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

{"title":"Inflammation Mediates the Relationship Between Serum Uric Acid and New-Onset Diabetes Risk in Patients with Coronary Heart Disease: Results from a Multicenter Cohort Study [Letter].","authors":"Liping Wei, Rong Zhao, Yanyan Song","doi":"10.2147/DMSO.S635777","DOIUrl":"https://doi.org/10.2147/DMSO.S635777","url":null,"abstract":"","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"635777"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165441","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":"Adipocytokines as Pathogenic Mediators and Therapeutic Targets in Metabolic Syndrome-Related Cardiocerebrovascular Events.","authors":"Yue Wu, Jialin Zhong, Xiaodan Yan, Lin Jin, Yunjiao Yang, Qiu Chen","doi":"10.2147/DMSO.S627279","DOIUrl":"https://doi.org/10.2147/DMSO.S627279","url":null,"abstract":"<p><p>Metabolic syndrome (MS), characterized by central obesity, hyperglycemia, hypertension, and dyslipidemia, substantially increases the risk of cardiovascular and cerebrovascular events. Adipose tissue is an active endocrine organ, and dysregulated adipokine secretion may contribute to the link between MS and vascular injury. In this narrative review, we synthesize evidence on adipokines implicated in MS-related cardiocerebrovascular disease and discuss their therapeutic potential. Adiponectin, fibroblast growth factor 21 (FGF21), and omentin are generally associated with improved insulin sensitivity, lipid handling, and endothelial homeostasis, whereas leptin, resistin, tumor necrosis factor-α, and interleukin-6 can promote inflammation and endothelial dysfunction through pathways including NF-κB and JAK/STAT. However, these associations may be modified by obesity, insulin resistance, disease stage, and other confounding factors, and some adipokines, such as adipsin, show context-dependent effects. Current translational evidence is strongest for strategies targeting adiponectin/FGF21 signaling and IL-1/IL-6-related inflammatory pathways, while evidence for cerebrovascular outcomes remains limited. Adipokine-directed interventions therefore remain promising but require rigorous clinical validation and disease-specific stratification.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"627279"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166788","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":"Research Progress on Artificial Intelligence in the Management of Diabetic Foot Ulcers.","authors":"Jinxia Du, Xiaoli Liu, Guihui Wu, Yin Huang, Yan Zhang, Xiang Long, Xiaoyi Yang, Yan Zhou","doi":"10.2147/DMSO.S637013","DOIUrl":"https://doi.org/10.2147/DMSO.S637013","url":null,"abstract":"<p><p>As a typical chronic complication of diabetes, the management of diabetic foot ulcers has long faced multiple challenges, including the highly subjective nature of wound assessment, patients'limited capacity for self-care at home, and the difficulty in predicting healing outcomes. The emergence of artificial intelligence (AI) technology offers new approaches to addressing these challenges. Based on recent domestic and international literature, this paper systematically reviews the research progress of artificial intelligence in the care of diabetic foot ulcers, focusing on four key dimensions: intelligent wound assessment (eg deep learning-based image analysis models achieving an F1 score of 93.1% for infection identification and 92.8% accuracy for area assessment), patient self-health management (eg mobile health applications and wearable monitoring devices), the development and application of smart dressings (eg responsive biomaterials and sensor integration), and the prediction of healing trends (eg machine learning prediction models, with support vector machines achieving 85.3% accuracy and an AUC of 0.922 in predicting complete DFU healing). It summarizes key technological achievements and the current status of clinical translation, provides an in-depth analysis of existing shortcomings (including insufficient algorithm generalizability, lack of prospective clinical validation, and absence of data standardization), and outlines future development directions (encompassing multimodal integration, explainable artificial intelligence, and implementation science research), with the aim of offering guidance for the further application of artificial intelligence technology in the field of chronic wound care.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"637013"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170577","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":"Development of a Non-Invasive Prediction Model for MASLD Using Routine Clinical and Biochemical Markers: A Retrospective Study.","authors":"Lidan Dong, Jialian Zheng","doi":"10.2147/DMSO.S617442","DOIUrl":"https://doi.org/10.2147/DMSO.S617442","url":null,"abstract":"<p><strong>Purpose: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a leading chronic liver condition associated with obesity and metabolic syndrome. Practical non-invasive models based on commonly available clinical and biochemical indicators may support risk stratification in health-check settings.</p><p><strong>Methods: </strong>This retrospective observational study included 8181 adults who underwent routine health examinations at the Health Examination Center of The First Hospital of Jiaxing from January 2024 to November 2024, including 4814 participants without MASLD and 3367 participants with ultrasound-reported hepatic steatosis after exclusion of secondary causes. Baseline comparisons, univariable logistic regression, multivariable logistic regression, Spearman correlation analysis, receiver operating characteristic (ROC) analysis, multicollinearity assessment, calibration assessment, and five-fold cross-validation were performed.</p><p><strong>Results: </strong>In the final model, older age, overweight, obesity, higher triglycerides, higher alanine aminotransferase, and higher uric acid were associated with higher odds of MASLD, whereas vitamin K was inversely associated with MASLD after adjustment. The final equation was logit(P) = -6.5363 + 0.0387 × age + 1.3838 × overweight + 2.6166 × obesity - 1.6016 × underweight + 1.0122 × triglycerides + 0.0267 × ALT + 0.0048 × uric acid - 0.1784 × vitamin K. The model achieved an AUC of 0.894 (95% CI 0.888-0.901). At the Youden-index cutoff of 0.402, sensitivity was 0.819 and specificity was 0.811. Five-fold cross-validation yielded a mean AUC of 0.894.</p><p><strong>Conclusion: </strong>A prediction model based on routine clinical and biochemical markers showed good discrimination for MASLD status in a single-center health examination cohort. Vitamin K was identified as an inversely associated exploratory marker, but this association should be interpreted cautiously and requires prospective and external validation before clinical or interventional conclusions can be drawn.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"617442"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164749","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":"Digital Health Interventions for Weight Management in Older Adults with Overweight or Obesity: A Scoping Review.","authors":"Lin Li, Keke Ren, Huanhuan Huang, Yangyang Hu, Yue Xiang, Xilin Yang, Qinghua Zhao","doi":"10.2147/DMSO.S641439","DOIUrl":"https://doi.org/10.2147/DMSO.S641439","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to systematically map the application of digital health interventions (DHIs) in weight management among older adults with overweight or obesity, identify knowledge gaps from the perspective of this population, and provide targeted evidence for the design and implementation of future age-friendly interventions.</p><p><strong>Methods: </strong>This scoping review followed the framework proposed by Arksey and O'Malley and was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). A systematic search was conducted in six databases-PubMed, Web of Science, Embase, Cochrane Library, CINAHL, and PsycINFO-from database inception to May 31, 2026. A total of 16 studies were ultimately included.</p><p><strong>Results: </strong>The included studies were published between 2012 and 2026 and involved a total of 1854 older adults with overweight or obesity; most studies were conducted in the United States. Regarding methodological quality, 25.00% of studies were high-quality RCTs, 31.25% were of moderate-to-high quality, and 43.75% were of poor quality owing to single-arm designs. DHIs used diverse technological carriers, which were categorized into communication modalities, sensing and monitoring devices, user-facing applications, and management platforms. Intervention content was diverse, predominantly comprising combined dietary and exercise interventions and supplemented by multiple BCTs, including action planning, instruction on how to perform the behavior, self-monitoring, feedback on behavior, and social support. Outcomes were multidimensional, encompassing objective clinical and physiological measures, physical function and frailty measures, health behavior measures, patient-reported outcomes (PROs) and psychosocial measures, and feasibility and acceptability measures.</p><p><strong>Conclusions: </strong>DHIs for weight management in older adults with overweight or obesity are characterized by diverse technological carriers, multifaceted intervention content, and multidimensional outcomes. Future efforts should focus on participatory age-friendly design involving older adults, development of a core outcome set (COS), and integration of emerging technologies to improve the precision, sustainability, and scalability of interventions.</p>","PeriodicalId":11116,"journal":{"name":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","volume":"19 ","pages":"641439"},"PeriodicalIF":3.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165050","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":"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}