Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

{"title":"Endocrine Disruptors, Gut Microbiota, and Type 2 Diabetes: Bridging Mechanisms to Probiotic-Based Therapeutic Approaches.","authors":"Shun-Man Cheung, Chi-Yung Cheng, Vinoth Kumar Ponnusamy, Kai-Fan Tsai, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Wen-Chin Lee, Fu-Jen Cheng, Venkata Chaithanya","doi":"10.2147/DMSO.S636877","DOIUrl":"https://doi.org/10.2147/DMSO.S636877","url":null,"abstract":"<p><p>Genetic and lifestyle factors alone cannot explain the rising global burden of type 2 diabetes mellitus (T2DM). Growing evidence implicates endocrine-disrupting chemicals (EDCs) found in plastics, pesticides, food packaging, industrial products, and contaminated water as significant environmental contributors to metabolic dysfunction. EDCs, including bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), and heavy metals, have been associated with insulin resistance, pancreatic β-cell dysfunction, oxidative stress, mitochondrial impairment, chronic inflammation, and epigenetic modifications that collectively promote T2DM pathogenesis. The gut microbiota has emerged as a potential mediator of EDC-associated metabolic disruption, whereby chemical exposures may alter microbial diversity, disturb the <i>Firmicutes/Bacteroidetes</i> ratio, impair short-chain fatty acid production, decrease intestinal barrier integrity, driving metabolic endotoxemia and systemic inflammation. This narrative review examines the major EDCs associated with diabetes, their molecular and metabolic mechanisms of action, and their interactions with the gut microbiota, drawing on current experimental and epidemiological evidence. Special emphasis is placed on probiotic supplementation as an emerging therapeutic strategy targeting the EDC-gut microbiota-metabolic axis. Current evidence for probiotics in EDC-associated metabolic dysfunction is predominantly preclinical, with studies suggesting improvements in microbial homeostasis, pancreatic oxidative damage, and glucose metabolism. However, available evidence remains heterogeneous and human clinical trials specifically examining probiotic intervention in EDC-exposed populations at risk of T2DM remain absent, representing a fundamental translational gap that future research must urgently address. Advancing precision medicine approaches, integrating microbiome profiling, metabolomics, epigenetic analysis, and coordinated efforts across toxicology, clinical medicine, and public health, will be essential to reducing the growing global burden of environmentally driven type 2 diabetes.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"636877"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithocholic Acid Improves Glucose Homeostasis by Activating the TGR5-GLP-1 Axis via Gut Microbiota-Derived Secondary Bile Acids: A Study Done on Diabetic Sprague-Dawley Rats.","authors":"Chiying Xu, Kun Yang, Renran Wu, Guanlei Liu, Lei Lin, Liqian Luo, Lingao Tao, Jinyuan Duan","doi":"10.2147/DMSO.S627840","DOIUrl":"https://doi.org/10.2147/DMSO.S627840","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the effects of lithocholic acid on glucose metabolism in streptozotocin -induced diabetic Sprague-Dawley (STZ-DM) rats and to explore its potential mechanisms.</p><p><strong>Methods: </strong>STZ-DM rats were randomly allocated into two groups (n=6 per group) and received LCA (50 mg/kg/d) or vehicle by daily gavage for 6 weeks. Longitudinal monitoring of body weight and fasting blood glucose was performed throughout the intervention, and oral glucose tolerance tests were conducted to evaluate glucose metabolic capacity. Fecal bile acid metabolomics and gut microbial community analyses were further conducted. Additionally, the transcriptional levels of ileal TGR5, FXR and GLP-1, as well as the key hepatic gluconeogenic genes G6PC and PCK1, were quantified by RT-qPCR at the mRNA level for mechanistic exploration.</p><p><strong>Results: </strong>LCA treatment reduced fasting glycemia and enhanced glucose tolerance, accompanied by a significant suppression of hepatic G6PC and PCK1 mRNA, with no significant impact on body weight. A marked elevation in fecal secondary bile acids was observed, showing a positive correlation with metabolic improvements. LCA supplementation enriched intestinal Clostridia, which correlated with secondary bile acid abundance and glucose homeostasis indicators. Meanwhile, ileal and hepatic TGR5 as well as ileal GLP-1 mRNA expression were upregulated following LCA administration.</p><p><strong>Conclusion: </strong>LCA is associated with improved glucose metabolism in STZ-DM rats, potentially through TGR5-GLP-1 activation and suppression of hepatic gluconeogenesis, in conjunction with Clostridium-enriched secondary bile acid production. However, this study only relies on mRNA expression data and lacks functional TGR5 receptor validation; the proposed correlative pathway requires further mechanistic verification to confirm causal effects.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"627840"},"PeriodicalIF":3.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical Activity, Myokine-Adipokine Signatures and Haemoglobin Glycation Index in Adults with Type 2 Diabetes.","authors":"Marwan Ismail, Mutaz Ibrahim Hassan, Akhtamova Shahzoda Fozilovna, Namoz Xalimovich Mavlonov, Nuriddin Nuritdinov, Elmotaz Abdelfatah","doi":"10.2147/DMSO.S621983","DOIUrl":"https://doi.org/10.2147/DMSO.S621983","url":null,"abstract":"<p><strong>Background: </strong>The Hemoglobin Glycation Index (HGI) reflects variability in hemoglobin glycation beyond ambient glycaemia and is a marker of metabolic heterogeneity, cardiovascular risk and treatment response in type 2 diabetes mellitus (T2DM). Whether circulating myokines and adipokines are related to HGI, or whether relationships differ across exercise modalities, is unclear.</p><p><strong>Objective: </strong>To examine associations of circulating myokines (irisin, myostatin, myonectin, IL-6, IL-15) and adipokines (leptin, adiponectin) with HGI, and whether associations differ between physically active and sedentary individuals and across exercise modalities.</p><p><strong>Methods: </strong>Cross-sectional study of 185 adults with T2DM recruited at Thumbay Hospital, Ajman, United Arab Emirates, classified as physically active (n=98) or sedentary (n=87), with active individuals sub-grouped by predominant modality: aerobic (70), resistance (11), combined (17). Measurements were obtained after an overnight fast. HGI was calculated as the residual of HbA1c regressed on fasting plasma glucose. Mann-Whitney U, Kruskal-Wallis, Spearman correlations with false discovery rate (FDR) correction and median regression adjusted for age, sex, BMI and fasting glucose were used.</p><p><strong>Results: </strong>Active participants had lower HGI than sedentary participants (median -0.44 vs 0.12; p = 0.001), with lower BMI, fasting glucose and HbA1c. HGI differed by modality (p < 0.001), most favourable in the combined-training group and least favourable in the aerobic-only group. IL-6 was inversely correlated with HGI in active participants and leptin in sedentary participants (both FDR p < 0.05). Physical activity remained an independent predictor of lower HGI after adjustment for age, sex and BMI (β = -0.65;p< 0.001), and persisted after adjustment for IL-15 and leptin.</p><p><strong>Conclusion: </strong>Precludes causal inference; if confirmed prospectively, associations may inform individualized exercise prescription and HGI-based risk stratification.Distinct myokine-adipokine signatures were associated with glycation variability beyond mean glycaemia and combined aerobic-plus-resistance training with the most favourable HGI profile. The cross-sectional design precludes causal inference; if confirmed prospectively, associations may inform individualized exercise prescription and HGI-based risk stratification.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"621983"},"PeriodicalIF":3.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13653552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Evogliptin and Dapagliflozin on Bone and Glucose Metabolism in Postmenopausal Women with Type 2 Diabetes: A Multicenter Randomized Exploratory Clinical Trial.","authors":"Hyun Jin Ryu, So Young Park, Ha-Young Kim, Dong Won Byun, Kee-Ho Song, Seongbin Hong, Jungbok Lee, Ki-Hyun Baek, Ho Yeon Chung","doi":"10.2147/DMSO.S618336","DOIUrl":"https://doi.org/10.2147/DMSO.S618336","url":null,"abstract":"<p><strong>Background: </strong>Postmenopausal women with type 2 diabetes mellitus (T2DM) are at increased risk of fragility fractures, emphasizing the importance of selecting antidiabetic agents that support glycemic control and bone health. Most dipeptidyl peptidase-4 inhibitors have shown neutral or favorable effects on bone metabolism; however, data specifically on evogliptin remain limited. This study evaluated the effects of evogliptin and dapagliflozin on bone metabolism and glycemic parameters in postmenopausal women with T2DM.</p><p><strong>Methods: </strong>This multicenter, randomized clinical trial enrolled postmenopausal women with T2DM assigned to receive evogliptin or dapagliflozin for 48 weeks. The primary outcome was change in bone mineral density (BMD). Glycemic indices were the secondary endpoints.</p><p><strong>Results: </strong>Sixty participants were included in the final analysis, with 30 in each group. After 48 weeks, the change in BMD at the L1-L4 spine and total hip did not differ significantly between groups. Femoral neck BMD decreased significantly in the dapagliflozin group compared with the evogliptin group, although the absolute between-group difference was small (0.00 ± 0.02 vs -0.02 ± 0.04 g/cm², p = 0.0402). After adjustment for baseline femoral neck BMD and 25OHD, the between-group difference was attenuated (p = 0.0763). The body mass index (BMI) decreased more in the dapagliflozin group than in the evogliptin group. In analyses of factors associated with femoral neck BMD change, no statistically significant predictors were identified, although decreasing BMI showed a trend toward association. Glycemic indices did not differ significantly between the groups.</p><p><strong>Conclusion: </strong>In postmenopausal women with T2DM, BMD remained stable with evogliptin, whereas dapagliflozin was associated with a small reduction in femoral neck BMD, although this finding was weakened after adjustment. These findings provide preliminary evidence regarding the skeletal effects of evogliptin and dapagliflozin and warrant confirmation in larger studies.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov (NCT04706637).</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"618336"},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13652039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Opaganib Protects Against High-Fat Diet-Induced Hypercholesterolemia and Liver Steatosis in Mice.","authors":"Lynn W Maines, Staci N Keller, Ryan A Smith, Charles D Smith","doi":"10.2147/DMSO.S617948","DOIUrl":"https://doi.org/10.2147/DMSO.S617948","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Sphingolipid metabolism is involved in many diseases including cancer, pathologic inflammation, viral infection, neuropathology and metabolic disorders, including obesity and diabetes. Opaganib inhibits the key enzymes sphingosine kinase-2 and dihydroceramide desaturase and has anticancer, anti-inflammatory and antiviral activities in multiple experimental models. Opaganib has been studied in clinical trials with nearly 500 patients having cancer or severe Covid-19 and demonstrated an excellent safety profile. We recently showed that opaganib protects against high-fat diet (HFD)-induced obesity and glucose intolerance in mice. In the present studies, the effects of oral administration of opaganib for 12 weeks to already obese C57BL/6 mice fed HFD were further assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Male C57BL/6 mice were fed Control Diet or HFD for up to 31 weeks. The plasma pharmacokinetics of opaganib given either subcutaneously or orally at doses up to 150 mg/kg and the biodistribution of oral 100 mg/kg opaganib were determined. Additionally, 13-week HFD-fed mice were treated orally with 0 (vehicle) or 100 mg/kg/day, 5 days per week for an additional 12 weeks. Body weights were monitored for the 12-week treatment period, and blood chemistry was assessed at the end of the treatment period. Additionally, livers were harvested after 12 weeks of vehicle or opaganib treatment and were assessed for histological damage and inflammatory cytokine expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Pharmacokinetic analyses demonstrated that plasma opaganib exposure is dose-related with oral 100 mg/kg providing high drug exposure for at least 12 hours. After oral administration, opaganib distributed into all tissues examined (liver, small intestine, kidney and brain) and declined with elimination kinetics similar to those of plasma. Interestingly, the area under the plasma opaganib concentration curve for obese mice was substantially higher than in normal lean mice. As previously reported, opaganib treatment significantly suppressed weight gain in obese mice on HFD Treatment with opaganib also significantly attenuated HFD-induced elevations in plasma cholesterol, albumin and blood urea nitrogen levels, implying improved overall health of the obese mice. Furthermore, opaganib treatment blocked HFD-induced increases in liver weight and reduced microsteatosis and hypertrophy in the livers of mice sacrificed after the 12-week treatment period. Hepatic levels of the proinflammatory cytokines IL-6 and TNFα were also lowered with opaganib treatment but the decreases did not reach statistical significance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Overall, the present studies further support the ability of opaganib to suppress HFD-induced pathologies associated with obesity, hypercholesterolemia and liver steatosis in mice. Because opaganib has already demonstrated excellent safety in human clinical trials, this oral drug has potential for c","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"617948"},"PeriodicalIF":3.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iron-Driven Ferroptosis in Diabetic Kidney Disease: From Molecular Mechanisms to Targeted Therapeutic Translation.","authors":"MengLing Zhang, HongLiang Lv, Shuang Fan, QiNan Wu","doi":"10.2147/DMSO.S638876","DOIUrl":"https://doi.org/10.2147/DMSO.S638876","url":null,"abstract":"<p><p>Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide, and current standard treatments cannot fully halt its progressive decline in renal function. Dysregulated iron metabolism and its downstream induction of ferroptosis - an iron-dependent, lipid peroxidation-driven form of regulated cell death - have now been recognized as a key pathogenic driver of renal injury in DKD. This narrative review systematically synthesizes up-to-date evidence on how aberrant iron uptake, storage and export in renal cells trigger ferroptosis, disrupt antioxidant defenses, and promote renal tubular damage, glomerular sclerosis and interstitial fibrosis. We clearly distinguish mechanistic findings from preclinical in vitro and in vivo studies from clinically validated observations, including emerging ferroptosis-related biomarkers detected in DKD patient cohorts. We further evaluate iron chelation, lipid peroxidation inhibition, and targeted antioxidant reinforcement as promising therapeutic strategies, while explicitly highlighting critical current limitations: the lack of fully validated, kidney-specific ferroptosis biomarkers, insufficient large-scale clinical trial evidence, poor targeted delivery to renal parenchyma, and unresolved safety risks of long-term iron modulation. In conclusion, targeting iron-driven ferroptosis represents a highly promising translational direction for DKD intervention, but rigorous validation of ferroptosis-related biomarkers, optimization of kidney-targeted delivery systems, and well-designed clinical trials are still required before these strategies can be reliably translated into routine clinical practice.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"638876"},"PeriodicalIF":3.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Mass Index and Cerebral Microbleeds in Type 2 Diabetes: Sex-Specific Thresholds from an Exploratory Study.","authors":"Jian Yuan, Yun Deng, Xingyu Chen, Feihong Chen, Linrui Wang, Ning Rong, Desheng Zhu","doi":"10.2147/DMSO.S620529","DOIUrl":"https://doi.org/10.2147/DMSO.S620529","url":null,"abstract":"<p><strong>Objective: </strong>To prospectively investigate the association between baseline body mass index (BMI) and the risk of incident cerebral microbleeds (CMBs) in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM), and to explore potential gender-specific risk thresholds in an exploratory analysis.</p><p><strong>Methods: </strong>This single-center prospective observational cohort study consecutively enrolled T2DM patients without baseline CMBs from April 2022 to March 2023. Baseline demographic, clinical, and biochemical data were collected. BMI was categorized according to Chinese criteria (normal weight BMI < 24 kg/m², overweight 24-28 kg/m², and obesity BMI ≥ 28 kg/m²). All participants underwent follow-up 3.0T magnetic resonance imaging (including susceptibility-weighted imaging sequence) every 12-18 months or earlier if clinically indicated to detect incident CMBs. The primary outcome was the occurrence of ≥1 incident CMBs during follow-up. Cox proportional hazards models were used to calculate hazard ratios (HRs). Restricted cubic spline (RCS) models and two-piecewise linear regression were employed to analyze the nonlinear relationship and threshold effects between BMI and CMBs risk.</p><p><strong>Results: </strong>The study ultimately included 936 T2DM patients without baseline CMBs, with a median follow-up of 30.00 months (range: 6-42 months; IQR: 12.0, 36.0 months). During follow-up, 100 patients (10.68%) developed incident CMBs. Multivariable Cox regression analysis revealed that compared with the normal weight group, the obesity group (BMI ≥ 28 kg/m²) had a significantly higher risk of incident CMBs (HR = 2.58, 95% CI: 1.46-4.54, p < 0.001). Each 1 kg/m² increase in baseline BMI was associated with a 15% increased risk of incident CMBs (HR = 1.15, 95% CI: 1.09-1.22, p < 0.001). Threshold effect analysis showed a nonlinear association between BMI and CMBs risk (p for nonlinearity < 0.001). The exploratory inflection point was 21.10 kg/m² for males; beyond this threshold, each unit increase in BMI increased CMBs risk by 18% (HR = 1.18, 95% CI: 1.10-1.26, p < 0.001). For females, the exploratory inflection point was 26.80 kg/m², beyond which risk increased by 25% per unit increase (HR = 1.25, 95% CI: 1.02-1.54, p = 0.029).</p><p><strong>Conclusion: </strong>In this single-center Chinese cohort, higher baseline BMI was associated with incident CMBs in middle-aged and elderly T2DM patients. Exploratory analysis suggested potential sex-specific inflection points (male: 21.10 kg/m²; female: 26.80 kg/m²). This study may inform future research on gender-differentiated weight management strategies, but these findings are not yet ready for clinical implementation.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"620529"},"PeriodicalIF":3.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic High-Fat Diet Downregulates M3 Muscarinic and β1-Adrenergic Receptor mRNA Expression and Alters Submandibular Gland Histology in Wistar Rats.","authors":"Desiana Fitria, Fifi Veronica, Putri Teesa Radhiyanti, Kartika Indah Sari, Hanna Goenawan","doi":"10.2147/DMSO.S636919","DOIUrl":"https://doi.org/10.2147/DMSO.S636919","url":null,"abstract":"<p><strong>Introduction: </strong>A chronic high-fat diet (HFD) is associated with metabolic disturbances, inflammation, oxidative stress, and functional impairment in several organs. However, its effects on autonomic receptor expression and submandibular gland histology remain insufficiently understood. The submandibular gland contributes 65 to 75% of basal salivary secretion and is central to salivary function. This study aimed to investigate the effect of chronic HFD exposure on M3 muscarinic receptor and β1-adrenergic receptor mRNA expression, as well as histological changes, in the submandibular glands of Wistar rats.</p><p><strong>Methods: </strong>This experimental study used a completely randomized design. Fourteen male Wistar rats were divided into two groups: a normal chow diet control group and an HFD group, with seven rats in each group. The HFD was administered for 21 weeks. Submandibular gland tissues were collected and analyzed for M3 muscarinic receptor and β1-adrenergic receptor mRNA expression using quantitative real-time polymerase chain reaction. Histological examination was performed using hematoxylin and eosin staining, and the mean number of secretory units per field of view was calculated. Data were analyzed using the Shapiro-Wilk normality test followed by an independent <i>t</i>-test.</p><p><strong>Results: </strong>M3 muscarinic receptor mRNA expression was significantly lower in the HFD group than in the control group (0.189 ± 0.057 vs 0.483 ± 0.101; p < 0.001). β1-adrenergic receptor mRNA expression was also significantly reduced in the HFD group compared with the control group (0.067 ± 0.031 vs 0.169 ± 0.071; p = 0.008). Histological analysis showed that the mean number of secretory units per field of view was significantly lower in the HFD group than in the control group (9.84 ± 0.654 vs 13.52 ± 2.171; p = 0.007).</p><p><strong>Conclusion: </strong>Chronic HFD exposure downregulated M3 muscarinic receptor and β1-adrenergic receptor mRNA expression and induced histological alterations in the submandibular glands of Wistar rats. These findings suggest that chronic HFD may affect salivary gland structure and autonomic regulation, providing a potential basis for salivary dysfunction and increased oral health risks. However, further studies incorporating direct functional assessments are needed to confirm its actual impact on saliva secretion.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"636919"},"PeriodicalIF":3.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Deficiency, Inflammatory Biomarkers, and MASLD in Older Adults with Type 2 Diabetes: A Cross-Sectional Study.","authors":"Yuanjun Zhang, Juxiang Liu, Xiang Chang, Haiyan Tai, Jinxing Quan","doi":"10.2147/DMSO.S635338","DOIUrl":"https://doi.org/10.2147/DMSO.S635338","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and metabolic dysfunction-associated steatotic liver disease (MASLD) in older patients with type 2 diabetes mellitus.</p><p><strong>Patients and methods: </strong>This retrospective cross-sectional study included 1044 older patients with T2DM who were treated at the Department of Endocrinology of Gansu Provincial Hospital between April 2021 and June 2024. MASLD was diagnosed by abdominal ultrasonography. Demographic, metabolic, and biochemical data were collected, including high-sensitivity C-reactive protein (hs-CRP), sialic acid (SA), and homocysteine (HCY). Binary logistic regression analysis was performed to assess the independent association between 25(OH)D levels and the presence of MASLD.</p><p><strong>Results: </strong>MASLD was present in 64.0% of participants. Serum 25(OH)D levels were significantly lower in the MASLD group than in the non-MASLD group. After adjusting for age, sex, diabetes duration, body mass index, glycemic parameters, lipid profiles, and inflammatory markers, each 1 ng/mL decrease in 25(OH)D level was associated with 27.6% higher odds of MASLD (odds ratio [OR] = 0.724, 95% confidence interval [CI]: 0.686-0.765, P < 0.001). Receiver operating characteristic (ROC) analysis demonstrated the discriminatory performance of 25(OH)D for MASLD, yielding an area under the curve of 0.856 (95% CI: 0.828-0.884, P < 0.001) and an optimal cutoff value of 19.95 ng/mL.</p><p><strong>Conclusion: </strong>Low serum 25(OH)D levels were independently associated with higher odds of MASLD in older patients with T2DM. Vitamin D status may have potential value for MASLD risk stratification, but prospective studies are required before treatment recommendations can be made.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"635338"},"PeriodicalIF":3.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-Frequency Electroacupuncture versus Sham Electroacupuncture for Diabetic Peripheral Neuropathy: Study Protocol for a Randomized Controlled Trial.","authors":"Nisang Chen, Rongrong Li, Ning Luo","doi":"10.2147/DMSO.S620786","DOIUrl":"https://doi.org/10.2147/DMSO.S620786","url":null,"abstract":"<p><strong>Background: </strong>Diabetic peripheral neuropathy (DPN) is a prevalent and disabling complication, with over 50% of diabetic patients affected. Current pharmacologic therapies are limited by adverse effects, highlighting the need for safer alternatives. Preliminary evidence suggests that low-frequency (2 Hz) electroacupuncture (EA) may be beneficial, but high-quality clinical trials investigating its mechanisms are lacking.</p><p><strong>Methods and analysis: </strong>This prospective, randomized, sham-controlled trial will enroll 92 patients with DPN, who will be randomly allocated in a 1:1 ratio to receive 6 weeks of treatment with either active 2 Hz EA or sham EA. The primary outcomes are overall response rate and lower-limb nerve conduction velocity (NCV). Secondary outcomes include pain intensity assessed using the Visual Analog Scale (VAS), quality of life scores, and serum biomarkers measured by enzyme-linked immunosorbent assay (ELISA), namely nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). All statistical analyses will be conducted according to the intention-to-treat (ITT) principle.</p><p><strong>Conclusion: </strong>This study is expected to provide clinical and mechanistic evidence for the potential role of standardized low-frequency EA as a non-pharmacological treatment option for DPN.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT07551726.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"620786"},"PeriodicalIF":3.5,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13634316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}