{"title":"Global burden of chronic liver disease due to NAFLD from 2012 to 2021: A trend, decomposition, and health inequality analysis.","authors":"Yanrui Wu, Zongbiao Tan, Zhou Liu, Yupei Liu, Chuan Liu, Junhai Zhen, Jixiang Zhang, Weiguo Dong","doi":"10.1186/s13098-025-01932-0","DOIUrl":"10.1186/s13098-025-01932-0","url":null,"abstract":"<p><strong>Background: </strong>Non-alcoholic fatty liver disease (NAFLD) is considered to be an important driver of the increasing burden of chronic liver disease (CLD) worldwide. It is necessary to analyze the burden of CLD due to NAFLD (CLD-NAFLD) systematically.</p><p><strong>Methods: </strong>Data related to CLD-NAFLD burden from 2012 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. The temporal trend of the incidence and disability-adjusted life years (DALYs) was quantified by average annual percentage change (AAPC). The driving factors of the incidence/DALYs change were explored through decomposition analysis. Slope index and concentration index were employed to investigate cross-country health inequalities.</p><p><strong>Results: </strong>During 2012-2021, the global age-standardized incidence rate (ASIR) of CLD-NAFLD increased from 551.52 to 592.78 (per 100,000 population), while the age-standardized DALY rate (ASDR) decreased from 31.92 to 30.90 (per 100,000 population). North Africa and Middle East had the highest age-standardized prevalence rate (ASPR), East Asia experienced the most rapid increase in ASIR, and Caribbean exhibited the most substantial increase in ASDR. Decomposition analysis showed that the main factors driving the increase in incident cases were population growth and epidemiologic changes, whereas population aging and population growth were the main driving factors for the increase of DALYs. There was cross-country health inequality in the DALYs, which showed a decreasing trend from 2012 to 2021. However, the health inequality in incidence was not significant.</p><p><strong>Conclusions: </strong>The burden of CLD-NAFLD continues to increase. Health policy makers must develop corresponding strategies for the primary health care of metabolic diseases.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"371"},"PeriodicalIF":3.9,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148173","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 elevated Alpha-1-Acid glycoprotein with MAFLD prevalence in young and middle-aged women: a cross-sectional study based on NHANES 2017-2020.","authors":"Yi Xiao, Xian Luo, Yinghao Fu, Haijuan Huang, Qiaoping Gao, Jiansong Liu, Daxin Pang, Xiaolu Liang, Huadi Chen, Hao Xu","doi":"10.1186/s13098-025-01931-1","DOIUrl":"10.1186/s13098-025-01931-1","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent metabolic condition lacking sensitive and accessible biomarkers for early detection and risk stratification.</p><p><strong>Objective: </strong>To investigate the association between serum alpha-1-acid glycoprotein (AGP) levels and MAFLD prevalence among young and middle-aged women, and to evaluate the dose-response relationship and diagnostic performance of AGP.</p><p><strong>Methods: </strong>Data were obtained from 2,003 female participants aged 20-49 years in the NHANES 2017-2020 cycles. Weighted multivariable logistic regression models assessed the association between AGP and MAFLD, with adjustments for demographic, metabolic, and inflammatory covariates. Restricted cubic spline (RCS) regression evaluated nonlinear trends, and ROC analysis assessed predictive accuracy.</p><p><strong>Results: </strong>Higher AGP levels were significantly associated with increased MAFLD risk. In the fully adjusted model, the highest AGP tertile had an odds ratio of 2.63 (95% CI: 1.65-4.19) compared to the lowest. RCS analysis showed a nonlinear, biphasic relationship with an inflection point around 0.9 g/L. ROC analysis indicated moderate discriminatory ability (AUC = 0.734), with AGP outperforming traditional liver enzymes. Subgroup analyses confirmed consistency across metabolic risk strata.</p><p><strong>Conclusion: </strong>AGP is independently and nonlinearly associated with MAFLD and may serve as a non-invasive biomarker for early identification of at-risk individuals. These findings support the potential clinical utility of AGP in MAFLD screening and risk assessment.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"370"},"PeriodicalIF":3.9,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12459064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136928","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: Type 1 diabetes in Brazil: a narrative overview of the Brazilian Type 1 Diabetes Study Group.","authors":"Marilia Brito Gomes, Carlos Antonio Negrato","doi":"10.1186/s13098-025-01921-3","DOIUrl":"10.1186/s13098-025-01921-3","url":null,"abstract":"","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"368"},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130304","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 high-density lipoprotein-related inflammatory indicators with diabetic foot ulcer in patients with diabetes: a population-based study.","authors":"Renhe Deng, Ruyi Tao, Huiyi Luo, Yueqi Gu, Mengyu Yang, Chaoqi Yin","doi":"10.1186/s13098-025-01962-8","DOIUrl":"10.1186/s13098-025-01962-8","url":null,"abstract":"<p><strong>Background: </strong>Early identification and treatment of diabetic foot ulcer (DFU) in diabetes mellitus (DM) patients is of great importance for improving life quality. This study aimed to investigate the association between high-density lipoprotein (HDL)-related inflammatory indicators, such as neutrophils-to-HDL ratio (NHR), monocyte-to-HDL ratio (MHR), lymphocyte-to-HDL ratio (LHR), platelet-to-HDL ratio (PHR), and the occurrence of DFU in DM patients.</p><p><strong>Methods: </strong>This study included 1211 DM patients from the National Health and Nutrition Examination Survey (1999-2004). The relationship between HDL-related inflammatory indicators and DFU was explored with logistic regression models. Using a threshold effects analysis model, the association and inflection points between HDL-related inflammatory indicators and diabetic foot ulcer were investigated. Subgroup analyses were performed to further confirm the relationship in different populations. Mediation analysis was conducted to examine how red blood cell mediates the relationship between HDL-related inflammatory indicators and DFU.</p><p><strong>Results: </strong>After multivariable adjustment, there is a strongly positive relationship between NHR, MHR, PHR, and DFU, whereas no such associations were found between LHR and DFU. Threshold effect analysis showed an inflection point of 0.29 between MHR and DFU, with a 4.51-fold increase in the prevalence of DFU for each unit rise in MHR when MHR was more than the inflection point. Mediation analysis revealed that red blood cell partially mediates the association between NHR and DFU.</p><p><strong>Conclusions: </strong>These findings reveal a clear association between NHR, MHR, PHR, and an increased prevalence of DFU, which can be used as potential biomarkers in the prevention and management of DFU.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"369"},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130319","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":"Serum copper modulates cognitive function in diabetic patients via an HDL-C-mediated pathway: identification of a 25 µg/dL exploratory threshold.","authors":"Jianlong Zhou, Wenxiang Shi, Yayi Jiang, Yadi Li, Rensong Yue","doi":"10.1186/s13098-025-01938-8","DOIUrl":"10.1186/s13098-025-01938-8","url":null,"abstract":"<p><strong>Background: </strong>Diabetes-associated cognitive dysfunction (DACD), a prevalent complication of diabetes with learning, memory, and executive function impairments, lacks targeted therapeutic options. While trace elements, oxidative stress, and inflammation are linked to DACD, the role of serum copper and its interaction with inflammatory/oxidative biomarkers in cognitive regulation remains unclear in diabetic populations.</p><p><strong>Methods: </strong>This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014, including 1,149 participants (861 non-diabetic, 288 diabetic). Cognitive function was assessed via the Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST). Serum copper levels were measured, alongside inflammatory indices: neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, neutrophil-to-monocyte-lymphocyte ratio, systemic immune-inflammation index and systemic inflammation response index; and oxidative stress markers: γ-glutamyl transferase, uric acid, and high-density lipoprotein cholesterol (HDL-C). Associations were analyzed using multivariable linear regression, causal mediation analysis, restricted cubic spline models and sex/age subgroup stratification.</p><p><strong>Results: </strong>Diabetic participants had lower DSST scores than non-diabetic individuals (P < 0.001). In diabetic participants, serum copper was negatively associated with AFT scores (β = - 0.132, P = 0.034) and positively correlated with HDL-C (β = 0.559, P = 2.11e-06). HDL-C was the sole factor that statistically mediated the association between serum copper and DSST scores (average causal mediation effect = 0.095, 95% CI: 0.046-0.153, P < 0.001). A non-linear relationship emerged: HDL-C remained stable at serum copper < 20 µg/dL but increased significantly when copper exceeded 25 µg/dL (P < 0.001). Stratified analyses revealed threshold heterogeneity (all P < 0.05): males had a lower serum copper threshold (24.5 µg/dL, 95% CI: 21.8-27.2) than females (26.1 µg/dL, 95% CI: 23.4-28.8), and adults ≥ 65 years had a higher threshold (27.3 µg/dL, 95% CI: 24.5-30.1) than those < 65 years (23.8 µg/dL, 95% CI: 21.1-26.5).</p><p><strong>Conclusions: </strong>This study identifies a diabetes-specific statistical association between serum copper, HDL, and cognitive function in DACD. The 25 µg/dL copper threshold (exploratory inflection point) marks where HDL-C-mediated effects become prominent, while sex- and age-specific threshold differences highlight population heterogeneity. This threshold offers a reference for trace element-lipid interaction research but requires validation in independent cohorts before potential use in DACD risk stratification.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"367"},"PeriodicalIF":3.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946093","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":"Comparison of nine insulin resistance surrogates for predicting cardiovascular disease: a cohort study.","authors":"Haoqi Zhou, Yu Shi, Xiaohua Zhou","doi":"10.1186/s13098-025-01933-z","DOIUrl":"10.1186/s13098-025-01933-z","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) is an established independent risk factor for cardiovascular disease (CVD). Although numerous simple surrogate indicators for IR have been proposed, their comparative predictive utility for CVD remains unclear. This study aimed to evaluate the associations between nine IR surrogate indicators and incident CVD and to comparatively assess their predictive capacities using nationally representative data from China.</p><p><strong>Methods: </strong>7,662 participants without CVD from the China Health and Retirement Longitudinal Study (CHARLS) were included in the study. Nine IR surrogate measures including triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein ratio (TG/HDL), metabolic score for insulin resistance (METS-IR), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), atherogenic index of plasma (AIP), triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist circumference (TyG-WC), and triglyceride glucose-waist-to-height ratio (TyG-WHtR) were calculated. Cox model and restricted cubic spline model were used to estimate the relationships between distinct IR surrogates and incident CVD. We also computed the time-dependent Harrell's concordance index (C-index) to compare the predictive performance of IR surrogates.</p><p><strong>Results: </strong>After a mean follow-up duration of 8.2 years, a total of 1,906 individuals developed CVD. The full adjusted cox model revealed that per SD increase in all IR indicators was significantly associated with elevated CVD risk, with the hazard ratio (95%CI) of 1.09 (1.04-1.14) for TyG; 1.05 (1.01-1.10) for TG/HDL-C; 1.09 (1.03-1.14) for METS-IR; 1.13 (1.08-1.19) for CVAI; 1.07 (1.03-1.12) for LAP; 1.08 (1.03-1.13) for AIP; 1.10 (1.05-1.15) for TyG-BMI; 1.11 (1.06-1.16) for TyG-WC; and 1.11 (1.05-1.16) for TyG-WHtR. Predictive performance analysis showed TyG had the highest C-index of 0.742 (95% CI, 0.737-0.747).</p><p><strong>Conclusions: </strong>Among nine IR surrogates, the TyG index exhibited the highest predictive performance for incident CVD in Chinese middle-aged and older adults. Acknowledging limitations such as the observational design and self-reported outcomes, our findings support the TyG index as a simple, powerful, and clinically accessible tool for early CVD risk prediction.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"365"},"PeriodicalIF":3.9,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946165","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}
Mayra Souza Botelho, Julia Simões Correa Galendi, Mariana Andrades Fiorini Monteiro Novo, Vania Dos Santos Nunes-Nogueira
{"title":"Efficacy of intermittently scanned continuous glucose monitoring in patients with types 1 or 2 diabetes receiving insulin therapy: a systematic review and meta-analysis.","authors":"Mayra Souza Botelho, Julia Simões Correa Galendi, Mariana Andrades Fiorini Monteiro Novo, Vania Dos Santos Nunes-Nogueira","doi":"10.1186/s13098-025-01935-x","DOIUrl":"10.1186/s13098-025-01935-x","url":null,"abstract":"<p><strong>Background: </strong>Monitoring glucose levels is crucial for managing glycemic control. Methods include self-monitored blood glucose (SMBG), continuous glucose monitoring (CGM), and intermittently scanned continuous glucose monitoring (isCGM).</p><p><strong>Objective: </strong>To assess the efficacy of isCGM versus SMBG in individuals with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) on insulin therapy.</p><p><strong>Methods: </strong>We conducted a systematic review including randomized controlled trials involving patients over 4 years old with T1DM or T2DM on multiple daily insulin regimens, comparing isCGM to SMBG. The outcomes analyzed were HbA1c (%), time below the target glucose range (TBR), patient satisfaction (DTSQ), device-related adverse events, time in range (TIR), and hypoglycemic events. Searches were performed in MEDLINE, EMBASE, and CENTRAL. Two independent reviewers screened studies, assessed the risk of bias, and extracted data. The meta-analyses employed a random-effects model, and the certainty of evidence was evaluated via the GRADE system.</p><p><strong>Results: </strong>Seventeen studies with 1,860 participants were included. The isCGM demonstrated a moderate certainty of evidence for reducing HbA1c (Mean difference [MD]: -0.25%, 95% confidence interval [95% CI]: -0.39- -0.10%; I²: 82.6% 13 studies; 1,482 patients) and enhancing patient satisfaction (MD: 4.5, 95% CI: 2.18- 6.82; I²: 92.9%; 10 studies; 1,150 patients). Meta-regression revealed that intervention duration was a significant moderator of HbA1c reduction. isCGM also favored a reduction in TBR, with an MD of -0.15% (95% CI: -0.23- -0.07%; I²: 96.7% 8 studies; 1,094 patients; low certainty). Mild device-related adverse events were more common in the isCGM group (Relative risk: 2.69, 95% CI: 1.5- 4.81; I²: 0%; 7 studies; 991 participants; moderate certainty). The overall frequency of participants who discontinued isCGM due to cutaneous adverse events was 1% (95% CI: 0-6%; 7 studies; 533 participants). No clear effects were observed for TIR (MD: 0.02%, 95% CI: -0.05- 0.1%; I²: 79.6%; 11 studies; 1,318 patients; very low certainty) or hypoglycemic episodes.</p><p><strong>Conclusions: </strong>Compared with SMBG, isCGM reduces HbA1c, enhances patient satisfaction, and reduces TBR. However, it may increase the incidence of mild device-related adverse events. No definitive effects were observed on the TIR or hypoglycemia frequency.</p><p><strong>Prospero registration: </strong>CRD42024562805.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"366"},"PeriodicalIF":3.9,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946156","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 CALLY index with NAFLD in U.S. adults from NHANES 2017-2020 assessed by vibration-controlled transient elastography.","authors":"Xunge Lin, Xiaozhen Huang, Ziqun Yi, Minran Li, Xujing Liang","doi":"10.1186/s13098-025-01926-y","DOIUrl":"10.1186/s13098-025-01926-y","url":null,"abstract":"<p><strong>Background: </strong>Non‑alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation and is closely associated with inflammation and metabolic dysregulation. The C‑reactive protein-albumin-lymphocyte (CALLY) index, a composite marker of inflammation, immunity, and nutritional status, remains understudied in relation to NAFLD.</p><p><strong>Methods: </strong>A crosssectional analysis was conducted using data from 7,271 U.S. adults in NHANES 2017-2020. NAFLD was defined by vibrationcontrolled transient elastography with a controlled attenuation parameter (CAP) > 274 dB/m. Weighted logistic regression, restricted cubic spline (RCS) modeling, and twopiecewise logistic regression were applied to assess linear and nonlinear associations between the CALLY index and NAFLD prevalence. Subgroup and sensitivity analyses were performed to evaluate the consistency and robustness of the findings.</p><p><strong>Results: </strong>The mean CALLY index was 8.08 (SD 12.42). Higher CALLY levels were inversely associated with NAFLD prevalence ( OR = 0.96; 95% CI, 0.95-0.98). Compared with the lowest quartile (Q1 < 1.90), the highest quartile (Q4 > 10.00) showed a 61% lower prevalence of NAFLD (OR = 0.39; 95% CI, 0.24-0.64). RCS analysis demonstrated a significant nonlinear relationship, with a threshold at 8.91; below this value, each unit increase in the CALLY index corresponded to a 10% reduction in NAFLD prevalence (OR = 0.90; 95% CI, 0.88-0.92). Subgroup and sensitivity analyses yielded consistent results, confirming the robustness of these findings.</p><p><strong>Conclusion: </strong>The CALLY index demonstrates a significant inverse association with NAFLD prevalence and may serve as a simple composite indicator for identifying individuals at higher likelihood of NAFLD, providing additional insights to inform future screening and risk‑stratification research.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"363"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946105","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":"Activation of M1 macrophages promotes diabetic kidney disease by modulating glycolysis via HIF-1α-HK2 signaling pathway.","authors":"Xiaoyan Pei, Lijuan Lu, Ziqiong Huang, Yu Wei, Yu Li, Qiong Wang, Yanli Yang, Langen Zhuang, Guoxi Jin","doi":"10.1186/s13098-025-01894-3","DOIUrl":"10.1186/s13098-025-01894-3","url":null,"abstract":"<p><strong>Objective: </strong>Macrophages and glycolysis play a pivotal role in diabetic kidney disease (DKD). However, the regulation of macrophage glycolysis and its mechanism are still unclear in DKD. Thus, this research intends to investigate the regulatory mechanism of macrophage glycolysis during DKD.</p><p><strong>Methods: </strong>Macrophage polarization in patients with DKD and in mice was assessed using RT-qPCR and immunofluorescence. DKD was induced in the mice through injection of streptozotocin, and a high-fat diet was administered. Hematoxylin and eosin staining and Masson's trichrome staining were employed to identify pathological alterations and visualize renal collagen fibers in the model mice. Glycolytic metabolite levels were quantified using a commercially available kit. Protein levels of HK2, PFK1, LDH, PK1, and GLUT1 were analyzed via western blotting. Hkb-20 cells exposed to high glucose were utilized as an in vitro experimental model. THP-1 cells were co-cultivated with Hkb-20 cells. The impact of macrophage polarization on the functionality of Hkb-20 cells was assessed through CCK8 assay, flow cytometry, and wound healing assay. Levels of IL-6, IL-1β, and TNF-α were evaluated using ELISA kits. Immunofluorescence staining was employed to examine the co-localization of hypoxia-inducible factor-1 (HIF-1α) and HK2.</p><p><strong>Results: </strong>We found that M1 macrophage polarization and enhanced glycolysis activity emerged in DKD patients and mice. Furthermore, we demonstrated that M1 macrophage polarization promotes glycolysis activity in macrophage and model mice. Moreover, we found that HIF-1α and HK2 were obviously enhanced in the serum of DKD cases and mice. Mechanically, we revealed that HIF-1α participates in M1 macrophage polarization and glycolysis activity in vitro by activating HK2 transcription.</p><p><strong>Conclusion: </strong>We demonstrated that M1 macrophage polarization mediated glycolysis contributed to DKD via regulating HIF-1α-HK2 signaling pathway.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"362"},"PeriodicalIF":3.9,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946181","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}