{"title":"SP1-activated CFL2 promotes high glucose-induced retinal pigment epithelial cell injury and involves the AMPK/mTOR pathway.","authors":"Jinan Xiao, Jingni Yu, Mei Ren","doi":"10.1111/jdi.70144","DOIUrl":"https://doi.org/10.1111/jdi.70144","url":null,"abstract":"<p><strong>Background: </strong>Cofilin-2 (CFL2) belongs to the cofilin family of actin-binding proteins and plays an important role in the actin homeostasis of muscle cells. CFL2 has been confirmed to regulate diabetic retinopathy (DR) progression. However, the current research is limited and more evidence is needed to reveal its role and mechanism in the DR process.</p><p><strong>Methods: </strong>Retinal pigment epithelial (RPE) cells (ARPE-19) were cultured in high-glucose (HG; 30 mM) conditions to mimic DR cell models. Cell proliferation and apoptosis were examined by CCK8 assay, EdU assay, flow cytometry, and caspase 3 activity detection. Cell oxidative stress, ferroptosis, and inflammation were evaluated by detecting ROS, MDA, SOD, GSH, Fe<sup>2+</sup>, TNF-α, and IL-1β levels. The mRNA and protein levels of CFL2 and special protein 1 (SP1) were tested by qRT-PCR and western blot. CFL2 and SP1 interaction was assessed by ChIP assay and dual-luciferase reporter assay.</p><p><strong>Results: </strong>HG suppressed ARPE-19 cell proliferation, while inducing apoptosis, oxidative stress, ferroptosis, and inflammation. Silencing of CFL2 alleviated HG-induced ARPE-19 cell injury by inhibiting cell apoptosis, oxidative stress, ferroptosis, and inflammation. SP1 could bind to CFL2 promoter regions to increase its expression. SP1 knockdown relieved HG-induced ARPE-19 cell injury via decreasing CFL2 expression. Besides, SP1 knockdown inhibited the activity of the AMPK/mTOR pathway, and CFL2 overexpression could reverse this effect.</p><p><strong>Conclusions: </strong>CFL2, activated by SP1, promoted HG-induced RPE cell injury through regulating the AMPK/mTOR pathway, which might provide a potential target for DR.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937467","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":"Dysregulation of miR-21-5p in diabetic nephropathy and its role in inflammatory response.","authors":"Yujiang Zhang, Qin Deng, Jianping Yi","doi":"10.1111/jdi.70098","DOIUrl":"https://doi.org/10.1111/jdi.70098","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) is an important microvascular complication of diabetes. MicroRNAs play an important role in the development of DN.</p><p><strong>Aims: </strong>This study aims to examine the expression and clinical significance of serum miR-21-5p in patients with type 2 diabetes mellitus (T2DM) and DN.</p><p><strong>Methods: </strong>This study enrolled a total of 106 T2DM patients, 106 T2DM patients with DN, and 70 healthy individuals. Real-time fluorescence quantitative PCR (RT-qPCR) was used to detect the expression of miR-21-5p, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-21-5p in DN. Pearson correlation analysis was performed to examine the association between miR-21-5p levels and estimated glomerular filtration rate (eGFR), urinary protein excretion rate (UAER) and other clinicopathological parameters of glomerulonephritis. Furthermore, the effects of miR-21-5p on the function and inflammation of human glomerular mesangial cells (HMCs) were analyzed.</p><p><strong>Results: </strong>Serum miR-21-5p is upregulated in DN and it can effectively distinguish DN patients from T2DM patients. Pearson correlation analysis showed a negative correlation between miR-21-5p and eGFR and a positive correlation with UAER. Finally, the knockdown of miR-21-5p reduced the levels of pro-inflammatory cytokines induced by high glucose (HG) and the proliferation of HMCs.</p><p><strong>Conclusions: </strong>Serum miR-21-5p is upregulated in DN and it might be a diagnostic marker for DN. Furthermore, miR-21-5p may be involved in the occurrence and progression of DN by regulating cell proliferation and inflammatory responses and is expected to become a potential therapeutic target for DN.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937405","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":"Critical methodological concerns regarding the nomogram prediction model for DKA in elderly diabetic patients.","authors":"Xiaoyan Zhang, Yingxia Jiang","doi":"10.1111/jdi.70145","DOIUrl":"https://doi.org/10.1111/jdi.70145","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937434","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":"Commentary on \"Liver function effects of SGLT2 inhibitor and GLP-1 receptor agonist combination treatment in patients with type 2 diabetes (post hoc analysis of RECAP study)\".","authors":"Yu Zhang, Yiyan Han, Qu Zheng, Xingxing Lin","doi":"10.1111/jdi.70143","DOIUrl":"10.1111/jdi.70143","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870610","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":"Effects of Tai Chi Chuan on balance function in adults 60 years or older with type 2 diabetes and mild cognitive impairment in China: A secondary analysis of a multi-center randomized clinical trial.","authors":"Jiawei Qin, Jia Huang, Jue Liu, Yannan Chen, Jia Luo, Liyuan Tao, Zhizhen Liu, Weilin Liu, Ying Xu, Shengxiang Liang, Cong Chen, Qiang Tang, Zhuhong Chen, Shangjie Chen, Lidian Chen, Jing Tao","doi":"10.1111/jdi.70138","DOIUrl":"https://doi.org/10.1111/jdi.70138","url":null,"abstract":"<p><strong>Aims: </strong>To investigate the effect of Tai Chi Chuan on balance function in adults 60 years or older with type 2 diabetes and mild cognitive impairment (MCI) in China.</p><p><strong>Materials and methods: </strong>This was a three-arm, parallel-group, randomized controlled trial with concealed allocation, assessor blinding, intention-to-treat (ITT), and per-protocol (PP) analysis. 328 adults 60 years or older, with a diagnosis of both type 2 diabetes and MCI, were randomly allocated into Tai Chi Chuan group, fitness walking group, and control group. All three groups were provided with a 30-min diabetes self-management education session, once every 4 weeks, for 24 weeks. In addition, the Tai Chi Chuan group received 24-form simplified Tai Chi Chuan. The fitness walking group received fitness walking training. Both Tai Chi Chuan and fitness walking groups took the training for 60 min/session, three times/week, for 24 weeks in a supervised setting. After completing the 24-week interventions, the participants were encouraged to continue exercise until the 36-week follow-up evaluation. The outcomes were time up and go (TUG) assessments, one leg standing test (OLST), functional reach test (FRT), grip strength, 5 time sit to stand test (5STS), modified fall efficacy scale (MFES), and falls data at baseline, 24 weeks, and 36 weeks follow-up.</p><p><strong>Results: </strong>At 36 weeks, the Tai Chi Chuan group was significantly more effective in decreasing the TUG-cognitive-motor (mean difference, -0.72; 95% CI -1.37 to -0.06), OLST (eyes-closed, right leg) (mean difference, 1.02; 95% CI 0.24-1.80), FRT (mean difference, 2.00; 95% CI 0.57-3.42), 5STS (mean difference, -0.66; 95% CI -1.28 to -0.04), and MFES (mean difference, 0.36; 95% CI 0.15-0.56) compared with the fitness walking group. The Tai Chi Chuan group showed significantly fewer total falls during 36-week experimental period compared with the fitness walking group. PP analysis demonstrated similar results as the ITT analysis.</p><p><strong>Conclusions: </strong>Among the older adults with type 2 diabetes and MCI, Tai Chi Chuan was more effective than fitness walking and control at improving balance function and reducing fall risk.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870612","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":"Effectiveness of the presence of diabetologists for perioperative complications in patients with diabetes undergoing colorectal cancer surgery: A nationwide inpatient database in Japan.","authors":"Masataka Shikata, Atsushi Goto, Sayuri Shimizu, Nozomu Kamei, Daisuke Chujo, Itaru Endo, Akira Shimada, Kiyohide Fushimi, Kohjiro Ueki, Kazuyuki Tobe","doi":"10.1111/jdi.70139","DOIUrl":"https://doi.org/10.1111/jdi.70139","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Little is known about the effect of diabetologists on perioperative complication risk. Given that colorectal cancer surgery is known to carry a high complication risk among patients with diabetes, this study aimed to examine the association between the presence of diabetologists at the facility level and the risk of perioperative complications during colorectal cancer surgery.</p><p><strong>Materials and methods: </strong>In this retrospective cohort study, we sourced the number of board-certified diabetologists from the Japan Diabetes Society and combined it with Diagnosis Procedure Combination (DPC) data, encompassing receipt data from acute care facilities across Japan. We used a modified Poisson model to estimate the risk of perioperative complications associated with the presence of diabetologists by adjusting for potential confounding patient and facility factors.</p><p><strong>Results: </strong>Analysis included 887 facilities, of which 299 (34%) had no diabetologists. A total of 24,714 patients with diabetes underwent colorectal cancer surgery between April 2018 and March 2019, with a median age of 73 years (interquartile range: 67-79 years) and 16,274 (66%) men. There were 3,165 (13%) perioperative complications. After adjustment, the risk of perioperative complications was 0.86 times (95% confidence interval: 0.77-0.96) lower in centers with at least one diabetologist than in those without a diabetologist.</p><p><strong>Conclusions: </strong>Our study suggests that the presence of a diabetologist may be important in reducing the risk of perioperative complications during colorectal cancer surgery in patients with diabetes. Future studies factoring in other facility factors and surgical types may be required to further validate our findings.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870611","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":"Letter to the Editor in response to the article 'Retrospective analysis of influences of sacubitril/valsartan in patients with diabetes with poorly controlled blood pressure in Japan'.","authors":"Daniyal Khalid, Muhammad Saim Siddiqui","doi":"10.1111/jdi.70142","DOIUrl":"https://doi.org/10.1111/jdi.70142","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854082","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":"Non-linear relationship between liver fibrosis and femoral neck bone mineral density in metabolic dysfunction-associated fatty liver disease patients with type 2 diabetes mellitus.","authors":"Jie Tao, Lin Wang, Honggang Wang, Juan Tan","doi":"10.1111/jdi.70129","DOIUrl":"https://doi.org/10.1111/jdi.70129","url":null,"abstract":"<p><strong>Aim: </strong>While both metabolic dysfunction-associated fatty liver disease (MAFLD) and osteoporosis are closely linked to metabolic disorders, their relationship remains controversial. This study aimed to investigate the association between liver fibrosis and femoral neck bone mineral density (BMD) in MAFLD patients with type 2 diabetes mellitus (T2DM-MAFLD) and to evaluate metabolic influences.</p><p><strong>Materials and methods: </strong>We retrospectively enrolled 569 hospitalized T2DM-MAFLD patients between September 2018 and May 2021. Liver fibrosis was assessed using the Fibrosis-4 score (FIB-4), and femoral neck BMD was measured by dual-energy X-ray absorptiometry. Generalized additive models evaluated non-linear relationships, piecewise linear regression identified threshold effects, and stratified analyses explored metabolic modifiers.</p><p><strong>Results: </strong>A non-linear, inverted U-shaped relationship was observed between FIB-4 and femoral neck BMD in postmenopausal women and men ≥50 years, with a turning point at FIB-4 = 2.091. Below this threshold, FIB-4 showed a significant positive correlation with femoral neck BMD (β = 0.039, 95%CI: 0.006-0.072, P = 0.020). Above the threshold, the association became negative but non-significant (β = -0.032, 95%CI: -0.075 to 0.011, P = 0.141). Stratified analysis revealed that in patients with triglycerides ≥1.7 mmol/L, FIB-4 was significantly negatively correlated with femoral neck BMD (β = -0.025, 95%CI: -0.048, -0.003), with a significant interaction effect (P = 0.011).</p><p><strong>Conclusions: </strong>A non-linear association between liver fibrosis and femoral neck BMD was observed in T2DM-MAFLD patients, particularly postmenopausal women and men aged ≥50 years, modulated by serum triglyceride. Hypertriglyceridemia may represent a crucial metabolic risk factor for osteoporosis development in MAFLD patients, suggesting the importance of bone loss screening in this patient population, particularly those with elevated triglycerides.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833561","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":"Anthropometric and lipid indices in relation to prediabetes and diabetes: A cross-sectional study in resource-limited areas of northwestern China.","authors":"Ling Ma, Yin Cheng, Lanqiqi Wu, Hongjuan Shi, Yining Liu, Jinyu Ma, Huitian Tong, Chao Shi","doi":"10.1111/jdi.70137","DOIUrl":"https://doi.org/10.1111/jdi.70137","url":null,"abstract":"<p><strong>Aims: </strong>This cross-sectional study was conducted to assess the association of triglyceridemic-waist phenotype, waist-to-height ratio (WHtR), lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride-glucose (TyG) index with prediabetes and diabetes (PAD) using data from the Ningxia Cardiovascular Disorders and Related Risk Factors Survey.</p><p><strong>Materials and methods: </strong>This study included 10,803 patients. Logistic regression analysis and restricted cubic splines were applied to identify the association between the PAD and each index. The receiver operating characteristic curve was analyzed to identify and compare the discriminative power of different indexes in identifying PAD.</p><p><strong>Results: </strong>A total of 43.87% patients were diagnosed with prediabetes and 11.75% patients were diagnosed with diabetes. After adjusting for confounders, participants with elevated high triglyceride levels with increased waist circumference (HTGW) were associated with a 2.65-fold (odds ratio [OR] 2.65, 95% confidence interval [95% CI] 2.31-3.03) risk of PAD. Comparing with the lowest quartile, those in the highest quartile of WHtR, LAP, VAI, and TyG index had a significantly increased risk of developing PAD. TyG index (area under the curve [AUC] 0.71, 95% CI 0.70-0.72) was better than WHtR (AUC 0.66, 95% CI 0.65-0.67), LAP (AUC 0.68, 95% CI 0.67-0.69), and VAI (AUC 0.65, 95% CI 0.64-0.66) at predicting the risk of PAD.</p><p><strong>Conclusions: </strong>The HTGW and elevated WHtR, LAP, VAI, and TyG index are associated with a greater risk of PAD. The TyG index is a more favorable anthropometric measure for predicting PAD, but its clinical utility needs to be validated in prospective cohorts, especially in resource-limited areas.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820255","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":"Machine learning for the prediction of atherosclerotic cardiovascular disease during 3-year follow up in Chinese type 2 diabetes mellitus patients","authors":"Jinru Ding, Yingying Luo, Huwei Shi, Ruiyao Chen, Shuqing Luo, Xu Yang, Zhongzhou Xiao, Bilin Liang, Qiujuan Yan, Jie Xu, Linong Ji","doi":"10.1111/jdi.14069","DOIUrl":"10.1111/jdi.14069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims/Introduction</h3>\u0000 \u0000 <p>Clinical guidelines for the management of individuals with type 2 diabetes mellitus endorse the systematic assessment of atherosclerotic cardiovascular disease risk for early interventions. In this study, we aimed to develop machine learning models to predict 3-year atherosclerotic cardiovascular disease risk in Chinese type 2 diabetes mellitus patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Clinical records of 4,722 individuals with type 2 diabetes mellitus admitted to 94 hospitals were used. The features included demographic information, disease histories, laboratory tests and physical examinations. Logistic regression, support vector machine, gradient boosting decision tree, random forest and adaptive boosting were applied for model construction. The performance of these models was evaluated using the area under the receiver operating characteristic curve. Additionally, we applied SHapley Additive exPlanation values to explain the prediction model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All five models achieved good performance in both internal and external test sets (area under the receiver operating characteristic curve >0.8). Random forest showed the highest discrimination ability, with sensitivity and specificity being 0.838 and 0.814, respectively. The SHapley Additive exPlanation analyses showed that previous history of diabetic peripheral vascular disease, older populations and longer diabetes duration were the three most influential predictors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The prediction models offer opportunities to personalize treatment and maximize the benefits of these medical interventions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":"14 11","pages":"1289-1302"},"PeriodicalIF":3.2,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jdi.14069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414464","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}