World Journal of Diabetes最新文献

{"title":"Reevaluating the relationship between COVID-19 and type 1 diabetes mellitus: Methodological considerations.","authors":"Er-Min Liang, Hong-Cheng Luo","doi":"10.4239/wjd.v16.i11.112939","DOIUrl":"10.4239/wjd.v16.i11.112939","url":null,"abstract":"<p><p>A recent nationwide cohort study reported an increased incidence and altered seasonality of type 1 diabetes mellitus (T1DM) during the coronavirus disease 2019 (COVID-19) pandemic. The study found that new-onset T1DM cases were significantly higher during the pandemic than in prior years, and the typical winter peak in T1DM diagnoses was blunted. This occurred alongside markedly reduced circulation of other respiratory viruses under lockdown measures. Carmon <i>et al</i> noted weak positive correlations between T1DM incidence and certain viruses (<i>e.g.</i>, influenza and respiratory syncytial virus), suggesting that reduced exposure to common infections - and possibly severe acute respiratory syndrome coronavirus 2 infection itself - might have contributed to the rise in T1DM. To highlight key methodological limitations of that study, which may affect the interpretation of the findings. We reviewed the study design and data of Carmon <i>et al</i> and discussed potential biases, including ecological inference, confounding factors, delayed diagnoses, lack of COVID-19-stratified analysis, and biases in viral surveillance data, supported by recent literature. The association observed by Carmon <i>et al</i> is at risk of ecological fallacy due to the absence of individual infection linkage. Uncontrolled confounders (healthcare access, socioeconomic changes) and not stratifying by COVID-19 infection status limit causal inference. Pandemic-related diagnostic delays likely inflated apparent T1DM incidence, as evidenced by higher rates of diabetic ketoacidosis in new cases. Biases in virological testing data (reduced testing and non-representative sampling) complicate conclusions about \"reduced\" viral circulation. The pandemic's impact on T1DM incidence is important but requires cautious interpretation. Future studies should employ individual-level analyses, adjust for confounders, distinguish true incidence increases from diagnostic delays, stratify by infection status, and use comprehensive viral exposure data to draw more robust conclusions.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"112939"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589579","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 tailored exercise on glycemic and nutritional outcomes in diabetic patients with colorectal cancer and on chemotherapy.","authors":"Lin Yang, Xian-Ping Liu, Xiao-Meng Deng","doi":"10.4239/wjd.v16.i11.111008","DOIUrl":"10.4239/wjd.v16.i11.111008","url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide and a frequent comorbidity among these patients is type 2 diabetes mellitus (T2DM). The coexistence of these conditions poses significant challenges to glycemic management, particularly during chemotherapy.</p><p><strong>Aim: </strong>To assess the effects of individualized exercise training (IET) on glycemic control and nutritional status in patients with T2DM undergoing chemotherapy for CRC.</p><p><strong>Methods: </strong>In this retrospective study, clinical data from 245 patients with T2DM and on chemotherapy for CRC between November 2023 and December 2024 were analyzed. Patients were stratified into two groups according to their treatment regimens: The standard care (SC) group (<i>n</i> = 111), which received conventional chemotherapy and diabetes management, and an IET group (<i>n</i> = 134), which received additional personalized exercise interventions alongside SC. Parameters assessed included fasting plasma glucose, glycosylated hemoglobin, glycemic variability indices, nutritional biomarkers, markers of intestinal permeability, and adverse events.</p><p><strong>Results: </strong>Patients in the IET group demonstrated significant improvements in glycemic control, nutritional biomarkers, and glycemic variability (all <i>P</i> < 0.05), compared with the SC group. The markers of intestinal permeability also improved significantly in the IET group (<i>P</i> < 0.05). Meanwhile, no statistically significant difference in the incidence of adverse events was found between the two groups (<i>P</i> > 0.05). These findings suggest that individualized exercise interventions can enhance metabolic, nutritional, and gastrointestinal outcomes without increasing treatment-related risks.</p><p><strong>Conclusion: </strong>Personalized exercise training may offer clinically meaningful benefits in glycemic regulation and nutritional status for patients with T2DM and on chemotherapy for CRC.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111008"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12666341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662408","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":"Comparison of three types of drugs for cardiovascular and renal benefits in type 2 diabetes mellitus.","authors":"Xue-Dong An, Xin-Qin Li, He Zhang, Qian-You Jia, Yue-Hong Zhang, Gui-Gui Yang","doi":"10.4239/wjd.v16.i11.111280","DOIUrl":"10.4239/wjd.v16.i11.111280","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM), one of the most common chronic metabolic diseases, is also one of the most significant risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD).</p><p><strong>Aim: </strong>To conduct a systematic review and network meta-analysis of cardiovascular (CV) and renal benefits of glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) in T2DM patients.</p><p><strong>Methods: </strong>We searched four databases-PubMed, EMBASE, Cochrane Library, and Web of Science- for publications from inception to March 6, 2025. Total 500 participants were enrolled and had an intervention period of at least one year (or 52 weeks). Eligible studies included adult patients with T2DM and interventions with a placebo or another GLP-1RA, SGLT2i, or nsMRA. Data were standardized using Stata 17.0 software. The quality of evidence was assessed using the CINeMA and GRADE approaches.</p><p><strong>Results: </strong>Total 14970 articles were retrieved, of which 25 high-quality studies were included for the systematic review and network meta-analysis, covering 189797 patients and three drug classes (14 drugs). Network meta-analysis revealed low heterogeneity, thus ensuring reliable results. Meta-regression analysis indicated that baseline factors, such as comorbidities and blood glucose levels, did not affect our results. Overall, all included drugs demonstrated significant CV and renal benefits compared with the placebo. nsMRA showed the best efficacy in reducing the incidence of major adverse CV events and myocardial infarction. SGLT2i were most effective in reducing all-cause mortality, CV mortality, and the incidence of renal outcomes. GLP-1RA showed the greatest benefits in reducing the incidence of stroke. SC-semaglutide had the most significant effect on reducing major adverse CV events, oral semaglutide was most effective in reducing all-cause mortality and CV mortality, empagliflozin had the strongest effect in reducing composite renal outcomes and renal replacement therapy, canagliflozin was most effective in slowing the progression of proteinuria, and dapagliflozin showed the most significant reduction in end-stage renal disease.</p><p><strong>Conclusion: </strong>T2DM, as one of the most common chronic metabolic diseases, is also one of the most significant risk factors for CVD and CKD. GLP-1RA, SGLT2i, and nsMRAs have emerged as novel therapeutic agents to comprehensively manage T2DM-related CVD and CKD. We conducted a network meta-analysis to compare the efficacy and safety of GLP-1RAs, SGLT2i, and nsMRA in patients with T2DM.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111280"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635768/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589331","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":"Crosstalk between oxidative stress and inflammatory pathways: Natural therapeutic approaches for diabetic wound healing.","authors":"Yan-Ling Guo, Wen-Jing Niu, Hao-Ran Jiao, Yun-Ping Li, Chuan Xu, Xin Zhou, Jun Wang","doi":"10.4239/wjd.v16.i11.111400","DOIUrl":"10.4239/wjd.v16.i11.111400","url":null,"abstract":"<p><p>Oxidative stress and inflammation are closely interrelated processes that are pivotal to the impaired wound healing associated with diabetes. Chronic hyperglycemia in diabetic patients induces excessive reactive oxygen species (ROS) production, which triggers heightened inflammatory responses. The resulting inflammation exacerbates oxidative damage, delays wound closure, and intensifies tissue injury, thereby creating a detrimental cycle that disrupts normal wound healing. Recent research has increasingly focused on the therapeutic potential of natural products in modulating oxidative stress and inflammation to enhance diabetic wound healing. Natural compounds, such as polyphenols, flavonoids, and terpenoids, have demonstrated significant efficacy in reducing oxidative damage and modulating inflammatory pathways. These bioactive agents exhibit potent antioxidant activity by scavenging ROS and enhancing endogenous antioxidant defenses while concurrently inhibiting the release of proinflammatory cytokines. Additionally, natural therapies have been shown to promote angiogenesis, enhance collagen synthesis, and improve fibroblast function, further facilitating wound repair. This review provides insights into the complex interplay between oxidative stress and inflammation in diabetic wound healing and evaluates the therapeutic potential of natural products as adjunctive treatments. Further clinical investigations are essential to validate the efficacy and safety of these natural interventions for diabetic wound management.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111400"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589388","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":"N7-methylguanosine-related gene decapping scavenger enzymes as a novel biomarker regulating epithelial cell function in diabetic foot ulcers.","authors":"Fu-Gang Xiao, Zhou Yang, Shi-Yan Yu, Qin Li, Peng-Cheng Huang, Guang-Bin Huang, Xiao-Gang Li, Jun-Lin Ran, Shun-Li Rui, Wu-Quan Deng","doi":"10.4239/wjd.v16.i11.109455","DOIUrl":"10.4239/wjd.v16.i11.109455","url":null,"abstract":"<p><strong>Background: </strong>Chronic nonhealing wounds, such as diabetic foot ulcer (DFU), suffer from delayed healing. Identifying effective biomarkers or targets is crucial for managing these refractory wounds. While N7-methylguanosine (m7G) methylation is important in RNA modification, its connection to chronic nonhealing wounds is poorly understood.</p><p><strong>Aim: </strong>To assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.</p><p><strong>Methods: </strong>Differential expression analysis and weighted gene coexpression network analysis identified key genes in DFU. Hub genes were determined through m7G-DFU intersection, and gene set enrichment analysis was conducted. Diagnostic potential of hub genes was assessed using receiver operating characteristic curves. The hub gene's expression (decapping scavenger enzyme, <i>DCPS</i>) was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence. <i>In vitro,</i> normal human epidermal keratinocyte models were knocked down for <i>DCPS</i>, and the function was assessed through flow cytometry, western blotting, immunofluorescence, Transwell assays, and scratch assays.</p><p><strong>Results: </strong>Weighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes, identifying hub gene <i>DCPS</i> as a candidate biomarker. Notably, its diagnostic value was confirmed with a test set and receiver operating characteristic curve, achieving an area under the curve of 0.98 and 0.99. Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of <i>DCPS</i> in the wound skin of DFU patients and streptozotocin-induced diabetic mice, indicating its role as a regulatory factor of m7G in diabetic wounds. Mechanistically, <i>in vitro</i> studies showed that <i>DCPS</i> knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression, disrupted the epithelial cell cycle, inhibited cell proliferation and migration, and increased apoptosis rates.</p><p><strong>Conclusion: </strong>DCPS was identified as a promising DFU biomarker and therapeutic target, regulating m7G to affect cell cycle, proliferation, and epithelial cell migration during DFU wound healing.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"109455"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589449","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":"Optimizing adipose-derived stem cell therapy for diabetic foot ulcers.","authors":"Jing Cao, Zi-Chao Liu, Wen-Qiang An, Sen Zhang, Xin Zhang, Li-Jie Li, Hai-Lian Ji, Xiao Long, Yue-Mei Yang","doi":"10.4239/wjd.v16.i11.109859","DOIUrl":"10.4239/wjd.v16.i11.109859","url":null,"abstract":"<p><strong>Background: </strong>Diabetic foot ulcers (DFUs) are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing. Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising therapeutic option for DFUs because of their angiogenic, immunomodulatory, and regenerative properties. However, studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.</p><p><strong>Aim: </strong>To investigate the dose-response relationship, the optimal administration route, persistence, and molecular mechanisms of ADSCs in DFU healing.</p><p><strong>Methods: </strong>In this study, human ADSCs were isolated and cultured, and their differentiation potential was characterized. A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly. Wound closure rate, angiogenesis, inflammation, and collagen deposition were assessed in the ADSC-treated and model groups. Additionally, <i>in vitro</i> experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.</p><p><strong>Results: </strong>ADSC treatment significantly enhanced wound closure, promoted angiogenesis, modulated inflammatory responses, and accelerated tissue regeneration in the DFU model. Notably, the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route, with subcutaneous injection of 5 × 10⁵ ADSCs yielding the most favorable outcomes, particularly when injected into the feet, which resulted in prolonged retention. <i>In vitro</i> experiments further revealed that ADSCs exert their therapeutic effects <i>via</i> multiple mechanisms, including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion, thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.</p><p><strong>Conclusion: </strong>ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds. These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"109859"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589485","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":"Nephroprotective mechanism of Kunkui Baoshen decoction in diabetic kidney disease: Targeting the HERC2/NCOA4-mediated autophagy-dependent ferroptosis pathway.","authors":"Si-Yuan Song, Chu-Chu Shan, Pei-Pei Zhou, Wei-Long Xu, Ying Tan, Xi-Qiao Zhou, Li-Ji Huang, Qian-Hua Yan, Jiang-Yi Yu","doi":"10.4239/wjd.v16.i10.109568","DOIUrl":"10.4239/wjd.v16.i10.109568","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) stands as the key contributor to chronic kidney disease worldwide. Clinical studies have shown that Kunkui Baoshen decoction (KKBS) effectively reduces proteinuria and enhances renal function in DKD patients. However, its precise molecular targets and therapeutic mechanisms remain to be thoroughly clarified.</p><p><strong>Aim: </strong>To evaluate the nephroprotective efficacy of KKBS in DKD and explore the underlying mechanisms of action.</p><p><strong>Methods: </strong>Liquid chromatography-tandem mass spectrometry was utilized to analyze the chemical constituents of KKBS. Metabonomic and transcriptomic analyses were conducted to identify key targets and pathways associated with the therapeutic effects of KKBS on DKD. The nephroprotective effects of KKBS were assessed both in high glucose-induced human kidney-2 cells and in db/db mice. A variety of assays were performed, including Cell Counting Kit-8, Western blot, quantitative reverse transcription-polymerase chain reaction, immunofluorescence, co-immunoprecipitation, periodic acid-Schiff staining, Masson staining, hematoxylin and eosin staining, immunohistochemistry, and mitochondrial morphology analysis.</p><p><strong>Results: </strong>The glutathione metabolic pathway emerged as the most prominent metabolic pathway in the metabonomic analysis of KKBS. Transcriptomic and bioinformatic analyses revealed that nuclear receptor coactivator 4 (NCOA4) was instrumental in regulating ferroptosis within renal tubules of mice with DKD. Both <i>in vitro</i> and <i>in vivo</i> experiments showed that KKBS ameliorated renal dysfunction, mitigated renal tissue damage, and repressed the expression of autophagy-dependent ferroptosis markers and inflammatory fibrosis. Mechanistically, KKBS enhanced the interaction between the homologous to E6-AP C-terminus and RCC1-like domain-containing E3 ubiquitin protein ligase (HERC2) and NCOA4, leading to K48-related ubiquitination and subsequent degradation of NCOA4. This process inhibited autophagy-dependent ferroptosis, reduced the release of pro-fibrotic inflammatory factors, and ultimately exerted an anti-fibrotic effect in DKD.</p><p><strong>Conclusion: </strong>KKBS confers nephroprotection in DKD by modulating HERC2/NCOA4-mediated autophagy-dependent ferroptosis, thereby alleviating renal fibrosis.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 10","pages":"109568"},"PeriodicalIF":4.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330472","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":"Advances in gestational diabetes mellitus screening: Emerging trends and future directions.","authors":"Didem Kaymak, Ayse Seval Ozgu-Erdinc","doi":"10.4239/wjd.v16.i10.111309","DOIUrl":"10.4239/wjd.v16.i10.111309","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) is a multifactorial metabolic disorder first recognized during pregnancy, with rising global prevalence and significant implications for both maternal and neonatal outcomes. This review provides a comprehensive synthesis of current diagnostic strategies, including standard screening protocols such as the one-step and two-step oral glucose tolerance tests, and evaluates their limitations in terms of sensitivity, timing, and practicality. The complex pathogenesis of GDM-centered on β-cell dysfunction, insulin resistance, adipose tissue dysregulation, placental transport abnormalities, and neurohormonal imbalance-is explored in detail, highlighting the interplay of metabolic, inflammatory, and epigenetic mechanisms. Particular emphasis is placed on the emerging role of predictive biomarkers, encompassing metabolic, inflammatory, placental, urinary, and genetic indicators. These biomarkers, including adipokines, angiogenic factors, and microRNAs, offer promising avenues for early identification of at-risk individuals prior to the onset of hyperglycemia. The review also assesses recent advances in machine learning-based risk prediction models, which have demonstrated superior accuracy over traditional algorithms and may facilitate personalized screening and management strategies. Despite encouraging findings, challenges such as biomarker standardization, ethnic variability, and model validation persist. This review underscores the necessity for integrated, multi-omic, and patient-centered approaches to optimize GDM prediction, early diagnosis, and long-term risk reduction for both mother and child.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 10","pages":"111309"},"PeriodicalIF":4.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330554","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":"Exosomal transfer of miR-375-3p from pancreatic β cells to hepatocytes impairs hepatic glycogenesis <i>via</i> Rbpj repression.","authors":"Fang-Zhi Xu, Lin Dou, Xi Wu, Chen-Xi Xia, Dong-Ni Yu, Yong Man, Tao Shen, Xiu-Qing Huang","doi":"10.4239/wjd.v16.i10.109815","DOIUrl":"10.4239/wjd.v16.i10.109815","url":null,"abstract":"<p><strong>Background: </strong>Glucotoxic pancreatic β cells impair glycogenesis of hepatocytes, with exosomes serving as novel mediators. miR-375-3p is the most abundant miRNA in the pancreas and critical for β-cell function, but whether it plays a role in pancreas-liver crosstalk remains unclear.</p><p><strong>Aim: </strong>To investigate the role of miR-375<i>-</i>3p, a key regulator of pancreatic β cells, in remotely regulating hepatocyte glycogenesis <i>via</i> exosomes.</p><p><strong>Methods: </strong>Mice fed a high-fat diet (HFD) served as animal models, and mouse primary pancreatic islet cells and the β-cell line MIN-6 were used as cellular models. miR-375<i>-</i>3p expression in pancreatic cells, hepatocytes and exosomes was detected in both animal and cellular models. Transwell assays, exosome treatment, and exosome-depleted supernatant culture were used to investigate the role of exosomal miR-375-3p in pancreatic-hepatocyte crosstalk. The AKT/GSK signaling pathway and hepatic glycogen content were used as indicators to evaluate hepatocyte glycogenesis. Luciferase reporter assays were used to evaluate the downstream targets of miR-375-3p.</p><p><strong>Results: </strong>Increased levels of miR-375-3p were observed in both the pancreas and liver of HFD-fed mice. In contrast to the <i>in vivo</i> results, high-glucose treatment exclusively increased the expression of miR-375-3p in pancreatic cells but had no effect on hepatocytes. Furthermore, hepatocytes treated with the supernatant and exosomes from glucotoxic pancreatic cells presented elevated expression of miR-375-3p. Additionally, exosomal transfer of miR-375-3p from pancreatic cells to hepatocytes suppressed the AKT/GSK signaling pathway, thereby reducing the hepatic glycogen content. Luciferase analysis indicated that the recombination signal binding protein for the immunoglobulin kappa J region (Rbpj) is a target gene of miR-375-3p. Rbpj inhibition impaired hepatic glycogenesis, and Rbpj overexpression reversed the effect on glycogenesis induced by miR-375<i>-</i>3p.</p><p><strong>Conclusion: </strong>Pancreatic cell-derived miR-375<i>-</i>3p can be delivered to hepatocytes <i>via</i> exosomes and inhibits hepatocyte glycogenesis by targeting Rbpj.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 10","pages":"109815"},"PeriodicalIF":4.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330579","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":"Blood glucose variability impacts heart rate dynamics in older type 2 diabetic and coronary heart disease patients.","authors":"An-Qi Li, Feng Zhang","doi":"10.4239/wjd.v16.i10.110722","DOIUrl":"10.4239/wjd.v16.i10.110722","url":null,"abstract":"<p><strong>Background: </strong>Cardiac autonomic neuropathy correlates intimately with cardiovascular complications and unexpected death. It is a typical clinical abnormality seen in coronary artery disease-affected individuals with concurrent type 2 diabetes mellitus (T2DM). Moreover, blood glucose (BG) variability has been clinically shown to induce cardiovascular events and sudden death.</p><p><strong>Aim: </strong>To investigate how BG variability impacts heart rate (HR) dynamics in older adults with T2DM + coronary heart disease (CHD) and to evaluate the ability of functional myocardial ischemia to predict outcomes in this cohort.</p><p><strong>Methods: </strong>We enrolled 143 older T2DM + CHD patients admitted to the First Affiliated Hospital, Hengyang Medical School, University of South China over a 3.5-year period (January 2018 to July 2021). Using a standard deviation of BG cutoff of 1.4 mmol/L, subjects were stratified into abnormal (<i>n</i> = 75) and normal (<i>n</i> = 68) fluctuation groups. All patients underwent 72-hour dynamic BG monitoring to detect BG fluctuation parameters. The time domain index of HR variability was measured by dynamic electrocardiogram. To determine how well glucose fluctuation measures predicted functional myocardial ischemia, the area under the receiver operating characteristic curve (AUC) was calculated.</p><p><strong>Results: </strong>The abnormal fluctuation group showed greater levels of mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), largest amplitude of glycemic excursions (LAGE), and mean postprandial glucose excursions (MPPGE) relative to the normal group (<i>P</i> < 0.05), along with lower levels of standard deviation of normal-to-normal (NN) interval (SDNN), standard deviation of the average NN interval (SDANN), standard deviation of NN intervals over every 5-minute period (SDNNindex), root mean square of successive differences (rMSSD), and percentage of NN intervals differing by > 50 ms (pNN50; <i>P</i> < 0.05). Pearson correlation analysis showed that MAGE, MODD, LAGE, and MPPGE were negatively correlated with SDNN, SDANN, SDNNindex, rMSSD, and pNN50 in older patients with T2DM complicated by CHD (<i>P</i> < 0.05). The AUC of MAGE combined with MPPGE in predicting the occurrence of functional myocardial ischemia was 0.912, which was significantly higher than 0.694 of SDNN (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>A negative correlation was found between BG variability and HR dynamics in older CHD + T2DM patients, and MAGE combined with MPPGE demonstrated better efficacy in predicting functional myocardial ischemia, which deserves clinical attention.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 10","pages":"110722"},"PeriodicalIF":4.6,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12531670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330610","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}