Fang Yang, Xueyue Sun, Kui Jiang, Mingxin Zhang, Chao Sun
Metabolic Dysfunction–associated Steatotic Liver Disease (MASLD) is a prevalent liver disease worldwide, with its prevalence rising alongside the increase in metabolic syndrome (MetS), obesity and ageing. Machine learning (ML), as a powerful analysis tool to handle and analyse massive data/information, has been employed to enhance and refine the diagnosis, risk assessment, non-invasive screening, and treatment options against MASLD. This review thoroughly explores the application of ML in identifying MASLD-related genes and lipidomic biomarkers, non-invasive screening technologies such as ultrasound and imaging, and predicting the risk of disease progression to metabolic dysfunction–associated steatohepatitis (MASH) or more advanced stages, such as cirrhosis. Additionally, ML models have shown potential and definitive performance in accurately predicting and effectively managing the risk of comorbidities in relation to MASLD. By integrating clinical data, biochemical markers, imaging techniques, and an individual's biochemical metrics, ML offers a personalised medical approach that improves therapeutic strategies and holds promise for significant contributions to public health in the future.
{"title":"Recent Advances in the Application of Machine Learning Models in Metabolic Dysfunction–Associated Steatotic Liver Disease","authors":"Fang Yang, Xueyue Sun, Kui Jiang, Mingxin Zhang, Chao Sun","doi":"10.1002/dmrr.70129","DOIUrl":"10.1002/dmrr.70129","url":null,"abstract":"<p>Metabolic Dysfunction–associated Steatotic Liver Disease (MASLD) is a prevalent liver disease worldwide, with its prevalence rising alongside the increase in metabolic syndrome (MetS), obesity and ageing. Machine learning (ML), as a powerful analysis tool to handle and analyse massive data/information, has been employed to enhance and refine the diagnosis, risk assessment, non-invasive screening, and treatment options against MASLD. This review thoroughly explores the application of ML in identifying MASLD-related genes and lipidomic biomarkers, non-invasive screening technologies such as ultrasound and imaging, and predicting the risk of disease progression to metabolic dysfunction–associated steatohepatitis (MASH) or more advanced stages, such as cirrhosis. Additionally, ML models have shown potential and definitive performance in accurately predicting and effectively managing the risk of comorbidities in relation to MASLD. By integrating clinical data, biochemical markers, imaging techniques, and an individual's biochemical metrics, ML offers a personalised medical approach that improves therapeutic strategies and holds promise for significant contributions to public health in the future.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146114328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gestational diabetes mellitus (GDM) is a common metabolic complication during pregnancy that poses significant risks to both maternal and foetal health. Although its pathogenesis is multifactorial, emerging evidence highlights a potential role of iron metabolism and its dysregulation in the development of GDM. Iron is essential for foetal growth and maternal physiological adaptation during pregnancy. However, both iron deficiency and excess iron are associated with adverse pregnancy outcomes. In particular, excess iron accumulation has been associated with elevated oxidative damage and impaired glucose regulation, potentially contributing to the onset of GDM. Ferroptosis, a regulated cell death caused by iron-dependent lipid peroxidation, has recently emerged as a potential mechanistic link between iron overload and cellular dysfunction in GDM. This review highlights the dynamic regulation of iron metabolism during normal pregnancy and its disruption in GDM. In the context of GDM, ferroptosis is implicated in promoting oxidative stress and lipid peroxidation that disrupts metabolic regulation. Existing research suggests that maternal iron status could serve as a biomarker for early GDM risk assessment and a potential therapeutic target. However, the molecular pathways linking iron metabolism, ferroptosis, and metabolic abnormalities remain uncertain. Further investigations are needed to understand these mechanisms and assess the potential of ferroptosis inhibitors in GDM. Bridging these knowledge gaps could lead to improved strategies for the prediction, prevention, and management of GDM and its associated complications.
{"title":"Death by Iron: Ferroptosis in the Aetiology and Outcome of Gestational Diabetes Mellitus","authors":"S. Monisha, K. L. Milan, K. M. Ramkumar","doi":"10.1002/dmrr.70130","DOIUrl":"10.1002/dmrr.70130","url":null,"abstract":"<p>Gestational diabetes mellitus (GDM) is a common metabolic complication during pregnancy that poses significant risks to both maternal and foetal health. Although its pathogenesis is multifactorial, emerging evidence highlights a potential role of iron metabolism and its dysregulation in the development of GDM. Iron is essential for foetal growth and maternal physiological adaptation during pregnancy. However, both iron deficiency and excess iron are associated with adverse pregnancy outcomes. In particular, excess iron accumulation has been associated with elevated oxidative damage and impaired glucose regulation, potentially contributing to the onset of GDM. Ferroptosis, a regulated cell death caused by iron-dependent lipid peroxidation, has recently emerged as a potential mechanistic link between iron overload and cellular dysfunction in GDM. This review highlights the dynamic regulation of iron metabolism during normal pregnancy and its disruption in GDM. In the context of GDM, ferroptosis is implicated in promoting oxidative stress and lipid peroxidation that disrupts metabolic regulation. Existing research suggests that maternal iron status could serve as a biomarker for early GDM risk assessment and a potential therapeutic target. However, the molecular pathways linking iron metabolism, ferroptosis, and metabolic abnormalities remain uncertain. Further investigations are needed to understand these mechanisms and assess the potential of ferroptosis inhibitors in GDM. Bridging these knowledge gaps could lead to improved strategies for the prediction, prevention, and management of GDM and its associated complications.</p>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 2","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70130","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Calvigioni, Edoardo Biancalana, Chiara Rossi, Diletta Mazzantini, Francesco Celandroni, Emilia Ghelardi, Anna Solini
Aims
A reduced compliance, due to urogenital minor infections, frequently compromises the clinical efficacy of SGLT2 inhibitors in subjects with type 2 diabetes (T2D). The combined use of SGLT2 inhibitors and dipeptidyl-peptidase four inhibitors seems to reduce the incidence of such side effects. We evaluated how these drugs, alone or in combination, might influence resident urinary microbiota.
Materials and Methods
An open label, randomised clinical study was conducted on 30 T2D individuals for 12 weeks to compare the impact of Empagliflozin and Empagliflozin/Linagliptin on clinical parameters and urinary microbiota. Fifteen healthy individuals served as baseline controls. The composition of urinary bacterial populations was evaluated by Real-Time quantitative PCR and 16S rRNA gene sequencing.
Results
BMI was reduced by both treatments, while fasting glucose and HbA1c significantly improved only with the combination. At baseline, T2D showed a higher total bacterial load and abundance of Bacillota than controls. The prevalence and proportion of bacterial species profoundly differed between the groups, revealing a urinary dysbiosis in T2D. A different effect of Empagliflozin alone or combined with Linagliptin on microbial populations was observed: Empagliflozin increased the total bacterial load of Bacillota and Aerococcus, while the combination therapy restored a microbial community similar to that of controls, further reducing the prevalence of potential urinary pathogens.
Conclusions
In T2D subjects, the combination of Empagliflozin and Ligandliptin might help in restoring a normal composition of the urinary microbiota, likely improving compliance and persistence in therapy with SGLT2 inhibitors.
{"title":"Effect of SGLT2 Inhibitors + DPP-4 Inhibitors on Urine Microbiota in Type 2 Diabetes","authors":"Marco Calvigioni, Edoardo Biancalana, Chiara Rossi, Diletta Mazzantini, Francesco Celandroni, Emilia Ghelardi, Anna Solini","doi":"10.1002/dmrr.70127","DOIUrl":"10.1002/dmrr.70127","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>A reduced compliance, due to urogenital minor infections, frequently compromises the clinical efficacy of SGLT2 inhibitors in subjects with type 2 diabetes (T2D). The combined use of SGLT2 inhibitors and dipeptidyl-peptidase four inhibitors seems to reduce the incidence of such side effects. We evaluated how these drugs, alone or in combination, might influence resident urinary microbiota.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>An open label, randomised clinical study was conducted on 30 T2D individuals for 12 weeks to compare the impact of Empagliflozin and Empagliflozin/Linagliptin on clinical parameters and urinary microbiota. Fifteen healthy individuals served as baseline controls. The composition of urinary bacterial populations was evaluated by Real-Time quantitative PCR and 16S rRNA gene sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BMI was reduced by both treatments, while fasting glucose and HbA1c significantly improved only with the combination. At baseline, T2D showed a higher total bacterial load and abundance of <i>Bacillota</i> than controls. The prevalence and proportion of bacterial species profoundly differed between the groups, revealing a urinary dysbiosis in T2D. A different effect of Empagliflozin alone or combined with Linagliptin on microbial populations was observed: Empagliflozin increased the total bacterial load of <i>Bacillota</i> and <i>Aerococcus</i>, while the combination therapy restored a microbial community similar to that of controls, further reducing the prevalence of potential urinary pathogens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In T2D subjects, the combination of Empagliflozin and Ligandliptin might help in restoring a normal composition of the urinary microbiota, likely improving compliance and persistence in therapy with SGLT2 inhibitors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingshuang Qin, Xiaojie Pan, Chen Wu, Yuhan Liu, Minghui Zhu, Min Li
Aim
To explore the impact of BMI-metabolic phenotypes and their changes on chronic multimorbidity.
Methods
Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), with participants aged ≥ 45. Analysing the metabolic heterogeneity of obesity through four BMI-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy overweight/obesity (MUOO), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy normal weight (MUNW). Transition of BMI-metabolic phenotype was assessed between 2011 and 2015. Chronic multimorbidity refers to the coexistence of ≥ 2 chronic diseases among 14 specified diseases. The association between changes in BMI-metabolic phenotypes and chronic multimorbidity was applied using Cox regression.
Results
Among 2528 individuals, the median age was 56.00 years, and 1244 (49.21%) had chronic multimorbidity. After adjusting for all variables at baseline, participants in the MUOO phenotype exhibited a 1.66-fold increased risk of chronic multimorbidity compared with the MHNW phenotype (95% CI: 1.42–1.94, p < 0.001), followed by the MUNW phenotype with a 1.25-fold increased risk (95% CI: 1.06–1.47, p = 0.008). However, in the MHOO phenotype, no statistically significant association was found (p > 0.05), which may reflect its heterogeneity and instability as a transient rather than benign metabolic state. In addition, obesity or unhealthy metabolism can also increase the risk of chronic multimorbidity.
Conclusions
Overall, for individuals aged ≥ 45, especially those with the MUOO phenotype, managing body weight and improving metabolic health are crucial for preventing chronic multimorbidity.
目的：探讨bmi代谢表型及其变化对慢性多发病的影响。方法：数据来自中国健康与退休纵向研究（CHARLS），参与者年龄≥45岁。通过代谢健康正常体重（MHNW）、代谢不健康超重/肥胖（MUOO）、代谢健康超重/肥胖（MHOO）和代谢不健康正常体重（MUNW）四种bmi代谢表型分析肥胖的代谢异质性。在2011年至2015年期间评估bmi代谢表型的转变。慢性多病是指在14种特定疾病中同时存在≥2种慢性病。使用Cox回归分析bmi代谢表型变化与慢性多病之间的关系。结果：2528例患者中位年龄56.00岁，1244例（49.21%）有慢性多病。在基线调整所有变量后，与MHNW表型相比，MUOO表型的参与者表现出1.66倍的慢性多病风险增加（95% CI: 1.42-1.94, p 0.05），这可能反映了其异质性和不稳定性，作为一种短暂而非良性代谢状态。此外，肥胖或不健康的新陈代谢也会增加慢性多种疾病的风险。结论：总体而言，对于年龄≥45岁的个体，特别是具有MUOO表型的个体，控制体重和改善代谢健康对于预防慢性多病至关重要。
{"title":"Associations Between Metabolic Heterogeneity of Obesity and Chronic Multimorbidity Progression: A Nationwide Prospective Cohort Study","authors":"Jingshuang Qin, Xiaojie Pan, Chen Wu, Yuhan Liu, Minghui Zhu, Min Li","doi":"10.1002/dmrr.70125","DOIUrl":"10.1002/dmrr.70125","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To explore the impact of BMI-metabolic phenotypes and their changes on chronic multimorbidity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS), with participants aged ≥ 45. Analysing the metabolic heterogeneity of obesity through four BMI-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy overweight/obesity (MUOO), metabolically healthy overweight/obesity (MHOO), and metabolically unhealthy normal weight (MUNW). Transition of BMI-metabolic phenotype was assessed between 2011 and 2015. Chronic multimorbidity refers to the coexistence of ≥ 2 chronic diseases among 14 specified diseases. The association between changes in BMI-metabolic phenotypes and chronic multimorbidity was applied using Cox regression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 2528 individuals, the median age was 56.00 years, and 1244 (49.21%) had chronic multimorbidity. After adjusting for all variables at baseline, participants in the MUOO phenotype exhibited a 1.66-fold increased risk of chronic multimorbidity compared with the MHNW phenotype (95% CI: 1.42–1.94, <i>p</i> < 0.001), followed by the MUNW phenotype with a 1.25-fold increased risk (95% CI: 1.06–1.47, <i>p</i> = 0.008). However, in the MHOO phenotype, no statistically significant association was found (<i>p</i> > 0.05), which may reflect its heterogeneity and instability as a transient rather than benign metabolic state. In addition, obesity or unhealthy metabolism can also increase the risk of chronic multimorbidity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, for individuals aged ≥ 45, especially those with the MUOO phenotype, managing body weight and improving metabolic health are crucial for preventing chronic multimorbidity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This multi-cohort study evaluated whether the cardiometabolic index (CMI)—a composite of waist-to-height ratio and triglyceride-to-HDL cholesterol ratio—serves as an early predictor of cardio-kidney risk and whether its predictive value varies across glycaemic states.
Methods
We analysed 327,902 adults in the UK Biobank to examine the association of CMI with baseline cardio-kidney comorbidities, incident cardio-kidney events (CKE)—defined as the composite occurrence of cardiovascular and chronic kidney outcomes, and mortality. Baseline comorbidities was assessed using logistic regression, and Cox models with stratified analyses and restricted cubic splines (RCS) evaluated prospective associations. Findings were externally validated in CHARLS and NHANES. Machine-learning survival models further assessed predictive performance.
Results
Higher CMI was associated with baseline cardio-kidney comorbidities (OR 2.25, 95% CI 2.10–2.42). Among 303,113 participants free of cardiovascular and/or kidney disease at baseline, CMI predicted incident CKE (HR 2.18, 95% CI 2.01–2.38; median follow-up 14.3 years), all-cause death (HR 1.10, 95% CI 1.06–1.14; 15.8 years), and cardio-kidney death (HR 1.55, 95% CI 1.37–1.76; 15.8 years). The strength of associations was greatest in normoglycemia and progressively attenuated in prediabetes and diabetes. RCS analyses revealed nonlinear dose–response relationships, with steep increases in CKE and cardio-kidney mortality below CMI thresholds (∼0.70 and ∼0.95) and more gradual rises thereafter. Results were directionally consistent in external cohorts, particularly for cardio-kidney comorbidities and incident CKE. ML models demonstrated strong discrimination and consistently ranked CMI among the top predictors of incident CKE.
Conclusions
CMI is a simple, robust predictor of cardio-kidney risk especially in earlier metabolic states, with particularly strong prognostic value in normoglycaemic individuals where excess risk appears at lower CMI levels.
目的：本多队列研究评估了心血管代谢指数（CMI）——腰高比和甘油三酯-高密度脂蛋白胆固醇比的组合——是否可以作为心脏-肾脏风险的早期预测指标，以及其预测价值是否因血糖状态而异。方法：我们分析了英国生物银行的327,902名成年人，以检查CMI与基线心肾合并症、心肾事件发生率（CKE）（定义为心血管和慢性肾脏结局的复合发生）和死亡率的关系。基线合并症采用逻辑回归评估，Cox模型采用分层分析和限制性三次样条（RCS）评估前瞻性关联。研究结果在CHARLS和NHANES中进行了外部验证。机器学习生存模型进一步评估了预测性能。结果：较高的CMI与基线心肾合并症相关（OR 2.25, 95% CI 2.10-2.42）。在303,113名基线时无心血管和/或肾脏疾病的参与者中，CMI预测CKE （HR 2.18, 95% CI 2.01-2.38；中位随访14.3年）、全因死亡（HR 1.10, 95% CI 1.06-1.14； 15.8年）和心肾死亡（HR 1.55, 95% CI 1.37-1.76； 15.8年）的发生率。这种相关性在血糖正常时最强，在糖尿病前期和糖尿病中逐渐减弱。RCS分析揭示了非线性剂量-反应关系，CKE和心肾死亡率在CMI阈值以下急剧增加（~ 0.70和~ 0.95），此后逐渐上升。外部队列的结果方向一致，特别是心肾合并症和CKE事件。ML模型表现出强烈的歧视，并始终将CMI列为CKE事件的最高预测因子。结论：CMI是一种简单、可靠的心肾风险预测指标，特别是在早期代谢状态下，对于血糖正常的个体，在低CMI水平下出现过度风险，具有特别强的预后价值。
{"title":"Glycaemic Status Modifies the Association Between Cardiometabolic Index and Cardio-Kidney Outcomes: A Multi-Cohort Analysis","authors":"Yingyi Xie, Yanjun Song, Shanshan Shi, Yuanlin Guo, Weihua Song, Kefei Dou","doi":"10.1002/dmrr.70124","DOIUrl":"10.1002/dmrr.70124","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This multi-cohort study evaluated whether the cardiometabolic index (CMI)—a composite of waist-to-height ratio and triglyceride-to-HDL cholesterol ratio—serves as an early predictor of cardio-kidney risk and whether its predictive value varies across glycaemic states.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed 327,902 adults in the UK Biobank to examine the association of CMI with baseline cardio-kidney comorbidities, incident cardio-kidney events (CKE)—defined as the composite occurrence of cardiovascular and chronic kidney outcomes, and mortality. Baseline comorbidities was assessed using logistic regression, and Cox models with stratified analyses and restricted cubic splines (RCS) evaluated prospective associations. Findings were externally validated in CHARLS and NHANES. Machine-learning survival models further assessed predictive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Higher CMI was associated with baseline cardio-kidney comorbidities (OR 2.25, 95% CI 2.10–2.42). Among 303,113 participants free of cardiovascular and/or kidney disease at baseline, CMI predicted incident CKE (HR 2.18, 95% CI 2.01–2.38; median follow-up 14.3 years), all-cause death (HR 1.10, 95% CI 1.06–1.14; 15.8 years), and cardio-kidney death (HR 1.55, 95% CI 1.37–1.76; 15.8 years). The strength of associations was greatest in normoglycemia and progressively attenuated in prediabetes and diabetes. RCS analyses revealed nonlinear dose–response relationships, with steep increases in CKE and cardio-kidney mortality below CMI thresholds (∼0.70 and ∼0.95) and more gradual rises thereafter. Results were directionally consistent in external cohorts, particularly for cardio-kidney comorbidities and incident CKE. ML models demonstrated strong discrimination and consistently ranked CMI among the top predictors of incident CKE.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CMI is a simple, robust predictor of cardio-kidney risk especially in earlier metabolic states, with particularly strong prognostic value in normoglycaemic individuals where excess risk appears at lower CMI levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya-Hui Lin, Tsung-Kun Lin, Pei-Lun Liao, Tsung-Yuan Yang, Gwo-Ping Jong
Background
Type 2 diabetes (T2D) and chronic kidney disease (CKD) increase the risk of ischaemic and haemorrhagic strokes. However, the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on reducing the risk of ischaemic and haemorrhagic strokes in patients with T2D and CKD remains unclear. Thus, this study was conducted to explore the role of SGLT2i in the prevention of ischaemic and haemorrhagic strokes.
Methods
In this retrospective cohort study, Cox regression analysis was employed to examine the hazard ratio (HR) between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes following 1:1 propensity score matching. The Kaplan–Meier method was used to determine the risk of study outcome over time between users and nonusers of SGLT2i. Finally, a sensitivity analysis of the HR was performed between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes after 1:2 sex and age matching.
Results
After 1:1 propensity score matching of patients by age, sex, T2D duration, and comorbidities, 107,819 users of SGLT2i and 107,819 nonusers were enrolled for analysis. SGLT2i therapy was associated with significantly reduced incidence of ischaemic and haemorrhagic strokes (HR 0.86, [95% CI, 0.81–0.90]; HR 0.80, [95% CI, 0.74–0.87]). Furthermore, the HR was even more significant in the sensitivity test for incident ischaemic and haemorrhagic strokes.
Conclusion
SGLT2i reduced the risk of incident ischaemic and haemorrhagic strokes among patients with T2D and CKD. The protective profile of the SGLT2i against incident ischaemic and haemorrhagic strokes makes it a clinical option for those with T2D with CKD.
{"title":"Risk of New-Onset Ischaemic and Haemorrhagic Stroke in Patients With Type 2 Diabetes With Chronic Kidney Disease on SGLT-2 Inhibitor Users: A Population-Based Cohort Study","authors":"Ya-Hui Lin, Tsung-Kun Lin, Pei-Lun Liao, Tsung-Yuan Yang, Gwo-Ping Jong","doi":"10.1002/dmrr.70122","DOIUrl":"10.1002/dmrr.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes (T2D) and chronic kidney disease (CKD) increase the risk of ischaemic and haemorrhagic strokes. However, the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on reducing the risk of ischaemic and haemorrhagic strokes in patients with T2D and CKD remains unclear. Thus, this study was conducted to explore the role of SGLT2i in the prevention of ischaemic and haemorrhagic strokes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this retrospective cohort study, Cox regression analysis was employed to examine the hazard ratio (HR) between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes following 1:1 propensity score matching. The Kaplan–Meier method was used to determine the risk of study outcome over time between users and nonusers of SGLT2i. Finally, a sensitivity analysis of the HR was performed between users and nonusers of SGLT2i on incident ischaemic and haemorrhagic strokes after 1:2 sex and age matching.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 1:1 propensity score matching of patients by age, sex, T2D duration, and comorbidities, 107,819 users of SGLT2i and 107,819 nonusers were enrolled for analysis. SGLT2i therapy was associated with significantly reduced incidence of ischaemic and haemorrhagic strokes (HR 0.86, [95% CI, 0.81–0.90]; HR 0.80, [95% CI, 0.74–0.87]). Furthermore, the HR was even more significant in the sensitivity test for incident ischaemic and haemorrhagic strokes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SGLT2i reduced the risk of incident ischaemic and haemorrhagic strokes among patients with T2D and CKD. The protective profile of the SGLT2i against incident ischaemic and haemorrhagic strokes makes it a clinical option for those with T2D with CKD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12801180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern that contributes to liver and cardiovascular complications. The prevalence of MASLD in women increases sharply around age 50 years, but the relationship between an earlier age at natural menopause and MASLD is unknown.
Methods
Using the TriNetX global federated network, we identified women with earlier menopause (< 50 years). The control cohort consisted of similarly aged pre-menopausal women. Cases of premature (< 40 years) or surgical menopause, non-MASLD causes of steatotic liver disease (SLD), or sex-hormone therapy were excluded. Propensity-score matching adjusted for baseline characteristics and metabolic risk factors, resulting in two matched cohorts of 20,979 women (total n = 41,958) in the final analysis. Outcomes included new diagnoses of MASLD (metabolic dysfunction-associated steatohepatitis) and the MASLD metabolic factors: pre-diabetes/diabetes, hypertension, dyslipidaemia, and overweight/obesity over 5 years of follow-up.
Results
Earlier menopause was associated with an increased risk of developing MASLD (HR 1.322, 95% CI 1.170–1.492), new-onset dyslipidaemia (1.083; 1.045–1.122) and pre-diabetes (1.130; 1.060–1.205). Findings were consistent across stratified analyses by pre-existing metabolic risk factors (HR 95% CI for MASLD with pre-existing dysglycaemia 1.370, 1.042–1.800; dyslipidaemia 1.340, 1.053–1.705; hypertension 1.230, 0.998–1.516; overweight 1.280, 1.086–1.510).
Conclusions
Risk of MASLD is increased following menopause before age 50. Further studies should assess the incorporation of menopause timing into female-specific cardiometabolic risk assessment.
{"title":"Earlier Menopause and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Global Cohort Study","authors":"Joshua Stokar, Rivka Dresner-Pollak","doi":"10.1002/dmrr.70121","DOIUrl":"10.1002/dmrr.70121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern that contributes to liver and cardiovascular complications. The prevalence of MASLD in women increases sharply around age 50 years, but the relationship between an earlier age at natural menopause and MASLD is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using the TriNetX global federated network, we identified women with earlier menopause (< 50 years). The control cohort consisted of similarly aged pre-menopausal women. Cases of premature (< 40 years) or surgical menopause, non-MASLD causes of steatotic liver disease (SLD), or sex-hormone therapy were excluded. Propensity-score matching adjusted for baseline characteristics and metabolic risk factors, resulting in two matched cohorts of 20,979 women (total <i>n</i> = 41,958) in the final analysis. Outcomes included new diagnoses of MASLD (metabolic dysfunction-associated steatohepatitis) and the MASLD metabolic factors: pre-diabetes/diabetes, hypertension, dyslipidaemia, and overweight/obesity over 5 years of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Earlier menopause was associated with an increased risk of developing MASLD (HR 1.322, 95% CI 1.170–1.492), new-onset dyslipidaemia (1.083; 1.045–1.122) and pre-diabetes (1.130; 1.060–1.205). Findings were consistent across stratified analyses by pre-existing metabolic risk factors (HR 95% CI for MASLD with pre-existing dysglycaemia 1.370, 1.042–1.800; dyslipidaemia 1.340, 1.053–1.705; hypertension 1.230, 0.998–1.516; overweight 1.280, 1.086–1.510).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Risk of MASLD is increased following menopause before age 50. Further studies should assess the incorporation of menopause timing into female-specific cardiometabolic risk assessment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12790266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yan Li, Minglan Yang, Jiang Yue, Zixuan Wang, Yicheng Qi, Qianjing Liu, Jing Ma
Background
The Agile 3+ score, recently developed based on transient elastography measurements, transaminase ratios, and metabolic parameters, effectively assesses fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the association between Agile 3+ and cardiovascular diseases (CVD) in MASLD and to compare its predictive performance with Agile 4, Fibrosis-4 (FIB-4), and FibroScan aspartate aminotransferase (FAST).
Methods
We analysed data in 3198 patients with MASLD during the 2017–March 2020 prepandemic from National Health and Nutrition Examination Survey. The associations between Agile 3+ and CVD were assessed using univariate and multivariable logistic regression models. Predictive accuracy was evaluated via receiver operating characteristic curves and decision curve analysis (DCA).
Results
Among 3198 patients with MASLD, 385 (12.0%) had CVD. After adjusting for confounders, a dose-dependent relationship was observed between Agile 3+ and CVD risk: compared to the reference group, the odds of CVD increased by 58% in the 0.45–0.68 group (OR 1.58, 95%CI 1.13–2.20, p = 0.008) and by 78% in the ≥ 0.68 group (OR 1.78, 95%CI 1.22–2.59, p = 0.003). In the context of CVD risk prediction, Agile 3+ and FIB-4 achieved the highest AUC (0.71), outperforming Agile 4 (0.64) and FAST (0.51). DCA revealed that Agile 3+ provided superior net benefit within the 20%–40% CVD risk threshold range. Furthermore, subgroup and sensitivity analyses further confirmed the robustness of the results.
Conclusions
Agile 3+ is independently associated with CVD in patients with MASLD and demonstrates better predictive performance than Agile 4, FIB-4, and FAST scores.
{"title":"Agile 3+ Index Is Independently Associated With Cardiovascular Diseases in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease: Analysis of NHANES 2017–2020","authors":"Yan Li, Minglan Yang, Jiang Yue, Zixuan Wang, Yicheng Qi, Qianjing Liu, Jing Ma","doi":"10.1002/dmrr.70123","DOIUrl":"10.1002/dmrr.70123","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Agile 3+ score, recently developed based on transient elastography measurements, transaminase ratios, and metabolic parameters, effectively assesses fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to evaluate the association between Agile 3+ and cardiovascular diseases (CVD) in MASLD and to compare its predictive performance with Agile 4, Fibrosis-4 (FIB-4), and FibroScan aspartate aminotransferase (FAST).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed data in 3198 patients with MASLD during the 2017–March 2020 prepandemic from National Health and Nutrition Examination Survey. The associations between Agile 3+ and CVD were assessed using univariate and multivariable logistic regression models. Predictive accuracy was evaluated via receiver operating characteristic curves and decision curve analysis (DCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 3198 patients with MASLD, 385 (12.0%) had CVD. After adjusting for confounders, a dose-dependent relationship was observed between Agile 3+ and CVD risk: compared to the reference group, the odds of CVD increased by 58% in the 0.45–0.68 group (OR 1.58, 95%CI 1.13–2.20, <i>p</i> = 0.008) and by 78% in the ≥ 0.68 group (OR 1.78, 95%CI 1.22–2.59, <i>p</i> = 0.003). In the context of CVD risk prediction, Agile 3+ and FIB-4 achieved the highest AUC (0.71), outperforming Agile 4 (0.64) and FAST (0.51). DCA revealed that Agile 3+ provided superior net benefit within the 20%–40% CVD risk threshold range. Furthermore, subgroup and sensitivity analyses further confirmed the robustness of the results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Agile 3+ is independently associated with CVD in patients with MASLD and demonstrates better predictive performance than Agile 4, FIB-4, and FAST scores.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145935724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Zheng, Sibiao Lu, Di Qiang, Jiale Xu, Yingying Xu
<div> <section> <h3> Aims</h3> <p>Type 1 diabetes accounts for approximately 10% of all diabetes cases, meaning that a substantial number of patients require lifelong insulin therapy. Although many individuals adapt to the demands of daily injections, they remain vulnerable to hypoglycaemia and long-term complications, particularly when glycaemic control is suboptimal. These persistent challenges have driven the search for effective treatments that may improve quality of life and potentially induce clinical remission. To address this need, we conducted a Bayesian network meta-analysis to evaluate the capacity of non-insulin therapies to preserve pancreatic β-cell function in type 1 diabetes.</p> </section> <section> <h3> Materials and Methods</h3> <p>We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for studies published between 1 January 2000 and 1 March 2025. The search included randomised controlled trials (RCTs) and non-randomised controlled trials (nRCTs) that evaluated non-insulin interventions such as stem cell transplantation (SCT), Janus kinase inhibitors (JAK/TKI), and monoclonal antibodies targeting T-cell CD3 molecules (CD3-Ab). The primary outcome measure was C-peptide level, and the secondary outcome was HbA1c.</p> </section> <section> <h3> Results</h3> <p>A total of 68 studies were included in our analysis, comprising 69 trials (64 RCTs and 5 nRCTs) involving 4779 patients with type 1 diabetes. These trials evaluated 15 non-insulin interventions in addition to conventional therapy (placebo). While most interventions showed superior results to placebo, only stem cell therapy (SCT) demonstrated significant C-peptide level improvement (MD = 0.20; 95% CrI: 0.04–0.36). Although the other 13 interventions (including JAK/TKI inhibitors and CD3 antibodies) produced positive mean differences, none of their 95% CrI contained 0, indicating a lack of statistical significance. In addition, anti-thymocyte globulin (ATG) was associated with a slight negative mean difference (MD = −0.02; 95% CrI: −0.32 to 0.28), suggesting a potentially detrimental effect on islet function. Analyses using HbA1c as an outcome metric indicated that Vit (MD = −1.5; 95% CrI: −2.1 to −0.78) and Cyto-Mod (MD = −0.72; 95% CrI: −1.4 to −0.12) conferred a relatively greater improvement in glycaemic control.</p> </section> <section> <h3> Conclusion</h3> <p>Although the clinical application of SCT is not yet fully mature, our meta-analysis further confirmed the notable effect of SCT on islet function in patients with type 1 diabetes mellitus. However, analyses of HbA1c did not demonstrate a significant effect of SCT on glycae
{"title":"Novel Therapeutic Approach to Preserving or Reversing Pancreatic Islet Beta Cells in Patients With Type 1 Diabetes: A Bayesian Network Meta-Analysis of Comparative Efficacy","authors":"Chen Zheng, Sibiao Lu, Di Qiang, Jiale Xu, Yingying Xu","doi":"10.1002/dmrr.70120","DOIUrl":"10.1002/dmrr.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Type 1 diabetes accounts for approximately 10% of all diabetes cases, meaning that a substantial number of patients require lifelong insulin therapy. Although many individuals adapt to the demands of daily injections, they remain vulnerable to hypoglycaemia and long-term complications, particularly when glycaemic control is suboptimal. These persistent challenges have driven the search for effective treatments that may improve quality of life and potentially induce clinical remission. To address this need, we conducted a Bayesian network meta-analysis to evaluate the capacity of non-insulin therapies to preserve pancreatic β-cell function in type 1 diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>We systematically searched PubMed, Web of Science, Embase, and the Cochrane Library for studies published between 1 January 2000 and 1 March 2025. The search included randomised controlled trials (RCTs) and non-randomised controlled trials (nRCTs) that evaluated non-insulin interventions such as stem cell transplantation (SCT), Janus kinase inhibitors (JAK/TKI), and monoclonal antibodies targeting T-cell CD3 molecules (CD3-Ab). The primary outcome measure was C-peptide level, and the secondary outcome was HbA1c.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 68 studies were included in our analysis, comprising 69 trials (64 RCTs and 5 nRCTs) involving 4779 patients with type 1 diabetes. These trials evaluated 15 non-insulin interventions in addition to conventional therapy (placebo). While most interventions showed superior results to placebo, only stem cell therapy (SCT) demonstrated significant C-peptide level improvement (MD = 0.20; 95% CrI: 0.04–0.36). Although the other 13 interventions (including JAK/TKI inhibitors and CD3 antibodies) produced positive mean differences, none of their 95% CrI contained 0, indicating a lack of statistical significance. In addition, anti-thymocyte globulin (ATG) was associated with a slight negative mean difference (MD = −0.02; 95% CrI: −0.32 to 0.28), suggesting a potentially detrimental effect on islet function. Analyses using HbA1c as an outcome metric indicated that Vit (MD = −1.5; 95% CrI: −2.1 to −0.78) and Cyto-Mod (MD = −0.72; 95% CrI: −1.4 to −0.12) conferred a relatively greater improvement in glycaemic control.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although the clinical application of SCT is not yet fully mature, our meta-analysis further confirmed the notable effect of SCT on islet function in patients with type 1 diabetes mellitus. However, analyses of HbA1c did not demonstrate a significant effect of SCT on glycae","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Glycaemic variability (GV) has emerged as an important prognostic indicator in critical illness, yet its predictive value among patients with sepsis remains unclear. This systematic review and meta-analysis aimed to evaluate the association between GV metrics and mortality outcomes in adult patients with sepsis.
Methods
Cohort studies enrolling septic patients and reporting in-hospital, 28-day, or 30-day mortality in relation to GV were identified through PubMed, Embase, Cochrane Library, Scopus, CNKI, and Wanfang databases. Pooled odds ratios (ORs) were calculated using a random-effects model. Sensitivity analyses were performed to assess the robustness of the findings.
Results
Ten studies comprising 18,337 patients were included. For categorical analysis, high-GV patients had nearly twice the mortality risk (OR = 1.99, 95% CI: 1.66–2.40, p < 0.0001; I2 = 45%). For continuous analysis, all 4 GV metrics showed significant associations with mortality: CoV (OR = 1.050, I2 = 76.6%), SD (OR = 1.0037, I2 = 83.5%), GLI (OR = 1.0171, I2 = 0.0%), and MAGE (OR = 1.0062, I2 = 0.0%). High GV was associated with prolonged ICU stay (0.95 days, p = 0.0018). Sensitivity analyses confirmed the result robustness.
Conclusions
Elevated GV is independently linked to an increased risk of death among patients with sepsis. GLI and MAGE are the most reliable GV metrics for prognostic assessment, whereas CoV and SD are less consistent. Standardised GV measurement and prospective studies are warranted to evaluate whether interventions targeting GV can improve outcomes in this population.
{"title":"Association Between Blood Glucose Variability and Clinical Outcomes in Patients With Sepsis: A Systematic Review and Meta-Analysis","authors":"Gelan Miao, Rui Lu, Tanyong Pipanmekaporn, Srisuluk Kacha, Atirut Supphapipat, Natsuda Phothikun, Phut Jewprasertpan, Kaweesak Chittawatanarat","doi":"10.1002/dmrr.70119","DOIUrl":"10.1002/dmrr.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Glycaemic variability (GV) has emerged as an important prognostic indicator in critical illness, yet its predictive value among patients with sepsis remains unclear. This systematic review and meta-analysis aimed to evaluate the association between GV metrics and mortality outcomes in adult patients with sepsis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cohort studies enrolling septic patients and reporting in-hospital, 28-day, or 30-day mortality in relation to GV were identified through PubMed, Embase, Cochrane Library, Scopus, CNKI, and Wanfang databases. Pooled odds ratios (ORs) were calculated using a random-effects model. Sensitivity analyses were performed to assess the robustness of the findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ten studies comprising 18,337 patients were included. For categorical analysis, high-GV patients had nearly twice the mortality risk (OR = 1.99, 95% CI: 1.66–2.40, <i>p</i> < 0.0001; <i>I</i><sup>2</sup> = 45%). For continuous analysis, all 4 GV metrics showed significant associations with mortality: CoV (OR = 1.050, <i>I</i><sup>2</sup> = 76.6%), SD (OR = 1.0037, <i>I</i><sup>2</sup> = 83.5%), GLI (OR = 1.0171, <i>I</i><sup>2</sup> = 0.0%), and MAGE (OR = 1.0062, <i>I</i><sup>2</sup> = 0.0%). High GV was associated with prolonged ICU stay (0.95 days, <i>p</i> = 0.0018). Sensitivity analyses confirmed the result robustness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Elevated GV is independently linked to an increased risk of death among patients with sepsis. GLI and MAGE are the most reliable GV metrics for prognostic assessment, whereas CoV and SD are less consistent. Standardised GV measurement and prospective studies are warranted to evaluate whether interventions targeting GV can improve outcomes in this population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11335,"journal":{"name":"Diabetes/Metabolism Research and Reviews","volume":"42 1","pages":""},"PeriodicalIF":6.0,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dmrr.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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