Journal of Diabetes Research最新文献

{"title":"Retinol Binding Protein 4 and Uric Acid as Risk Factors for Insulin Resistance in Type 2 Diabetes Mellitus.","authors":"Linyan Cheng, Liyan Wu, Tao-Hsin Tung, Zijun Chai, Yufen Zheng, Bo Shen","doi":"10.1155/jdr/9446806","DOIUrl":"10.1155/jdr/9446806","url":null,"abstract":"<p><strong>Background: </strong>Hyperuricemia (HUA) is closely associated with insulin resistance (IR). Retinol-binding protein 4 (RBP4) plays a critical role in inducing IR. However, the combined effects of uric acid (UA) and RBP4 on IR remain unclear. This study aimed to identify the risk factors for IR in type 2 diabetes mellitus (T2DM) patients and to investigate the potential relationship between UA and RBP4 in this context.</p><p><strong>Methods: </strong>This study included 570 patients aged 18-60 years with T2DM who were treated at Taizhou Hospital in Zhejiang Province. Univariate and multivariate logistic regression analyses were performed to evaluate the associations of UA and RBP4 levels with IR risk in T2DM patients. Mediation analysis was conducted to assess the mediating role of RBP4 in the relationship between UA and homeostasis model assessment of insulin resistance (HOMA-IR). Finally, ROC curve analysis was performed to examine the evaluation value of the model for IR in patients with T2DM.</p><p><strong>Results: </strong>RBP4 and UA levels were significantly correlated with HOMA-IR (p < 0.01). Mediation analysis revealed that RBP4 partially mediated the relationship between UA and IR (p < 0.05, with the mediating effect accounting for 23.2%). Furthermore, both RBP4 and UA were identified as significant risk factors for IR in patients with T2DM (p < 0.05). The risk of IR associated with HUA was greater when RBP4 ≥ 36.6 mg/L (p < 0.001). The ROC analysis showed that compared with UA or RBP4 alone, the combination of RBP4 and UA was more effective in detecting IR and represented a superior assessment model (AUC = 0.788, p < 0.001).</p><p><strong>Conclusions: </strong>RBP4 played a partial mediating role between UA and IR. Both RBP4 and UA were risk factors for IR in T2DM patients. The combined use of these two indicators can better evaluate the risk of IR. Further research is needed to validate the reliability of using UA and RBP4 levels to evaluate IR.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9446806"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13244560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148199104","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":"Qinggan Mingshi Granules Inhibited Ferroptosis to Treat Diabetic Retinopathy in Mice Through NRF2/GPX4 Axis.","authors":"Zhongyong Zhang, Qianqian Jin, Hongmin Zhao, Yingkai Liu, Meng Wang, Zhongqian Han, Jin Wu, Shuquan Lv, Xiaoyun Wang, Wei Chen, Qingjin Wang, Hailong Bai, Yuansong Wang","doi":"10.1155/jdr/9978155","DOIUrl":"https://doi.org/10.1155/jdr/9978155","url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is a common microvascular complication of diabetes, which seriously affected the life quality in diabetic patients. Developing novel therapy to improve DR is essential. Qinggan Mingshi granules (QGMS) have been demonstrated with protective effects on DR clinically. However, the mechanisms of QGMS remain unclear.</p><p><strong>Method: </strong>In order to more thoroughly investigate the mechanism underlying the positive effects of QGMS on DR, a mouse model of DR was established in this study, and the positive effects of QGMS on the DR mice were observed. Next, the effects of QGMS on ferroptosis and the NRF2/GPX4 axis were investigated. In addition, we used an NRF2 inhibitor to determine whether QGMS inhibits ferroptosis in DR mice via the NRF2/GPX4 axis.</p><p><strong>Result: </strong>Our results revealed the therapeutic effects of QGMS on DR including improving the permeability of blood-retina barrier (BRB), reducing the pathological changes and ferroptosis in retina. QGMS also induced the expression of NRF2/GPX4 axis in retina. Furthermore, ML385, an NRF2 inhibitor, abolished the effects of QGMS on DR.</p><p><strong>Conclusion: </strong>This study revealed that QGMS can effectively treat DR by alleviating retinal damage through enhancing the expression of NRF2/GPX4 axis-related proteins and thus scavenging of LPOs, ultimately reducing ferroptosis.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9978155"},"PeriodicalIF":3.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Peer Stress on Disordered Eating Behaviors in Youths With Type 1 Diabetes: A Parallel Mediation Effect of Dual-Mode Self-Control.","authors":"Meijing Zhou, Yueting Qin, Hong Wang, Jian Yu, Min Zhu, Hong Yun Zhu, Yang Lei, Jingjing Xu","doi":"10.1155/jdr/9964884","DOIUrl":"10.1155/jdr/9964884","url":null,"abstract":"<p><strong>Background: </strong>Disordered eating behaviors (DEBs) have been a prevalent issue among youths with type 1 diabetes (T1D), leading to impaired glycemic control, significant short- and long-term complications, and elevated mortality risk. Peer stress plays a critical role in the development of DEBs in adolescents. However, the association between peer stress and DEBs in youths with T1D remains unestablished, and the underlying mechanisms are unclear. This study investigated how peer stress influences DEBs and examined the parallel mediating role of dual-mode self-control-comprising both impulsive and control systems-in this relationship.</p><p><strong>Methods: </strong>This cross-sectional study included 180 youths with T1D who were recruited from two tertiary hospitals in Nanjing, China, between December 2021 and September 2022. Data were collected using the peer stress subscale of the Diabetes Stress Questionnaire for Youths, the Dual-Mode Self-Control Scale, and the Diabetes Eating Problem Survey-Revised. Descriptive analyses and Pearson correlations were conducted in SPSS 22.0. Parallel mediation effects were tested via Model 4 of the PROCESS macro, using bias-corrected bootstrap with 5000 resamples to determine significant mediation.</p><p><strong>Results: </strong>Peer stress significantly predicted DEBs (B = 0.55, p < 0.001). Only the impulsive system demonstrated partial mediation in the pathway from peer stress to DEBs (indirect effect = 0.13, 95% CI [0.04, 0.25]), accounting for 22.41% of the total effect.</p><p><strong>Conclusions: </strong>Peer stress directly influences DEBs and indirectly exacerbates DEBs through the activation of the impulsive system. These findings advance theoretical frameworks on peer stress and DEBs, informing interventions targeting peer stress reduction and impulse regulation to mitigate DEBs in youths with T1D.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9964884"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772935","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":"Routinely Derived Metabolic Indices for IDF-Defined Metabolic Syndrome in Chinese Adults: A Cross-Sectional Study.","authors":"Qiuman Lin, Fen Zhou, Yongjian Zhang, Qianqian Zhong, Jianxin Liu","doi":"10.1155/jdr/4648598","DOIUrl":"10.1155/jdr/4648598","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study is to compare the standardized associations, cross-sectional discrimination, and distributional robustness of 13 routinely derived metabolic indices for International Diabetes Federation (IDF)-defined metabolic syndrome (MetS).</p><p><strong>Methods: </strong>We included 9660 Chinese adults who underwent routine health examinations at Peking University Shenzhen Hospital between August 2024 and March 2026. Associations were assessed using logistic regression with standardized indices and restricted cubic splines, and overall and prespecified subgroup discrimination were evaluated using receiver operating characteristic analyses. Fully adjusted analyses included age, sex, low-density lipoprotein cholesterol, total bilirubin, blood urea nitrogen, creatinine, and uric acid. Robustness was examined after 1st-99th percentile winsorization using self-standard deviation (self-SD) and fixed main-sample standard deviation (fixed main-SD) standardization.</p><p><strong>Results: </strong>Among 9660 participants, 1635 had MetS (16.93%). The cardiometabolic index (CMI) showed the strongest standardized association (odds ratio (OR) per standard deviation increment, 19.437), followed by the triglyceride-glucose waist circumference index (TyG-WC; OR, 16.332). TyG-WC had the highest overall area under the receiver operating characteristic curve (AUC, 0.934; 95% confidence interval (CI), 0.929-0.939) and the highest AUC in 9 of 11 prespecified strata. After winsorization, TyG-WC retained strong standardized associations under self-SD and fixed main-SD scaling (ORs, 17.181 and 18.638, respectively) and stable discrimination (AUC, 0.935), whereas CMI, the lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-total cholesterol-body weight index (TCBI) showed substantial scale dependence. All indices showed nonlinear associations (p < 0.001).</p><p><strong>Conclusion: </strong>The 13 indices differed in association strength, discrimination, and distributional robustness. TyG-WC showed the most balanced overall profile and maintained strong discrimination across most prespecified subgroups. These findings support the further evaluation of TyG-WC in routine health examination settings. Further validation in independent multicenter populations is required.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e4648598"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194549","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 Between Exercise and Brain-Derived Neurotrophic Factor (BDNF) Levels in Diabetes Mellitus: A Systematic Review and Meta-Analysis.","authors":"Rumeesa Parveen, M Abdur Rahman Aizaz, Sarah Sohail, Sara Jawaid, Abdullah Amjad, Syeda Sana-E-Zehra Naqvi, Dirha Amjad, Araj Naveed Siddiqui, Asma Azam, Laiba Shamim, Umaimah Naeem, Sakan Binte Imran","doi":"10.1155/jdr/5163895","DOIUrl":"10.1155/jdr/5163895","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus (DM) is a metabolic disorder characterized by a consistently elevated blood sugar level. DM poses a major risk factor for many neurodegenerative diseases, causing a decline in cognitive function. BDNF (brain-derived neurotrophic factor) is a neurotrophin in the central and peripheral nervous systems that plays a crucial role in the development of brain circuits. Hence, disturbance in levels of BDNF is linked to the occurrence of neurodegenerative diseases and cognitive decline in diabetic patients. Physical exercise has emerged as a nonpharmacological intervention in elevating BDNF levels. Our systematic review and meta-analysis evaluate the relationship between a globally affecting metabolic disorder, diabetes, with decreased BDNF levels, and explore exercise as a promising potential intervention.</p><p><strong>Methods: </strong>After screening 37 articles, 4 studies have been included in the systematic review and meta-analysis, out of which 3 of them are randomized controlled trials (RCTs), and 1 is a crossover trial. The search was conducted on PubMed (MEDLINE), ScienceDirect, Embase, Scopus, and Cochrane Central databases from inception to June 2025. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to conduct a systematic review. Cochrane risk-of-bias tool was used to assess the quality of the studies. Data were pooled using a random effect model. The protocol for this systematic review was registered in PROSPERO.</p><p><strong>Results: </strong>A total of 37 articles were screened, 3 RCTs and 1 crossover trial with 131 participants were included in the meta-analysis. Serum BDNF levels were higher in the exercise group compared with controls (MD = 73.50; p = 0.05). A small reduction in body fat percentage in the exercise group compared with the control was found (MD = -1.24%; p = 0.17), which was not statistically significant. Body weight and fasting blood glucose (FBG) showed no statistically significant differences between the exercise and control groups (MD = 0.97; p = 0.65), (MD = -27.20; p = 0.31). Moderate to high heterogeneity was noticed across the data analyzed.</p><p><strong>Conclusion: </strong>This meta-analysis overall concludes that regular exercise positively affects serum BDNF levels in diabetics. However, the small number of trials and small sample sizes has limited the conclusions. Further large-scale RCTs are required to determine the long-term neurological effects of exercise in diabetics.</p>","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/PMC13686373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238455","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 Impact of Different Oral Antidiabetic Drugs on Insulin Pump Intensive Therapy in Type 2 Diabetes Patients: A Clinical Study.","authors":"Miaoguan Peng, Yijuan Xie, Naifeng Liang, Shiyun Wen, Yaojie Zhai, Yingjun Xie, Yuyi Chen","doi":"10.1155/jdr/9957473","DOIUrl":"10.1155/jdr/9957473","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to compare the effects of insulin pump intensive therapy alone with those of insulin pump intensive therapy combined with metformin or dapagliflozin on the time to achieve glycemic targets, total insulin dose at the end of intensive therapy, and pancreatic function. The study aimed to understand the impact of adding the traditional antidiabetic drug metformin and the novel antidiabetic drug dapagliflozin to routine intensive insulin therapy on treatment outcomes.</p><p><strong>Methods: </strong>A total of 110 patients with newly diagnosed T2DM (with glycated hemoglobin >9%, fasting blood glucose >11.1 mmol/L, or obvious symptoms of hyperglycemia) were enrolled in a single-center randomized controlled trial. Patients were randomized into three groups. The final analysis included 81 participants (73.6% of the enrolled) with complete data for the primary outcomes, distributed as follows: Group 1 (insulin only, n = 25), Group 2 (insulin plus dapagliflozin, n = 20), and Group 3 (insulin plus metformin, n = 36). The term \"newly diagnosed\" was defined as a diagnosis confirmed within 1 year prior to enrollment, in accordance with the Chinese guidelines for the prevention and treatment of T2DM. All patients were either treatment-naïve or had not received any sustained glucose-lowering pharmacotherapy for more than 2 weeks since diagnosis. The primary outcomes were the time to achieve glycemic targets, total insulin dose at the end of intensive therapy, and pancreatic function.</p><p><strong>Results: </strong>The fasting insulin levels in all the treatment groups changed over time, with greater decreases observed in the insulin pump therapy alone group and the insulin pump therapy + dapagliflozin group than in the insulin pump therapy + metformin group.</p><p><strong>Conclusion: </strong>These findings suggest that compared with metformin, dapagliflozin combined with intensive insulin pump therapy holds greater promise for optimizing glycaemic control in patients with T2DM, thus providing a more promising option for clinical practice.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9957473"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581378","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":"Safety Assessment of Glucagon-Like Peptide 1 Receptor Agonists Based on the FAERS Database: Focus on Tumorigenic Risk in Subpopulations.","authors":"Zhenhan Li, Jun Huang, Sha Zhou, Yongan Luan, Huang Xie, Zhongpei Chen, Juan Xu, Jun Qian","doi":"10.1155/jdr/8893769","DOIUrl":"10.1155/jdr/8893769","url":null,"abstract":"<p><p>GLP-1 receptor agonists (GLP-1RAs) are extensively used in treating Type 2 diabetes due to their therapeutic benefits. However, clinical reports have highlighted adverse events, particularly the underexplored association with tumor development. This study investigates GLP-1RA-related adverse events, focusing on tumorigenic risks, using data from the FDA Adverse Event Reporting System (FAERS). FAERS data from Q1 2005 to Q4 2023 were analyzed using the proportional reporting ratio (PRR) method to identify GLP-1RA-associated adverse events. Detailed analyses examined event distribution across genders, ages, and body weights, with an emphasis on tumor-related risks in vulnerable subpopulations. A total of 195,250 GLP-1RA-related adverse event reports were identified, spanning 25 system organ classes (SOCs). The most reported SOCs were gastrointestinal disorders (n = 110,451, PRR 2.44), investigative findings (n = 80,126, PRR 2.46), and metabolism and nutrition disorders (n = 25,236, PRR 2.21). Notably, 7457 cases involved benign, malignant, and unspecified tumors (PRR 0.5). Further analysis revealed that the risk of GLP-1RA-associated tumorigenesis varied by age, sex, and weight, suggesting that tumorigenesis risk differed in specific subpopulations. These findings underscore the need for vigilance regarding GLP-1RA-related adverse events, particularly tumor risks in specific subgroups. Clinicians should consider patient-specific factors, such as age, gender, and body weight, to ensure safe and effective GLP-1RAs therapy.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e8893769"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491289","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 Validation of Digital PCR for Precise m.3243A>G Heteroplasmy Quantification in Early-Onset Diabetes.","authors":"Xiaomu Kong, Lei Bei, Peng Gao, Lixia Lu, Haoyan Zhu, Yongwei Jiang, Meimei Zhao, Yi Liu, Guozhen Wang, Mo Li, Ziyi Feng, Guoxiong Deng, Yongtong Cao, Liang Ma","doi":"10.1155/jdr/9298888","DOIUrl":"10.1155/jdr/9298888","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial DNA m.3243A>G variant causes maternally inherited diabetes with deafness. We developed a droplet digital PCR (dPCR) assay to quantify m.3243A>G heteroplasmy and investigated its prevalence in Chinese Han early-onset diabetes patients.</p><p><strong>Methods: </strong>The dPCR method was validated using plasmid mixtures (10⁴ copies) for sensitivity, specificity, dynamic range (10-10⁵ copies/μL), accuracy, and precision. We screened 1506 unselected early-onset diabetes patients, analyzing blood and urinary sediment DNA. This population comprised 1474 diagnosed type 2 diabetes patients (97.88%), 31 diagnosed type 1 diabetes patients (2.06%), and one patient with mitochondrial diabetes (0.07%). The dPCR results were compared with Sanger sequencing and next generation sequencing (NGS) to evaluate the accuracy of heteroplasmy rate quantification.</p><p><strong>Results: </strong>The dynamic range spans from 10 to 10⁵ copies/μL. The assay detected heteroplasmy as low as 0.05% with 100% specificity. The method can reliably quantify the heteroplasmy rate at 0% to 100% for an input copy number of 10⁴. Using the dPCR method, we identified 0.80% (n = 12) had >5% m.3243A>G heteroplasmy in peripheral blood and/or urinary sediment, and 0.40% (n = 6) had 1%-5% among the early-onset diabetes patients. The dPCR approach was more sensitive than Sanger sequencing. When compared with NGS results, the dPCR method accurately genotyped m.3243A>G and quantified its heteroplasmy rate in clinical samples. Furthermore, it demonstrated that urine is a reliable noninvasive sample source for determining the m.3243A>G heteroplasmy rate.</p><p><strong>Conclusion: </strong>The developed method can provide an accurate, reliable, rapid, simple, and low-cost evaluation of the heteroplasmy rate of m.3243A>G for both peripheral blood and urinary sediment. Thus, it is highly promising as a genetic screening method for early-onset diabetes related to m.3243A>G.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e9298888"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13140937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521175","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":"GSTP1-Mediated Inhibition of Rac1-Mineralocorticoid Receptor Signaling Underlies the Renoprotective Effect of Huangqi Tujian Decoction in Diabetic Nephropathy.","authors":"Xinyuan Liu, Li Zhao, Dehai Yin, Yuanlin Piao","doi":"10.1155/jdr/1934049","DOIUrl":"https://doi.org/10.1155/jdr/1934049","url":null,"abstract":"<p><p>Diabetic nephropathy (DN) is a leading cause of end-stage renal disease, and current therapies often fail to adequately address oxidative stress-induced podocyte injury. Huangqi Tujian Decoction (HTD), a traditional Chinese herbal formula, has shown promise in the clinical management of DN, yet its molecular mechanisms remain incompletely understood. This study aimed to elucidate the protective role of HTD and its interplay with glutathione S-transferase P1 (GSTP1) and the Rac1-mineralocorticoid receptor (MR) signaling pathway. Integrated bioinformatic analysis of human DN transcriptomes identified GSTP1 as a central hub gene. In vivo studies using db/db mice and streptozotocin-induced GSTP1-knockout models revealed that HTD significantly improved renal function; reduced albuminuria, serum creatinine, and blood urea nitrogen levels; and restored podocyte integrity markers (ZO-1 and Nephrin). HTD treatment also suppressed Rac1-MR activation and downregulated NADPH oxidase subunits, thereby alleviating oxidative stress and apoptosis. Importantly, GSTP1 deficiency completely abolished these protective effects. Coimmunoprecipitation assays demonstrated direct binding between GSTP1 and both Rac1 and MR, suggesting that GSTP1 disrupts the pathogenic Rac1-MR complex. In summary, HTD ameliorates DN by normalizing GSTP1 expression toward physiological levels, thereby disrupting the pathogenic Rac1-MR complex and attenuating oxidative damage and podocyte injury. These findings reveal a novel molecular pathway for HTD and highlight GSTP1 as a promising therapeutic target and potential biomarker for DN.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e1934049"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations Between a Surrogate Index of Insulin Resistance and Hyperuricemia in Young and Middle-Aged Patients With Type 2 Diabetes Mellitus.","authors":"Hongping Wang, Yunyi Yang, Jie Gao, Tao Lei, Juan Xia, Cuiping Zhang, Tian Shen, Jun Lu, Zongjun Liu","doi":"10.1155/jdr/6682372","DOIUrl":"10.1155/jdr/6682372","url":null,"abstract":"<p><strong>Background: </strong>This study is aimed at examining the associations between insulin resistance (IR) surrogate indices, including TyG, TyG-BMI, TG/HDL-C, and METS-IR, and hyperuricemia (HUA) in young and middle-aged patients with Type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>A total of 1005 patients with T2DM were included in this cross-sectional study. Participants were classified into HUA and nonhyperuricemia (NHUA) groups according to serum uric acid concentrations and further stratified by age into young (18-44 years) and middle-aged (45-59 years) subgroups. Multivariable logistic regression analyses were performed to assess the associations between IR surrogate indices and HUA. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the discriminatory ability of these indices for HUA across sex- and age-specific subgroups.</p><p><strong>Results: </strong>All IR surrogate indices were significantly higher in the HUA group than in the NHUA group. TyG and TG/HDL-C showed stable associations with HUA across the regression models, while the association for TyG-BMI was attenuated after additional adjustment when modeled continuously, although individuals in the highest quartile remained associated with higher odds of HUA. METS-IR was associated with HUA only in unadjusted models. Age-stratified analyses showed that none of the IR surrogate indices remained significantly associated with HUA after multivariable adjustment in younger patients, whereas TyG and TG/HDL-C remained associated with higher odds of HUA in middle-aged patients. ROC analyses indicated limited to moderate discriminatory performance (AUC < 0.75). TyG-BMI showed the highest AUC in younger patients (AUC = 0.715), while TG/HDL-C demonstrated relatively higher specificity in middle-aged patients. Sex-stratified analyses showed slightly higher AUC values in males than in females, although overall discrimination remained modest.</p><p><strong>Conclusion: </strong>IR surrogate indices showed varying associations with HUA in young and middle-aged patients with Type 2 diabetes. TyG and TG/HDL-C showed relatively stable associations with HUA across the regression models, whereas the associations for TyG-BMI and METS-IR were attenuated after additional adjustment. Overall, these indices demonstrated limited discriminatory performance and are not suitable as standalone diagnostic tools but may serve as adjunctive markers for preliminary risk stratification.</p>","PeriodicalId":15576,"journal":{"name":"Journal of Diabetes Research","volume":"2026 1","pages":"e6682372"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368650","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}