Shuang Liu,1,* Juan Ye,2,* Long Suo,1 Tao Xu,3 Yiyi Chen,4 Wei Liu11Department of Ophthalmology, Jiangsu Province (Suqian) Hospital, Suqian, Jiangsu, 223800, People’s Republic of China; 2Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, People’s Republic of China; 3Department of Geriatric Medicine, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, 211166, People’s Republic of China; 4Department of Ophthalmology, People’s Hospital of Yangzhong City, Zhenjiang, Jiangsu, 212000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Liu, Email m13813182298@163.comBackground: Diabetic retinopathy (DR), a leading cause of blindness, is driven by redox imbalance and ferroptosis in retinal endothelial cells. While 6-Gingerol exhibits antioxidant properties, its role in modulating exosome-mediated redox signaling in DR remains unexplored. This study investigates whether 6-Gingerol protects against DR by regulating ferroptosis via the exosomal miR-148b-3p/ACSL4 axis.Methods: Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) ± 6-Gingerol. Ferroptosis was assessed via lipid ROS, intracellular iron, and key markers (GPX4, ACSL4, FTH1). Exosomal miRNAs were profiled by sequencing, with miR-148b-3p validated as a regulator of ACSL4 through luciferase assays. Functional rescue experiments confirmed pathway specificity.Results: 6-Gingerol suppressed HG-induced ferroptosis, reducing lipid ROS by 2.1-fold (P< 0.01) and iron accumulation by 1.8-fold (P< 0.05), while upregulating GPX4 (3.2-fold, P< 0.001). Exosomal miR-148b-3p was downregulated under HG but restored by 6-Gingerol (4.5-fold, P< 0.001). miR-148b-3p directly targeted ACSL4, whose knockdown mimicked 6-Gingerol’s effects, whereas ACSL4 overexpression or miR-148b-3p inhibition abolished protection.Conclusions: 6-Gingerol mitigates DR progression by inhibiting ferroptosis through exosomal miR-148b-3p/ACSL4-dependent redox regulation. These findings unveil a novel crosstalk between exosomal miRNAs and iron metabolism, positioning 6-Gingerol as a potential redox-targeted therapy for DR. Nonetheless, as the data are exclusively obtained from an in vitro model, in vivo validation is essential prior to making any translational inferences.Keywords: 6-gingerol, ferroptosis, miR-148b-3p/ACSL4 axis, diabetic retinopathy, exosome
ZhiWei Xu,1,* JinXing He,2,* Yangli Zhang,3,* JianHong Jin,4 Fei Pan,5 Ai Mi,1 XueQian Peng,1 WenHong Liu,1,6 YanFang Yang,1 Hui Wang1,21Jinhua Academy, Zhejiang Chinese Medical University, Jinhua, Zhejiang, 321000, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhuji Hospital of Traditional Chinese Medicine, Zhuji, Zhejiang, 311800, People’s Republic of China; 4Hangzhou Traditional Chinese Medicine Hospital, Hangzhou, Zhejiang, 310053, People’s Republic of China; 5Hangzhou Lin’an Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, 311300, People’s Republic of China; 6School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China*These authors contributed equally to this workCorrespondence: YanFang Yang, Jinhua Academy, Zhejiang Chinese Medical University, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86 17627851798, Email yyf121068@163.com; Hui Wang, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China, Tel +86 13656716323, Email 17357322049@163.comPurpose: This study aimed to investigate the protective effects and underlying mechanisms of Yiqi Huoxue Yangyin Decoction (YHY), a multi-herb formula composed of Astragalus membranaceus, Ligusticum chuanxiong, Pueraria lobata, Rehmannia glutinosa, and Trichosanthes kirilowii, against diabetic nephropathy (DN), focusing on its role in modulating autophagy and attenuating podocyte senescence via the AMPK/mTOR signaling pathway.Materials and Methods: Using network pharmacology and UPLC-Q-TOF-MS, this study examined the active constituents and targets of YHY. The type 2 diabetes db/db mouse model (leptin receptor-deficient BKS.Cg-Lepr/+ mice, random blood glucose ≥ 16.7 mmol/L) was used to construct a DN model in vivo. Mice received daily oral gavage of YHY or vehicle for 4 weeks (n=10). YHY’s protective benefits were assessed by physiological measurements, serum insulin and HbA1c by ELISA, histopathological evaluation of glomerular and tubular regions, glomerular basement membrane thickness by TEM, and protein expression in renal cortex by immunohistochemistry, immunofluorescence, and Western blot. In vitro, using a high-glucose-induced MPC-5 model, CCK-8, wound healing assays, qRT-PCR, and Western blot were performed (n=3-6) to investigate the mechanisms of YHY.Results: YHY demonstrated significant protective effects against DN. The expression levels of autophagy markers (ULK1, P62, and LC3B) in renal tissue were restored following YHY intervention. Through the AMPK/mTOR pathway, YHY regulated the expression of autophagy-related genes (ULK1, Beclin-1, P62, LC3B, ATG5, ATG7) and senescence-related genes (P21, P53), and improved the survival and migratory capabilities of high-glucose-induced MPC-5 cells. Furthermore, YHY enhanced the expression of podocyte structural proteins, including Nephrin, NPHS2, and SYNPO.Conclusion: YHY treatment was associated with activation of autophagy and attenuation of podocyte senescence, potentially through modulation of the AMPK/mTOR signaling pathway, a finding that requires validation in future mechanistic studies.Keywords: diabetic nephropathy, Yiqi Huoxue Yangyin Decoction, autophagy, AMPK/mTOR signaling pathway, senescence, MPC-5
Ezequiel Hernán Forte,1,* Matias Fernando Arrupe,2,* Leonardo Bufi,3,* Sergio Gimenez,4,* Augusto Lavalle Cobo,5,* Maria Gabriela Matta,6,* Juan Patricio Nogueira,7,* Nicolas Federico Renna,2,* Emiliano Salmeri,8,* Laura Schreier,9,* Pablo Corral10,*1Cardiovascular Department, CENDIC (Cardiovascular Diagnostic Center Concordia), Concordia, Entre Rios, Argentina; 2Department of Cardiology- Hospital Español de Mendoza, Mendoza, Argentina; 3Department of Internal Medicine, ICM - Instituto de Clínica Médica, Mar del Plata, Buenos Aires, Argentina; 4Department of Cardiology, Obra Social de Empleados Públicos de Mendoza (OSEP), Mendoza, Argentina; 5Department of Cardiology, Sanatorio Otamendi, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; 6FASTA University, Pharmacology and Research Department, Department of Cardiology, Division of Specialist Medical Services, Gold Coast Hospital and Health Services, Southport, QLD, Australia; 7Universidad Nacional de Formosa, Formosa, Argentina; 8Instituto Argentino de Diagnóstico y Tratamiento, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina; 9Clinical Biochemistry Department, Laboratory Lipids & Atherosclerosis, Buenos Aires University, Buenos Aires, Argentina; 10FASTA University, Pharmacology and Research Department, Instituto De Investigaciones Clínicas (IIC), Mar del Plata, Argentina*Argentine Lipoprotein(a) Study Group [GAELp(a)]Correspondence: Ezequiel Hernán Forte, CENDIC - Concordia Cardiovascular Diagnostic Center, Concordia, Entre Ríos, CP 3200, Argentina, Tel +54 9 345 5290342, Email ezeforte@yahoo.comBackground: Lipoprotein(a) [Lp(a)] is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Although both obesity and elevated Lp(a) are highly prevalent, their interrelationship and combined impact on ischemic heart disease (IHD) remain incompletely understood, particularly in Latin American populations.Objective: To evaluate the distribution of elevated Lp(a) across body mass index (BMI) categories, assess its association with ischemic heart disease (IHD), and determine whether this association differs across BMI categories.Methods: We conducted a multicenter observational study including 2975 adults from specialized centers in Argentina. Patients were stratified into BMI categories: Group 1: < 25, Group 2 BMI: 25– 29.9, Group 3: 30– 34.9 kg/m2, with exploratory subgroups ≥ 35 and ≥ 40 kg/m2. Elevated Lp(a) was defined as > 50 mg/dL or > 125 nmol/L.Results: Median Lp(a) levels decreased across higher BMI categories. The prevalence of elevated Lp(a) declined across increasing BMI categories (34.6% in BMI < 25 kg/m2, 29.8% in BMI 25-29.9, 30.1% in BMI ≥ 30, 26.4% in BMI ≥ 35 and 24.6% in BMI ≥ 40). However, after adjustment for demographic and cardiometabolic factors, overweight and obesity were associated with higher odds of elevated Lp(a) compared with normal weight (BMI 25– 29.9: OR 1.97, 95% CI 1.38– 2.82; BMI ≥ 30: OR 1.85, 95% CI 1.22– 2.81) suggesting that crude prevalence estimates and adjusted associations were influenced by differences in baseline risk profiles across BMI categories. Elevated Lp(a) was independently associated with IHD across all BMI categories, without significant interaction between BMI and Lp(a).Conclusions: In this cross-sectional study, elevated Lp(a) was associated with prevalent ischemic heart disease across BMI categories despite lower crude prevalence among individuals with higher BMI. Because of the observational cross-sectional design, causal inferences cannot be made. Nevertheless, these findings support consideration of Lp(a) assessment across the BMI spectrum.Keywords: lipoprotein(a), obesity, cardiovascular disease
Objective:To translate and psychometrically validate the Persian version of the Instrument for Self-care in Preventing Diabetic Foot (P-ISPDF) as a reliable, culturally appropriate tool for assessing foot-specific self-care behaviors among Persian-speaking adults, predominantly those with type 2 diabetes mellitus. Methods:The ISPDF was translated using a forward-backward procedure, followed by expert review (n=5) and cognitive debriefing with patients (n=10). A split-sample design was used: exploratory factor analysis (EFA; n=289) and a series of confirmatory factor analyses (CFAs), including first-order, second-order, and a hierarchical general-factor model in an independent sample (n=250). Items were rated on a 5-point Likert scale (1-5). Reliability (Cronbach's alpha, McDonald's omega, intraclass correlation coefficient [ICC]) and validity (EFA, CFA) were evaluated using SPSS 25, AMOS 24, and JASP. Results:EFA supported a three-factor structure: self-care maintenance (10 items), monitoring (9 items), and management (7 items). The hierarchical measurement model showed good fit (χ 2/df=2.80, CFI=0.974, TLI=0.954, RMSEA=0.060). Cronbach's alpha was 0.93 for the total scale, with subscale alphas ranging from 0.81 to 0.92. Test-retest reliability was excellent (two-way mixed-effects, absolute agreement ICCs 0.93-0.98 with 95% CIs reported). Conclusion:The P-ISPDF demonstrated strong reliability and preliminary structural validity. However, due to mixed evidence regarding convergent validity and the absence of external validation, the findings should be interpreted with caution. Further psychometric refinement and longitudinal studies are needed to establish its clinical utility.
Studies suggest that alterations of intestinal barrier function and a subsequent increased translocation of bacterial endotoxins may be critical in type 1 diabetes mellitus (T1DM) and may contribute to the proinflammatory state of patients. If Gram-positive derived bacterial toxins are also altered in the setting of T1DM is not yet clarified. In the present study, using a SEAP reporter assay and ELISA, markers of intestinal permeability, concentration of Toll like receptor (TLR) 2 ligands and soluble CD14 (sCD14) were assessed in serum of individuals with T1DM (n=19, m: 10/ f: 9) and age-matched healthy controls (n=18, m: 3/ f: 15) from the LatDiane study. BMI and HbA1c were significantly higher in individuals with T1DM. Serum concentrations of intestinal fatty acid binding protein (I-FABP) were significantly higher in individuals with T1DM than in controls as were concentrations of TLR2 ligands and sCD14 protein. A multivariable linear regression analysis revealed an independent association of T1DM with higher TLR2 ligand levels. Our findings indicate that not only bacterial endotoxin but also TLR2 ligands are elevated in patients with T1DM.
Purpose:Thyroid hormones are linked to prognostic outcomes for a range of diseases. The link between thyroid hormone levels and diabetic kidney disease (DKD) risk in euthyroid individuals with type 2 diabetes mellitus (T2DM) was investigated in this study. Patients and Methods:Overall, 2945 T2DM cases were enrolled and grouped as with or without DKD. Thyroid hormones were analyzed both as continuous variables and by quartiles. Logistic regression models and smooth curve fitting were applied to assess associations. Stratified analyses and interaction tests were also conducted to examine effect modification. Results:Patients with DKD had significantly decreased free triiodothyronine (FT3) levels compared to those without DKD, while free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were comparable across groups. Relative to the bottom FT3 quartile (Q1), the respective adjusted odds ratios (ORs) for DKD in Q2, Q3, and Q4 were 0.63 (95% CI: 0.50-0.80, p < 0.001), 0.60 (95% CI: 0.47-0.77, p < 0.001), and 0.63 (95% CI: 0.49-0.82, p = 0.001). The relationship between FT3 and DKD followed a nonlinear, L-shaped pattern (p for nonlinearity < 0.001), with a threshold at approximately 3.09 pg/mL. Below this inflection point, an adjusted OR for DKD of 0.622 (95% CI: 0.515-0.751, p < 0.001) was evident. Subgroup analysis suggested that this association was generally consistent across most subsets of study subjects, but was not statistically significant in several strata. Conclusion:Lower FT3 levels are independently linked to greater prevalence of DKD in euthyroid individuals with T2DM. The observed L-shaped association suggests a threshold effect, with 3.09 pg/mL as the approximate inflection point.
Background:Diabetic retinopathy (DR), a common microvascular complication of diabetes, is increasingly viewed as a systemic disorder involving the retina-brain axis. Although neuroimaging studies have reported brain abnormalities in DR, large-scale network reorganization and its biological substrates remain unclear. Methods:This cross-sectional study included 47 patients with type 2 diabetes mellitus and non-proliferative diabetic retinopathy (T2DM-NPDR) and 45 matched healthy controls. Structural MRI data were used to construct individualized regional radiomics similarity networks (R2SNs). Group differences in network architecture were examined using multiscale network analysis and gradient mapping. Epicenter mapping identified candidate regions related to network abnormalities. Imaging-transcriptomic analysis based on the Allen Human Brain Atlas, cell-type enrichment analysis, and spatial associations with normative neurotransmitter receptor and transporter maps were performed. Machine learning classifiers and an interpretable graph neural network assessed the discriminative value of R2SN-derived features. Results:Patients with T2DM-NPDR showed widespread cortical and subcortical alterations in R2SN organization. Gradient analysis revealed a systematic shift in macroscale hierarchy, indicating disrupted cortical hierarchical organization. Epicenter mapping highlighted frontal regions, especially the inferior frontal gyrus, middle frontal gyrus, and orbitofrontal cortex, with additional involvement of the insula and parahippocampal gyrus, suggesting abnormalities beyond primary visual pathways and implicating higher-order integrative systems. Imaging-transcriptomic analysis showed that the spatial pattern of R2SN alterations was associated with gene expression profiles enriched in neuronal and glial cell populations. R2SN abnormalities also showed significant spatial correspondence with normative neurotransmitter receptor and transporter maps. Predictive models demonstrated that R2SN-derived features could distinguish patients with T2DM-NPDR from healthy controls. Conclusions:T2DM-NPDR is associated with multiscale structural brain network alterations beyond the visual system. Integrating radiomics-based network modeling, gradient analysis, molecular mapping, and graph-based prediction provides a framework for characterizing brain network disruption and potential biological associations in T2DM-NPDR.
Qingqing ShanDepartment of Respiration, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, 610095, People’s Republic of ChinaCorrespondence: Qingqing Shan, Department of Respiration, Chengdu Integrated TCM & Western Medicine Hospital, No.18, Wangxiang North Road, High-Tech Zone, Chengdu, Sichuan Province, 610095, People’s Republic of China, Tel +86 028 85311622, Email shanqingqing52377@126.com
Irma Melyani Puspitasari,1,2,* Dimas Setyadi Putra,2,* Alifa Nisa Deliyana,3 Nurqisthi Iqlima Adiputri,3 Lily Indriani Octovia,4 Sekar Ayu Paramita,5 Rano Kurnia Sinuraya1,2,*1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 2Center of Excellence for Pharmaceutical Care Innovation (PHARCI), Universitas Padjadjaran, Sumedang, Indonesia; 3Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia; 4Department of Nutrition, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; 5Department of Public Health, Graduate School of Medicine, Gunma University, Maebashi, Japan*These authors contributed equally to this workCorrespondence: Irma Melyani Puspitasari, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia, Tel +62 22 84288888 Ext 3510, Email irma.melyani@unpad.ac.idAbstract: Obesity remains a major global public health challenge associated with increased morbidity, mortality, and reduced quality of life, necessitating effective treatment strategies beyond lifestyle modifications. The present scoping review aimed to synthesize recent evidence on the effectiveness and safety of anti-obesity medications (AOMs). A structured literature search was conducted in PubMed and Scopus in May 2025 to identify original studies published within the previous five years involving individuals with overweight or obesity receiving pharmacological interventions. A total of 42 articles representing 41 unique studies, predominantly randomized controlled trials (RCTs), were included in the evidence synthesis. The review encompassed glucagon-like peptide-1 receptor agonists (GLP-1 RA), including semaglutide, liraglutide, exenatide, and orforglipron; multi-receptor incretin agonists, including tirzepatide, retatrutide, and survodutide; amylin-based combination therapy (cagrilintide plus semaglutide); established non-incretin AOMs (orlistat, phentermine, phentermine/topiramate, and naltrexone/bupropion); microbiome-targeted therapies; and nutraceutical-based interventions. Among these, GLP-1 RA consistently demonstrated substantial weight-loss efficacy, with semaglutide achieving approximately 10– 16% weight loss, while tirzepatide produced approximately 15– 21% weight reduction over treatment durations of 20– 70 weeks. Emerging multi-receptor incretin agonists also demonstrated promising efficacy, whereas established non-incretin AOMs, microbiome-targeted therapies, and nutraceutical-based interventions generally produced modest or more heterogeneous outcomes. Gastrointestinal adverse events (AEs) were the most frequently reported across incretin-based therapies. Overall, incretin-based therapies currently provide the greatest weight-loss benefit, although evidence for several emerging pharmacotherapies, microbiome-targeted therapies, and nutraceutical-based interventions remains limited. Further well-designed comparative trials, mechanistic studies, and long-term real-world investigations are needed to better establish the durability, safety, and clinical applicability of emerging AOMs.Keywords: anti-obesity medication, anti-obesity pharmacotherapy, weight change, weight management, clinical outcomes
Objective:To quantify the acute effects of exercise snacks on glucose and lipid metabolism in individuals with metabolic disorders (including those with type 2 diabetes, metabolic syndrome, and overweight or obesity) compared with sedentary behavior and continuous exercise, and to examine their effects across different exercise modalities. Methods:Following the PRISMA 2020 guidelines, four databases (PubMed, Embase, Web of Science, and Scopus) were searched up to February 4, 2026, to identify randomized crossover trials that examined the acute effects of exercise snacks on glucose and lipid metabolism in individuals with metabolic disorders. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and the quality of evidence was assessed using the GRADE approach. The "meta" and "metafor" packages in R (version 4.5.2) were used to calculate pooled effect estimates (using Hedges' g as the effect size) and to conduct publication bias tests, subgroup analyses, and regression analyses. Results:The analysis included 20 randomized crossover trials (21 studies) involving 392 participants. Compared with prolonged sedentary behavior, exercise snacks significantly reduced postprandial glucose AUC (Hedges' g = -0.37, 95% CI -0.53 to -0.22, P < 0.01, I2 = 6.6%, moderate certainty of evidence) and insulin AUC (Hedges' g = -0.49, 95% CI -0.68 to -0.30, P < 0.01, I2 = 15.7%, moderate certainty of evidence), whereas no significant improvement was observed for triglycerides (Hedges' g = -0.014, 95% CI -0.18 to 0.15, P = 0.87, I2 = 0.0%, low certainty of evidence). Compared with a single session of continuous exercise, exercise snacks showed no statistically significant differences in postprandial glucose (Hedges' g = -0.14, 95% CI -0.73 to 0.45, P = 0.64, I2 = 57.6%, low certainty of evidence), insulin, or triglycerides. The included studies did not provide separate data for individuals with a confirmed diagnosis of MetS; therefore, the subgroup analysis was limited to overweight or obese individuals and those with T2DM. When stratified by study population, exercise snacks significantly reduced the postprandial glucose AUC in overweight or obese individuals (Hedges' g = -0.36, 95% CI: -0.52 to -0.20, P < 0.001), whereas the effect estimate in the T2DM group did not reach statistical significance (Hedges' g = -0.45, 95% CI: -1.47 to 0.56, P = 0.385), and the difference between the two subgroups was not significant (P between subgroups = 0.86). Insulin AUC was significantly reduced in both the overweight or obese group (Hedges' g = -0.42, 95% CI: -0.61 to -0.24, P < 0.001) and the T2DM group (Hedges' g = -1.15, 95% CI: -1.76 to -0.54, P < 0.001), and the difference between subgroups was significant (P = 0.03 between subgroups); however, the estimate for the T2DM subgroup was based on only one study. Regression analysis indicated that older participants experienced a greater reduction in insulin levels (β = -0.01, 95% CI -0.02 to 0.00, P = 0.02). Conclusion:In individuals with metabolic disorders, repeatedly interrupting sedentary behavior with short bouts of mild- to moderate-intensity aerobic exercise (2-5 minutes of activity every ≤30 minutes) can acutely reduce postprandial glucose and insulin responses. A meta-regression analysis suggests that studies involving participants with a higher average age showed a greater reduction in postprandial insulin AUC. No statistically significant differences in short-term glycemic control were observed between exercise "snacks" and a single continuous exercise session; however, this comparison was based on only four studies with small sample sizes and is therefore insufficient to demonstrate the non-inferiority or equivalence of the two exercise patterns. Exercise "snacks" can serve as a low-barrier complementary strategy to regular exercise and other lifestyle management approaches.
Background:An elevated triglyceride-glucose (TyG) index is strongly linked to an increased risk of cardiovascular events in patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM). However, the potential impact of increasing diabetes duration on the association between the TyG index and cardiovascular risk remains unclear. Methods:Consecutive patients admitted for ACS with T2DM received PCI between March 2016 and March 2020 were enrolled in the analysis. A total of 7093 patients were categorized into tertiles according to the TyG index and T2DM duration. The primary outcome was ischemic events, composed of cardiac death, myocardial infarction, and/or stroke at 5 years. The main secondary outcomes were 5-year cardiac death and all-cause death. Interaction terms and non-linear associations of the TyG index with the clinical outcomes were examined across diabetes durations. Results:Over 5 years, 753 (10.6%) experienced ischemic events, 375 (5.3%) cardiac death, and 636 (9.0%) all-cause death. Higher TyG index and longer diabetes duration independently associated with all outcomes. Compared with the lowest TyG tertile, the highest tertile had adjusted hazard ratios (HRs) of 1.55 (95% CI: 1.29-1.88) for ischemic events and 1.23 (1.10-1.38) for all-cause death. The association between TyG index and ischemic events was strongest in the shortest duration group (HR: 1.43), with significant interaction for ischemic and cardiac death (both p < 0.05). Conclusions:A higher TyG index was independently associated with an increased risk of ischemic events and mortality among patients with ACS and T2DM. This association appeared to be attenuated with longer diabetes duration, suggesting that the prognostic relevance of the TyG index may vary according to the chronicity of diabetes.
Aims:Current diabetes mellitus (DM) prevention and treatment strategies rely on risk factors adapted from developed countries, which may not be effective in most poor sub-Saharan Africa settings. This study investigated the association between diabetic treatment outcomes and complications with sociodemographic and diabetic risk factors among type 2 DM (T2DM) patients in Rwanda. Methods:This cross-sectional study analyzed the records of T2DM patients who accessed care at Kigali University Teaching Hospital (CHUK) between January and December 2020, using a non-random sampling technique. Treatment outcomes (improved or not improved based on glycemic control target) and complication outcomes (presence or absence of DM-related microvascular and macrovascular events) were the primary outcome variables. Data were analyzed using t-tests, chi-square tests, and multivariable analyses as appropriate. Results:After adjusting for confounders, only age remained significantly associated with treatment and complication outcomes. The adjusted prevalence ratio (PR) of treatment outcomes for patients aged <50 years was 1.43 (95% CI 1.07-1.92; p = 0.016) and for those aged 50-64 years was 1.12 (95% CI 0.83-1.52; p = 0.462), both relative to the ≥65 years reference category. The adjusted PR for complication outcomes was 0.59 (95% CI 0.40-0.86; p = 0.005) for patients aged <50 years and 0.72 (95% CI 0.57-0.91; p = 0.007) for those aged 50-64 years, compared with the ≥65 years reference category. The adjusted PRs for smoking, alcohol consumption, pharmacological therapy, non-pharmacological therapy, and diet were attenuated and no longer statistically significant (all p > 0.05). Conclusion:The outcomes of diabetic treatment in Rwanda are associated with the age of the patients, rather than the type of therapy or the assessed sociodemographic and risk factors. The causal interpretation and generalizability of this study are limited by its cross-sectional design, non-random sampling, and the single-center setting.
Insulin resistance is one of the main causes of type 2 diabetes mellitus and metabolic disorders. Histone deacetylase 9 (HDAC9) belongs to the class IIa histone deacetylase family. It remodels chromatin structure and modulates gene expression to regulate adipocyte differentiation, inflammatory responses, and hepatic glucose homeostasis, thereby inhibiting insulin signaling. However, the complete and precise molecular mechanisms underlying these processes remain unclear. This review systematically summarizes the molecular characteristics and regulatory mechanisms of HDAC9, and analyzes its biological functions under insulin resistance from the perspectives of chromatin remodeling and transcriptional regulation. This review further explores whether HDAC9 exacerbates insulin resistance through regulating adipocyte differentiation, mediating inflammatory responses and disrupting hepatic glucose metabolic homeostasis. Meanwhile, this review evaluates HDAC9-targeted therapeutic prospects for metabolic diseases and offer theoretical support for future precision interventions.
Objective:The functional status of regulatory T cells expressing the gut-homing receptor CCR9 (CCR9+ Tregs) in type 1 diabetes mellitus (T1DM) remains unclear. This study aims to investigate the functional alterations of CCR9+ Tregs in a T1DM model and evaluate the interventional effect of targeting the IL-21/IL-17 axis on their dysfunction. Methods:The spontaneous T1DM non-obese diabetic (NOD) mouse model was employed. CCR9+ and CCR9- Treg subsets were isolated from the spleen by flow cytometry. Their in vitro suppressive capacity on effector T cell (Teff) proliferation was assayed, and cytokine expression was analyzed using flow cytometry and qPCR. In vitro, CCR9+ Tregs were treated with different concentrations (50 and 100 ng/mL) of the anti-IL-21 monoclonal antibody (Avizakimab) to assess its effects on IL-21/IL-17A secretion and immunosuppressive function. In vivo, T1DM NOD mice were randomly assigned to a saline control group (n=3) and an Avizakimab treatment group (n=3, 10 mg/kg, tail vein injection, every other day for 2 weeks). Fasting blood glucose levels were monitored, pancreatic insulitis and pathological damage were evaluated by H&E staining, and the proportion of peripheral blood IL-17A+ cells was analyzed by flow cytometry. Results:Compared to CCR9- Tregs, CCR9+ Tregs exhibited a significantly reduced ability to suppress Teff proliferation, secreted less of the anti-inflammatory cytokine IL-10, and showed significantly upregulated expression of the pro-inflammatory cytokines IL-17A and IL-21. Avizakimab effectively and dose-dependently inhibited the abnormal secretion of IL-21 and IL-17A by CCR9+ Tregs in vitro and restored their suppressive function on Teff proliferation. In vivo, Avizakimab treatment significantly lowered fasting blood glucose levels in T1DM NOD mice, alleviated pancreatic insulitis and pathological damage, and downregulated the proportion of IL-17A+ cells in peripheral blood. Conclusion:In the T1DM milieu, CCR9+ Tregs become dysfunctional and shift towards a pro-inflammatory phenotype, thereby exacerbating the autoimmune response. The anti-IL-21 monoclonal antibody Avizakimab can reverse the dysfunction of CCR9+ Tregs and ameliorate disease symptoms by inhibiting the IL-21/IL-17 axis, providing a novel potential strategy for the immunotherapy of T1DM and highlighting the translational potential of targeting this axis.
Diabetic complications, driven by chronic hyperglycemia and complex pathogenic mechanisms, are a major global health challenge, yet the basis of tissue-specific injury and repair remains unclear. Wnt/β-catenin signaling has emerged as an important regulator in these complications, but its role is highly context dependent, promoting pathological remodeling in some tissues while impairing repair in others. This review is distinguished by its integration of current evidence on the dual and often opposing roles of Wnt/β-catenin signaling across six major diabetic complications: diabetic nephropathy (DN), diabetic retinopathy (DR), diabetic cutaneous ulcers (DCU), diabetic cardiomyopathy (DCM), diabetic neuropathy, and diabetic osteoporosis (DOP). We first outline the major pathological features and clinical significance of each complication, highlighting the recurring observation that hyperglycemia often causes aberrant activation of this pathway in DN, DR, and DCM, where it promotes epithelial-to-mesenchymal transition, extracellular matrix accumulation, fibrosis, inflammation, and pathological angiogenesis. In contrast, we then examine conditions in which Wnt/β-catenin signaling is suppressed, particularly in DCU, DOP, and certain forms or stages of DPN, leading to impaired wound healing, reduced bone formation, and defective nerve regeneration. We subsequently analyze the cell type- and stage-specific mechanisms underlying these divergent effects, including cross-talk with oxidative stress, the renin-angiotensin system, and transforming growth factor-β signaling. Following a detailed discussion of emerging therapeutic strategies, such as LRP6-targeting biologics, small-molecule modulators, and agents derived from traditional Chinese medicine, we summarize preclinical evidence showing that carefully tuned, context-specific modulation of Wnt/β-catenin can improve both pathological and functional outcomes. This review is intended to clarify the potential mechanisms linking Wnt/β-catenin signaling to diabetic complications and to guide the rational development of new therapies that take into account its tissue-specific and stage-specific effects.
Dandan Chi, Yuntao GuanDepartment of Endocrinology, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Yuntao Guan, Department of Anesthesiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China, Tel +86 18842869236, Email 18842869236@163.com
Bing Zhao,1– 3,* Feilong Wang,1– 3,* Yerui Bi,1,4,* Lei Li,1,4,* Yabin Xia,1– 3 Yan Jin1– 3,*1Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, 241001, People’s Republic of China; 2Department of Hernia and Bariatric Surgery, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu, Anhui, 241001, People’s Republic of China; 3Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation (Wannan Medical University), Wuhu, Anhui, 241001, People’s Republic of China; 4Wannan Medical University, Wuhu, Anhui, 241001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yabin Xia, Department of Gastrointestinal Surgery & Department of Hernia and Bariatric Surgery, The First Affiliated Yijishan Hospital of Wannan Medical University, Wuhu, Anhui, 241001, People’s Republic of China, Tel +86-18805536006, Email 77278431@qq.com Yan Jin, Department of Gastrointestinal Surgery & Department of Hernia and Bariatric Surgery, The First Affiliated Yijishan Hospital of Wannan Medical University, Wuhu, Anhui, 241001, People’s Republic of China, Tel +86-13545905510, Email jinyanyijishan@wnmc.edu.cnAbstract: Metabolic and bariatric surgery (MBS) plays an important role in the management of obesity and related metabolic disorders, particularly in patients who meet established surgical criteria. The field has transitioned from open procedures to laparoscopic surgery, and the current landscape includes multiple operations with distinct efficacy-risk profiles. Alongside established procedures such as sleeve gastrectomy (SG), newer approaches—such as endoscopic metabolic interventions and robot-assisted platforms—are being evaluated for their feasibility, safety, learning curve, and potential outcome benefits. However, important questions remain regarding long-term durability, complication patterns, revisional surgery, patient selection, cost-effectiveness. To map these developments, we screened PubMed literature up to March 10, 2026 using terms such as "metabolic and bariatric surgery” and "sleeve gastrectomy”, with emphasis on the International Federation for Surgery and Other Therapies for Obesity (IFSO) and higher-level evidence when available. We then synthesize findings across surgical technique evolution, indications and complications, unresolved challenges, and future directions, including how artificial intelligence (AI) and machine learning (ML) may support perioperative risk prediction and individualized treatment planning. This work aims to support clinicians in tailoring MBS plans and to guide future research priorities.Keywords: metabolic and bariatric surgery, obesity, diabetes, follow-up data, complications
Juan Tu,1 Guoxin Lin,1 Feng Zhu,1 Feipeng Xu,1 Yuan Gao,2 Qiulan Gan,1 Yali Chen,1 Xiaofang Hu,3 Rui Tang41Department of Endocrinology, The First Hospital of Putian City, Putian, Fujian, People’s Republic of China; 2The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Nursing School of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Health Science Center, Hunan Normal University, Changsha, Hunan, People’s Republic of China; 4School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Rui Tang, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email 2396258206@qq.com Xiaofang Hu, Hunan Normal University Health Science Center, No. 371 Tongzipo Road, Yue-Lu District, Changsha, Hunan, 410013, People’s Republic of China, Email hxf20179@163.comObjective: This study aimed to identify the predisposing, enabling, and reinforcing factors associated with glycemic control in patients with type 2 diabetes mellitus, and to provide preliminary evidence for developing continuity management programs across hospital and community settings.Methods: A cross-sectional survey design was used. Based on the PRECEDE-PROCEED planning model, 220 patients with type 2 diabetes were assessed using a general information questionnaire, the Chronic Disease Management Self-Efficacy Scale, the Type 2 Diabetes Self-Management Behavior Scale, and the Social Support Rating Scale. Data were analyzed using the chi-square test, Spearman correlation analysis, and multiple linear regression analysis.Results: The average age of patients with type 2 diabetes was 57.90 (SD=14.28), and the average course of disease was 8.76 (SD=7.52). Overall, 25% of patients achieved the glycemic control target of HbA1c < 7%. Age, disease duration, smoking history, self-efficacy, self-management behavior, and social support were significantly associated with HbA1c and jointly accounted for 44.4% of its variance.Conclusion: The rate of adequate glycemic control among patients with type 2 diabetes mellitus remains suboptimal. Within the PRECEDE-PROCEED framework, self-efficacy may represent a predisposing factor, self-management behaviors an enabling factor, and social support both an enabling and reinforcing factor affecting glycemic control. These findings indicate that future continuity management programs should integrate tailored interventions targeting self-efficacy enhancement, self-management behavior improvement, and social support reinforcement. The incorporation of intelligent terminal technologies may further support personalized diabetes management and improve long-term glycemic outcomes.Keywords: type 2 diabetes mellitus, glycemic control, PRECEDE-PROCEED model, influencing factors
Background:Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder that affects women of reproductive age. There is no absolute treatment for PCOS, but it is managed symptomatically. Adopting a healthy lifestyle comprising a balanced diet and physical exercise is the major recommendation for management of PCOS. Objective:To evaluate the effectiveness of aerobic exercise as an intervention for improving metabolic profiles in women suffering from PCOS. Methods:A systematic search was performed in 4 databases; Scopus, MEDLINE (via PubMed), Embase, and Web of Science, since inception till 28.2.2025. Risk of bias was performed using Cochrane RoB 2.0 tool and meta-analysis was done by using random-effects models. Results:Twenty-five RCTs were included in the review for qualitative synthesis and 5 RCTs with a total of 192 participants were included for quantitative analysis. A low but statistically significant decrease was observed in waist-to-hip ratio). Lipid profile analysis revealed a significant reduction in low-density lipoprotein (LDL) cholesterol. Further, HIIT also improved insulin sensitivity, by decreasing fasting insulin levels and HOMA-IR. A non-significant reduction was observed in body mass index (BMI), waist circumference, total cholesterol, and fasting glucose. Changes in triglycerides, and HDL were also non-significant. Conclusion:Aerobic exercise, especially HIIT, appears effective in improving regional fat distribution, LDL cholesterol, and insulin resistance in PCOS women, though evidence for BMI and hormonal changes remains inconclusive. Larger, longer-term RCTs are needed to confirm these findings and clarify hormonal outcomes. Prospero Registration crd420251003425:
Background:Diabetic foot ulcers (DFUs) remain the leading cause of non-traumatic lower-extremity amputation (LEA). Most published risk-stratification tools require specialized testing and are difficult to apply in routine practice. We sought to build a simple nomogram for amputation risk using only routinely available clinical indicators. Methods:This single-center retrospective cohort study included 508 hospitalized patients with type 2 diabetes-related DFUs treated between January 2019 and June 2025. The cohort was randomly split into training (n=357, 84 amputations) and validation (n=151, 35 amputations) sets at a 7:3 ratio with stratification on outcome. The outcome was lower-extremity amputation (minor or major) during the index hospitalization. Twenty-four baseline variables were screened for selection in the training set (84 events) using two independent methods: LASSO regression with 10-fold cross-validation (at λ.1se) and 1000 bootstrap stepwise logistic regression replicates (selection frequency >80%). Variables retained by both methods were entered into the final multivariable logistic regression model, from which a nomogram was constructed. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC); calibration was evaluated using calibration plots, the Hosmer-Lemeshow test, and the calibration slope; and clinical utility was assessed by decision curve analysis (DCA). Internal validity was further examined by bootstrap resampling with optimism correction. Results:Four variables were retained by both LASSO and bootstrap screening: serum albumin (protective), platelet count, smoking history, and hypertension (predictors of higher risk). The nomogram achieved an AUC of 0.788 (95% CI 0.735-0.840) in the training cohort and 0.755 (95% CI 0.671-0.839) in the validation cohort; the wide validation confidence interval reflects the limited number of validation events (n = 35). On bootstrap internal validation (1000 resamples), the optimism-corrected AUC was 0.776. Calibration was acceptable in both cohorts (Hosmer-Lemeshow P = 0.794; calibration slope 0.944 [bootstrap-corrected]), and DCA suggested potential clinical utility. Conclusion:A four-variable nomogram based on serum albumin, platelet count, smoking history, and hypertension estimated in-hospital LEA risk in hospitalised patients with type 2 diabetes-related DFUs with moderate discrimination and acceptable calibration, and decision curve analysis suggested potential clinical utility. Because every predictor is available from routine clinical history and standard laboratory testing, the model may support early in-hospital risk stratification rather than treatment decisions. As this was a single-centre study with internal validation only, external multi-centre validation is required before routine clinical use.
