Diabetology & Metabolic Syndrome最新文献

{"title":"Heterogeneity in the treatment effect of sodium-glucose cotransporter-2 inhibitor on chronic kidney disease risk reduction: a prevalent new user cohort study applying double/debiased machine learning.","authors":"Tanawan Kongmalai, Panu Looareesuwan, Amarit Tansawet, Sukanya Siriyotha, Patratorn Kunakorntham, Burin Boonwatcharapai, John Attia, Gareth J McKay, Ammarin Thakkinstian","doi":"10.1186/s13098-026-02249-2","DOIUrl":"10.1186/s13098-026-02249-2","url":null,"abstract":"<p><strong>Background: </strong>Despite strong evidence supporting the benefits of sodium-glucose cotransporter-2 inhibitor (SGLT2i) for managing type 2 diabetes, heterogeneity of treatment response is rarely assessed. This study aims to demonstrate the heterogeneity effects of SGLT2i for preventing chronic kidney disease (CKD) via a causal machine learning model.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted. Data from 2,280 type 2 diabetes patients were used to develop a double/debiased machine learning (DDML) model for CKD prediction; a conventional treatment effect (TE) model was also constructed for comparison. Model performance was evaluated using area under the receiver operating characteristic curve, and calibration plot. Subsequently, average treatment effects (ATEs) and conditional average treatment effects (CATEs) of SGLT2i versus non-SGLT2i were estimated and compared among models.</p><p><strong>Results: </strong>A neural network (NN) was selected for the DDML framework for CKD prediction. Although the conventional TE model demonstrated slightly better discrimination and calibration, the DDML-NN produced comparable results. The ATEs (95% confidence interval) estimated by DDML-NN and conventional TE models were -0.0399 (-0.0600, -0.0199) and - 0.0424 (- 0.0616, - 0.0232), respectively. Corresponding CATE ranges were -0.3945 to 0.2495 and - 0.6968 to 0.0026. Patients gaining higher benefits from SGLT2i trended to be older, male, and overweight, compared to who were benefited less from SGLT2i.</p><p><strong>Conclusion: </strong>The protective effect of SGLT2i against CKD was indicated, albeit heterogeneous. Counterfactual models including DDML-NN and conventional TE models demonstrated similar performance. However, data from a larger cohort are still required to draw a firm conclusion.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13689252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GlycA-gene interactions in cardiovascular-kidney-metabolic syndrome: evidence from genetic association.","authors":"Mingyang Yuan, Suwen Cao, Xing Wan, Yuting Yang, Siyu Fan, Jiang Xie, Han Wang","doi":"10.1186/s13098-026-02252-7","DOIUrl":"10.1186/s13098-026-02252-7","url":null,"abstract":"<p><strong>Objective: </strong>Cardiovascular-Kidney-metabolic (CKM) syndrome is a concept introduced by the American Heart Association, describing systemic diseases resulting from the pathophysiological interaction among obesity, stroke, type 2 diabetes, chronic kidney disease, and cardiovascular disease. Glycoprotein acetyls (GlycA) is a novel biomarker for systemic inflammation and cardiovascular risk. This study aims to uncover the shared genetic architecture between GlycA and CKM, identify common risk loci and key tissues, and clarify the mechanisms linking these conditions.</p><p><strong>Methods: </strong>Using summary data from large-scale GWAS studies, we evaluated both global and local genetic correlations between GlycA and various components of CKM. A cross-trait pleiotropic analysis was conducted to identify shared pleiotropic loci and related genes. FUSION was used to find susceptibility genes linked to GlycA and CKM. A comprehensive set of functional annotations and tissue-specific analyses was performed to uncover potential connections between these traits. Furthermore, a multi-trait colocalization method was utilized to explore the underlying mechanisms of the association between GlycA and CKM.</p><p><strong>Results: </strong>Our study revealed a close genetic correlation between GlycA and CKM. We identified 260 potential SNPs that were corrected using the Bonferroni method, of which 30 passed the colocalization test (PP.H4 > 0.70). Notably, locus 9q34.2 appeared in both GlycA-T2D and GlycA-HF trait pairs. By integrating post-GWAS methods, we identified 53 potentially drug targets (CMIP, DNAJC5G, FCGRT, etc.). FUSION analysis identified 23 shared susceptibility genes for GlycA and CKM (ZPR1, IL6R, PABPC4, etc.). Analysis of tissue enrichment at the SNP level revealed pleiotropic mechanisms associated with whole blood and liver. Gene-level analysis highlighted important roles of metabolic signaling pathways. Furthermore, multi-trait colocalization analysis suggested that rs1260326 and rs2925979 may play significant roles in the mechanistic link between GlycA and CKM.</p><p><strong>Conclusion: </strong>Our study confirmed a significant genetic association and shared genetic structure between GlycA and CKM, revealing potential mechanisms that may be involved.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of mazdutide vs. dulaglutide in adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.","authors":"Muhammad Hassan, Muhammad Hussain, Saifullah Khan, Muhammad Tayyab Azam, Zain Ul Abideen Shahid, Abdul Hannan, Muhammad Mussawir Khuhro, Sahil Bhagia, Hasibullah Aminpoor","doi":"10.1186/s13098-026-02248-3","DOIUrl":"10.1186/s13098-026-02248-3","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus (T2DM) is closely linked to obesity and carries a high risk of metabolic complications. While GLP-1 receptor agonists like dulaglutide improve blood sugar and support modest weight loss, many patients do not reach their treatment goals. Mazdutide, a dual GLP-1 and glucagon receptor agonist, may offer stronger metabolic benefits.</p><p><strong>Objective: </strong>To compare the efficacy and safety of mazdutide versus dulaglutide in adults with T2DM.</p><p><strong>Methods: </strong>We systematically reviewed randomized controlled trials comparing mazdutide and dulaglutide. Primary outcomes included changes in HbA1c, body weight, and achievement of glycemic and weight-loss targets. Safety outcomes included treatment-emergent adverse events. Data were pooled using random-effects models, and evidence certainty was assessed using GRADE.</p><p><strong>Results: </strong>Three trials met inclusion criteria. Mazdutide led to greater reductions in HbA1c (- 0.25%) and body weight (- 2.97 kg) compared with dulaglutide. Patients were more likely to achieve HbA1c < 7.0%, ≥ 5% weight loss, and the combined target of ≥ 5% weight loss with HbA1c < 7.0%. Fasting plasma glucose was numerically but not significantly improved. Mazdutide was associated with higher rates of gastrointestinal side effects and decreased appetite, with a non-significant numerical increase in hypoglycemia, while serious adverse events and discontinuations were similar between treatments. Glycemic and major weight outcomes were supported by high-certainty evidence; most safety outcomes were moderate-certainty.</p><p><strong>Conclusions: </strong>Mazdutide, based on evidence from three RCTs, provides preliminary evidence of meaningful improvements in blood sugar control and weight loss compared with dulaglutide, though with an increased risk of mostly manageable gastrointestinal effects; given the limited number of trials, these findings should be considered preliminary and supporting its potential role as a promising dual-action therapy for T2DM management, pending confirmation in larger, longer-term trials.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of body mass index categories with all-cause mortality across metabolic status in 3518 Japanese adults: a 10- and 22-year prospective cohort follow-up study.","authors":"Ryuichi Kawamoto, Asuka Kikuchi, Daisuke Ninomiya, Masanori Abe, Teru Kumagi","doi":"10.1186/s13098-026-02245-6","DOIUrl":"10.1186/s13098-026-02245-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate whether metabolic status modifies the association between body mass index (BMI) and all-cause mortality in a Japanese general population.</p><p><strong>Methods: </strong>We analyzed data from 3518 community-dwelling adults (1554 men and 1964 women; mean age: 64 ± 13 years) enrolled in the Nomura cohort studies (baseline surveys in 2002 or 2014). Mortality status was confirmed using Japan's Basic Resident Register. Participants were classified into phenotypes based on BMI categories and the number of MetS components. Cox proportional hazards models with age as the time scale were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality.</p><p><strong>Results: </strong>Over a median follow-up period of 17.3 years, 34.0% of participants died. Mortality risks varied according to BMI category and metabolic status. Among participants with 0-1 and 2 MetS components, underweight individuals consistently exhibited the highest incidence rates, the lowest cumulative survival, and significantly increased HRs for all-cause mortality (1.71; 95% CI, 1.25-2.34 and 2.26; 95% CI, 1.47-3.48, respectively). In contrast, among individuals with 3-4 MetS components, mortality risk was highest in those with obesity (2.07; 95% CI, 1.18-3.64), followed by those with underweight. A significant interaction was observed between BMI and metabolic status (p = 0.030). Across BMI categories, participants with greater numbers of MetS components generally exhibited higher incidence rates of all-cause mortality.</p><p><strong>Conclusions: </strong>The association between BMI and all-cause mortality differed according to metabolic status. These findings suggest that metabolic status may influence the relationship between BMI and mortality risk in Japanese adults.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"18 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycemic instability in renal decline: a review of HbA1c variability and outcomes in chronic kidney disease.","authors":"Fan Zhang, Rong Wu, Yan Bai, Yifei Zhong","doi":"10.1186/s13098-026-02207-y","DOIUrl":"10.1186/s13098-026-02207-y","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD), and glycemic assessment is complicated by altered glucose/insulin handling and biased glycated hemoglobin (HbA1c) values in advanced kidney disease. Beyond mean HbA1c, long-term visit-to-visit HbA1c variability has emerged as an additional dimension of risk. This review aims to summarize the definition, measurement, and clinical significance of long-term HbA1c variability in diabetes with CKD, and to discuss implications for risk stratification and management, including complementary biomarkers and continuous glucose monitoring (CGM).</p><p><strong>Methods: </strong>We narratively reviewed observational cohorts, meta-analyses, and dialysis/advanced CKD studies evaluating metrics of long-term glycemic variability (e.g., HbA1c-standard deviation, HbA1c-coefficient of variation, HbA1c variability score) and their associations with renal outcomes, cardiovascular events, and mortality, alongside evidence on alternative biomarkers and CGM-derived indices.</p><p><strong>Results: </strong>Across diverse populations, higher HbA1c variability is consistently associated with faster CKD progression, greater risk of ESKD, increased cardiovascular events, and higher all-cause mortality, often independent of mean HbA1c. In advanced CKD and dialysis, HbA1c limitations and treatment-related glucose swings heighten the value of CGM and, in selected settings, glycated albumin/fructosamine.</p><p><strong>Conclusion: </strong>Long-term HbA1c variability is a robust prognostic marker in diabetic CKD and should complement mean HbA1c in clinical assessment; prospective trials are needed to test whether variability-targeted strategies improve hard outcomes.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13673849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of AIP and cystatin C: a study on cardiovascular risk prediction in populations with different glycemic statuses.","authors":"Kuangyi Wang, Yufeng Jiang, Liangping Zhao, Yafeng Zhou","doi":"10.1186/s13098-026-02231-y","DOIUrl":"10.1186/s13098-026-02231-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Cardiovascular disease (CVD) poses a major global health burden. The Atherogenic Index of Plasma (AIP) and Cystatin C are novel biomarkers reflecting lipid metabolism disorders and renal/micro-inflammatory status, respectively. Their combined indicator (AIP-Cys, the product of AIP × Cystatin C) may provide improved predictive value beyond either marker alone. This study aimed to investigate the predictive role of AIP-Cys for the risk of incident CVD across different glycemic statuses: normal glucose regulation (NGR), pre-diabetes (preDM), and diabetes mellitus (DM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;This study was based on the prospective China Health and Retirement Longitudinal Study (CHARLS) cohort. A total of 6,035 participants aged ≥ 45 years without a history of CVD at baseline (2011) were included. The primary exposure was baseline AIP-Cys (the product of AIP × Cystatin C), and the outcome was the first self-reported incident heart disease or stroke event during follow-up (until 2020). Glycemic status was defined based on fasting plasma glucose and glycated hemoglobin levels. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs). Restricted cubic splines and piecewise linear models were applied to analyze nonlinear relationships. Mediation and sensitivity analyses were conducted to verify the robustness of the results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During a median follow-up of 9.0 years, 651 incident CVD cases occurred. In the fully adjusted model, AIP-Cys was independently associated with CVD risk in the overall (HR per unit increase: 1.34; 95% CI: 1.06-1.69), NGR (HR: 1.60; 95% CI: 1.13-2.26), and preDM (HR: 1.32; 95% CI: 1.02-1.70) populations, but not in the DM population. RCS analysis revealed a significant nonlinear relationship in the NGR and preDM groups (P for nonlinearity &lt; 0.05). Piecewise regression identified inflection points (0.47 for NGR; 0.37 for preDM), below which risk increased sharply. Quartile analysis showed the highest risk in Q3 rather than Q4, suggesting a saturation effect. Mediation analysis indicated that systolic blood pressure partially mediated this association (mediating proportion: 14.6% in overall population). The predictive performance of AIP-Cys was modest for short-term risk (1-year AUC: 0.64-0.67) but limited for long-term prediction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The composite indicator AIP-Cys, derived from AIP and Cystatin C, is an independent risk factor for incident CVD in individuals with NGR and preDM. The association exhibits a nonlinear threshold pattern. However, its predictive value is limited in the DM population, and its long-term predictive performance is modest. Additionally, the self-reported nature of cardiovascular outcomes represents a limitation that should be considered when interpreting these findings. By integrating lipid metabolism and renal/inflammatory pathways, this indicator offers a novel ","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond TIR: the impact of technology on glucose variability in a cohort of preschool children with T1D.","authors":"Mariangela Martino, Lorena Matonti, Annalisa Deodati, Maria Elisa Amodeo, Paolo Ciampalini, Valentina Pampanini, Novella Rapini, Francesca Silvestri, Rosanna Squintani, Antonella Lorubbio, Chiara Carducci, Stefano Cianfarani, Riccardo Schiaffini","doi":"10.1186/s13098-026-02239-4","DOIUrl":"10.1186/s13098-026-02239-4","url":null,"abstract":"<p><strong>Background: </strong>In preschool children, high glucose levels and glucose fluctuations have been associated with detrimental effects on the developing brain. Although many studies show how Advanced Hybrid Closed Loop (AHCL) systems enhance common metrics, the evidence regarding their effect on glucose variability in this age group remains limited.</p><p><strong>Aim: </strong>To compare the effectiveness of Multiple Daily Injection (MDI) plus Continuous Glucose Monitoring (CGM) versus Sensor Augmented Pump (SAP) and AHCL in preschool children with T1D, focusing on glucose variability.</p><p><strong>Methods: </strong>A retrospective, one-year, observational, real-world study was performed involving 54 children with Type 1 Diabetes (T1D) < 6 years of age. CGM data were downloaded and entered into GlyCalculator3 software at three-month intervals (t3, t6, t9, t12).</p><p><strong>Results: </strong>Patients were categorized into three groups according to the insulin delivery system used: MDI + CGM (n = 31), SAP (n = 12) and AHCL (n = 11). AHCL showed significantly greater TIR compared to MDI at all timepoints (p < 0.05). Similarly, TAR > 180 mg/dL (p < 0.05 at t6, t9, t12) and TAR > 250 mg/dL (p < 0.05 at t3, t6, t9, t12) were significantly reduced in the AHCL group versus MDI + CGM group. Both mean and median sensor glucose (SG) levels showed significant improvement in pump users. Although HbA1c did not reach statistical significance, the Glucose Management Indicator (GMI) was significantly lower in the AHCL group from t6 onwards. The high blood glucose index (HBGI) significantly improved in AHCL group showing statistical significance from t6 and persisting throughout the observation period (p < 0.05 at t6, t9, t12). The multivariable linear regression analysis indicated that AHCL and SAP were associated with lower GMI, HBGI and Mean Amplitude of Glucose Excursion (MAGE) than MDI + CGM.</p><p><strong>Conclusion: </strong>Both AHCL and SAP systems significantly reduce glucose variability in preschool children with T1D and should be preferred over MDI + CGM in this age group. AHCL outperformed across standard glycemic metrics, supporting its use as the optimal therapeutic strategy.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world efficacy and safety of SGLT2 inhibitor add-on triple therapy in south indian patients with type 2 diabetes mellitus: a 24-week prospective observational cohort study.","authors":"Ananya Ginjupalli, Sreeram Thiriveedhi, Pavan Sai Nelluri, Sai Sravanth Reddy Tamma, Gitanjali Boppana, Suman Maharjan","doi":"10.1186/s13098-026-02240-x","DOIUrl":"10.1186/s13098-026-02240-x","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 2 diabetes mellitus (T2DM) in South Asian populations is characterised by early-onset disease, visceral adiposity disproportionate to body mass index, and accelerated pancreatic β-cell decline which is collectively termed the Asian Indian Phenotype. This study evaluated the glycaemic, anthropometric, haemodynamic, hepatorenal, and mechanistic effects of adding a sodium-glucose cotransporter-2 (SGLT2) inhibitor to existing Metformin and Glimepiride dual therapy in South Indian patients with suboptimally controlled T2DM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This prospective, single-arm observational cohort study (TREND statement for nonrandomised studies followed) enrolled 87 adult South Indian patients with T2DM inadequately controlled on Metformin (≥ 1500 mg/day) and Glimepiride (2-4 mg/day), with HbA1c 7.5-10.0% and eGFR ≥ 60 mL/min/1.73 m². Treatment was allocated at the discretion of the treating physician rather than by randomisation; patients received Dapagliflozin 10 mg (n = 52) or Empagliflozin 10-25 mg (n = 35) for 24 weeks. As an exploratory study, no a priori sample size calculation was performed and findings are considered hypothesis-generating. Continuous variables were assessed for normality (Shapiro-Wilk test and Q-Q plots); intra-group comparisons used the paired t-test with 95% confidence intervals (CIs). Subgroup, correlation, responder, and multivariable regression analyses were prespecified and are exploratory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;HbA1c declined from 8.62 ± 0.74% to 7.71 ± 0.58% at Week 24 (mean reduction: -0.91%; 95% CI: -1.08 to - 0.74%; p &lt; 0.001). By Week 24, 60 patients (69.0%) achieved HbA1c &lt; 8.0%, 31 (35.6%) achieved &lt; 7.5%, and 9 (10.3%) reached &lt; 7.0%. Fasting plasma glucose fell by 35.6 mg/dL (95% CI: -42.8 to - 28.4; p &lt; 0.001) and post-prandial glucose by 47.6 mg/dL (95% CI: -57.9 to - 37.3; p &lt; 0.001). Body weight decreased by 2.27 kg (95% CI: -4.29 to - 0.25; p = 0.028) and waist circumference by 2.36 cm (95% CI: -4.19 to - 0.53; p = 0.012). Systolic blood pressure fell by 6.3 mmHg (95% CI: -9.9 to - 2.7; p = 0.001). A biphasic eGFR trajectory was documented: dip to 83.1 ± 11.9 mL/min/1.73 m² at Week 12, recovering to 85.6 ± 11.2 at Week 24 (p = 0.007 vs. baseline). ALP decreased significantly (- 11.7 U/L; 95% CI: -18.4 to - 5.0; p = 0.001). Baseline HbA1c was the only independent predictor of glycaemic response on multivariable regression (β=-0.47 per %; p &lt; 0.001; adjusted R²=0.32). No between-drug difference was detected (p = 0.62), though the study was not powered to demonstrate equivalence. Patients with baseline HbA1c 8.5-10.0% achieved a greater absolute reduction (- 1.15%) than those with 7.5-8.5% (- 0.63%; p = 0.003), a gradient partly attributable to regression to the mean; the lower-baseline subgroup, however, more frequently reached glycaemic targets. Genital mycotic infections occurred in 10.3% of women versus 2.1% of men. No serious adverse events occurred","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of healthy lifestyle with incident cardiovascular diseases in individuals with type 1 diabetes mellitus: a prospective cohort study.","authors":"Yaoyao Wang, Junyu Liu, Fang Cao, Yuge Wang, Zhisheng Li, Hanyue Zeng, Mengna Zhou, Qingyue He, Weixi Jiang, Yifeng Li, Junxia Yan","doi":"10.1186/s13098-026-02216-x","DOIUrl":"10.1186/s13098-026-02216-x","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular diseases (CVDs) remain a major complication of type 1 diabetes mellitus (T1DM). Although healthy lifestyle behaviors are associated with lower cardiovascular risk in the general population and in individuals with type 2 diabetes mellitus, evidence specific to T1DM is limited. This study aimed to examine the associations of individual and composite healthy lifestyle factors with incident CVDs among individuals with T1DM.</p><p><strong>Methods: </strong>This prospective cohort study included participants with T1DM from the UK Biobank who were free of CVDs at baseline. A composite lifestyle score was constructed from six factors: smoking status, alcohol consumption, body mass index (BMI), diet quality, physical activity, and sleep duration. The primary outcomes were incident CVDs, including coronary heart disease (CHD), heart failure (HF), and stroke. Associations were assessed using Cox proportional hazards models, with subgroup analyses stratified by key demographic and clinical characteristics.</p><p><strong>Results: </strong>Over a median follow-up of 14.38 years, 455 incident CVD events were documented among 1,390 participants with T1DM. Maintaining a BMI of 25 to < 30 kg/m² (HR, 0.65; 95% CI, 0.52-0.81) or 18.5 to < 25 kg/m² (0.59; 0.45-0.78), adhering to a healthy diet (0.83; 0.69-0.99), and obtaining adequate sleep duration (0.77; 0.63-0.92) were independently associated with a reduced risk of CVDs. Compared with participants with a lifestyle score of 0-2, those with a score 4-6 had a significantly lower risk of composite CVDs (0.58; 0.46-0.73), CHD (0.63; 0.49-0.81), and HF (0.49; 0.34-0.70). These associations were generally consistent across subgroups.</p><p><strong>Conclusions: </strong>Among individuals with T1DM, healthy lifestyle profiles were associated with a lower risk of incident CVDs, particularly through weight management, healthy diet, and adequate sleep duration. These findings support the potential value of incorporating lifestyle assessment and promotion into cardiovascular risk management for individuals with T1DM.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of vitamin D supplementation on the liver function in non-alcoholic fatty liver disease patients: a systematic review and meta-analysis of randomized controlled trials.","authors":"Mahdi Vajdi, Negin Nikrad, Mahsa Khajeh, Nooshin Noshadi, Mahsa Maroofi, Melika Darzi, Fatemeh Pourteymour Fard Tabrizi, Gholamreza Askari","doi":"10.1186/s13098-026-02225-w","DOIUrl":"10.1186/s13098-026-02225-w","url":null,"abstract":"<p><strong>Background: </strong>Empirical studies examining the impact of vitamin D supplementation on the liver function in non-alcoholic fatty liver (NAFLD) disease patients have yielded incongruous outcomes. In this systematic review and meta-analysis of randomized controlled trials (RCTs), we investigated the effect of vitamin D supplementation on liver enzymes (alanine transaminase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)) in NAFLD patients.</p><p><strong>Methods: </strong>A systematic literature search was conducted using scientific databases including PubMed/Medline, Embase, Web of Science, Cochrane library and Scopus, through May 2026. The search strategy included terms for the interventions (vitamin D, cholecalciferol, calcitriol) and outcomes (ALT, AST, ALP, and GGT) in NAFLD patients. Weighted/standardized mean differences (WMD, SMD) and 95% CI were analyzed utilizing a random-effects model.</p><p><strong>Results: </strong>Overall, 16 RCTs met our inclusion criteria. The current meta-analysis demonstrates a significant reduction in ALT (SMD: -0.45; 95% CI: - 0.87 to -0.04; P = 0.032), and ALP (WMD: -12.91 IU/L; 95% CI: - 18.75 to -7.08; P < 0.001). However, analysis of studies indicated a non-significant effect on AST, GGT. Subgroup analysis showed that the effect of vitamin D on AST is more pronounced in studies with a dose ≤ 3500 IU/day, duration > 12 weeks and using cholecalciferol (as opposed to calcitriol).</p><p><strong>Conclusion: </strong>The findings of this study indicate that vitamin D supplementation may be associated with improvements in ALT and ALP levels, while no significant effects were observed for AST and GGT. These results suggest a possible beneficial role of vitamin D in supporting liver function among patients with NAFLD; however, the evidence remains inconclusive. Future studies are needed to investigate the effect of vitamin D on health status in in NAFLD patients.</p><p><strong>Prospero code: </strong>CRD42024545499.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}