World Journal of Diabetes最新文献

{"title":"Targeting N-methyl-D-aspartate 2B receptor in painful diabetic neuropathy - mechanisms, challenges, and emerging therapeutics.","authors":"Nayab Khalid, Nazlahshaniza Shafin, Idris Long, Hidani Hasim, Che Aishah Nazariah Ismail","doi":"10.4239/wjd.v17.i1.110108","DOIUrl":"https://doi.org/10.4239/wjd.v17.i1.110108","url":null,"abstract":"<p><p>A notable number of patients with diabetes suffer from painful diabetic neuropathy (PDN), which is a debilitating complication of diabetes mellitus. Prolonged hyperglycaemia and metabolic dysregulation lead to PDN, a condition characterised by chronic pain, sensory dysfunction, and reduced quality of life. Although various treatment options are available, clinical management is challenging due to the complex and multifactorial nature of PDN pathophysiology. N-methyl-D-aspartate receptors (NMDARs), particularly the NR2B subtype (NMDAR-2B), have emerged as a key player in the pathophysiology of chronic pain states, including PDN. This review highlights the mechanistic NMDAR-2B involvement in the pathophysiology of PDN, focusing on its upregulation role in pain-processing regions, interaction with inflammatory mediators, glia-derived mediators, and oxidative stress mechanisms. Advancements in targeting NMDAR-2B as a mechanistically driven approach to PDN management also offer potential in enhancing the therapeutic efficacy of NMDAR-2B. Consequently, this review provides a novel perspective on understanding the role of NMDAR-2B in PDN for the future development of effective treatment strategies for managing the condition.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"17 1","pages":"110108"},"PeriodicalIF":4.6,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12836031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094492","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":"Addressing the dual challenge: Managing smoking cessation in patients with diabetes.","authors":"Cristina Russo, Magdalena Walicka, Gal Cohen, Carlo Maria Bellanca, Giulio Geraci, Pasquale Caponnetto, Dario Elvio Noviello, Roberta Chianetta, Jacob George, Roberta Sammut, Eward Franek, Riccardo Polosa","doi":"10.4239/wjd.v16.i12.105241","DOIUrl":"10.4239/wjd.v16.i12.105241","url":null,"abstract":"<p><p>Smoking increases complications and mortality in people with diabetes. Quitting delivers major benefits, but physiological (weight gain, insulin sensitivity shifts) and psychological barriers make cessation harder in this group. Our review article examined strategies tailored to people with diabetes. All smokers with diabetes should receive clear, personalized advice to quit, embedded in routine care. Among the available medications, varenicline has the strongest evidence in this population. Nicotine replacement therapy and bupropion may help but have limited diabetes-specific data, so they should be used with caution. Tobacco harm reduction (e-cigarettes, heated tobacco products) may facilitate switching away from combustible cigarettes and reduce exposure, although the long-term safety and efficacy in diabetes remain uncertain. Glucagon-like peptide-1 receptor agonists can aid weight and glycemic control and may indirectly support cessation. Digital tools (apps, wearables, and remote monitoring) offer real-time support and adherence tracking, although diabetes-specific effectiveness is still being established. Smoking cessation in people with diabetes requires urgent attention. Evidence-based interventions should be integrated into routine care, with particular attention given to early monitoring of glucose, body weight, and blood pressure after quitting, plus structured follow-up. More research should develop and test tailored, long-term strategies for this high-risk group, including pragmatic trials integrating harm reduction and digital support.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"105241"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890385","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":"Methylation status of leptin gene promoter in relatively lean Chinese adults with prediabetes and type 2 diabetes mellitus.","authors":"Shi-Qi Sun, Sheng-Ze Liang, Qi Huang, Jia-Zhong Sun","doi":"10.4239/wjd.v16.i12.112789","DOIUrl":"10.4239/wjd.v16.i12.112789","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic regulation of leptin (LEP) plays a critical role in metabolic disorders, yet its promoter methylation patterns in lean diabetic populations remain poorly characterized. Emerging evidence suggests DNA methylation may precede clinical hyperglycemia, offering potential for early risk stratification. While obesity-associated LEP methylation is well-studied, lean Asian populations who exhibit high diabetes prevalence despite lower adiposity, represent an underexplored cohort. This study hypothesizes that LEP promoter methylation in peripheral leukocytes decreases progressively from normoglycemia to prediabetes and type 2 diabetes mellitus (T2DM), correlating inversely with serum LEP levels in lean Chinese adults [body mass index (BMI) < 24 kg/m²].</p><p><strong>Aim: </strong>To investigate LEP promoter methylation status and its association with serum LEP levels across glycemic states in lean Chinese adults.</p><p><strong>Methods: </strong>We enrolled 392 participants including 120 normoglycemic controls, 94 prediabetes [44 impaired fasting glucose (IFG)/50 impaired glucose tolerance (IGT)], 178 T2DM aged 40-60 years with BMI < 24 kg/m². Genomic DNA from peripheral leukocytes underwent bisulfite conversion followed by methylation-specific PCR to assess CpG methylation in the LEP promoter. Serum LEP was quantified <i>via</i> enzyme-linked immunosorbent assay, with other parameters measured through standard assays. Statistical analyses included analysis of variance, <i>χ</i>² tests, and Pearson correlation (Bonferroni-corrected <i>P</i> value).</p><p><strong>Results: </strong>Methylation frequencies declined progressively: 59.2% (controls) reduced to 43.6% (prediabetes; IFG: 38.6%, IGT: 48%) reduced to 31.5% (T2DM) (all <i>P</i> < 0.05 <i>vs</i> controls; T2DM <i>vs</i> IGT: <i>P</i> = 0.030). Serum LEP levels increased significantly in T2DM (16.94 ± 4.19 μg/L) <i>vs</i> controls (11.33 ± 3.10 μg/L; <i>P</i> = 0.002), with intermediate values in prediabetes (IFG: 13.79 ± 3.32 μg/L; IGT: 12.62 ± 4.81 μg/L). A near-perfect inverse correlation between methylation and LEP levels was observed (<i>r</i> = -0.95, 95%CI: -0.97 to -0.92, <i>P</i> < 0.001), persisting after adjusting for age and BMI (<i>β</i> = -0.91, <i>P</i> < 0.001).</p><p><strong>Conclusion: </strong>LEP promoter hypomethylation parallels worsening glycemic status in lean Chinese adults, suggesting its potential as a blood-based epigenetic biomarker for diabetes progression, pending validation in longitudinal cohorts.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"112789"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889647","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":"Effect of glucagon-like peptide-1 receptor agonists on gastric mucosal visibility during upper endoscopy in Asian patients with diabetes.","authors":"Young Eun Oh, Tae-Se Kim, Sang Ah Chi, Hyun Jung Park, Yang Won Min, Hyuk Lee, Jun Haeng Lee, Poong-Lyul Rhee, Jae J Kim, Byung-Hoon Min","doi":"10.4239/wjd.v16.i12.112694","DOIUrl":"10.4239/wjd.v16.i12.112694","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly being used to treat type 2 diabetes mellitus (T2DM) and obesity. Although GLP-1RAs delay gastric emptying, their impact on gastric mucosal visibility during upper endoscopy remains uncertain, especially in Asian patients.</p><p><strong>Aim: </strong>To investigate the association between GLP-1RA treatment and gastric mucosal visibility during upper endoscopy in Asian patients with T2DM.</p><p><strong>Methods: </strong>The study population included Korean patients who underwent esophagogastroduodenoscopy (EGD) with concomitant GLP-1RA or dipeptidyl peptidase 4 inhibitor (DPP4i) for the treatment of T2DM. A 1:2 propensity score matching between GLP-1RA and DPP4i users resulted in 198 matched patients and 295 matched patients in each group, respectively. Gastric mucosal visibility was assessed by reviewing endoscopy images with a validated scale (POLPREP). In addition, the rates of aborted and repeat EGD and pulmonary aspiration were also assessed.</p><p><strong>Results: </strong>Of the 493 matched patients, mean body mass index was 26.0 kg/m². The rate of inadequate gastric mucosal visibility (gastric POLPREP score 0 or 1) was significantly higher in GLP-1RA group than matched DPP4i group (8.6% <i>vs</i> 1.4%, <i>P</i> = 0.0007). The rates of aborted EGD and repeat EGD were also significantly higher in GLP-1RA than DPP4i group (7.6% <i>vs</i> 0.7% in both aborted and repeat EGD, <i>P</i> = 0.0011). Multivariable logistic regression revealed GLP-1RA use as an independent risk factor for both inadequate gastric mucosal visibility (odds ratio = 6.143, 95% confidence interval: 2.289, 20.318, <i>P</i> = 0.0008) and aborted EGD (odds ratio = 11.099, 95% confidence interval: 3.172, 63.760, <i>P</i> = 0.0010). Despite gastric residue, no pulmonary aspiration was reported in either group.</p><p><strong>Conclusion: </strong>GLP-1RA use was associated with a higher risk of inadequate gastric mucosal visibility and aborted and repeat procedures during upper gastrointestinal endoscopy in Korean patients with T2DM while pulmonary aspiration was not observed.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"112694"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890322","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":"Impact of diabetes mellitus on mortality and atrial fibrillation in hypertrophic cardiomyopathy: A systematic review and meta-analysis.","authors":"Nanush Damarlapally, Roopeessh Vempati, Kesha Mayank Doshi, Manavjot Singh, Kesar Prajapati, Dhruvi Modi, Pooja Singh, Rupak Desai","doi":"10.4239/wjd.v16.i12.110494","DOIUrl":"10.4239/wjd.v16.i12.110494","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a significant risk factor for cardiovascular diseases and can worsen the risk of cardiovascular events among patients with hypertrophic cardiomyopathy (HCM). However, strong evidence is needed to show the impact of DM on all-cause mortality (ACM) and atrial fibrillation (AF), which we explored in this systematic review and meta-analysis.</p><p><strong>Aim: </strong>To determine the impact of DM on ACM and AF in patients with HCM.</p><p><strong>Methods: </strong>PubMed, Google Scholar, and EMBASE databases were searched for studies showing the effect of DM on ACM and AF in HCM. A binary random effects model with a 95% confidence interval (CI) was used to pool odds ratios (ORs) for ACM and AF outcomes. Study quality was assessed using the Joanna Briggs Institute's critical appraisal tool and leave-one-out sensitivity analysis. <i>P</i> < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>Fourteen studies (<i>n</i> = 106138) with a mean age of 61.76 ± 19.84 years and 61.55% males were included in our systematic review; ten studies (<i>n</i> = 102882) were eligible for meta-analysis. In the unadjusted analysis, DM was not significantly associated with ACM (OR = 0.96; 95%CI: 0.43-2.15; <i>P</i> = 0.93). However, after adjustment, DM showed a significant association with higher ACM risk (adjusted OR = 1.37; 95%CI: 1.16-1.61; <i>P</i> < 0.01). DM was significantly associated with AF in both unadjusted (OR = 2.02; 95%CI: 1.14-3.58; <i>P</i> = 0.04) and adjusted analyses (adjusted OR = 2.68; 95%CI: 1.68-4.27; <i>P</i> = 0.01). The Joanna Briggs Institute tool revealed a low risk of bias. Leave-one-out sensitivity analysis, performed by sequentially excluding each study, demonstrated no significant change in the overall effect estimates, indicating the robustness and stability of our results.</p><p><strong>Conclusion: </strong>DM significantly increased the risk of ACM and AF, highlighting the importance of tighter glycemic control and cardiovascular risk factor modification among patients with HCM.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"110494"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890337","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":"Oral <i>Akkermansia muciniphila</i> may ameliorates immune dysregulation in a murine model of streptozotocin-induced type 1 diabetes.","authors":"Bao-Jiang Huang, Song Guo, Xiao-Ya Lin, Yan-Hong Li, Hua-Mei Ma, Jun Zhang, Qiu-Li Chen","doi":"10.4239/wjd.v16.i12.111771","DOIUrl":"10.4239/wjd.v16.i12.111771","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;&lt;i&gt;Akkermansia muciniphila&lt;/i&gt; (&lt;i&gt;A. muciniphila&lt;/i&gt;) has been shown to have positive effects on various metabolic diseases and partially prevent the onset of spontaneous type 1 diabetes mellitus (T1DM) in nonobese diabetic mice; however, its therapeutic efficacy in T1DM mice that have already developed T1DM remains unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To assess the effects of &lt;i&gt;A. muciniphila&lt;/i&gt; intervention on the intestinal barrier, immune parameters [regulatory T (Tregs) cells/T helper 1 cells balance, signal transducer and activator of transcription 1 (STAT1)/nuclear factor kappa-B (NF-κB) signal] and intestinal flora in a streptozotocin (STZ)-induced mouse model of T1DM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Thirty male C57BL/6 mice were randomized into three groups (&lt;i&gt;n&lt;/i&gt; = 10 for each): Normal control (NC group), STZ-induced T1DM (STZ group), and &lt;i&gt;A. muciniphila&lt;/i&gt;-treated T1DM (&lt;i&gt;A. muciniphila&lt;/i&gt; group). T1DM was induced with STZ (50 mg/kg/day intraperitoneally, 5 days). Body weight, blood glucose, and water intake were monitored weekly. T1DM was modelled in all STZ- and &lt;i&gt;A. muciniphila&lt;/i&gt;-treated mice (random blood glucose &gt; 16.7 mmol/L). &lt;i&gt;A. muciniphila&lt;/i&gt; group mice received oral &lt;i&gt;A. muciniphila&lt;/i&gt; (5 × 10&lt;sup&gt;7&lt;/sup&gt; colony-forming units/mouse) for 3 days. Following sacrifice, pancreatic histopathology, cytokines in splenic tissue, colonic zonula occludens-1 (ZO-1)/zonulin expression, cluster of differentiation (CD) 4&lt;sup&gt;+&lt;/sup&gt;/CD8&lt;sup&gt;+&lt;/sup&gt; T-cell ratios, forkhead box P3 (FoxP3&lt;sup&gt;+&lt;/sup&gt;) Tregs, STAT1/NF-κB p65 signaling, and gut microbiota composition were analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Compared with STZ group alone, &lt;i&gt;A. muciniphila&lt;/i&gt; group did not affect metabolic parameters. Histopathologically, STZ group and &lt;i&gt;A. muciniphila&lt;/i&gt; group pancreatic islet cells underwent vacuolar degeneration and necrosis, exhibiting reduced counts and significantly decreased insulin positivity (&lt;i&gt;P&lt;/i&gt; &lt; 0.05 &lt;i&gt;vs&lt;/i&gt; NC), with no intergroup differences. Flow cytometry and enzyme-linked immunosorbent assay revealed elevated tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and zonulin levels and decreased ZO-1 expression in STZ &lt;i&gt;vs&lt;/i&gt; NC mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Compared with STZ alone, &lt;i&gt;A. muciniphila&lt;/i&gt; group reduced TNF-α, TGF-β, and zonulin levels while increasing the CD4&lt;sup&gt;+&lt;/sup&gt;/CD8&lt;sup&gt;+&lt;/sup&gt; ratio, FoxP3&lt;sup&gt;+&lt;/sup&gt; Tregs, interleukin-4, and ZO-1 (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Colonic NF-κB p65 expression was higher in STZ &lt;i&gt;vs&lt;/i&gt; NC mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), with no significant &lt;i&gt;A. muciniphila&lt;/i&gt; group/NC difference after the intervention of &lt;i&gt;A. muciniphila&lt;/i&gt;. The expression of NF-κB p65 in &lt;i&gt;A. muciniphila&lt;/i&gt; group was lower than that in STZ group. STAT1 expression was lower in &lt;i&gt;A. muciniphila vs&lt;/i&gt; STZ mice (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). 16S sequencing revealed reduced &lt;i&gt;Actinobacteria&lt;/i&gt; abundance in &lt;i&gt;A. muciniphila vs&lt;/i&gt; STZ mice (&lt;i&gt;P&lt;","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"111771"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890215","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":"Clinical and genetic characteristics of young-onset diabetes with concurrent mitochondrial m.3243A>G and <i>CEL</i> gene mutations: A case report.","authors":"Xiao-Dan Che, Zheng-Liang Wei, Wuriliga Gong, Ling Qin, Shuang Liu, Yuan-Hui Jin, He-Yuan Wang","doi":"10.4239/wjd.v16.i12.113238","DOIUrl":"10.4239/wjd.v16.i12.113238","url":null,"abstract":"<p><strong>Background: </strong>Only a few cases of diabetes mellitus with concurrent mutations in the mitochondrial <i>MT-TL1</i> and <i>CEL</i> genes have been reported worldwide. Racial differences may influence mutation frequency, the presentation of symptoms, and disease progression. This case report describes the clinical features, potential genetic mechanisms, and diagnostic complexity of young-onset diabetes mellitus with concurrent m.3243A>G mutation in <i>MT-TL1</i> and c.1336G>A mutation in <i>CEL</i>. The objective is to inform precise typing, genetic counseling, and personalized treatment of monogenic diabetes mellitus, while expanding the evidence base on rare forms of diabetes mellitus.</p><p><strong>Case summary: </strong>A 30-year-old man, diagnosed with diabetic ketoacidosis six years earlier, presented with poor response to insulin therapy (glycated hemoglobin, 15.35%), marked wasting (body mass index: 15.06 kg/m²), sensorineural deafness, diabetic retinopathy, and peripheral neuropathy. Whole-exome sequencing revealed concurrent mutations: Mitochondrial <i>MT-TL1</i> m.3243A>G (heteroplasmy 41.76%) and <i>CEL</i> c.1336G>A. Family investigation identified his mother, who also had diabetes, as a carrier of the <i>CEL</i> mutation, and his sister as harboring both mutations without diabetes.</p><p><strong>Conclusion: </strong>This case highlights the genetic heterogeneity of monogenic diabetes and expands the known mutational spectrum. Comprehensive genetic testing is recommended to enhance diagnostic accuracy in cases of suspected monogenic diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"113238"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890388","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":"Long-term and short-term exposure to outdoor air pollution and its association with glycolipid metabolic disorders.","authors":"Chang Zhou, Gao-Yuan Cui, Yi-Hu Tang, Wu-Yang Zhang, Xue-Lun Zou","doi":"10.4239/wjd.v16.i12.110028","DOIUrl":"10.4239/wjd.v16.i12.110028","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The association between ambient air pollution and glycolipid metabolic disorders (GMDs, including diabetes mellitus and dyslipidemia) is still not well understood, especially when it comes to the different effects of long-term &lt;i&gt;vs&lt;/i&gt; short-term exposure and the sources of pollutants (indoor or outdoor).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To look at how outdoor particulate matter (PM&lt;sub&gt;1&lt;/sub&gt;, PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;) and ozone (O&lt;sub&gt;3&lt;/sub&gt;), as well as indoor pollutants from solid fuels, are related to the risk of developing GMDs in a cohort that represents the national population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used a longitudinal cohort design to look at how different time periods of air pollution exposure (long-term: 5-year averages; short-term: 1-year averages) affect the incidence of GMDs in middle-aged and elderly adults. Multivariable logistic regression models, which took into account key factors such as age, sex, and smoking status, were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our study found that exposure to air pollution (1 μg/m&lt;sup&gt;3&lt;/sup&gt;) has different effects on GMDs. Long-term exposure to outdoor pollutants like PM&lt;sub&gt;1&lt;/sub&gt;, PM&lt;sub&gt;2.5&lt;/sub&gt;, PM&lt;sub&gt;10&lt;/sub&gt;, and O&lt;sub&gt;3&lt;/sub&gt; consistently increased the risk of diabetes (PM&lt;sub&gt;1&lt;/sub&gt;: OR = 1.106, 95%CI: 1.018-1.205; PM&lt;sub&gt;2.5&lt;/sub&gt;: OR = 1.038, 95%CI: 1.007-1.071; PM&lt;sub&gt;10&lt;/sub&gt;: OR = 1.023, 95%CI: 1.004-1.043) and dyslipidemia (PM&lt;sub&gt;1&lt;/sub&gt;: OR = 1.150, 95%CI: 1.064-1.249; PM&lt;sub&gt;2.5&lt;/sub&gt;: OR = 1.053, 95%CI: 1.023-1.086; PM&lt;sub&gt;10&lt;/sub&gt;: OR = 1.032, 95%CI: 1.014-1.052). Short-term exposure showed even stronger associations, particularly for PM&lt;sub&gt;1&lt;/sub&gt; with dyslipidemia (OR = 1.078, 95%CI: 1.044-1.114) and PM&lt;sub&gt;1&lt;/sub&gt; with diabetes (OR = 1.047, 95%CI: 1.007-1.089). Notably, certain components of PM&lt;sub&gt;2.5&lt;/sub&gt; - chloride (Cl&lt;sup&gt;-&lt;/sup&gt;), ammonium (NH&lt;sub&gt;4&lt;/sub&gt; &lt;sup&gt;+&lt;/sup&gt;), sulfate (SO&lt;sub&gt;4&lt;/sub&gt; &lt;sup&gt;2-&lt;/sup&gt;), and nitrate (NO&lt;sub&gt;3&lt;/sub&gt; &lt;sup&gt;-&lt;/sup&gt;) - showed a dose-dependent relationship with both conditions (for example, Cl&lt;sup&gt;-&lt;/sup&gt;: Diabetes OR = 1.797 per 1 μg/m&lt;sup&gt;3&lt;/sup&gt;, 95%CI: 1.086-2.991; dyslipidemia OR = 2.627, 95%CI: 1.728-4.012). However, neither long-term nor short-term exposure to indoor solid fuel pollutants was significantly associated with diabetes (long-term OR = 1.034, 95%CI: 0.801-1.333; short-term OR = 0.970, 95%CI: 0.774-1.209) or dyslipidemia (short-term OR = 1.159, 95%CI: 0.967-1.386).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This national cohort study shows that outdoor air pollution - particularly PM&lt;sub&gt;1&lt;/sub&gt;, PM&lt;sub&gt;2.5&lt;/sub&gt;, and their chemical components - is an important environmental factor contributing to GMDs, with long-term exposure showing greater metabolic toxicity than short-term exposure. The lack of association between indoor solid fuel pollutants and GMDs underscores the urgent need for targeted interven","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"110028"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890441","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":"Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy.","authors":"Hadi Karimkhani","doi":"10.4239/wjd.v16.i12.108609","DOIUrl":"10.4239/wjd.v16.i12.108609","url":null,"abstract":"<p><p>A recent study in the <i>World Journal of Diabetes</i> by Yang <i>et al</i> explored how Rheb1 signaling influenced pancreatic β cell fate and its potential as a therapeutic target. This invited commentary by a senior diabetes researcher discussed the findings of Yang <i>et al</i> in the context of current knowledge on β cell biology, providing critical insight into the role of Rheb1 in β cell survival and function and the prospects for diabetes treatment. Key outcomes of the study were interpreted alongside established literature on Rheb1- mechanistic target of rapamycin signaling in islet cells. Rheb1 emerges as a pivotal regulator of β cell growth and insulin secretory function, aligning with evidence that β cell-specific Rheb1 deletion impairs β cell mass and glucose-stimulated insulin secretion. The commentary highlighted how modulating this pathway could preserve or restore the β cell population in diabetes while cautioning about potential off-target effects (<i>e.g.</i> in α cells). Targeting Rheb1 signaling represents a promising new frontier in diabetes therapy to enhance β cell resilience; however, a balanced approach addressing both its benefits and risks is essential. This letter discussed the scientific implications and future research directions needed to translate Rheb1 modulation into clinical application for diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"108609"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890186","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":"Glycemic control, weight-loss effects, and safety of cotadutide in individuals with type 2 diabetes: A systematic review and meta-analysis.","authors":"Abul Bashar Mohammad Kamrul-Hasan, Deep Dutta, Lakshmi Nagendra, Sindhu Doddabokikere Basavarajappa, Harish Bukkasagar Girijashankar, Ameya Joshi, Joseph M Pappachan","doi":"10.4239/wjd.v16.i12.112830","DOIUrl":"10.4239/wjd.v16.i12.112830","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cotadutide (MEDI0382) is a twincretin that acts as an agonist for both the glucagon-like peptide-1 and glucagon receptors. Several randomized controlled trials (RCTs) have been published evaluating the use of cotadutide in individuals with type 2 diabetes (T2D), showing promising results. However, the efficacy and safety of the drug use have been inadequately explored by systematic reviews and meta-analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;To assess the clinical efficacy and safety of cotadutide in individuals with T2D having overweight or obesity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The systematic reviews and meta-analyses have been registered with International Prospective Register of Systematic Reviews (CRD42024511703), and the protocol summary can be accessed online. Several databases and registries, including MEDLINE (&lt;i&gt;via&lt;/i&gt; PubMed), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov, were systematically searched using related terms from their inception to May 15, 2025, for RCTs involving individuals with T2D receiving cotadutide in the intervention group. Review Manager web was used to conduct meta-analysis using random-effects models. The co-primary outcomes of interest were the changes in glycated hemoglobin (HbA1c) and the percent changes in body weight from baseline. The results of the outcomes were expressed as mean differences (MDs) or risk ratios (RRs) with 95% confidence intervals (CIs). The analysis of outcomes was stratified according to whether the control group received a placebo, denoted as the placebo control group (PCG), or an active comparator, referred to as the active control group (ACG).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Nine RCTs (mostly phase 2 RCTs, &lt;i&gt;n&lt;/i&gt; = 1525) with study durations varying from 28 days to 54 weeks that met all the inclusion criteria were analyzed; five studies had a low overall risk of bias, while the other four had some concerns. Compared to the PCG, greater reductions in HbA1c were achieved with cotadutide 100 μg (MD -0.77%, 95%CI: -1.06 to -0.47), 200 μg (MD -0.68%, 95%CI: -1.12 to -0.23), 300 μg (MD -0.67%, 95%CI: -0.79 to -0.56), and 600 μg (MD -0.69%, 95%CI: -0.97 to -0.41). Cotadutide 100 μg (MD -1.74%, 95%CI: -3.23 to -0.25), 200 μg (MD -2.56%, 95%CI: -3.37 to -1.75), 300 μg (MD -3.49%, 95%CI: -4.14 to -2.84), and 600 μg (MD -5.45%, 95%CI: -7.17 to -3.73) achieved greater percent reductions in body weight from baseline. However, the certainty of evidence for HbA1c and percent body weight reductions was very low to low. Cotadutide, at all doses, also outperformed PCG in reducing fasting plasma glucose and absolute body weight. The changes in HbA1c, percent body weight, fasting plasma glucose, and absolute body weight were similar between the cotadutide group and the ACG. Compared to PCG, pooled doses of cotadutide increased the risks of treatment-emergent adverse events (AEs), treatment-related AEs, and discontinuatio","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"112830"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890328","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}