Metabolism: clinical and experimental最新文献

{"title":"Postprandial glucose profiles may reflect heterogeneity in insulin secretion and sensitivity in type 2 diabetes.","authors":"Annalisa Giosuè, Viktor Skantze, Roberta Testa, Giovanna D'Abbronzo, Giuseppina Costabile, Marilena Vitale, Alessandra Corrado, Mats Jirstrand, Rikard Landberg, Gabriele Riccardi, Lutgarda Bozzetto","doi":"10.1016/j.metabol.2026.156626","DOIUrl":"https://doi.org/10.1016/j.metabol.2026.156626","url":null,"abstract":"<p><strong>Background: </strong>Continuous glucose monitoring (CGM) reveals heterogeneity of postprandial glucose responses (PPGR), a key target for optimizing glycemic control in type 2 diabetes (T2D). We analyzed PPGR patterns to identify subtypes reflecting pathophysiological differences.</p><p><strong>Methods: </strong>Cross-sectional CGM data from 100 individuals with T2D were collected over 4 h following a standardized meal consumed twice. Dynamic PPGR features-glucose peak, incremental area under the curve (iAUC), rise and fall rates, final vs. fasting glucose-were used for K-Means clustering, with stability assessed using a Random Forest classifier trained on the first meal. In 50 participants, postprandial plasma glucose and insulin were measured, and clinical/metabolic parameters compared across clusters using one-way ANOVA.</p><p><strong>Results: </strong>Three CGM-defined PPGR clusters were identified. Cluster 1 (n = 19) showed the highest peak and iAUC, with post-meal glucose remaining persistently above baseline. Cluster 2 (n = 56) and 3 (n = 25) had lower peaks and iAUCs, but Cluster 3 exhibited higher rise and fall rates than Cluster 2. Clusters did not differ in age, sex, BMI, or diabetes duration, but metformin use was lower in Cluster 3. Cluster 1 showed significantly lower insulin secretion (HOMA2-B%: 77.42 ± 25.64 vs. 104.96 ± 43.94) and higher insulin resistance (HOMA-IR: 7.94 ± 3.27 vs. 4.84 ± 2.78) than Cluster 3, with intermediate values for Cluster 2, confirmed by postprandial indices. Cluster 3 had a higher early insulin response than Cluster 1 and 2 (60-min insulinogenic index: 1.67 ± 1.07, 0.84 ± 0.31, 0.84 ± 0.58, respectively; p < 0.05).</p><p><strong>Conclusions: </strong>CGM-derived PPGR features could identify T2D subtypes with similar clinical profiles but distinct insulin secretion and sensitivity impairments, supporting targeted interventions.</p>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"181 ","pages":"156626"},"PeriodicalIF":11.9,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PFKFB3 nuclear translocation improves diabetic retinopathy by attenuating endothelial cell senescence through inhibition of USP7-p53 axis","authors":"Peiyu Liu ,&nbsp;Ning Shen ,&nbsp;Yali Zhou ,&nbsp;Jingyi Wu ,&nbsp;Meng Hao ,&nbsp;Shuchang Zhang ,&nbsp;Yifan Wang ,&nbsp;Xiaoqian Wang ,&nbsp;Huiming Li ,&nbsp;Zhipeng You ,&nbsp;Huimin Fan ,&nbsp;Xun Xu ,&nbsp;Ning Wang ,&nbsp;Dandan Sun ,&nbsp;Fang Wei","doi":"10.1016/j.metabol.2026.156553","DOIUrl":"10.1016/j.metabol.2026.156553","url":null,"abstract":"<div><h3>Background</h3><div>Endothelial cell (EC) senescence is a key contributor to retinal vascular dysfunction in diabetic retinopathy (DR), yet its molecular mechanisms remain incompletely understood. While PFKFB3 is well recognized for its critical function in modulating EC glycolysis and angiogenesis, its contribution to endothelial senescence in DR has not been elucidated.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing was used to profile EC senescence signatures and barrier/tight-junction programs in diabetic retinas. PFKFB3/USP7 abundance and senescence in vivo and in vitro were assessed by Western blotting, SA-β-gal staining, immunofluorescence, and cell-cycle flow cytometry. PFKFB3-USP7 interaction was examined by co-immunoprecipitation, mass spectrometry, and nuclear colocalization. Retinal vascular dysfunction was quantified by Evans blue leakage and PAS-stained retinal trypsin digests.</div></div><div><h3>Results</h3><div>Single-cell analysis identified EC subclusters enriched for senescence transcripts and simultaneously depleted for barrier/tight-junction pathways in diabetic retinas. Hyperglycemia reduced PFKFB3 and impaired its nuclear entry, leading to prominent cellular senescence in vitro and in vivo, and restoration of PFKFB3 effectively reversed this phenotype. By establishing stable endothelial cell lines expressing PFKFB3 only in the nucleus (NLS mutant) or cytoplasm (K472Q mutant), we revealed that anti-senescent activity required PFKFB3 nuclear localization. Nuclear-localized PFKFB3 interacted with USP7, a critical modulator of the p53 pathway, and regulated the USP7-p53 axis by constraining their coupling, thereby promoting proteasomal degradation of p53. As a downstream effector of PFKFB3, USP7 abrogated the protective effect of PFKFB3, whereas its inhibition attenuated hyperglycemia-induced senescence and mitigated retinal vascular dysfunction.</div></div><div><h3>Conclusions</h3><div>Our findings highlighted the essential role of nuclear PFKFB3 dysfunction and USP7-p53 axis dysregulation in mediating EC senescence under diabetic stress, suggesting that targeting PFKFB3 nuclear translocation may be a novel therapeutic strategy for the prevention of diabetic retinopathy.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156553"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enduring improvements in hepatic insulin sensitivity predict sustained remission of prediabetes during a 3-year lifestyle intervention: results from the PREVIEW multinational diabetes prevention trial","authors":"Ruixin Zhu ,&nbsp;Jie Guo ,&nbsp;Maija Huttunen-Lenz ,&nbsp;Gareth Stratton ,&nbsp;Nils Swindell ,&nbsp;Ian A. Macdonald ,&nbsp;Teodora Handjieva-Darlenska ,&nbsp;Svetoslav Handjiev ,&nbsp;Santiago Navas-Carretero ,&nbsp;Sally D. Poppitt ,&nbsp;Marta Silvestre ,&nbsp;Wolfgang Schlicht ,&nbsp;Mikael Fogelholm ,&nbsp;J. Alfredo Martinez ,&nbsp;Anne Raben ,&nbsp;Jennie Brand-Miller","doi":"10.1016/j.metabol.2026.156546","DOIUrl":"10.1016/j.metabol.2026.156546","url":null,"abstract":"<div><h3>Background</h3><div>Recent investigation advocates the use of prediabetes remission as a goal of diabetes prevention. We aimed to compare changes in metabolic markers in participants with and without sustained remission of prediabetes during a 3-year lifestyle intervention.</div></div><div><h3>Methods</h3><div>This <em>post-hoc</em> analysis used data from the PREVIEW trial, a 3-year, multinational, multicenter, randomized controlled trial aiming to examine the effects of lifestyle interventions on prevention of type 2 diabetes among high-risk adults. Adult participants with prediabetes and overweight/obesity underwent 8-weeks of rapid weight loss followed by a 148-week lifestyle intervention for weight loss maintenance. Participants who completed the full protocol and had available data (<em>n</em> = 846) were included in the current analysis. Participants were classified into prediabetes maintainers, relapsers, and non-responders according to blood glucose levels at 1 and 3 years. Changes in metabolic markers over 3 years were compared in those who achieved sustained remission (maintainers, <em>n</em> = 102) vs those who failed (non-responders, <em>n</em> = 618), as well as those who were successful at 1 year but then relapsed (relapsers, <em>n</em> = 126).</div></div><div><h3>Results</h3><div>Only 12% participants experienced sustained remission at 3 years. After adjusting for baseline covariates, compared with non-responders, maintainers achieved greater weight loss (mean difference −4.0 kg; 95% CI −5.8, −2.2 kg) and fat mass loss at 3 years. Maintainers also made further improvements in markers of hepatic insulin sensitivity, regardless of weight change. Compared with relapsers, maintainers had greater decreases in weight and fat mass, but changes in visceral adiposity index were similar. Relapsers gradually reverted to an insulin resistant state at 2 and 3 years compared with maintainers, independent of weight change.</div></div><div><h3>Conclusions</h3><div>In a long-term lifestyle intervention, sustained remission of prediabetes was associated with enduring improvements in hepatic insulin sensitivity, regardless of weight change. In addition to weight loss, targeting hepatic insulin sensitivity per se may help prevent relapse in prediabetes.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156546"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rising burden of MASLD and CKM syndrome in Asia: A decade of trends and future projections","authors":"Tianqi Duo ,&nbsp;Yun Wen ,&nbsp;Yu Bian ,&nbsp;Yizheng Wang ,&nbsp;Xiaofang Zhang ,&nbsp;Jin Ju ,&nbsp;Yanjie Lu ,&nbsp;Zhiguo Wang ,&nbsp;Jinghao Wang ,&nbsp;Baofeng Yang","doi":"10.1016/j.metabol.2026.156549","DOIUrl":"10.1016/j.metabol.2026.156549","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To analyze epidemiological trends and project the future burden of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome in Asia using data from the Global Burden of Disease (GBD) Study. This analysis quantifies the substantial co-occurrence of MASLD and CKM syndrome, which together accounted for 50.9% of the total disease prevalence in Asia in 2021, by evaluating incidence, prevalence, deaths, and disability-adjusted life years (DALYs) from 2010 to 2021.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Data from the GBD 2021 database were used to assess the burden of MASLD and CKM syndrome in Asia. The study analyzed incidence, prevalence, deaths and DALYs for nine metabolic diseases or related conditions: MASLD, atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), hypertension heart disease (HHD), lower extremity peripheral arterial disease (PAD), type 2 diabetes mellitus (T2DM), stroke, and chronic kidney disease (CKD) due to hypertension (HTN) and T2DM. Age-standardized rates (ASRs) and estimated annual percentage changes (EAPCs) were calculated. The autoregressive integrated moving average (ARIMA) model was applied to forecast the trend of MASLD over the next 20 years. This model, widely used in time-series forecasting, identifies trends, cyclical variations, and random fluctuations to provide scientifically grounded projections.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In 2021, the collective burden of the nine CKM-related conditions analyzed (including MASLD) accounted for 50.9% of total disease prevalence and 34.4% of all deaths in Asia, with 12.68 million deaths and 306.82 million DALYs. Among the nine metabolic diseases analyzed, MASLD had the highest incidence and prevalence, with MASLD-related liver cirrhosis (MASLD-LC) and MASLD-related steatohepatitis (MASLD-SH) affecting approximately 786.69 million and 786.65 million individuals, respectively. IHD and stroke were the leading causes of death and DALYs. Between 2010 and 2021, the incidence (MASLD-LC/MASLD-SH: +25.4%) and prevalence (MASLD-LC/MASLD-SH: +38.0%) of MASLD increased substantially. T2DM showed the greatest rise in age-standardized incidence rate (EAPC: +1.7%) and age-standardized prevalence rate (EAPC: +2.0%). Geographically, MASLD represented the predominant metabolic burden in most Asian countries, with the exception of Central and South Asia, where IHD prevailed. ARIMA projections suggest that the MASLD burden will continue to grow, with a projected increase in incidence of approximately 34% compared to 1990 levels (MASLD-LC: +34.01%; MASLD-SH: +34.04%), underscoring the need for timely and proactive interventions.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;MASLD and CKM syndrome constitute a major and growing health challenge in Asia. These findings underscore the need for early diagnosis, targeted interventions, and comprehensive public health strategies. Future research should ","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156549"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of sepiapterin versus sapropterin in patients with phenylketonuria: Results from the Phase 3, randomized, crossover, open-label, active-controlled AMPLIPHY trial","authors":"Maria Giżewska ,&nbsp;Anita Inwood ,&nbsp;Renáta Tyčová ,&nbsp;Suresh Vijay ,&nbsp;Olivia Fjellbirkeland ,&nbsp;Francjan van Spronsen ,&nbsp;Eva Maria Venegas-Moreno ,&nbsp;Laura Guilder ,&nbsp;Alberto Burlina ,&nbsp;Heidi Peters ,&nbsp;Murray Potter ,&nbsp;Urh Grošelj ,&nbsp;Anupam Chakrapani ,&nbsp;Amaya Bélanger-Quintana ,&nbsp;François Maillot ,&nbsp;Frank Rutsch ,&nbsp;Jean-Baptiste Arnoux ,&nbsp;Michel Tchan ,&nbsp;Kim Ingalls ,&nbsp;Zhenming Zhao ,&nbsp;Ania C. Muntau","doi":"10.1016/j.metabol.2026.156513","DOIUrl":"10.1016/j.metabol.2026.156513","url":null,"abstract":"<div><h3>Aim</h3><div>AMPLIPHY is the first Phase 3 study comparing sepiapterin versus sapropterin in children and adults with phenylketonuria (PKU).</div></div><div><h3>Methods</h3><div>AMPLIPHY was an international, Phase 3, two-part, open-label study in participants with PKU aged ≥2 years. Participants responsive to sepiapterin (60 mg/kg/day) in Part 1 (≥20% reduction in blood phenylalanine [Phe]) entered Part 2, a crossover treatment period, and were randomized 1:1 to alternative treatment sequences of sepiapterin (60 mg/kg/day, licensed dosage) and sapropterin (20 mg/kg/day, maximum licensed dosage) for 4 weeks each, with a 14-day washout between treatments. The primary endpoint was mean change in blood Phe from baseline to Weeks 3–4 of each treatment period (Part 2).</div></div><div><h3>Results</h3><div>Of 82 participants enrolled, 67 (81.7%) and 62 (75.6%) had reductions in blood Phe ≥20% and ≥30%, respectively, in Part 1. Sixty-two participants were randomized in Part 2 (mean [SD] age, 15.8 [10.8] years). In the primary analysis set (≥30% reduction in blood Phe in Part 1, <em>n</em> <em>=</em> 58), mean (SD) baseline blood Phe before sepiapterin and sapropterin treatment was 725.8 (302.1) and 790.4 (370.0) μmol/L, respectively. Least-squares mean (SE) reduction in blood Phe from baseline was −437.0 (28.0) and −256.6 (28.2) μmol/L, respectively, representing a least-squares mean difference of −180.4 μmol/L (95% CI: −229.5, −131.4; <em>p</em> &lt; 0.0001) and a relative 70% greater reduction with sepiapterin versus sapropterin. Both treatments were well tolerated, with safety profiles consistent with previous reports.</div></div><div><h3>Conclusions</h3><div>Sepiapterin was superior to the highest approved dose of sapropterin in lowering blood Phe. No new safety signals were observed.</div><div>The trial was registered in the UK Clinical Study Registry, ISRCTN, on January 29, 2024 (ID number, ISRCTN79102999; <span><span>https://www.isrctn.com/ISRCTN79102999</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156513"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Response Factor (SRF) promotes actin cytoskeletal organization in adipocytes to support adaptive hypertrophic expansion and tissue remodeling during obesity in mice","authors":"Jisun So ,&nbsp;Jamie Wann ,&nbsp;Kyungchan Kim ,&nbsp;Solaema Taleb ,&nbsp;Hyeong-Geug Kim ,&nbsp;Manju Kumari ,&nbsp;Alexander S. Banks ,&nbsp;X. Charlie Dong ,&nbsp;Hyun Cheol Roh","doi":"10.1016/j.metabol.2026.156548","DOIUrl":"10.1016/j.metabol.2026.156548","url":null,"abstract":"<div><h3>Background</h3><div>Adipocyte hypertrophy, the unique capacity of adipocytes to enlarge in response to energy surplus, is a crucial determinant of metabolic health during obesity. Nonetheless, the molecular mechanisms governing this adaptive growth remain incompletely characterized.</div></div><div><h3>Methods</h3><div>Super-enhancer landscapes in adipocytes were mapped <em>via</em> H3K27ac chromatin immunoprecipitation sequencing analysis of adipocyte nuclei from mice fed either a standard chow diet or high-fat diet (HFD) to identify transcriptional regulators activated under obesogenic conditions. Functional validation was conducted through both <em>in vitro</em> and <em>in vivo</em> experiments, including adipocyte-specific gene deletion mouse models, followed by single-nucleus RNA sequencing.</div></div><div><h3>Results</h3><div>Super-enhancer profiling identified Serum Response Factor (SRF) as a critical driver of actin cytoskeletal remodeling in adipocytes during obesity. SRF was shown to be both necessary and sufficient for regulation of actin cytoskeletal gene expression in 3T3-L1 adipocytes. Adipocyte-specific SRF ablation in mice led to reduced expression of actin cytoskeletal genes, disruption of actin filament organization, and impaired adipocyte enlargement under HFD feeding. Despite comparable body weight, SRF-deficient mice developed exacerbated insulin resistance and ectopic lipid accumulation in the liver and brown adipose tissue, indicative of compromised lipid storage within adipocytes. Single-nucleus RNA-seq further revealed that cell-intrinsic actin cytoskeletal defects in adipocytes propagated to tissue-level dysfunction, impairing vascularization and increasing inflammation.</div></div><div><h3>Conclusion</h3><div>These findings establish SRF as a central regulator of actin cytoskeletal organization that promotes healthy adipocyte hypertrophy and adipose tissue remodeling. Enhancing SRF-dependent cytoskeletal remodeling in adipocytes may offer a therapeutic strategy to preserve metabolic health in obesity.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156548"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The multifaceted role of GLP-1 in metabolic disorders, chronic inflammation, and aging: Mechanisms and therapeutic potential","authors":"Mo Li ,&nbsp;Shenghao Xu ,&nbsp;Hanqing Cai ,&nbsp;Jianlin Xiao ,&nbsp;Yanguo Qin","doi":"10.1016/j.metabol.2026.156547","DOIUrl":"10.1016/j.metabol.2026.156547","url":null,"abstract":"<div><div>Glucagon-like peptide-1 (GLP-1), an incretin secreted by intestinal L-cells in response to nutrients, regulates glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and reducing appetite via hypothalamic signaling. Beyond these canonical actions, emerging evidence reveals GLP-1's pleiotropic functions across multiple systems, with relevance to metabolic disorders, chronic inflammation, and aging-related pathologies. This review summarizes molecular mechanisms underlying GLP-1's protective roles, highlighting its contributions to metabolic balance, inhibition of NF-κB-mediated inflammation, and attenuation of cellular aging through mitochondrial enhancement and autophagy promotion. GLP-1 also influences immune cell function and alleviates hallmarks of senescence, thereby offering therapeutic potential beyond diabetes. We further critically assess the translational potential of GLP-1 receptor agonists (GLP-1RAs), pharmacological agents with superior pharmacokinetics versus native GLP-1, in treating conditions linked to dysregulated metabolism, persistent inflammation, and accelerated aging. Despite demonstrated efficacy in preclinical models and clinical studies, important challenges persist, including inter-individual variability, off-target risks, and uncertainties regarding long-term safety. We conclude by emphasizing the necessity of integrated strategies to target the metabolic–inflammatory–aging axis and by advocating optimization of GLP-1RA formulations, identification of predictive biomarkers, and expansion of their utility for age-associated diseases.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"178 ","pages":"Article 156547"},"PeriodicalIF":11.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian robustness and glycemic control: From wearable data to clinical implications.","authors":"Guobin Guobin Liu, Xin Yuan","doi":"10.1016/j.metabol.2026.156606","DOIUrl":"https://doi.org/10.1016/j.metabol.2026.156606","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156606"},"PeriodicalIF":11.9,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147674966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to letter to the editor: Circadian robustness and glycemic control: From wearable data to clinical implications.","authors":"Da Young Lee, Jung-Been Lee, Inha Jung, So Young Park, Ji Hee Yu, Ji A Seo, Heon-Jeong Lee, Nan Hee Kim","doi":"10.1016/j.metabol.2026.156604","DOIUrl":"10.1016/j.metabol.2026.156604","url":null,"abstract":"","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"156604"},"PeriodicalIF":11.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147616370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging incretin- and multi-agonist-based treatments – the continued refinement and continuous expansion of a potent therapeutic armamentarium for cardio-kidney-liver-metabolic diseases and beyond","authors":"Emir Muzurović ,&nbsp;Niki Katsiki ,&nbsp;Špela Volčanšek ,&nbsp;Fulvio Plescia ,&nbsp;Manfredi Rizzo ,&nbsp;Christos S. Mantzoros","doi":"10.1016/j.metabol.2026.156494","DOIUrl":"10.1016/j.metabol.2026.156494","url":null,"abstract":"<div><div>While the use of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) has achieved a central position in our therapeutic armamentarium, new and innovative incretin- and multi-agonist-based treatment strategies hold further promise as potential game-changers for obesity and cardio-kidney-liver-metabolic diseases. Molecular pathways of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), amylin, glucagon and peptide YY have been consistently involved in improved outcomes associated with obesity and related disorders. Single, dual, and even triple drug combinations are being researched throughout all phases of clinical trials. The similarities in GLP-1, GIP, and glucagon peptide sequences enable the development of unimolecular multi-receptor activating agonists and/or antagonists. Furthermore, subcutaneously administered peptides are being supplemented with oral analogs currently in development. Both well-designed clinical trials and real-world evidence are fuelling the development of incretin and multi-agonist-based therapies, thereby holding the promise to deliver an increasing double-digit percent weight loss in addition to addressing many obesity-related comorbidities and complications. It is increasingly evident that early initiation of incretin-based therapy across a broad spectrum of cardio-kidney-metabolic disorders improves body weight, dysglycemia, and cardiovascular risk factor management and consequently is expected to reduce cardio-kidney-liver-metabolic and vascular morbidity and mortality and soon most probably those from obesity-related malignancies, Alzheimer's, and other neurocognitive diseases. This review explores new incretin- and multi-agonist-based therapies undergoing clinical trials for chronic weight management, type 2 diabetes mellitus with its complications, chronic kidney disease, metabolic dysfunction-associated steatotic liver disease and obstructive sleep apnea; it also highlights areas of uncertainty regarding the potency, safety, tolerability, and sustainability of incretin-based approaches for obesity and cardio-kidney-liver-metabolic disorders and finally, we discuss future directions.</div></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"177 ","pages":"Article 156494"},"PeriodicalIF":11.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}