomorphometric counts of osteoblasts and osteoclasts. mRNA expression levels of osteogenesis-related factors were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). Protein expression was evaluated by immunohistochemistry. Data were analyzed using Student's t-test, with significance set at P < 0.05. RESULTS: T2DM significantly altered the alveolar bone remodeling microenvironment. The diabetic group exhibited reduced osteoblast numbers and decreased mRNA expression of transforming growth factor-β (Tgf-β), insulin-like growth factor-1 (Igf-1) and periostin (Postn), as well as reduced protein expression of TGF-β, IGF-1, and POSTN (P < 0.05). Conversely, osteoclast numbers were increased, accompanied by elevated Runx2 mRNA and RUNX2 protein expression (P < 0.05). This bone imbalance resulted in reduced periapical bone volume and disorganized periodontal tissue structure. Consequently, the degree of tooth supraeruption was significantly reduced in T2DM mice compared to controls (P < 0.05). CONCLUSION: T2DM impairs tooth supraeruption by downregulating osteoblast-related factors, increasing osteoclast numbers and activity, and disrupting alveolar bone remodeling capacity. This study provides a theoretical foundation for future clinical research on the mechanism by which type 2 diabetes mellitus affects tooth supraeruption.

BACKGROUND: With an ageing population and increased physical activity, distal radius fractures (DRF) are relatively common. Surgical treatment is becoming increasingly prevalent, yet postoperative complications including complex regional pain syndrome (CRPS), tendon irritation/rupture, carpal tunnel syndrome, internal fixation‑related discomfort, and non‑union/malunion significantly impact functional recovery and quality of life. Identifying associated risk factors is crucial for optimising treatment strategies. OBJECTIVE: To investigate the clinical and injury-related risk factors for specific postoperative complications in patients undergoing surgical treatment for distal radius fractures. METHODS: A retrospective observational study was conducted. Medical records of patients undergoing surgical treatment for DRF at our hospital between January 2022 and June 2025 were collected. Patients were categorised into a complication group and a non-complication group based on the occurrence of specific postoperative complications. Propensity score matching (PSM) was used to balance baseline differences, resulting in 60 cases per group. Primary outcomes comprised the incidence of specific postoperative complications and independent risk factors. Secondary outcomes included wrist range of motion, grip strength, and DASH (Disabilities of the Arm, Shoulder, and Hand) scores at 6 months postoperatively; injury-related factors [AO (Arbeitsgemeinschaft für Osteosynthesefragen) fracture classification, open fracture status, time from injury to surgery]; surgical factors (surgical approach, operative time, use of internal fixation); postoperative complications (diabetes mellitus, osteoporosis); postoperative management (immobilisation duration); and rehabilitation protocols. Univariate and multivariate logistic regression analyses were employed to identify risk factors. RESULTS: After PSM, 60 cases and 60 controls were analysed. Among the 60 cases, the most common complication types were tendon irritation/rupture (31.7%) and internal fixation-related discomfort (23.3%), followed by carpal tunnel syndrome (20.0%) and CRPS (13.3%). Non-union/malunion occurred in 11.7% of cases. These proportions reflect the distribution of complication subtypes within the case group and do not represent population incidence rates. Multivariate analysis revealed that an operative time exceeding 90 min (OR = 4.006, 95% CI: 1.806-3.888) constituted an independent risk factor for postoperative complications (p < 0.05). Analysis of secondary outcomes revealed that the complication group exhibited significantly poorer wrist flexion/extension range of motion, percentage of grip strength recovery, and DASH scores at 6 months postoperatively compared to the non-complication group (p < 0.05). The incidence rates of all three major complications exhibited a significant increasing trend with higher fracture classification grades (p < 0.05). No statistically significant differences were observed between the complication and non-complication groups regarding gender, timing of surgery, approach selection, or type of internal fixation (p > 0.05). CONCLUSION: The occurrence of specific complications following distal radius fracture surgery is closely associated with multiple factors, including surgical technique, injury severity, and postoperative management. The key finding is that operative time > 90 min was strongly associated with complications (OR 4.01), but this association likely reflects underlying case complexity rather than a direct causal effect. Fracture severity (AO-C) and early rehabilitation showed only associative patterns that were either confounded or bidirectional. Thus, the study's primary contribution is to highlight the need for caution in interpreting operative time as a modifiable risk factor without adjusting for complexity, and to identify key unmeasured confounders for future research.

OBJECTIVE: To characterize longitudinal metabolic alterations associated with gestational diabetes mellitus (GDM) and to identify candidate metabolite signals for earlier risk assessment using a widely targeted metabolomics platform. METHODS: In this prospective cohort, 35 women who developed GDM and 35 matched healthy controls underwent fasting blood sampling in early pregnancy (6-13 weeks) and mid-pregnancy (24-28 weeks). Widely targeted metabolomics and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Multivariate analyses, logistic regression, receiver operating characteristic (ROC) analysis, internal cross-validation, and restricted cubic spline modeling were applied within an exploratory framework. RESULTS: In early pregnancy, 11 differential metabolites were identified, including 6 amino acid-related metabolites, but no robust signal remained after false discovery rate (FDR) correction. By mid-pregnancy, 35 differential metabolites were identified, including 13 amino acid-related metabolites. Among 19 amino acid-related metabolites examined in focused analyses, L-arginine was the only amino acid-related metabolite that remained significant after FDR correction (FDR = 0.043). Higher mid-pregnancy L-arginine was associated with increased odds of GDM (aOR = 2.840, 95% CI 1.481-5.446), was positively correlated with 1-h (r = 0.28) and 2-h (r = 0.26) glucose levels during OGTT, and showed modest discrimination (AUC = 0.754; mean cross-validated AUC = 0.754). Quartile analyses showed a more pronounced risk increase in the highest exposure group, and restricted cubic spline analysis suggested an overall positive association with a possible nonlinear trend at higher levels. KEGG analyses highlighted arginine- and amino acid-related pathways, including arginine and proline metabolism and arginine biosynthesis, while network analysis suggested a potential link to mTOR signaling. CONCLUSION: In this exploratory longitudinal analysis, pregnancies complicated by GDM showed progressively increasing amino acid-related metabolic disturbances from early to mid-pregnancy. Mid-pregnancy L-arginine emerged as a candidate metabolic signal associated with GDM risk, post-load glycemia, and greater risk elevation at higher levels. These findings support further investigation of amino acid-focused metabolic profiling as a research-stage approach for earlier GDM risk identification.

BACKGROUND: Second-generation antipsychotics, a cornerstone of psychiatric disorder management, render treated patients highly prone to metabolic abnormalities. To address this unmet clinical need, this post-hoc analysis drew on data from a previous trial to examine the correlations between plasma short-chain fatty acid (SCFA) level alterations and metabolic changes in the context of probiotic-fiber intervention. METHODS: In this trial, individuals diagnosed with schizophrenia or bipolar disorder, who were undergoing stable atypical antipsychotic therapy, were recruited for this study. They were subsequently randomized in a 1:1:1:1 ratio to four treatment groups: combined probiotics (1680 mg/d) and dietary fiber (60 g/d); probiotics (1680 mg/d) with dietary fiber placebo; dietary fiber (60 g/d) with probiotics placebo; and double placebo (probiotics placebo plus dietary fiber placebo). Assessments were conducted at screening/baseline, week 4, and week 12, and the measurement of circulating SCFAs was performed via liquid chromatography-mass spectrometry. The analysis, employing the last-observation-carried-forward method, encompassed 79 participants who provided at least one follow-up plasma sample for the quantification of SCFAs. RESULTS: The 12-week combined administration of probiotics and dietary fiber was associated with changes in circulating levels of SCFAs and improvements in metabolic indices. More importantly, the higher levels of propionate were associated with decreased weight (adjusted odds ratio [OR]: 0.61 per quartile increase, 95% confidence interval [CI]: 0.38-0.96) and homeostatic model assessment of insulin resistance (HOMA-IR) (adjusted OR:0.58, 95% CI: 0.36-0.94). Also, the higher levels of butyrate were associated with a 42% lower odds (adjusted OR: 0.58, 95%CI:0.36-0.93) of elevated body mass index (BMI) and a 49% lower odds (adjusted OR: 0.51, 95%CI:0.31-0.86) of elevated insulin levels. CONCLUSIONS: The findings of this study suggested that elevated circulating levels of butyrate and propionate might be associated with reduced weight gain and improved insulin resistance in individuals receiving antipsychotic medications. TRIAL REGISTRATION: ClinicalTrials.gov NCT03379597, trial registration date: 11/29/2017. Overall Recruitment Status: completed.

OBJECTIVE: To analyze the temporal trends of both Alzheimer's disease and Diabetes mellitus-related mortality in adults aged > 45years in the United States between 1999 and 2023, and to evaluate the changes in mortality patterns over time. BACKGROUND: Alzheimer's Disease and Diabetes Mellitus are two different diseases that have diverse underlying pathophysiology, but they often coexist, having common pathways. There is a high prevalence of concurrence between these two conditions, yet their combined mortality trend is underexplored. METHODS: We utilize mortality data from the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER). Individuals aged > 45 were included who had both Alzheimer's disease (G30) and Diabetes mellitus(E10-14). Age-adjusted mortality rates (AAMRs) and crude mortality rates (CMRs) per 100,000 were calculated and were standardized to the 2000 U.S population. Joint point regression models were used to identify the temporal variations and to calculate Annual Percentage Change (APC) and Average Annual Percentage Change (AAPC) with 95% confidence intervals. RESULTS: Overall, a total of 224,082 deaths occurred in patients of both Alzheimer's disease and Diabetes mellitus, in the age group ≥ 45 years, from 1999 to 2023. There is an upward trajectory noted from 2.82 in 1999 to 4.42 in 2023, with the highest incidence between 2017 and 2020, followed by a decline. Mortality rose in both sexes, with a persistently higher rate in females. The mortality rise from 1999 to 2023 in middle-aged people (45-64 years), and there was a rise in the trend of around 41% among adults ≥ 65 years. White individuals show higher deaths (78.9%), yet higher AAMR is observed in Black and Hispanic populations, showing racial disparities. Regionally, the West shows the highest AAMR, while non-metropolitan areas show higher mortality than metropolitan areas. CONCLUSION: The trend of mortality in individuals with both Alzheimer's disease and Diabetes Mellitus has increased in the past two decades, but there is a sharp rise observed after 2020 that may show the impact of the COVID-19 pandemic. These findings emphasized public health strategies.

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) has been validated as a reliable indicator of insulin resistance in critically ill patients. Despite its established prognostic value in cardiovascular and metabolic disorders, its role in sepsis outcomes remains controversial. The aim of this study was to clarify the nonlinear relationship between TyG-BMI and all-cause mortality in intensive care unit (ICU)-admitted patients with sepsis. METHODS: Adult patients with sepsis admitted to the ICU for the first time were enrolled from the MIMIC-IV database and stratified into tertiles on the basis of TyG-BMI. The primary outcome was 360-day all-cause mortality, whereas the secondary outcome was 30-day all-cause mortality. Chi-square tests and Kaplan-Meier survival curves were constructed to evaluate survival outcomes across the three groups. Restricted cubic splines, Cox proportional hazards regression models, and exploratory subgroup analyses were further employed to systematically investigate the nonlinear association between TyG-BMI and prognosis in patients with sepsis. RESULTS: A total of 1249 patients were enrolled in this study, with a median age of 64.3 years and a median TyG-BMI of 261.3, among whom 489 (39.2%) were female. Compared with Tertiles 2 and 3, Tertile 1 had the highest mortality rate, with statistically significant associations observed between TyG-BMI and 360-day all-cause mortality (P = 0.028). Restricted cubic spline analysis confirmed a significant U-shaped association between TyG-BMI and 360-day all-cause mortality, with a turning point at TyG-BMI = 289.4. No statistically significant nonlinear association was found between TyG-BMI and the secondary endpoint of 30-day all-cause mortality. In the fully adjusted two‑piecewise Cox regression model (Model 3), each unit increase in TyG‑BMI was associated with a significantly decreased risk of 360‑day all‑cause mortality below the turning point (HR = 0.996, 95% CI 0.993-0.999, P = 0.014), and a significantly increased risk above the turning point (HR = 1.002, 95% CI 1.001-1.004, P = 0.011). Exploratory stratified analyses revealed significant interactions with age, gender, race, and congestive heart failure status, which should be interpreted with caution. CONCLUSIONS: In this cohort, TyG-BMI shows a significant U-shaped association with 360-day all-cause mortality in sepsis patients. The clinical value of TyG‑BMI requires further validation in large‑scale multi‑center studies.

BACKGROUND: Poor glycemic control and inadequate self-management drive the global diabetes mellitus (DM) burden. In conflict-affected Palestine, structural barriers worsen outcomes, yet diabetes management self-efficacy (DMSE) remains understudied. AIM: To assess diabetes management self-efficacy and glycemic control, their interrelationship, and the independent predictors of each among patients with diabetes mellitus in conflict-affected Palestine. METHODS: A cross-sectional study was conducted among 418 adults with type 1 or type 2 DM attending governmental diabetes clinics in the Hebron governorate, West Bank, Palestine. Data were collected using the Arabic-validated Diabetes Management Self-Efficacy Scale (DMSES) and a structured clinical questionnaire. Non-parametric tests and two multiple linear regression models were applied to identify independent predictors, with HbA1c and DMSE scores specified as the two dependent variables. RESULTS: Glycated hemoglobin (HbA1c) was suboptimal (median = 7.50, IQR = 2.30), while DMSE was moderate (median = 3.45/5, IQR = 1.10). Blood glucose management was the strongest subdomain, whereas physical exercise was the weakest. Former smoking (β = 0.202, 95% CI: 0.430, 1.494, p < .001), lower physical activity frequency (β = 0.156, 95% CI: 0.098, 0.455, p = .003), and diabetes-related complications (β =-0.154, 95% CI: -1.132, - 0.210, p = .004) independently predicted higher HbA1c. Lower physical activity (β =-0.177, 95% CI: -0.208, - 0.060, p < .001), longer disease duration (β =-0.135, 95% CI: -0.177, - 0.021, p = .013), lower income (β = 0.163, 95% CI: 0.081, 0.348, p = .002), and lower education (β = 0.127, 95% CI: 0.018, 0.227, p = .022) independently predicted lower DMSE. CONCLUSION: Clinical, behavioral, and socioeconomic factors independently predicted glycemic control and self-efficacy. The DMSE-HbA1c disconnect indicates structural barriers impede self-management behavior. Integrating clinical education with economic and structural support is essential to improve diabetes outcomes in conflict-affected settings.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is imposing a substantial and rapidly growing global health burden. Disease estimates vary widely across geographies and time periods, reflecting not only true differences in disease occurrence but also variation in demographic structures, risk factor exposures, diagnostic practices, surveillance capacity, and biological heterogeneity within T2DM itself. METHODS: A narrative, integrative synthesis of global epidemiological evidence was conducted. Data were sourced from major international platforms, supplemented with peer-reviewed literature. Evidence was synthesized across time, place, and person, with explicit attention to differences in case definitions, biomarker use, screening intensity, and modeling assumptions. Conceptual frameworks were applied to interpret observed patterns. RESULTS: Harmonized NCD-RisC analyses show a sustained rise in age-standardized prevalence from 1980 to 2014, increasing from 4.3% to 9.0% in men and from 5.0% to 7.9% in women. According to the IDF, the global burden is projected to reach 852.5 million by 2050. Approximately 42.8% (251.7 million) of cases remain undiagnosed, with the highest proportions concentrated in low-income regions. Substantial geographic heterogeneity is shaped by population aging, rising adiposity, dietary and physical activity transitions, urbanization, commercial food environments, and health system detection capacity. Subtype distribution and biological heterogeneity further contribute to variation in disease trajectories and complication profiles across populations. CONCLUSIONS: Global T2DM prevalence reflects the interaction of biological, social, and health system processes rather than incidence alone. Prevalence trajectories must be interpreted in light of surveillance limitations, diagnostic context, and within-disease heterogeneity. Addressing future burden requires combining improved detection and chronic-care capacity with upstream, life-course-oriented prevention strategies.

Adipose tissue has emerged as a dynamic endocrine organ that coordinates systemic energy balance and cardiometabolic health. This Review highlights the dual humoral and neuronal pathways through which adipose tissue regulates systemic metabolism. Humoral signals include peptide hormones, lipid mediators, metabolites, chemokines and exosomal microRNAs secreted by adipose depots. Neuronal circuits control adipose function rapidly and precisely: sympathetic efferents trigger lipolysis in white adipose tissue and thermogenesis in brown adipose tissue, whereas sensory afferents detect chemical, thermal and mechanical signals to adjust sympathetic activity. Nutritional and environmental stimuli (for example, diet, cold exposure and exercise), along with pathological states (for example, obesity, type 2 diabetes mellitus, lipodystrophy and ageing-associated disorders), dynamically modulate these endocrine and neural outputs. Methodological innovations, such as omics based on mass spectrometry or liquid chromatography-mass spectrometry, secretome labelling, adipose tissue organoid models and click chemistry, enable high-resolution characterization of adipose-derived signals and their targets. Finally, we discuss translational opportunities, including synthetic analogues of lipophilic hormones, and future therapeutic strategies that harness adipose communication networks.

Diabetic kidney disease (DKD) is a type of chronic renal injury induced by diabetes mellitus and is characterized by persistent proteinuria and progressive decreases in the glomerular filtration rate. Recent studies have highlighted the significance of histone lactylation and necroptosis in the pathogenesis of DKD. We explored the mechanisms by which lactate-induced histone H3 lysine-18 lactylation (H3K18la) and H3K27la promote necroptosis in DKD. Lactate-induced H3K18la and H3K27la modulated Fas transcription, contributing to necroptosis and DKD progression. Moreover, keratin 18 (KRT18), identified as a lactyltransferase, regulated H3K18la and H3K27la levels, subsequently inducing Fas transcription and necroptosis. Furthermore, ginsenoside Rc (gRc) inhibited KRT18 lactyltransferase activity by competing for the lactate binding site in KRT18. Notably, gRc treatment reduced the KRT18, H3K18la, H3K27la, and Fas levels and alleviated necroptosis and renal dysfunction in DKD models. In conclusion, KRT18 functions as a lactyltransferase to induce Fas transcription and necroptosis. Moreover, inhibiting KRT18-mediated histone lactylation via gRc is a potential strategy for treating DKD.

The triglyceride-glucose (TyG) index and atherogenic cholesterol markers, including non-HDL cholesterol and remnant cholesterol, are significant predictors of atherosclerotic cardiovascular disease (ASCVD). However, the joint effects and predictive value of TyG and atherogenic cholesterol markers for incident stroke remain insufficiently understood. We included participants from the China Health and Retirement Longitudinal Study (CHARLS) enrolled at baseline in 2011 and followed them through 2020. Participants were categorized into four groups according to the median values of the TyG index and each cholesterol marker, with those having both values below the median serving as the reference group. Cox proportional hazards models were used to evaluate the independent and joint associations of TyG and atherogenic cholesterol markers with incident stroke. Restricted cubic spline models were applied to assess dose-response relationships, and receiver operating characteristic (ROC) curve analyses were used to examine predictive performance. A total of 8,544 participants were included (mean [SD] age 59.0 [9.5] years; 52.1% female). 522 incident stroke events occurred during a maximum follow-up of 9.0 years. TyG, non-HDL cholesterol and remnant cholesterol were all independently associated with stroke risk. Compared with participants with both TyG and cholesterol markers below median, those with both markers above median had the greatest stroke risk in fully adjusted models (HR for high TyG and high non-HDL cholesterol: 1.76 [95% CI 1.41-2.20]; HR for high TyG and high remnant cholesterol: 1.45 [95% CI 1.18-1.77]). Adding TyG and each cholesterol marker to traditional risk factors modestly improved risk discrimination, with the model combining TyG and non-HDL cholesterol yielding the highest AUC. The TyG index and atherogenic cholesterol markers were independently and jointly associated with increased stroke risk among middle-aged and older adults. Adding these routinely available metabolic and lipid markers modestly improved discrimination for incident stroke.

Periodontitis has been recognized as a contributing factor in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the precise mechanisms through which periodontitis influences the pathogenesis of MASLD remain unclear. This study aimed to investigate the association between experimental periodontitis and MASLD severity and to explore the potential underlying mechanisms using a ligature-induced periodontitis model under low-fat diet (LFD) and high-fat diet (HFD) conditions. A total of 40 mice were divided into four groups: low-fat diet control group (LFD-Ctrl), low-fat diet with periodontitis group (LFD-Perio), high-fat diet control group (HFD-Ctrl), and high-fat diet with periodontitis group (HFD-Perio), with 10 mice initially assigned to each group. Mice were fed an HFD for 12 weeks to establish the MASLD model, followed by ligature-induced periodontitis for 4 weeks. Periodontal inflammation and alveolar bone loss were assessed using micro-computed tomography (Micro-CT), hematoxylin and eosin (H&E) staining, and tartrate-resistant acid phosphatase (TRAP) staining, while MASLD severity was evaluated via hepatic H&E staining, Oil Red O staining, periodic acid-Schiff (PAS) staining, Masson's Trichrome staining, nonalcoholic fatty liver disease activity score (NAS), alpha-smooth muscle actin (α-SMA) expression, pericellular fibrosis, and serum lipid and liver enzyme measurements. Compared with HFD-Ctrl mice, HFD-Perio mice exhibited aggravated MASLD-related phenotypes, including elevated fasting blood glucose, significantly increased homeostatic model assessment for insulin resistance (HOMA-IR) (2.89 ± 0.67 vs. 1.93 ± 0.26, P < 0.0001), higher nonalcoholic fatty liver disease activity score (NAS) (4.57 ± 0.71 vs. 2.30 ± 0.33, P < 0.01), and more pronounced pericellular fibrosis. Gut microbiota analysis showed that the Firmicutes/Bacteroidota ratio was further increased in HFD-Perio mice compared with HFD-Ctrl mice (9.39 ± 2.82 vs. 5.48 ± 1.98, P < 0.05), accompanied by enrichment of the genus Helicobacter. These findings indicate that experimental periodontitis aggravates HFD-induced MASLD phenotypes, potentially via metabolic dysregulation, liver inflammation and fibrosis, and gut microbiota dysbiosis, highlighting the need for further studies to clarify whether periodontal health influences MASLD progression.

BACKGROUND: To investigate the impact of 1-hour plasma glucose (1 h-PG) on the metabolic characteristics and pregnancy outcomes in polycystic ovary syndrome (PCOS). METHODS: This multicenter study analyzed 970 PCOS patients (2019-2025), including 289 undergoing assisted reproductive technology (198 successful deliveries). Participants were stratified by glucose tolerance: Group 1 (normal: fasting PG [FPG] ≤ 6.1, 1 h-PG < 8.6, 2-hour PG [2 h-PG] <7.8 mmol/L); Group 2 (isolated 1 h-prediabetes: 8.6 ≤ 1 h-PG < 11.6, FPG ≤ 6.1, 2 h-PG < 7.8 mmol/L); Group 3 (traditional 2 h-prediabetes: 7.8 ≤ 2 h-PG ≤ 11.1, FPG ≤ 6.1 mmol/L). Data included anthropometrics, metabolic biomarkers, sex hormones, and pregnancy outcomes were compared across three groups. RESULTS: PCOS with isolated 1 h-prediabetes (Group 2) had a more unfavorable metabolic profile with regard to metabolic traits, but were not significantly different from those of the traditional 2 h-prediabetes (Group 3). The adjusted odds ratios (ORs) for hypertension, hyperlipidemia, metabolic syndrome (MetS), and hyperuricemia in PCOS with Group 2 were 1.451 (1.013-2.079, P = 0.042), 1.706 (1.188-2.450, P = 0.004), 2.957 (1.755-4.981, P < 0.001), 1.890 (1.327-2.692, P < 0.001), respectively. For pregnancy outcomes, PCOS in Group 2 were more likely to progress to gestational diabetes mellitus (GDM) than those of Group 1, which was similarly observed in Group 3. The adjusted OR for GDM in the Group 2 was 4.065 (1.530-10.800, P = 0.005). CONCLUSIONS: Our study demonstrated that similar to 2 h-PG, elevated 1 h-PG was associated with different metabolic disorders and GDM. Therefore, 1 h-PG may serve as an additional marker of adverse metabolic status in women with PCOS.