Metabolism open最新文献

{"title":"Effectiveness of a multidisciplinary “2+N system therapy” in achieving remission and metabolic improvement in type 2 diabetes: A real-world study with 1,000 patients","authors":"Kejing Zeng ,&nbsp;Bo Chen ,&nbsp;Hejun Li ,&nbsp;Nina Ren ,&nbsp;Yingying Song ,&nbsp;Minlin Liang ,&nbsp;Yin Yang ,&nbsp;Yali Huang ,&nbsp;Ting Liu ,&nbsp;Yiguang Lin ,&nbsp;Gugen Xu","doi":"10.1016/j.metop.2025.100436","DOIUrl":"10.1016/j.metop.2025.100436","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is a major global health challenge characterized by insulin resistance and β-cell dysfunction. Traditional treatments often fail to achieve sustained remission. This study evaluated a comprehensive “2 + N system therapy” combining Western and traditional Chinese medicine (TCM) with individualized lifestyle interventions to promote T2DM remission and improve metabolic health.</div></div><div><h3>Methods</h3><div>In a real-world observational study, 1000 T2DM patients (disease duration ≤5 years; BMI ≥24 kg/m² or elevated waist circumference; preserved C-peptide) were treated with 2 + N therapy at Guangdong Second Provincial General Hospital (2015–2022). The “2” phase involved intensive insulin therapy transitioning to non-insulin agents with tailored TCM; the “N” phase included calorie-restricted low-carbohydrate diet, exercise, and psychological support. Primary outcome was diabetes remission (HbA₁c &lt; 6.5 % for ≥3 months without medication). Secondary outcomes included changes in weight, BMI, waist/hip circumference, glycemic indices, insulin resistance (HOMA-IR), β-cell function (HOMA-β), lipids, uric acid, and MRI-assessed hepatic and pancreatic fat in a subset.</div></div><div><h3>Results</h3><div>At 6 months, 70.5 % of participants achieved remission. Significant metabolic improvements were observed, including mean weight reduction (9.2 ± 4.3 kg), BMI decrease (3.2 ± 1.4 kg/m²), waist circumference reduction (11.0 ± 4.2 cm), and notable improvements in glycemic control (HbA₁c decreased from 7.3 ± 1.3 % to 5.3 ± 0.4 %). Lipid profiles significantly improved, with triglycerides declining from 6.34 ± 3.25 to 1.39 ± 0.95 mmol/L and total cholesterol from 7.41 ± 2.20 to 3.76 ± 0.86 mmol/L. MRI analysis of a subgroup (n = 26) showed significant reductions in hepatic fat (28.8 %) and pancreatic fat (25.0 %).</div></div><div><h3>Conclusions</h3><div>The “2+N system therapy” demonstrated a high remission rate and extensive metabolic benefits, including substantial weight loss, improved glycemic control, enhanced insulin sensitivity, and reductions in ectopic fat. However, causality cannot be established without a control group and further prospective controlled trials are required to confirm its efficacy.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100436"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene and non-coding RNA expression in human cumulus cells in polycystic ovary syndrome: A systematic review","authors":"Faezeh Soheili Azad","doi":"10.1016/j.metop.2025.100441","DOIUrl":"10.1016/j.metop.2025.100441","url":null,"abstract":"<div><h3>Objective</h3><div>This systematic review aimed to synthesize and critically appraise human studies on coding and non-coding RNA expression in cumulus cells (CCs) from women with Polycystic Ovary Syndrome (PCOS), to map consistently dysregulated pathways, evaluate links to oocyte competence, and identify key methodological limitations.</div></div><div><h3>Methods</h3><div>A systematic search of five electronic databases (MEDLINE/PubMed, Embase, Web of Science, Scopus, Cochrane CENTRAL) was conducted from inception to October 25, 2025. Peer-reviewed human studies comparing CC RNA expression in PCOS versus controls, with explicit cumulus isolation and primary RNA data, were included. Study selection, quality assessment, and data extraction followed pre-defined analytic prisms focusing on cell-type specificity, oocyte maturation stage, stimulation protocol, and clinical phenotype. A qualitative synthesis was performed due to substantial clinical and methodological heterogeneity.</div></div><div><h3>Results</h3><div>Thirty-three studies were included. The CC transcriptome in PCOS is characterized by a coherent phenotype: pathway-level enrichment of EGFR-MAPK and PI3K-AKT/insulin signaling, an imbalanced TGF-β/oocyte-somatic cell axis, and blunted induction of cumulus expansion/extracellular matrix (ECM) genes (e.g., TNFAIP6, PTX3). Non-coding RNA profiles (miRNAs, lncRNAs, circRNAs) corroborate these findings, targeting the same pathways. These signatures are strongly modified by oocyte maturation stage (largest differences at Germinal Vesicle stage), stimulation protocols, and clinical phenotypes (e.g., insulin resistance, obesity).</div></div><div><h3>Conclusion</h3><div>The cumulus cell phenotype in PCOS reflects a rewired signaling environment that converges on defective matrix assembly, providing a molecular framework for impaired oocyte competence. Future research requires stage-aware, phenotype-stratified designs with standardized reporting to translate these findings into robust biomarkers for assisted reproduction.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100441"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists and obstructive lung disease: Beyond metabolic control to respiratory outcomes","authors":"Vasiliki Epameinondas Georgakopoulou ,&nbsp;Maria Dalamaga","doi":"10.1016/j.metop.2026.100449","DOIUrl":"10.1016/j.metop.2026.100449","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) and asthma are increasingly recognized as systemic conditions shaped by metabolic comorbidities, particularly obesity and type 2 diabetes mellitus (T2DM). Beyond traditional airway-directed therapies, increasing attention has turned to whether metabolic interventions may influence respiratory outcomes. In this context, glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for the treatment of T2DM and obesity, have emerged as unexpected candidates with potential relevance for obstructive lung disease control. The aim of this review is to synthesize emerging clinical, real-world, and mechanistic evidence linking GLP-1RA therapy to respiratory outcomes in COPD and asthma.</div><div>Accumulating real-world evidence from population-based cohorts, comparative effectiveness studies, and recent meta-analyses consistently associates GLP-1RA use with reduced rates of moderate and severe exacerbations in patients with COPD or asthma and comorbid T2DM, particularly when compared with sulfonylureas and dipeptidyl peptidase-4 inhibitors. Notably, these associations appear most pronounced among patients with obesity, frequent exacerbations, or high healthcare utilization. In contrast, randomized cardiovascular outcome trials of GLP-1RAs have generally shown neutral effects on respiratory endpoints, a finding that likely reflects the absence of prespecified pulmonary outcomes and limited event capture rather than a true absence of biological effect. Importantly, recent proof-of-principle disease-focused randomized trials in obesity-related COPD have begun to report respiratory-specific benefits, complementing large real-world and nationwide observational data.</div><div>From a mechanistic perspective, the observed respiratory signal may reflect a combination of indirect metabolic effects, such as weight loss, improved glycemic control, and reduced systemic inflammation, together with direct airway and immune-modulatory actions mediated by GLP-1R expression in airway smooth muscle and immune cells. Importantly, recent proof-of-principle and disease-focused randomized trials in obesity-related asthma and COPD are now specifically designed to interrogate these pathways and address limitations inherent to observational data. Although the current evidence base remains largely observational and subject to residual confounding, its consistency across diverse settings supports that GLP-1RAs may act as systemic metabolic modulators with potential respiratory relevance. Prospective RCTs with prespecified respiratory endpoints will be important to establish causality and define the role of GLP-1RAs beyond metabolic control, toward clinically meaningful respiratory outcomes in obstructive lung disease.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100449"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 and metabolic health: Lessons from a global pandemic","authors":"Maria Dalamaga ,&nbsp;Irene Karampela ,&nbsp;Junli Liu","doi":"10.1016/j.metop.2026.100448","DOIUrl":"10.1016/j.metop.2026.100448","url":null,"abstract":"<div><div>The COVID-19 pandemic has highlighted the critical role of metabolic health in shaping susceptibility to infection, disease severity, therapeutic response, and vaccine-induced immunity. Accumulating clinical and experimental evidence has shown a bidirectional relationship between SARS-CoV-2 infection and metabolic dysfunction, whereby pre-existing cardiometabolic disorders exacerbate clinical outcomes, while COVID-19 itself induces acute and persistent metabolic derangements. This Special Issue explores COVID-19 through an immune-metabolic lens, integrating mechanistic insights, clinical perspectives, therapeutic strategies, and preventive approaches. Its contributions address key pathways linking SARS-CoV-2 to insulin resistance, adipose tissue dysfunction, hepatic inflammation, and immune dysregulation. They also critically evaluate metabolism-oriented pharmacological interventions, including drug repurposing and host-directed therapies, and examine the role of nutrition, lifestyle factors, and metabolic health in modulating disease severity and vaccine-induced humoral responses. Collectively, these works underscore metabolism as a central biological interface in COVID-19 pathophysiology and highlight integrated, host-centered strategies spanning prevention, treatment, and immune resilience. This Special Issue aims to advance understanding at the intersection of infectious disease and metabolism, and to stimulate future research toward improved risk stratification, therapeutic innovation, and long-term public health preparedness.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100448"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147649453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of smoking cessation before and during pregnancy and risk of gestational diabetes: A systematic review","authors":"Areti Tsirozoglou ,&nbsp;Vikentia Harizopoulou ,&nbsp;Angeliki Bolou ,&nbsp;Victoria Vivilaki ,&nbsp;Ermioni Palaska ,&nbsp;Vasiliki Epameinondas Georgakopoulou ,&nbsp;Maria Vlachou ,&nbsp;Athina Diamanti","doi":"10.1016/j.metop.2026.100452","DOIUrl":"10.1016/j.metop.2026.100452","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Gestational diabetes mellitus (GDM) is one of the most common metabolic complications of pregnancy, with a steadily increasing global prevalence. Cigarette smoking is a well-established modifiable risk factor for metabolic disorders; however, its association with gestational diabetes mellitus remains unclear, partly due to the widespread use of simplified, binary exposure definitions. Of particular interest is the timing of smoking cessation before or during pregnancy, as it may differentially influence the risk of glucose dysregulation during gestation.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;The objective of this systematic review was to synthesize available evidence from original studies that classify maternal smoking according to cessation timing—before pregnancy, during early pregnancy, or continued smoking beyond the first trimester—and to examine the association of these exposure patterns with gestational diabetes mellitus and pregnancy-related dysglycemia.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;This review was designed and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive systematic search was conducted in MEDLINE, Embase, Scopus, and Web of Science from inception with no date restrictions. Eligible studies were original observational investigations including pregnant women without pregestational diabetes, in which smoking exposure was clearly defined with respect to cessation timing. The primary outcome was gestational diabetes mellitus, while secondary outcomes included pregnancy-related dysglycemia. Due to substantial heterogeneity in exposure definitions and outcome assessment, results were synthesized narratively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Of 1672 identified records, four studies met the inclusion criteria. Overall, continued smoking beyond early pregnancy was consistently associated with an increased risk of gestational diabetes mellitus. In contrast, smoking cessation before pregnancy or during the first trimester appeared to attenuate or eliminate this excess risk, although some estimates did not reach statistical significance due to limited statistical power. Findings related to pregnancy dysglycemia further highlighted the complex interplay between smoking behavior, gestational weight gain, and maternal glucose metabolism.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;The timing of smoking cessation is a critical modifier of gestational diabetes mellitus risk. Continued smoking after the first trimester is associated with increased metabolic risk, whereas early cessation before or during early pregnancy appears beneficial. These findings underscore the importance of timing-sensitive smoking exposure assessment in both epidemiological research and clinical counseling of pregnant women. However, these findings are based on a very limited evidence base, as only four observational studies met the inclusion criteria","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100452"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventions for metabolic bone disease of prematurity: A systematic review and meta-analysis","authors":"Yazan Jumah Alalwani ,&nbsp;Mujood Ali Alatta ,&nbsp;Khawlah Abdullah Almana ,&nbsp;Amal Alomari ,&nbsp;Reem Hameed Alshammari ,&nbsp;Ghadi Naif Alsharif ,&nbsp;Asma Mossa Soweedi ,&nbsp;Sofia Sharif Abualmeza ,&nbsp;Sara Abdulrahman Alharbi ,&nbsp;Marwa Abdullrahman Maghrabi ,&nbsp;Kholoud Khalid Alshehri ,&nbsp;Abdullah Alburaey ,&nbsp;Ahmed Y. Azzam","doi":"10.1016/j.metop.2026.100445","DOIUrl":"10.1016/j.metop.2026.100445","url":null,"abstract":"<div><h3>Introduction</h3><div>Metabolic bone disease of prematurity (MBDP) affects up to 30 % of very low birth weight infants; however, evidence regarding prevention and treatment strategies remains limited. We aimed to evaluate the efficacy and safety of nutritional, mechanical, and pharmacological interventions for MBDP.</div></div><div><h3>Methods</h3><div>Following PRISMA 2020 guidelines, we searched five databases from inception to May 5, 2025, for studies evaluating interventions for MBDP in preterm infants (&lt;37 weeks or &lt;1500g). Primary outcomes included MBDP incidence, bone mineral density, and safety profiles. Random-effects meta-analyses, trial sequential analysis (TSA), and GRADE assessments were conducted.</div></div><div><h3>Results</h3><div>Eighteen studies (1577 infants) from ten countries met inclusion criteria. Nutritional prophylaxis significantly reduced MBDP incidence by 54 % (risk ratio [RR] = 0.46, 95 % confidence interval [CI] 0.30–0.68, P-value&lt;0.001), with early calcium/phosphorus supplementation achieving 74–84 % risk reduction. TSA confirmed conclusive evidence, with cumulative Z-score (−5.99) crossing the O'Brien-Fleming boundary at 270.9 % of required information size. Number needed to treat was five at 40 % baseline risk. Mechanical interventions improved bone mineral content by 28 % (P-value&lt;0.01), quantitative ultrasound speed-of-sound (mean difference [MD] = 75.3 m/s, 95 % CI 45.2–105.4), and weight gain (MD = 5.11 g/kg/day, 95 % CI 3.95–6.27). Both interventions demonstrated favorable safety profiles, with mechanical protocols reporting no adverse events.</div></div><div><h3>Conclusions</h3><div>Nutritional prophylaxis conclusively reduces MBDP incidence, while mechanical interventions effectively improve bone mineralization. Although no studies directly evaluated combined approaches, the complementary mechanisms of nutritional and mechanical interventions suggest that optimal prevention may involve integrating both strategies. Critical gaps persist in orthopedic management, necessitating future research on fracture protocols and surgical interventions.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100445"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146023109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the causal roles of cholesterol and triglyceride subfractions across lipoproteins in irritable bowel syndrome: a Mendelian randomization study","authors":"Fang Peng ,&nbsp;Kemin Xu ,&nbsp;Qinwen Ba ,&nbsp;Hao Bi ,&nbsp;Yanjun Lu","doi":"10.1016/j.metop.2025.100434","DOIUrl":"10.1016/j.metop.2025.100434","url":null,"abstract":"<div><h3>Background</h3><div>Dietary composition and nutrient intake are increasingly recognised as key modulators of symptom onset and severity in a substantial subset of patients with irritable bowel syndrome (IBS). Among dietary lipids, cholesterol and triglycerides have emerged as potential contributors. Nevertheless, the causal relationship remains poorly understood, and evidence in this area remains limited. To address this gap, we conducted a Mendelian randomization (MR) study to dissect the putative causal effects of cholesterol and triglycerides on IBS risk in individuals of European ancestry.</div></div><div><h3>Methods</h3><div>Instrumental variables were constructed for 17 lipid traits—total cholesterol, free cholesterol, triglycerides, and 13 size-specific High-density lipoprotein(HDL), Low-density lipoprotein(LDL), and Very low-density lipoprotein (VLDL) sub-fractions—using summary-level data from the largest available genome-wide association studies (GWAS). Lipid exposures were derived from a meta-analysis of 115,082 European-ancestry individuals. IBS outcomes were ascertained in an independent cohort of 486,601 participants of European descent. Causal estimates were obtained with five complementary MR methods: inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. Robustness was further interrogated with leave-one-out permutation, MR-Egger intercept evaluation of directional pleiotropy, and Cochran's Q assessment of heterogeneity.</div></div><div><h3>Results</h3><div>The MR analysis indicated that cholesterol or free cholesterol content of chylomicrons and extremely large VLDL particles were causally associated with an increased risk of developing IBS (β = 0.0679, odds ratios (OR) = 1.070, 95 % CI 1.015–1.128, P = 0.0118; and β = 0.0650, OR = 1.0672, 95 % CI 1.0179–1.1189, P = 0.0007, respectively). Conversely, equivalent increments in cholesterol or free cholesterol carried by very large HDL or very small VLDL conferred protection (β = −0.0626, OR = 0.9392, 95 % CI 0.8992–0.9810, P = 0.0047; and β = -0.0604, OR = 0.9412, 95 % CI 0.9023–0.9819, P = 0.005). Total circulating triglycerides also displayed a positive causal effect on IBS susceptibility (β = 0.0798, OR = 1.083, 95 % CI 1.0268–1.1423, P = 0.0033), with concordant directional estimates observed across the majority of lipoprotein sub-fractions.</div></div><div><h3>Conclusion</h3><div>Whereas triglycerides conveyed a uniformly adverse effect on IBS risk regardless of lipoprotein carrier, cholesterol displayed a net protective signal across most particle classes. This dichotomy implies that lipid-centred interventions should discriminate between the two moieties: dietary or pharmacological strategies that selectively lower triglycerides while preserving—or even augmenting—cholesterol in specific lipoprotein fractions may offer a rational, mechanistically grounded approach to IBS prevention and management.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100434"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning–based binary classification of elevated HbA1c (≥6.5 %) for risk assessment","authors":"Dler Hussein Kadir ,&nbsp;Azhin Mohammed Khudhur ,&nbsp;Hewir Abdulqadir Khidir","doi":"10.1016/j.metop.2025.100428","DOIUrl":"10.1016/j.metop.2025.100428","url":null,"abstract":"<div><h3>Objective</h3><div>One of the most important biomarkers for evaluating long-term glycemic management and estimating the risk of diabetes is glycated hemoglobin (HbA1c). Early risk assessment and intervention techniques can be improved by identifying important clinical and demographic variables. Through the integration of clinical indicators (lipid profiles, albumin, and liver enzymes) and demographic characteristics (age, gender), this study seeks to create a comprehensive HbA1c prediction model.</div></div><div><h3>Study design</h3><div>To find the most important factors, logistic regression was used to evaluate 482 cases using a stepwise selection process.</div></div><div><h3>Results</h3><div>With an area under the curve (AUC) of 0.797, the final model had strong predictive ability. Age (OR = 1.085, p &lt; 0.001), glutamate pyruvate transaminase (GPT) (OR = 1.011, p = 0.0127), high-density lipoprotein (HDL) (OR = 0.969, p = 0.017), VitaminD3 (OR = 1.023, p = 0.014), and very low-density lipoprotein (VDL) (OR = 1.016, p = 0.018) were all significant predictors.</div></div><div><h3>Conclusions</h3><div>The greatest predictor was age, which was positively correlated with elevated HbA1c levels, whereas HDL had a protective impact. The addition of VitaminD3, VDL, and GPT implies that indicators of liver and metabolic function have a major role in the variability of HbA1c. These results demonstrate how normal clinical and demographic data may be incorporated into predictive models for early diabetes risk assessment, enabling more individualized medical care and bettering patient outcomes.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100428"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecystectomy with jejunoileal bypass ameliorates diabetic metabolism in mice with type 2 diabetes through modulation of FXR and TGR5 signaling","authors":"Haixin Yin ,&nbsp;Weijie Chen ,&nbsp;Xiaodong He ,&nbsp;JianPing Zeng","doi":"10.1016/j.metop.2025.100437","DOIUrl":"10.1016/j.metop.2025.100437","url":null,"abstract":"<div><h3>Objectives</h3><div>Our aim was to investigate the improvement in glucose and lipid profiles and the mechanism involving bile acid receptors FXR and TGR5 following cholecystectomy with jejunoileal bypass(CJB) in mice with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Methods</h3><div>Twenty male mice with T2DM were randomly assigned to CJB and sham groups. We analyzed fasting blood glucose (FBG), insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and total bile acids (TBA) levels. Expression levels of the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5) in liver, muscle, and adipose tissue were assessed post-sacrifice.</div></div><div><h3>Results</h3><div>Despite pair-feeding, the CJB group exhibited lower body weights than the sham group at 24 weeks post-surgery (<em>P</em> = 0.004). The levels of FBG (<em>P</em> &lt; 0.001) and insulin (<em>P</em> = 0.013) in the CJB group significantly decreased compared to the baseline. The intraperitoneal glucose and insulin tolerance tests demonstrated improved glucose tolerance (<em>P</em> = 0.004) and insulin sensitivity (<em>P</em> = 0.001). GLP-1 levels significantly increased (<em>P</em> = 0.002). The levels of TC (<em>P</em> &lt; 0.001) and LDL-C (<em>P</em> &lt; 0.001) were decreased, while the levels of TG (<em>P</em> = 0.003), HDL-C (<em>P</em> &lt; 0.001), and FFA (<em>P</em> &lt; 0.001) were increased at the 24th postoperative week. Furthermore, TBA concentrations were higher in the CJB group than in the control group (<em>P</em> &lt; 0.001). The expression of FXR in the liver (<em>P</em> = 0.034), muscle (<em>P</em> = 0.003) and adipose tissue (<em>P</em> = 0.045) and that of TGR5 in the liver (<em>P</em> = 0.024), muscle (<em>P</em> = 0.026) and adipose tissue (<em>P</em> = 0.004) were upregulated after surgery.</div></div><div><h3>Conclusions</h3><div>In mice with T2DM, cholecystectomy with jejunoileal bypass modulates BA–FXR/TGR5 signaling and is associated with metabolic improvement.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100437"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of in vitro and in vivo antidiabetic potential of hydromethanol extract and solvent fraction of the leaves of Ajuga integrifolia (Lamiaceae) in diabetic mice models","authors":"Yalo Daba ,&nbsp;Monas Kitessa ,&nbsp;Kindessa Ahmed ,&nbsp;Demis Million ,&nbsp;Ayalew Temesgen ,&nbsp;Meseret Amde ,&nbsp;Tsegu Kiros ,&nbsp;Dine Walo ,&nbsp;Anteneh Belayneh ,&nbsp;Jemal Abdela","doi":"10.1016/j.metop.2026.100443","DOIUrl":"10.1016/j.metop.2026.100443","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus is a spectrum of distinct metabolic disorders marked by sustained elevation of blood glucose levels that arises from deficiencies in either insulin action, insulin secretion, or a combination of both. <em>Ajuga integrifolia</em> is traditionally used to control diabetes.</div></div><div><h3>Objective</h3><div>To evaluate the antidiabetic effects of hydromethanol and solvent fraction extracts from the leaves of <em>Ajuga integrifolia</em> using in vitro and in vivo methods.</div></div><div><h3>Method</h3><div>The plant leaves were extracted using the maceration technique. The plant's acute oral toxicity test was evaluated according to the guidelines of the Organization for Economic Cooperation and Development. In vitro α-amylase inhibition activity of the hydromethanol and solvent fraction extracts of the leaves of <em>Ajuga integrifolia</em> was evaluated by using the 3, 5-dinitrosalicylic acid method.</div><div>The study examined the effects of hydromethanol and solvent fraction extracts at doses of 250, 500, and 1000 mg/kg on lowering blood glucose levels in a diabetic mouse model.</div></div><div><h3>Result</h3><div>An acute toxicity study of the hydromethanol extract of the leaves of the <em>Ajuga integrifolia</em> did not show any sign of toxicity or mortality. The greatest alpha amylase inhibition was revealed by hydromethanol extracts (57.63 ± 0.38 %) (800 μg/mL), while the n-hexane fraction (23.18 ± 0.78 %) (800 μg/mL) showed the lowest effect. The hydromethanol extract 500 mg/kg (p &lt; 0.001) and 1000 mg/kg (p &lt; 0.001) at 2 and 4 h significantly reduced the blood glucose level in normoglycemic mice. At 2 h, both the 500 mg/kg and 1000 mg/kg doses of hydromethanol extract significantly lowered BGL when compared to the 30-min BGL and the negative control group (P &lt; 0.001). The hydromethanol extract and aqueous fraction showed significant (P &lt; 0.001) antidiabetic activity at a dosage of 1000 mg/kg, resulting in a 39.2 % and 37.5 % reduction in blood glucose levels in the diabetic mice model, respectively.</div></div><div><h3>Conclusion</h3><div>Acute treatment with hydromethanol extract is safe and well-tolerated when administered orally. The study supported the traditional use of <em>Ajuga integrifolia</em> leaves for patients with diabetes.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100443"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}