Cardiovascular Diabetology最新文献

{"title":"Genetically proxied glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptor pathway modulation is associated with favorable aging phenotypes: a drug-target Mendelian randomization study.","authors":"Jiang Li, Jie Li, Xiaoqin Xu, Ningjian Wang, Yingli Lu, Bin Wang","doi":"10.1186/s12933-026-03304-y","DOIUrl":"10.1186/s12933-026-03304-y","url":null,"abstract":"<p><strong>Background: </strong>Glucagon-like peptide-1 receptor (GLP1R) agonists and dual glucose-dependent insulinotropic polypeptide receptor/glucagon-like peptide-1 receptor (GIPR/GLP1R) agonists are established treatments for diabetes and obesity, but their potential effects on biological aging remain uncertain.</p><p><strong>Methods: </strong>In this drug target Mendelian randomization study, we assessed the associations of genetically proxied modulation of GLP1R, GIPR, and dual GIPR/GLP1R pathways with four aging phenotypes, including frailty index, phenotypic age (PhenoAge) acceleration, telomere length, and longevity.</p><p><strong>Results: </strong>Glycated hemoglobin (HbA1c) lowering via GIPR, modeling the glucose-lowering effect of variants in GIPR loci, was consistently associated with a lower frailty index (primary dataset: β = - 0.10 [95% CI: - 0.18, - 0.02]; replication dataset: - 0.14 [- 0.27, - 0.01]), reduced PhenoAge acceleration (primary: - 0.82 [- 1.17, - 0.48]; replication - 1.04 [- 1.81, - 0.27]), longer telomere length (primary: 0.06 [0.003, 0.11]; replication: 0.09 [0.002, 0.19]), and greater odds of longevity (primary: odds ratio [OR] = 2.90 [95% CI: 1.93, 4.36]; replication: 6.54 [2.92, 14.65]). Body mass index (BMI) lowering via GIPR, modeling appetite-suppressing and weight-reducing effects of variants, was associated with a lower frailty index (primary: - 0.07 [- 0.13, - 0.01]; replication: - 0.19 [- 0.35, - 0.04]) and higher odds of longevity (primary: 2.11 [1.22, 3.66]). In contrast, HbA1c lowering via GLP1R was associated exclusively with longevity (primary: OR = 3.72 [2.25, 6.18]; replication: 16.53 [4.28, 63.80]), whereas BMI lowering via GLP1R was not associated with any aging phenotype. Analyses of dual GIPR/GLP1R yielded results broadly similar to those for GIPR, with the exception of a null effect on frailty index.</p><p><strong>Conclusions: </strong>Genetically proxied HbA1c- and BMI-lowering effects through GLP1R- and GIPR-related pathways were favorably associated with aging phenotypes, with broader associations observed for HbA1c lowering. Further clinical studies are warranted to clarify the relevance of these pathways to healthy aging.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"25 1","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13504813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between body mass index reduction and epicardial adipose tissue changes across pharmacological and lifestyle interventions: a multilevel meta-regression analysis.","authors":"Aleksandra Mączyńska, Piotr Olbryś, Mateusz Smoliński, Miłosz Rosa, Marta Kacperska, Milena Froń, Paweł Leśniewski, Oliwia Łuniewska, Adam Sander, Maciej Mączewski, Hanna Czerwińska, Aleksandra Paterek, Michał Mączewski","doi":"10.1186/s12933-026-03299-6","DOIUrl":"10.1186/s12933-026-03299-6","url":null,"abstract":"<p><strong>Background: </strong>Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot implicated in cardiometabolic disease. Although EAT reductions are commonly attributed to weight loss, the extent to which EAT change is explained by body mass index (BMI) reduction versus intervention-specific effects remains unclear.</p><p><strong>Methods: </strong>We performed a systematic review and multilevel meta-regression of interventional studies reporting pre- and post-intervention changes in EAT and BMI. MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to April 2026. Standardized mean change using pre-test standardization (SMCR) was calculated for both outcomes. Multilevel meta-regression assessed the association between BMI and EAT change while adjusting for intervention class, follow-up duration, and imaging modality. BMI-adjusted residual analyses were used descriptively to evaluate deviations from model-predicted EAT responses.</p><p><strong>Results: </strong>Forty-two studies comprising 50 intervention arms and 1,890 participants were included. Across all interventions, both EAT and BMI decreased significantly. In the multivariable meta-regression model, BMI reduction was associated with EAT reduction (β = 0.19, p = 0.03), although BMI explained only a limited proportion of variability in EAT response. Intervention class remained a significant moderator of EAT change (p < 0.001). Larger observed reductions in EAT were seen with dietary interventions, GLP-1 receptor agonists, and bariatric surgery. In descriptive residual analyses, dietary interventions and GLP-1 receptor agonists demonstrated greater-than-predicted reductions in EAT relative to the overall study-level BMI-EAT relationship. These findings should be interpreted cautiously because intervention-specific comparisons were exploratory and do not constitute formal comparative efficacy estimates.</p><p><strong>Discussion: </strong>EAT reduction is only partially explained by systemic weight loss, and substantial heterogeneity exists across intervention classes. These findings support the concept that EAT remodeling may be influenced by factors beyond generalized adiposity reduction. However, intervention-specific patterns observed in this study are descriptive and hypothesis-generating and require confirmation in adequately powered comparative studies. Moreover, overall certainty of evidence was low for pooled EAT reduction and very low for intervention-specific comparative patterns.</p><p><strong>Trial registration: </strong>PROSPERO (CRD420261367140).</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoprotein(a), insulin resistance, and cardiovascular outcomes in metabolic dysfunction-associated steatotic liver disease.","authors":"Bingtian Dong, Yuping Chen, Fang He, Biao Li, Biao Wu, Zhengdong Chen, Enfa Zhao, Yongjian Chen, Chaoxue Zhang","doi":"10.1186/s12933-026-03294-x","DOIUrl":"10.1186/s12933-026-03294-x","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk. Lipoprotein(a) [Lp(a)] and insulin resistance (IR) are established cardiovascular risk factors, yet their joint associations with cardiovascular outcomes in MASLD remain poorly understood.</p><p><strong>Methods: </strong>We analyzed data from the UK Biobank and included 101,348 adults with MASLD for CVD mortality analyses and 94,089 individuals without baseline CVD for incident CVD analyses. IR was assessed using the triglyceride-glucose (TyG) index. Participants were categorized according to Lp(a) levels (< 125 vs. ≥ 125 nmol/L) and TyG index (low vs. high, defined by the 75th percentile) and further classified into four joint Lp(a)/IR groups, with low Lp(a)/low IR serving as the reference group. Cox proportional hazards models were used to evaluate associations of Lp(a), TyG, and their combined categories with incident CVD and CVD mortality.</p><p><strong>Results: </strong>During a median follow-up of 15.7 years, elevated Lp(a) and higher TyG levels were each independently associated with increased risks of incident CVD and CVD mortality, regardless of each other's status. In the fully adjusted model, each SD increase in Lp(a) was associated with a 14% higher risk of CVD mortality (HR, 1.14; 95% CI 1.10-1.19; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI, 1.07-1.11; P < 0.001). Similarly, each SD increase in TyG was associated with a 27% higher risk of CVD mortality (HR, 1.27; 95% CI 1.21-1.34; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI 1.07-1.12; P < 0.001). Compared with participants in the reference group with Lp(a) < 125 nmol/L and low IR, those with concomitantly elevated Lp(a) and high IR exhibited the highest cardiovascular risk, with adjusted HRs of 2.04 (95% CI 1.63-2.55) for CVD mortality and 1.49 (95% CI 1.35-1.64) for incident CVD (both P < 0.001), with a significant dose-response trend across groups (P for trend < 0.001). These associations remained consistent across subgroups stratified by age, sex, obesity, diabetes, and hypertension.</p><p><strong>Conclusions: </strong>Elevated Lp(a) and IR were independently associated with adverse cardiovascular outcomes in MASLD, with the highest risk observed among individuals with concomitant elevations in both markers.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 cumulative exposure and dynamic trajectories of the cholesterol-HDL-glucose index and its obesity-related derivatives with cardiovascular disease: a nationwide prospective cohort study.","authors":"Han Wang, Guirong Song, Guorong Li, Dongmei Hu, Ying Zhang, Zhuowei Sun, Chenxi Zhai, Dongyong Zhang, Xiao Tang","doi":"10.1186/s12933-026-03295-w","DOIUrl":"10.1186/s12933-026-03295-w","url":null,"abstract":"<p><strong>Background: </strong>Integrating metabolic biomarkers with anthropometric indicators has been shown to enhance the discriminative capacity for cardiovascular disease (CVD). However, the impact of the cholesterol-HDL-glucose index (CHG) and its derivatives on CVD risk remains unclear. This study aimed to investigate the associations of CHG and its derivatives with CVD and to compare their discriminative performance.</p><p><strong>Methods: </strong>This prospective study included 3,359 CVD-free participants from the China Health and Retirement Longitudinal Study (CHARLS). Repeated measurements obtained in 2011 and 2015 were used to derive cumulative exposure and longitudinal trajectory patterns of CHG and its derivatives. Associations of baseline values, cumulative exposure, and longitudinal trajectories of these indicators with incident CVD and stroke were examined using Cox proportional hazards regression models.</p><p><strong>Results: </strong>During a median follow-up of 5 years, 466 participants (13.9%) developed CVD. Both CHG and its derivatives were significantly associated with CVD across baseline measurements, cumulative exposure, and longitudinal trajectories. Cumulative CHG derivatives showed significantly better discriminative power than isolated cumulative CHG (Delong's test P < 0.05), with the highest associations observed for cumulative CHG-waist circumference (HR = 1.29) and cumulative CHG-Chinese visceral adiposity index (HR = 1.28). Regarding trajectory patterns, participants with stably high CHG-CVAI exhibited the greatest risk compared with those maintaining stable low levels (HR = 1.79), followed by CHG-WC (HR = 1.65). Additionally, ascending and declining trajectories of both CHG-CVAI and CHG-WC were associated with increased CVD risk (ascending CHG-CVAI: HR = 1.79; declining CHG-CVAI: HR = 1.54; ascending CHG-WC: HR = 1.45; declining CHG-WC: HR = 1.54).</p><p><strong>Conclusions: </strong>CHG and its derivatives were strongly associated with incident CVD, with CHG-CVAI and CHG-WC exhibiting the most pronounced associations. Moreover, ascending and declining trajectories of CHG-CVAI and CHG-WC were linked to higher risk, highlighting the importance of tracking dynamic increases while also accounting for baseline metabolic status. These indicators may facilitate the identification of individuals at elevated risk for CVD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between the combined cholesterol, high-density lipoprotein, glucose index and frailty index and new-onset cardiovascular disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: evidence from CHARLS.","authors":"Zhonghua Sun, Kexue Wang, Chiwei Guo, Jiajun Qiu, Wencai Wang, Yameng Xu, Yi Tang, Kaisaierjiang Kadier, Song Wen, Wenhong Zhang","doi":"10.1186/s12933-026-03293-y","DOIUrl":"10.1186/s12933-026-03293-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Early-stage cardiovascular-kidney-metabolic (CKM) syndrome, encompassing stages 0-3, represents a critical window for identifying individuals at risk before the development of clinical cardiovascular disease (CVD). Metabolic dysregulation and frailty-related physiological vulnerability may jointly contribute to cardiovascular susceptibility in middle-aged and older adults. However, conventional single-domain markers may not adequately capture this combined risk burden. This study aimed to evaluate the association and predictive utility of the combined cholesterol, high-density lipoprotein, glucose index and frailty index (CHG-FI) for new-onset CVD, heart disease, and stroke among individuals with early-stage CKM syndrome.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This cohort study used longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 4,603 participants with CKM stages 0-3. New-onset CVD, defined as the occurrence of heart disease or stroke during follow-up, was the primary outcome; new-onset heart disease and stroke were analyzed separately as secondary outcomes. CHG-FI was calculated as the product of the cholesterol, high-density lipoprotein, glucose (CHG) index and frailty index (FI). Multivariable Cox proportional hazards models were used to assess the associations of CHG-FI with new-onset cardiovascular outcomes. Restricted cubic splines were applied to examine nonlinear dose-response relationships. Joint-exposure analyses were used to characterize CVD risk across combined CHG and FI categories, and multiplicative and additive interaction analyses were performed to assess whether CHG and FI interacted in relation to new-onset CVD. Predictive performance was compared with CHG, FI, triglyceride-glucose index (TyG), atherogenic index of plasma (AIP), and metabolic score for insulin resistance (METS-IR) using receiver operating characteristic curves, DeLong tests, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Formal incremental modeling was further performed by separately adding CHG-FI and comparator indices to the fully adjusted base model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During a median follow-up of 9 years, 1,189 participants (25.8%) developed new-onset CVD. In fully adjusted models, each one-unit increase in CHG-FI was associated with higher risks of new-onset heart disease (HR = 1.59; 95% CI 1.42-1.77), stroke (HR = 1.56; 95% CI 1.32-1.83), and composite CVD (HR = 1.56; 95% CI 1.41-1.72). Participants in the highest CHG-FI quartile had more than two-fold higher risks of all cardiovascular outcomes compared with those in the lowest quartile. Restricted cubic spline analyses showed nonlinear associations, with cardiovascular risk increasing more steeply across lower to moderate CHG-FI levels. In joint-exposure analyses, participants with both high CHG and high FI had the highest risk of new-onset CVD (HR = 2.05; 95% CI 1.71","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular outcomes of empagliflozin-GLP-1RA combination therapy in type 2 diabetes: EMPRISE study.","authors":"Phyo T Htoo, Hanseul Cho, Julie M Paik, Katsiaryna Bykov, Brendan M Everett, Robert J Glynn, Christina Shay, Niklas Schmedt, Deborah J Wexler, Elisabetta Patorno","doi":"10.1186/s12933-026-03287-w","DOIUrl":"10.1186/s12933-026-03287-w","url":null,"abstract":"<p><strong>Background: </strong>Evidence on the cardiovascular benefits of combining empagliflozin with glucagon-like peptide-1 receptor agonists (GLP-1RA) is limited, derived primarily from indirect comparisons or subgroup analyses of cardiovascular outcome trials.</p><p><strong>Methods: </strong>We conducted a cohort study emulating two comparative effectiveness trials using US healthcare databases (2013-2022), including federal Medicare and commercial claims data (Optum Clinformatics and MarketScan). Among adults with type 2 diabetes in routine care, we compared cardiovascular outcomes in patients initiating: (i) empagliflozin first, followed by augmentation with either GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP-4i), and (ii) GLP-1RA first, followed by augmentation with either empagliflozin or sulfonylureas. Primary outcomes were modified major adverse cardiovascular events (MACE; composite of myocardial infarction, stroke, and all-cause mortality) and a composite of hospitalization for heart failure (HHF) or all-cause mortality. We estimated hazard ratios (HR) and rate differences (RD) per 1,000 person-years with 95% confidence intervals (CI), adjusting for over 130 baseline covariates using propensity score matching weights.</p><p><strong>Results: </strong>Compared with empagliflozin-DPP-4i initiators, empagliflozin-GLP-1RA was associated with lower risk of MACE [HR: 0.81 (95% CI: 0.67, 0.97); RD: -3.7 (-7.1, -0.2)] and lower HHF-mortality [HR: 0.61 (0.48, 0.77); RD: -6.6 (-9.3, -3.9)]. Compared with the GLP-1RA-sulfonylurea combination, the GLP-1RA-empagliflozin combination had lower risks of MACE [HR: 0.68 (0.56, 0.81); RD: -5.3 (-7.9, -2.6)] and HHF-mortality [HR: 0.62 (0.51, 0.76); RD: -3.7 (-6.1, -1.8)].</p><p><strong>Conclusions: </strong>In US clinical practice, adding GLP-1RA to empagliflozin was associated with lower risks of MACE and HHF-mortality compared with adding DPP-4i. Among GLP-1RA initiators, adding empagliflozin was associated with lower cardiovascular risk than adding sulfonylureas, supporting potential additive cardiovascular benefits of GLP-1RA-empagliflozin combination therapy.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13644152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex- and menopause-specific inverse associations between metabolic dysfunction-associated steatotic liver disease and serum lipoprotein(a) concentrations: evidence from SHIP and UK Biobank.","authors":"Júlia Galbiati de Souza, Till Ittermann, Nicole Werner, Sabine Schipf, Nele Friedrich, Matthias Nauck, Marcio Hiroshi Miname, Fábio Fernandes, Raul Dias Santos, Jelena-Rima Ghadri, Davide Di Vece, Martin Bahls, Giovanni Targher, Elisabeth Steinhagen-Thiessen, Christian Templin, Nágila Raquel Teixeira Damasceno, Marcello Ricardo Paulista Markus","doi":"10.1186/s12933-026-03289-8","DOIUrl":"10.1186/s12933-026-03289-8","url":null,"abstract":"<p><strong>Background: </strong>The association between metabolic dysfunction-associated steatotic liver disease (MASLD) and serum lipoprotein(a) (Lp[a]) levels remains controversial, with no sex- or menopausal status-stratified analyses. We aimed to analyse the associations between MASLD, liver fat content (LFC) and transaminases with Lp(a) concentrations stratified by sex and menopausal status.</p><p><strong>Methods: </strong>We analysed data from 3825 individuals (1961 females; 51.3%) aged 32 to 70 years from the SHIP-START-0 cohort, and from 28,504 individuals (14,926 females; 52.4%) aged 38 to 72 years from the UK Biobank cohort. MASLD was determined by liver ultrasound examinations in SHIP-STAR-0 and by magnetic resonance imaging in UK Biobank. We examined sex- and menopausal status-specific associations of MASLD, LFC, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) with lipoprotein(a) [Lp(a)] concentrations, after adjustment for age, body mass index, haemoglobin A1c, glucose-lowering medication use, hypertension, smoking, and alcohol consumption.</p><p><strong>Results: </strong>In SHIP-START-0, MASLD, higher ALT, AST, and GGT levels were independently associated with lower Lp(a) concentrations only in males but not in females. However, after stratification by menopausal status, higher ALT levels were associated with lower Lp(a) concentrations in postmenopausal females, but not in premenopausal females. In UK Biobank, MASLD severity (moderate and severe), higher LFC, and higher serum transaminase levels were independently associated with lower Lp(a) concentrations in males. Higher LFC was also associated with lower Lp(a) concentrations in females, but serum liver enzymes were not. After stratification by menopausal status, MASLD severity and higher LFC were associated with lower Lp(a) concentrations in postmenopausal females, but not in premenopausal females. Males with MASLD had 24% and 9% lower Lp(a) concentrations than those without MASLD in SHIP-START-0 and UK Biobank.</p><p><strong>Conclusions: </strong>Our findings from two large community-based studies show that MASLD and higher LFC and ALT values were independently associated with lower Lp(a) concentrations in postmenopausal females and males. Future studies are needed to determine whether the cardiovascular risk in patients with MASLD remains elevated even when Lp(a) concentrations are reduced and whether these patients require more intensive treatment to further reduce Lp(a) concentrations below the currently recommended cut-off values.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13366839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics signatures of circulating factors associated with cardiorespiratory fitness adaptations in individuals with prediabetes.","authors":"Candela Diaz-Canestro, Kit Cheung, Enrique Roche, Jose Manuel Sarabia, Michael Andrew Tse, Aimin Xu","doi":"10.1186/s12933-026-03286-x","DOIUrl":"10.1186/s12933-026-03286-x","url":null,"abstract":"<p><strong>Background: </strong>Patients with insulin resistance exhibit reduced cardiorespiratory fitness (CRF), assessed by peak oxygen consumption (VO₂peak), compared with healthy age-matched individuals. Although high-intensity interval training (HIIT) can substantially improve VO₂peak, there is considerable interindividual variability in this response. Therefore, further research is needed to elucidate the molecular mechanisms underlying the heterogeneous response of VO₂peak to HIIT in individuals with prediabetes.</p><p><strong>Methods: </strong>Proteomic analyses of serum samples, along with fecal metagenomic and targeted metabolomic profiling, were conducted in medication-naïve, overweight and obese Chinese men with prediabetes (n = 35; aged 24-62 years). All participants underwent a 12-week HIIT intervention, and biological samples were collected both before and after the intervention to evaluate exercise-induced alterations in circulating proteins, gut microbial composition, and metabolite profiles.</p><p><strong>Results: </strong>After 12 weeks of HIIT, mean VO₂peak increased by 0.47 L/min with individual responses ranging from 0 to 1.7 L/min. Baseline levels of short-chain fatty acid (SCFA)-producing genera, including Prevotella (β = 105.65, P = < 0.001, FDR = 0.034), Coprococcus (β = 50.22, P = 0.01, FDR = 0.39), and Hungatella (β = 40.72, P = 0.025, FDR = 0.50), were positively associated with ΔVO₂ peak. In contrast, baseline levels of the erythropoiesis-stimulating hormone erythropoietin (EPO) (β = -279.03, P = 0.024, FDR = 0.99) were negatively associated with ΔVO₂ peak. Exercise-induced changes in growth hormone 1 (β = 63.97, P = 0.04, FDR = 0.99) were positively associated with ΔVO₂ peak, whereas exercise-induced changes in BTB and CNC Homology 1 (β = -250.82, P = 0.01, FDR = 0.99), a repressor of heme oxygenase-1, were negatively associated with ΔVO₂ peak. In multiple linear regression analysis including clinical variables, percentage lean mass (β = 64.17, P = 0.0005) was the strongest variable associated with ΔVO₂peak. The clinical model explained 27% of the variance which increased to 37% (P = 0.002) upon inclusion of exercise-associated circulating factors such as EPO.</p><p><strong>Conclusions: </strong>Our findings reveal that baseline proteomic and metagenomic signatures are associated with VO₂peak adaptations. These multi-omics signatures may support the clinical implementation of personalized exercise interventions to improve CRF in individuals with prediabetes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma proteomic profiling deciphers molecular dynamics linking insulin resistance to multiple chronic diseases and mortality.","authors":"Zong-Lei Zhou, Li-Gang Zhou, Chun-Hua Qu, Chun-Xiang Fan, Hai-Hong Qu, Jun Li, Cheng-Xia Wei, Wu Wang, Xu-Hui Bao, Ji-Yu Li","doi":"10.1186/s12933-026-03273-2","DOIUrl":"10.1186/s12933-026-03273-2","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) correlates with a wide spectrum of diseases and death. However, the specific proteomic signatures of IR and their associations with health outcomes remain incompletely understood.</p><p><strong>Methods: </strong>Leveraging data of 2,920 plasma proteins from 19,556 individuals in UK biobank study, we employed the elastic net model to dissect IR-related proteins and construct proteomic signature scores. Cox proportional hazards model was fitted to examine the longitudinal associations of distinct IR indicators and their proteomic signatures with multiple chronic disease and mortality. Mediation analyses were conducted to explore the role of individual proteins and proteomic signatures in IR-disease associations.</p><p><strong>Results: </strong>Over a mean follow-up of over 12 years, higher levels of IR surrogate makers were linked to cardiovascular-kidney-metabolic events and mortality, with eGDR outperforming other metrics in predictive discrimination. Furthermore, most IR proteomic signatures were prospectively associated with the incidence of type 2 diabetes mellitus, ischemic heart diseases, stroke, chronic kidney diseases, and mortality. Proteins associated with IR were primarily enriched in inflammation, immune response, and lipid metabolism, with immune-related proteins holding crucial roles. Multiple IR-disease associations were significantly mediated by proteomic signatures and specific proteins, like HAVCR1, CXCL17, and GDF15.</p><p><strong>Conclusion: </strong>This study probed into the plasma proteomic profiles in IR settings and the associations of relevant protein signatures with multiple chronic diseases and mortality, providing additional guidelines on targeted intervention strategies for cardiovascular-kidney-metabolic outcomes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent mitochondrial and fibrotic signatures in atrial fibrillation: insights from organoids and GEO data.","authors":"Jihee Won, Hyocheol Jung, Jin Chul Kim, Ji-Eun Jeong, Young Il Park, Biaggio Uricoli, Sanghee Lee, Young Hoon Son, Gun-Jae Jeong","doi":"10.1186/s12933-026-03291-0","DOIUrl":"10.1186/s12933-026-03291-0","url":null,"abstract":"<p><strong>Background: </strong>Atrial fibrillation (AF) remains a major clinical burden because structural and metabolic remodeling, particularly mitochondrial dysfunction and fibrosis, often persists beyond rhythm control. Human-relevant models that disentangle these axes and connect them to patient data are limited.</p><p><strong>Methods: </strong>Human atrial organoids were exposed to two AF-relevant stressors: rapid pacing (FP) and angiotensin II (AngII). We assessed mitochondrial and fibrotic remodeling by transcript/protein analyses, imaging, and contractility readouts, and benchmarked organoid responses against four public AF transcriptomic datasets (GEO: GSE128188, GSE138252, GSE222793, GSE239321). Statistical analyses used predefined contrasts versus matched controls with multiple-testing correction.</p><p><strong>Results: </strong>FP predominantly suppressed mitochondrial biogenesis/oxidative programs and increased stress-response features, resembling signatures observed in AF with heart failure (e.g., downregulation of mitochondrial regulators and altered cytochrome c patterns). AngII elicited stronger profibrotic signaling with a mixed mitochondrial response, mirroring profiles more typical of AF without heart failure. Both stressors impaired organoid contractility. Protein and immunostaining corroborated mitochondria-fibrosis crosstalk, with changes in PGC1α and cytochrome c alongside increased extracellular matrix deposition and myofibroblast markers (COL1A1, αSMA), consistent with stimulus-specific but partially overlapping remodeling trajectories.</p><p><strong>Conclusion: </strong>Distinct AF-relevant stressors drive divergent mitochondrial and fibrotic remodeling in human atrial organoids that recapitulate key features of patient datasets. These organoid models provide a translational platform to prioritize mitochondria-targeted and antifibrotic interventions and to inform biomarker development for residual dysfunction in AF.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148418983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}