Journal of Diabetes Research最新文献

{"title":"Association of Nontraditional Lipid Indices With Poor Glycemic Control in Patients With Type 2 Diabetes: A Cross-Sectional Study.","authors":"Amirhossein Yadegar, Fatemeh Mohammadi, Shima Loni, Sepideh Yadegar, Ali Mohammadi Naeini, Amirhossein Tayebi, Mahsa Abbaszadeh, Soghra Rabizadeh, Alireza Esteghamati, Manouchehr Nakhjavani, Sahar Karimpour Reyhan","doi":"10.1155/jdr/6993567","DOIUrl":"10.1155/jdr/6993567","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the association between poor glycemic control, defined as HbA1c ≥ 7.5%, and multiple nontraditional lipid indices, including AC, AIP, LCI, TG/HDL-C ratio, CRI-I, and CRI-II, and to evaluate their diagnostic performance for identifying poor glycemic control.</p><p><strong>Methods: </strong>In this cross-sectional study, 6424 individuals diagnosed with Type 2 diabetes (T2D) who visited a diabetes clinic from 2014 to 2024 were included. The relationships between nontraditional lipid indices and poor glycemic control were evaluated using RCS models and multivariable logistic regression. Diagnostic performance was examined using ROC analysis.</p><p><strong>Results: </strong>Nontraditional lipid indices were significantly elevated in patients with poor glycemic control (p < 0.001). In RCS models, significant nonlinear associations were observed between all lipid indices and poor glycemic control, with progressively higher odds of HbA1c ≥ 7.5% as index values increased (p for nonlinearity < 0.05). When analyzed as continuous variables, all indices were positively associated with poor glycemic control, with AIP showing the strongest association (OR = 2.25 [1.84-2.76]). Individuals in higher quartiles of each lipid index had significantly greater odds of poor glycemic control compared with those in the first quartile. All indices showed modest discriminatory ability (AUCs ≥ 0.684) for poor glycemic control, with AIP demonstrating the highest AUC (0.687 [0.657-0.718]). However, no statistically significant differences in AUC were detected among the indices.</p><p><strong>Conclusions: </strong>The observed nonlinear associations between nontraditional lipid indices and poor glycemic control highlight the close interplay between atherogenic dyslipidemia and glycemic dysregulation. As these indices are derived from routinely measured lipid parameters, they can act as practical complementary tools for identifying individuals at higher risk of poor glycemic control, especially in settings where HbA1c measurement is limited or not cost-effective. Further research is required to confirm these findings and determine causal relationships.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e6993567"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148911989","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":"Preservation of Nociceptor Intraepidermal Nerve Fibres in Diabetic Neuropathic Pain.","authors":"Lisa A Lione, Lydia D Hardowar, Michael T Lanigan, Jessica Bates, William Blackstone-Whines, Harry Jones, Richard P Hulse","doi":"10.1155/jdr/4561974","DOIUrl":"10.1155/jdr/4561974","url":null,"abstract":"<p><p>Peripheral painful sensory neuropathy represents a prevalent and disabling complication of Type 1 and Type 2 diabetes. Unfortunately, despite the clinical need for improved analgesic approaches, clinicians remain inadequately provisioned to treat these patients as many analgesics are ineffective or initiate undesirable health-impacting side effects. During diabetes, the viability of the peripheral sensory nervous system is vulnerable, depicted by sensory neurodegeneration and neuropathic pain. However, it remains undefined how nociceptor intraepidermal fibre innervations are affected in patients and rodent models. Here, rodent models of chemically induced Type 1 and dietary induced prediabetes/Type 2 diabetic peripheral sensory neuropathy were utilised to investigate the impact upon nociceptor degeneration in painful diabetic neuropathy. Streptozotocin-induced Type 1 diabetes as well as 42% and 60% high-fat diets caused mechanical allodynia when compared with age-matched controls. Furthermore, dietary interventions led to a sustained hypersensitivity to thermal stimuli and a transient mechanical allodynia that was observed in the early phase, which later resolved. Histological analysis of plantar skin of the hind limbs demonstrated a significant reduction in total intraepidermal nerve fibre (IENF) density (PGP9.5 labelled), indicating sensory neurodegeneration in Type 1 and prediabetes/Type 2 diabetic rodent models. However, CGRP-positive nociceptor IENFs remain preserved, pointing to differential vulnerability among sensory fibre subtypes. Additionally, in Type 1, there was an increased presence of Langerhan cells, whereas this was not presented in the dietary induced models. This provides mechanistic insight into painful diabetic neuropathy and provides fundamental understanding that will support improved treatment of diabetic sensory neuropathy.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e4561974"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900709","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":"'If You Cut Me, I'd Probably Bleed Coca-Cola': A Qualitative Exploration of Barriers and Facilitators to Type 2 Diabetes Management Among Chinese Adults in the UK.","authors":"Tarnjit Sehmbi, Ran Cao, Raju Sapkota, Shahina Pardhan","doi":"10.1155/jdr/8119786","DOIUrl":"10.1155/jdr/8119786","url":null,"abstract":"<p><strong>Objectives: </strong>Chinese populations are at an elevated risk of type 2 diabetes mellitus (T2DM) and related complications, yet limited research has explored diabetes self-management in the UK Chinese community. This study aimed to explore barriers and facilitators to T2DM self-management in the UK Chinese community.</p><p><strong>Design: </strong>This study adopted a qualitative design. Three focus group discussions (FGDs) were conducted on Zoom with 22 Chinese participants with self-reported type 2 diabetes living in the UK. The participants ranged from 24 years to 85 years (mean age = 66 years, SD = 17.1). A purposive sample was recruited through study adverts in Chinese community centres and via snowball sampling. Data were analysed using Braun and Clarke's thematic analysis (TA).</p><p><strong>Results: </strong>This paper discusses four themes in detail. (1) Key barriers to healthy eating were time constraints and convenience, cultural expectations and lack of nutritional knowledge. (2) Facilitators for healthy eating included having a support network, health education and modifying eating habits. (3) Barriers to physical activity included low importance of exercise, work and family commitments and environmental constraints. (4) Facilitators for physical activity were community-based exercise, culturally appropriate exercise such as Tai Chi, and benefits to mental health. It was found that dietary changes were perceived as important in diabetes management; however, physical activity was seen as less important when considering diabetes management.</p><p><strong>Conclusion: </strong>Diabetes self-management among UK Chinese adults is shaped by collectivist family structures, culturally embedded food practices, and barriers within healthcare provision. Interventions should move beyond individualised behaviour change models and incorporate family-inclusive education, bilingual resources, and community-embedded physical activity programmes. Culturally appropriate diabetes services may enhance engagement and support self-management within this population.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e8119786"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13051851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616238","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":"Achieving Diabetes Remission Through Dietary Intervention: A 12-Month Randomized Controlled Trial of Caloric-Carbohydrate Restriction in Overweight Patients With Early-Stage Type 2 Diabetes Mellitus.","authors":"Hongquan Wang, Qiong Wang, Jieqiong Chen, Yu Chen, Yanyao Tang","doi":"10.1155/jdr/7230214","DOIUrl":"10.1155/jdr/7230214","url":null,"abstract":"<p><strong>Objective: </strong>We are aimed at evaluating the effects of a calorie-restricted low-carbohydrate diet (CR-LCD) on diabetes remission, weight control, and metabolic parameters in overweight patients with early-stage Type 2 diabetes mellitus (T2DM).</p><p><strong>Research design and methods: </strong>This 6-month randomized intervention trial with a 12-month follow-up randomly assigned 68 adults with early-stage T2DM to receive either a CR-LCD or a control diet. Of the original cohort, data from 66 participants (two dropouts in the CR-LCD group) were analyzed. The primary outcome was diabetes remission, defined as achieving a glycated hemoglobin (HbA1c) level < 6.5% without glucose-lowering medications; secondary outcomes included anthropometric, glycemic, and lipid parameters.</p><p><strong>Results: </strong>The CR-LCD group had a significantly higher 6-month diabetes remission rate than the control group (62.50% vs. 35.29%, χ² = 4.885, p = 0.027). After multivariate adjustment, the intervention was associated with higher remission rates (odds ratio [OR] = 4.592, 95% confidence interval [CI]: 1.276-16.524; p = 0.020). At 12 months, between-group comparisons following false discovery rate (FDR) correction revealed significant differences in body mass index (FDR - adjusted p = 0.006, η²p = 0.150), waist circumference (FDR - adjusted p = 0.040, η²p = 0.085), fasting blood glucose (FDR - adjusted p < 0.001, r = 0.613), 2-h postprandial blood glucose (FDR - adjusted p = 0.040, η²p = 0.088), and high-density lipoprotein cholesterol (FDR - adjusted p = 0.040, η²p = 0.095). No severe adverse events were reported.</p><p><strong>Conclusions: </strong>A CR-LCD was effective in inducing diabetes remission in early-stage T2DM, suggesting that it may offer a viable nonpharmacological management strategy for this condition.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry: ChiCTR2600118189.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e7230214"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055006","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":"Navigating Continuous Glucose Monitoring Adoption: Insights From Hispanic Adults With Insulin-Treated Type 2 Diabetes.","authors":"Diana Soliman, Giuliana Arevalo, Rodolfo J Galindo, Benjamin Churba, Keilecia G Malden, Daniel E Jimenez, Francisco J Pasquel, David A Baidal, Ashby F Walker","doi":"10.1155/jdr/7474846","DOIUrl":"10.1155/jdr/7474846","url":null,"abstract":"<p><strong>Objective: </strong>Hispanic individuals are disproportionately affected by type 2 diabetes (T2D) and face access limitations in diabetes technology utilization. Despite proven benefits, continuous glucose monitoring (CGM) use remains low among Hispanic adults with insulin-treated T2D. This study used a social-ecological model (SEM) framework to identify societal/policy, interpersonal/community, and individual level barriers to CGM access and adoption within this population.</p><p><strong>Methods: </strong>Two focus groups were conducted in Spanish at the University of Miami (UM) with Hispanic adults (n = 16) with T2D. Inclusion criteria were age ≥18 years, HbA1c ≥8%, ≥1 daily insulin injection, and no CGM use in the past 2 years. The initial focus group was conducted to identify barriers to CGM initiation. At the end of the focus group, participants were provided with real-time CGMs for 30 days of use. After completing the wear period, the same participants returned for a follow-up focus group to explore factors related to CGM adoption and acceptance. Focus groups were analyzed using a thematic analysis, systematically coding and categorizing key concepts and ideas expressed by participants.</p><p><strong>Results: </strong>The mean age was 59.68 ± 13.37 years, and baseline HbA1c was 9.78 ± 1.14. Key barriers included high device costs, limited insurance coverage, alarm fatigue, and lack of culturally concordant provider guidance. Facilitators for CGM use included manufacturer discounts, peer modeling, and the desire to avoid fingersticks. After a 30-day CGM trial, most participants reported improved dietary awareness, glycemic control, and a strong desire for continued use.</p><p><strong>Conclusion: </strong>This pilot study provides novel insights into the experiences of the Hispanic population and highlights the complex interplay of societal, interpersonal, and individual-level factors influencing CGM use. Tailored interventions addressing these barriers are crucial for improving CGM utilization in this population.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e7474846"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772945","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":"Mediation by Lipid-Glucose Metabolic Indices in the Association Between Overweight and T2DM Among Shanghai Community-Dwelling Older Adults.","authors":"Jia Bo, Hongfei Mo, Fei Wu, Jiayun Zhu, Qinghua Yan, Fan Wang, Minna Cheng","doi":"10.1155/jdr/8449810","DOIUrl":"10.1155/jdr/8449810","url":null,"abstract":"<p><strong>Objective: </strong>This study is aimed at exploring the mediating roles of the triglyceride-glucose (TyG) index, cholesterol-HDL-glucose (CHG) index, and atherogenic index of plasma (AIP) in the association between overweight and Type 2 diabetes mellitus (T2DM) among older adults in Shanghai, China.</p><p><strong>Methods: </strong>A total of 44,715 participants aged ≥ 60 years from the Shanghai Non-communicable Diseases Management Cohort were included. Overweight was defined as a body mass index (BMI) ≥ 24 kg/m². T2DM was diagnosed clinically by physicians. Mediation analysis was performed to estimate direct, indirect, and total effects.</p><p><strong>Results: </strong>The mean age of the participants was 77 ± 6.8 years, 16,835 (37.65%) were diagnosed with T2DM, and 27,880 (62.35%) did not. In covariate-adjusted models, overweight older adults had a 26% higher odds of T2DM than nonoverweight older adults. The TyG, CHG, and AIP indices were all associated with T2DM. In the mediation analysis, the proportions of the total effect mediated by the TyG, CHG, and AIP indices were 22.03%, 32.24%, and 6.47%, respectively.</p><p><strong>Conclusion: </strong>The lipid-glucose metabolic indices examined, particularly CHG and TyG indices, partially mediated the association between overweight and T2DM. These biomarkers may serve as early intervention targets to prevent T2DM among overweight older adults.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e8449810"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13307189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148338661","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":"RETRACTION: Quercetin Improves Glucose and Lipid Metabolism of Diabetic Rats: Involvement of Akt Signaling and SIRT1.","authors":"Journal Of Diabetes Research","doi":"10.1155/jdr/9878214","DOIUrl":"10.1155/jdr/9878214","url":null,"abstract":"","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9878214"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772922","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":"Association of Family Meals and Prediabetes Among South Korean Adults Without Diabetes.","authors":"Eun-Ji Jung, Jae Hyeok Lim, Kui Son Choi, Min Jin Ha, Eun-Cheol Park","doi":"10.1155/jdr/7457214","DOIUrl":"10.1155/jdr/7457214","url":null,"abstract":"<p><strong>Introduction: </strong>Prediabetes is a reversible yet often overlooked condition that represents a critical window for early intervention. Family meal practices may support effective disease management during this stage. In this study, we aimed to investigate the association between family meal practices and the prevalence of prediabetes among South Korean adults.</p><p><strong>Methods: </strong>Data from the 2019-2023 Korea National Health and Nutrition Examination Survey were analyzed. Family meal practices were defined as sharing at least one meal (breakfast, lunch, or dinner) with family members three or more times per week. Prediabetes was defined as fasting glucose levels of 100-125 mg/dL or glycated hemoglobin of 5.7%-6.4%. Sex-stratified multivariable logistic regression analyses were performed, adjusting for covariates.</p><p><strong>Results: </strong>Among 16,957 adults without diabetes (6907 men and 10,050 women), the prevalence of prediabetes was 49.1% in men and 42.3% in women. Men who participated in family meals had 16% lower odds of prediabetes (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.73-0.97) compared with men who did not, whereas the association was not significant for women (OR: 0.97, 95% CI: 0.84-1.11). Among men, this association tended to be more pronounced in socioeconomic subgroups characterized by urban residence, higher household income, higher educational level, white-collar occupations, and married status.</p><p><strong>Conclusions: </strong>Regular participation in family meals was associated with a lower prevalence of prediabetes among South Korean adult men without diabetes. This finding may help identify population subgroups that could benefit from targeted lifestyle-based interventions for diabetes prevention.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e7457214"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182342","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":"Causal Association Between Commonly Used Medicines and Diabetes-Related Eye Diseases: Univariable and Multivariable Mendelian Randomization Study.","authors":"Yu Wang, Chak Kwong Cheng, Lamusi A, Mingyue Jin, Chang Wang","doi":"10.1155/jdr/6075025","DOIUrl":"10.1155/jdr/6075025","url":null,"abstract":"<p><strong>Background: </strong>Diabetic patients require long-term polypharmacy, yet the causal effects of these medications on ocular complications-specifically diabetic retinopathy (DR), diabetic maculopathy (DMac), and glaucoma-remain unclear due to confounding in observational studies.</p><p><strong>Methods: </strong>We performed a Mendelian randomization (MR) study using GWAS summary statistics for 23 common medication classes and five diabetic eye diseases. Multivariable MR (MVMR) was employed to adjust for key comorbidities (e.g., hypertension, type 2 diabetes), while enrichment analyses explored biological mechanisms.</p><p><strong>Results: </strong>In the univariable MR (UVMR) analysis, drugs used in diabetes, agents acting on the renin-angiotensin system, and several other medication classes showed significant associations with increased risks of diabetic eye diseases. Crucially, MVMR confirmed robust causal links after adjusting for key comorbidities. Specifically, drugs used in diabetes remained associated with DMac (OR = 1.44, p = 1.31 × 10^-11), DR (OR = 1.23, p = 1.26 × 10^-8), neovascular glaucoma (OR = 1.19, p = 0.003), and senile cataract (OR = 1.10, p = 9.25 × 10^-12) independent of type 2 diabetes liability. Similarly, thyroid preparations retained significance for DMac (OR = 1.26, p = 4.35 × 10^-10), DR (OR = 1.17, p = 9.53 × 10^-10), and senile cataract (OR = 1.04, p = 0.004) after adjusting for hypothyroidism. Additionally, adrenergic inhalants were independently linked to senile cataract (OR = 1.07, p = 0.008) after adjusting for asthma. Pathway analysis highlighted hormone transport and MAPK signaling as potential mechanisms.</p><p><strong>Conclusion: </strong>Our findings provide genetic evidence supporting potential comorbidity-independent causal links between specific systemic medications-particularly diabetes and thyroid drugs-and ocular complications, suggesting the importance of ophthalmological monitoring in these patients.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e6075025"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13129224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772894","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":"The AGEs/RAGE Axis Contributes to Myocardial Cell Death in Type 1 Diabetic Cardiomyopathy via the ROS/NF-κB/NLRP3 Inflammasome Pathway.","authors":"Xiaoqun Li, Shujie Chen, Ke Wang, Ke Xu, Yannan Wang, Zechao Zhang, Xue Liu","doi":"10.1155/jdr/6438008","DOIUrl":"https://doi.org/10.1155/jdr/6438008","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 1 diabetes mellitus (T1DM) cardiomyopathy is a severe complication that typically follows an insidious onset and then progresses rapidly to heart failure and premature death. AGEs accumulate in the myocardium under hyperglycemic conditions and have emerged as important mediators of this diabetic complication, although the full signaling cascades engaged by AGEs remain largely unresolved. In the present study, we therefore investigated whether AGEs induce myocardial injury in T1DM via NLRP3 inflammasome activation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A T1DM mouse model was established using streptozotocin (STZ) injections, and an in vitro model was generated by treating primary neonatal mouse cardiomyocytes with AGEs. Cardiac performance and morphological changes were examined via echocardiography and histopathological staining. Expression and activation of the NLRP3 signaling cascade were evaluated by Western blotting, ELISA, and immunofluorescence. Pyroptotic cell death was assessed by SYTOX green staining, PI uptake, and lactate dehydrogenase (LDH) release assay. Correlations between whole-blood RAGE gene expression and inflammatory cytokine levels (IL-1β and IL-18) in T1DM patients, along with myocardial abundance of RAGE, NLRP3, and N-GSDMD in the experimental mice, were analyzed as exploratory descriptive observations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;STZ-induced T1DM mice exhibited sustained hyperglycemia (fasting blood glucose ≥ 11.1 mmol/L) and impaired cardiac function. Myocardial tissue from T1DM animals showed marked engagement of the NLRP3 signaling cascade, as evidenced by elevated NLRP3, cleaved caspase-1 P20, and N-GSDMD, enhanced ASC speck formation, and increased serum IL-1β levels. In vitro, AGEs treatment directly triggered the NLRP3 pathway and drove cardiomyocyte pyroptosis. Mechanistically, AGEs binding to RAGE triggered a burst of intracellular ROS, which led to NF-κB activation and subsequent NLRP3 activation. These effects were suppressed by either the RAGE inhibitor FPS-ZM1 or the ROS scavenger N-acetylcysteine (NAC). Furthermore, MCC950 treatment significantly attenuated AGE-induced caspase-1 activation, IL-1β/IL-18 secretion, and N-GSDMD expression, confirming that NLRP3 is a necessary mediator of this signaling cascade. SYTOX green staining, PI uptake, and LDH release assays further demonstrated that AGE-induced pyroptotic cell death was blocked by FPS-ZM1, NAC, and MCC950, indicating that pyroptosis occurs specifically through the RAGE/ROS/NLRP3 axis. Correlation analyses revealed that RAGE transcript levels in whole blood from T1DM patients positively correlated with circulating IL-1β and IL-18. In the diabetic mouse heart, RAGE, NLRP3, and N-GSDMD protein levels were analyzed as exploratory descriptive observations and showed a consistent pattern of coexpression at the individual level.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;AGEs promote NLRP3 inflammasome activation in cardiomyocytes vi","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149268588","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}