World Journal of Diabetes最新文献

{"title":"Longitudinal assessment of pancreatic exocrine dysfunction in type 1 diabetes.","authors":"Federico Bolado, Lucía Zabalza, Joaquín de-Carlos, Ibai Tamayo-Rodríguez, Carlos Prieto-Martínez, Nerea Hervás-Palacios","doi":"10.4239/wjd.v16.i12.112799","DOIUrl":"10.4239/wjd.v16.i12.112799","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that individuals with type 1 diabetes (T1D) frequently present with reduced fecal elastase levels, suggesting exocrine pancreatic insufficiency. However, the underlying determinants and the longitudinal trajectory of these changes remain poorly understood.</p><p><strong>Aim: </strong>To evaluate longitudinal changes in fecal elastase among individuals with T1D, identify associated factors, and determine clinical implications.</p><p><strong>Methods: </strong>Pancreatic exocrine function was evaluated in a cohort of patients with T1D by measuring fecal elastase concentrations (FECs). After a mean follow-up of 8.5 ± 0.5 years, participants were recontacted, and a second stool sample was obtained. At both time points, detailed medical histories were collected, including information on diabetes progression, metabolic control, complications, gastrointestinal symptoms, and nutritional status. The study was approved by the institutional ethics committee, and written informed consent was obtained from all participants.</p><p><strong>Results: </strong>A total of 106 individuals with T1D (mean age = 46.2 years; 50% male) were enrolled. At baseline, the median FEC was 239.5 µg/g, with 44 participants (41.5%) demonstrating abnormally low levels (< 200 µg/g). Reduced fecal elastase was significantly associated with male sex, diabetes-related complications, particularly retinopathy, and higher glycated hemoglobin levels. No significant differences in gastrointestinal symptoms, body mass index, nor most serum nutritional markers were observed between individuals with normal <i>vs</i> reduced fecal elastase levels. Sixty-six participants completed follow-up. Their median fecal elastase was 171.5 µg/g, with 59.1% presenting levels below 200 µg/g. Paired analysis showed a non-significant decline in FEC s over time. No clinical nor metabolic variables predicted longitudinal changes in FEC independently.</p><p><strong>Conclusion: </strong>Fecal elastase levels are frequently reduced in individuals with T1D and may show a gradual decline over time. The clinical impact of these changes appears to be limited.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"112799"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890326","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":"Liraglutide alleviates diabetic cardiomyopathy in streptozotocin-induced diabetic rats by enhancing mitophagy mediated by the AMPK-Parkin signaling pathway.","authors":"Ya-Xin Zhu, Wei Zhang, Hui-Lin Qu, Yue Zhang, Ruo-Qian Zhou, Ping Li, Fang Wang, Yan Zhang, Hui-Hui Liu, Sha Li, Qian Dong, Ke-Fei Dou, Yuan-Lin Guo, Jian-Jun Li, Rui-Xia Xu","doi":"10.4239/wjd.v16.i12.112423","DOIUrl":"10.4239/wjd.v16.i12.112423","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have shown that liraglutide, a glucagon-like peptide-1 receptor agonist, has unexpected cardioprotective effects. However, the distinctive effects of liraglutide on diabetic cardiomyopathy (DCM), particularly its effect on mitophagy, have not been fully elucidated.</p><p><strong>Aim: </strong>To investigate the effects of liraglutide on cardiac damage and mitophagy in DCM rats.</p><p><strong>Methods: </strong>A high-fat diet and streptozotocin were used to induce DCM in rats. After 12 weeks of liraglutide treatment, rats underwent assessments of cardiac function, serum biochemical parameters, histological changes, apoptosis index, and protein levels. Furthermore, neonatal rat cardiomyocytes (NRCMs) were exposed to 25 mmol/L glucose plus 250 μmol/L palmitate (high glucose + palmitic acid), with or without 200 nmol/L liraglutide, to investigate the effects of liraglutide on cardiomyocyte injury and the underlying mechanisms.</p><p><strong>Results: </strong>Liraglutide improved myocardial function and ameliorated cardiac damage in DCM rats, as indicated by reduced myocardial apoptosis, hypertrophy, and interstitial fibrosis (<i>P</i> < 0.05). In NRCMs, Liraglutide alleviated mitochondrial morphological and functional damage as well as oxidative stress, improved mitophagic defects, and reduced cell apoptosis (<i>P</i> < 0.05). Mechanistically, liraglutide alleviated NRCMs damage by enhancing mitophagy mediated by the adenosine monophosphate-activated protein kinase (AMPK)-Parkin signaling pathway, which was evidenced by the reversal of its effects upon compound C treatment.</p><p><strong>Conclusion: </strong>Liraglutide exerted cardioprotective effects in DCM rats by inhibiting cardiomyocyte apoptosis and promoting mitophagy mediated by the AMPK-Parkin signaling pathway.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"112423"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890382","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 fish scale ointment on diabetic foot ulcer by inducing ferroptosis <i>via</i> the nuclear factor E2-related factor 2 pathway.","authors":"Lin Li, Xiao-Na Liu, Shuang Guo, Yan-Ling Ju, Lan-Yue Guo, Chun-Hua Zhang, Jin-Jun Wang","doi":"10.4239/wjd.v16.i12.111789","DOIUrl":"10.4239/wjd.v16.i12.111789","url":null,"abstract":"<p><strong>Background: </strong>Excessive oxidative stress plays a key role in the development of diabetic complications, including impaired ulcer healing. Previous studies have shown that fish scale ointment can promote wound healing.</p><p><strong>Aim: </strong>To preliminarily investigate the effect of fish scale ointment on wound healing in a diabetic foot ulcer (DFU) rat model by examining its regulation of the nuclear factor E2-related factor 2 (Nrf2) pathway and induction of ferroptosis.</p><p><strong>Methods: </strong>Fish scale ointment (collagen product) was prepared from 500 g of silver carp scales. A diabetic rat model was induced by high-fat and high-sugar feeding combined with intraperitoneal streptozotocin injections. For the DFU rat model, ulcer wounds were created by removing dorsal foot hair and cutting the skin to the fascia. The diabetic rats were randomized into five groups: Model, fish scale collagen (FSC), control + liproxstatin-1 (Lip-1), model + Lip-1, and FSC + Lip-1. In each group, treatments were administered once daily by topical application and intraperitoneal injection for 14 days. Wound healing was evaluated on days 7 and 14 after treatment. Hematoxylin and eosin staining was used to assess wound injury and capillary formation. Basic fibroblast growth factor (bFGF) and CD31 levels in wound tissue were measured by immunohistochemistry. Additionally, malondialdehyde (MDA), glutathione (GSH), ferroptosis-associated genes, and iron ion concentrations were quantified using assay kits. Protein levels of Nrf2, heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) were determined using Western blotting.</p><p><strong>Results: </strong>Compared with the control group, the model group showed slower wound healing, reduced angiogenesis, decreased bFGF and CD31 levels, increased iron ion concentration and MDA levels, reduced GSH levels, and decreased Nrf2, HO-1, and GPX4 protein expression (all <i>P</i> < 0.05). The FSC, model + Lip-1, and FSC + Lip-1 groups showed increased wound healing and angiogenesis, elevated bFGF and CD31 expression, lowered iron ion concentration and MDA levels, increased GSH levels, and enhanced Nrf2, HO-1, and GPX4 protein levels compared with the model group (<i>P</i> < 0.05). Improvements were more pronounced in the FSC + Lip-1 group compared with the FSC group (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>Fish scale ointment promotes angiogenesis and wound healing in DFU rat models by inhibiting ferroptosis, possibly through the activation of the Nrf2 pathway.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 12","pages":"111789"},"PeriodicalIF":4.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12754101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890415","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 cardiorespiratory fitness and impaired vascular function in type 2 diabetes.","authors":"Shi-Ting Zhao, Yi-Ming Zhu, Ying-Ying Chen, Zi-Lin Sun, Shan-Hu Qiu","doi":"10.4239/wjd.v16.i11.111472","DOIUrl":"10.4239/wjd.v16.i11.111472","url":null,"abstract":"<p><strong>Background: </strong>Cardiorespiratory fitness (CRF) is inversely associated with the risk of cardiovascular disease, which is related to impaired vascular function. However, its relationship with vascular function remains unknown in patients with type 2 diabetes.</p><p><strong>Aim: </strong>To assess the relationship of CRF with vascular function in type 2 diabetes.</p><p><strong>Methods: </strong>Patients with type 2 diabetes who were aged ≥ 18 years and underwent an incremental and symptom-limited exercise test were included. Vascular function was assessed by the construction of the vascular health index (VHI), which is defined as a composite score of ankle-brachial index, transcutaneous oxygen pressure, pulse wave velocity, and carotid intima-media thickness. Impaired vascular function is defined as a VHI of < 8 points. Linear and logistic regression analyses were used to assess the associations.</p><p><strong>Results: </strong>We included 343 patients with type 2 diabetes. CRF was positively correlated with VHI <i>(β</i> = 0.10, <i>P</i> = 0.047), particularly with ankle-brachial index and pulse wave velocity. The odds ratio (OR) of impaired vascular function was 0.44 [95% confidence interval (CI): 0.20-0.96] for the highest <i>vs</i> the lowest CRF category. For each one metabolic equivalent increase in CRF, the OR of impaired vascular function was 0.73 (95%CI: 0.57-0.93).</p><p><strong>Conclusion: </strong>Higher CRF was associated with better vascular function and lower odds of impaired vascular function in patients with type 2 diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111472"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589311","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":"Novel Kruppel-like factor 11 variant of maturity-onset diabetes of the young type 7: A case report.","authors":"Mauricio Alvarez, Elias Quintero, Oswaldo Rincon, Carlos Llanos, Rawdy Reales, Isaac Guzman","doi":"10.4239/wjd.v16.i11.111106","DOIUrl":"10.4239/wjd.v16.i11.111106","url":null,"abstract":"<p><strong>Background: </strong>Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes often misdiagnosed as type 1 or type 2. The MODY7 subtype, attributed to variants in the Kruppel-like factor 11 (<i>KLF11</i>) gene, is exceedingly rare, and its clinical spectrum is not fully characterized. Precise genetic diagnosis is essential for appropriate management but is challenging due to phenotypic overlap with other diabetes types. This case report describes a patient with a novel <i>KLF11</i> variant, contributing to the understanding of this rare condition and its clinical implications.</p><p><strong>Case summary: </strong>A 50-year-old female with a family history of MODY in her son was initially diagnosed with type 2 diabetes. Due to the family history and a non-obese phenotype, a comprehensive genetic panel for monogenic diabetes was performed. The analysis identified a novel heterozygous missense variant, p.Cys105Phe, in the <i>KLF11</i> gene, establishing a definitive diagnosis of MODY7. Following this diagnosis, the patient's treatment was adjusted to include lifestyle modifications, resulting in adequate glycemic control. The patient has since maintained target glycated hemoglobin levels.</p><p><strong>Conclusion: </strong>Monogenic diabetes type MODY7, caused by a mutation in the <i>KLF11</i> gene, is extremely rare. Although some studies question its existence, compatible cases continue to be diagnosed, given its inclusion in genetic panels for MODY.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111106"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589389","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":"Mechanisms behind the anti-diabetic and anti-obesity effects of seaweeds or macroalgae and their bioactive compounds.","authors":"S'thandiwe Nozibusiso Magwaza, Md Shahidul Islam","doi":"10.4239/wjd.v16.i11.112847","DOIUrl":"10.4239/wjd.v16.i11.112847","url":null,"abstract":"<p><p>Obesity and diabetes have become global health crises, with rising prevalence and a strong association with various chronic diseases such as cardiovascular disease, stroke, and certain cancers. These conditions contribute to significant morbidity and mortality, highlighting the urgent need for effective therapeutic interventions. Marine products, including fish oils and marine plants, have been increasingly recognized for their potential in mitigating these diseases. Among these, seaweed stands out due to their diverse bioactive compounds and promising therapeutic effects. This comprehensive review explores the mechanisms of action through which seaweeds, and their compounds exert anti-diabetic and anti-obesity effects, including the regulation of adipogenesis, appetite control, modulation of gut microbiota, enhancement of insulin sensitivity, and reduction of inflammation, oxidative stress, and β-cell dysfunction. Despite the promising potential, challenges such as variability of bioactive compounds and low bioavailability remain there. Advances in bioactive delivery systems and along with large-scale clinical trials, are crucial for optimizing the therapeutic use of bioactive compounds from seaweeds. Future research should also explore synergistic strategies combining seaweed compounds with other bioactive substances. Overall, seaweed offers a promising foundation for developing functional foods and nutraceuticals aimed at promoting long-term metabolic health, providing an innovative approach to addressing obesity and diabetes.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"112847"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589471","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 achieving glycated hemoglobin targets on cardiovascular events/mortality: <i>Post-hoc</i> analysis of the nephropathy in diabetes type 2 trial.","authors":"Alfredo Caturano, Vittorio Simeon, Raffaele Galiero, Vincenzo Russo, Luca De Nicola, Paolo Chiodini, Luca Rinaldi, Erica Vetrano, Teresa Salvatore, Caterina Conte, Carlo Acierno, Celestino Sardu, Raffaele Marfella, Roberto Minutolo, Ferdinando C Sasso","doi":"10.4239/wjd.v16.i11.111698","DOIUrl":"10.4239/wjd.v16.i11.111698","url":null,"abstract":"<p><strong>Background: </strong>Achieving optimal glycemic control is a cornerstone of cardiovascular risk reduction in type 2 diabetes (T2D). However, the extent to which multifactorial interventions influence this relationship remains uncertain.</p><p><strong>Aim: </strong>To evaluate the association between glycated hemoglobin (HbA1c) target achievement and long-term cardiovascular outcomes in patients receiving standard of care (SoC) or multifactorial intensive therapy (MT).</p><p><strong>Methods: </strong>This <i>post-hoc</i> analysis of the nephropathy in diabetes type 2 cluster-randomized trial included 323 patients with T2D, albuminuria, and retinopathy (SoC: <i>n</i> = 139; MT: <i>n</i> = 184), who underwent a 4-year intervention phase. Outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. Associations with HbA1c target achievement (≤ 7% <i>vs</i> > 7%) were assessed using Kaplan-Meier curves and shared frailty Cox regression models.</p><p><strong>Results: </strong>During a median follow-up of 12.1 years, 190 MACEs and 139 deaths occurred. Achievement of the HbA1c target was not associated with reduced mortality in either group. However, a significant reduction in MACEs was observed only among SoC patients achieving HbA1c ≤ 7% (<i>P</i> = 0.031), whereas no benefit was seen in the MT group (<i>P</i> = 0.645). In multivariable Cox regression models adjusted for cluster effect, in the MT group age [hazard ratio (HR) = 1.07, <i>P</i> < 0.001] and female sex (HR = 0.38, <i>P</i> < 0.001) were independent predictors of MACE, while in the SoC group only age (HR = 1.04, <i>P</i> = 0.009). For all-cause mortality, age (HR = 1.11, <i>P</i> < 0.001) and blood pressure control (HR = 0.55, <i>P</i> = 0.041) were significant predictors in the MT group, whereas age (HR = 1.06, <i>P</i> = 0.002) was independently associated with increased mortality in the SoC group.</p><p><strong>Conclusion: </strong>In high-risk patients with T2D receiving standard care, achieving an HbA1c ≤ 7% was associated with fewer cardiovascular events only under standard care, but not with reduced mortality. This association was not observed in patients managed with a multifactorial strategy. These findings suggest that the prognostic value of glycemic control depends on the broader treatment context and highlight the central role of comprehensive risk factor management in microvascular-complicated T2D.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111698"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589425","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":"Evolution of the risk concept and assessment tools for diabetes during Ramadan fasting: A narrative review.","authors":"Salem A Beshyah","doi":"10.4239/wjd.v16.i11.110007","DOIUrl":"10.4239/wjd.v16.i11.110007","url":null,"abstract":"<p><strong>Background: </strong>The categorization and assessment of diabetes-related risks during Ramadan have evolved significantly over three decades. Research interest in the health effects of fasting has grown significantly, with diabetes emerging as the most extensively studied condition.</p><p><strong>Aim: </strong>To explore the historical development of risk stratification approaches for Ramadan fasting in people with diabetes, culminating in the 2021 International Diabetes Federation-Diabetes and Ramadan (IDF-DAR) risk assessment tool. We also evaluated the evidence for its validation and real-world utility.</p><p><strong>Methods: </strong>The PubMed and Google Scholar databases were searched using the term \"Diabetes AND Ramadan AND Risk Assessment\". Eligible studies included full-text articles on risk stratification concept and tools for diabetes during Ramadan. Selected studies were reviewed and synthesized thematically.</p><p><strong>Results: </strong>Risk categorization began with a dichotomy and tripartite models and progressed to a four-tier narrative scale. In 2021, the IDF-DAR tool introduced a point-based system with three risk categories. Validation studies across diverse populations demonstrated strong predictive value, though moderate inter-clinician variability and potential overestimation in type 2 diabetes cases were noted.</p><p><strong>Conclusion: </strong>The IDF-DAR risk stratification tool significantly advances individualized diabetes care during Ramadan. Its conservative bias in some populations and variability in physician scoring suggests the need for standardized training.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"110007"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589473","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":"Correction to \"<i>Lactobacillus rhamnosus</i> LRa05 on glycemic control and gut microbiota in patients with type 2 diabetes\".","authors":"Lin Geng, Ting-Ting Sun, Wen-Bo Xia, Ying Qin, Di Huo, Guang-Jin Qu","doi":"10.4239/wjd.v16.i11.114013","DOIUrl":"10.4239/wjd.v16.i11.114013","url":null,"abstract":"<p><p>[This corrects the article on p. 106821 in vol. 16, PMID: 40697596.].</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"114013"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589338","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":"RRM2 attenuates the renal tubular ferroptosis in diabetic kidney disease through PI3K/Akt/Nrf2 pathway.","authors":"Chang-Chun Gao, Fen-Fen Ding, Xia Jiang","doi":"10.4239/wjd.v16.i11.111223","DOIUrl":"10.4239/wjd.v16.i11.111223","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is associated with significant metabolic and renal complications, including diabetic nephropathy (DN).</p><p><strong>Aim: </strong>To investigate the role of ribonucleotide reductase regulatory subunit M2 (RRM2) in T2DM and its potential involvement in renal injury through oxidative stress, apoptosis, and ferroptosis.</p><p><strong>Methods: </strong>A cross-sectional study was conducted, comprising 194 patients with T2DM and 120 healthy controls at our hospital between January 2022 and December 2023. The data were analyzed to ascertain the correlation between RRM2 levels and DN onset in patients with T2DM. The apoptosis rate, reactive oxygen species (ROS) levels, oxidative stress, cystine uptake, and ferrous ion (Fe²⁺) levels were quantified using the HK-2 cell lysates. Reverse transcription quantitative PCR and western blotting were used to assess mRNA and protein expression, respectively.</p><p><strong>Results: </strong>Serum RRM2 levels were significantly higher in T2DM patients than in controls (<i>P</i> < 0.05) but declined in the macroalbuminuria subgroup. Receiver operating characteristic analysis identified 30 pg/mL as the optimal cut-off (area under the curve = 0.958; sensitivity = 86%; specificity = 95%). RRM2 was negatively correlated with age, diabetes duration, systolic blood pressure, fasting blood glucose, glycosylated hemoglobin, serum creatinine, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and malondialdehyde, and positively correlated with estimated glomerular filtration rate, glutathione (GSH), solute carrier family 7 member 11 (SLC7A11), and GSH peroxidase 4 (GPX4). Logistic regression confirmed RRM2 as an independent protective factor against DN [odds ratio (OR) = 0.820, 95% confidence interval (95%CI) = 0.712-0.945, <i>P</i> = 0.006]. <i>In vitro</i>, RRM2 overexpression enhanced HK-2 cell proliferation, activated PI3K/Akt signaling, and reduced apoptosis, ROS, oxidative stress, and ferroptosis, accompanied by the restoration of GSH, Nrf2, SLC7A11, and GPX4. These protective effects were abolished by PI3K/Akt inhibition, highlighting RRM2's renoprotective, pathway-dependent role.</p><p><strong>Conclusion: </strong>These findings suggest that RRM2 plays a crucial protective role against diabetic renal injury by mitigating oxidative stress, apoptosis, and ferroptosis <i>via</i> PI3K/Akt activation. Serum RRM2 may serve as a novel biomarker for early DN detection, and therapeutic strategies targeting RRM2 may offer potential benefits in preventing diabetic kidney disease progression.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 11","pages":"111223"},"PeriodicalIF":4.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12635758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145589660","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}