Cardiovascular Diabetology最新文献

{"title":"Unveiling biomarkers via plasma metabolome profiling for diabetic macrovascular and microvascular complications.","authors":"Zhixi Li, Yuhan Ren, Feng Jiang, Kai Zhang, Xuan Meng, Yingfeng Zheng, Mingguang He","doi":"10.1186/s12933-025-02899-y","DOIUrl":"10.1186/s12933-025-02899-y","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysregulation plays a crucial role in the development of diabetic vascular complications. Current models for diabetic vascular complications predominantly rely on three conventional parameter classes: demographic characteristics, clinical measures, and standard laboratory indices. In contrast, the potential prognostic value of the plasma metabolome remains substantially under characterized in this context. This study aims to systemically reframe the value of circulating metabolites, providing new insights into both assessment and pathophysiology of diabetic complications.</p><p><strong>Methods: </strong>This study included 333,870 participants from the UK Biobank (n = 115,078) and FinnGen Biobank (n = 218,792). The initial analysis utilizing longitudinal data from 7,711 patients with diabetes was used to screen 249 plasma metabolites associated with diabetic vascular complications. These metabolites were carefully quantified using nuclear magnetic resonance (NMR) to profile the metabolites of these participants. A total of 1,457 and 1,635 people were found to have developed macrovascular (including heart failure, stroke and coronary heart disease [CHD]) and microvascular complications (including diabetic neuropathy [DN], kidney disease and retinopathy) at follow-ups, respectively. A Least Absolute Shrinkage and Selection Operator-Cox (LASSO-Cox) regression was conducted to define the potential biomarkers, adjusting for conventional factors including age, sex, race, smoking status, diet intake, Townsend deprivation index, systolic and diastolic blood pressure, body mass index, plasma triglycerides, low-density lipoprotein (LDL) cholesterol, plasma creatinine and estimated glomerular filtration rate. Subsequently, a multivariate Cox proportional hazards regression model was used to estimate the hazard ratios (HRs). Finally, a bidirectional two-sample Mendelian randomization (MR) analysis was employed to evaluate the relationships between the selected metabolomics and diabetic complications to analyze causal associations.</p><p><strong>Results: </strong>Over a 13.06 ± 3.59 years of follow-up, 15 out of 249 plasma metabolites demonstrated significant associations with incident macrovascular complications in LASSO-Cox regression, while 33 metabolites were linked to microvascular complications after 12.77 ± 3.90 years of follow-up (all P < 0.05). In the multivariate Cox proportional hazards regression, 6 metabolites including creatinine (HR = 1.32, 95% confidence interval [CI] 1.17-1.50, P < 0.001), albumin (HR = 0.87, 95% CI 0.81-0.94, P < 0.001), tyrosine (HR = 0.91, 95% CI 0.85-0.96, P = 0.001), glutamine (HR = 1.08, 95% CI 1.01-1.15, P = 0.020), lactate (HR = 1.07, 95% CI 1.01-1.14, P = 0.023), and the ratio of phospholipids to total lipids in small LDL (HR = 1.10, 95% CI 1.01-1.19, P = 0.023) were correlated with macrovascular complications, while 8 metabolites including glucose (HR = 1.25, 95% CI 1.18-1.3","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"341"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871604","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":"Heme oxygenase-1 polymorphisms associate with ischemic cardiac complications and all-cause mortality in type 1 diabetes.","authors":"Heli Segersvärd, Niina Sandholm, Valma Harjutsalo, Heidi Tikkanen, Riikka Kosonen, Mika Laine, Ilkka Tikkanen, Per-Henrik Groop, Päivi Lakkisto","doi":"10.1186/s12933-025-02895-2","DOIUrl":"10.1186/s12933-025-02895-2","url":null,"abstract":"<p><strong>Background: </strong>Heme oxygenase 1 (HO-1), encoded by the HMOX1 gene is a highly inducible enzyme with multiple cardiovascular protective properties. Polymorphisms of the HMOX1 gene, especially a guanine-thymine dinucleotide repeat polymorphism (GTn), affects its transcriptional activity and is associated with cardiovascular complications in the general population. We studied the association of HMOX1 polymorphisms and HO-1 serum concentrations with vascular complications and all-cause mortality in individuals with type 1 diabetes (T1D).</p><p><strong>Methods: </strong>The study population consists of individuals with T1D participating in the Finnish Diabetic Nephropathy Study (FinnDiane). We genotyped the HMOX1 GTn repeat (n = 3990), extracted from genome-wide genotyping data two single nucleotide polymorphisms (SNPs) (-413A/T upstream variant rs2071746, and + 99G/C p.Asp7Asn missense variant rs2071747; n = 4278), and measured the serum HO-1 concentrations (n = 861) from blood samples taken during their study visit. The GTn repeats were divided into short (S) and long (L) alleles where the cutoff point was L ≥ 30 repeats.</p><p><strong>Results: </strong>In men, the LL genotype was associated with ischemic cardiac events (LL 22.9% vs. SS/SL 17.0%, p = 0.001) and all-cause mortality (p = 0.031). The association was detected in all individuals (LL 19.5% vs. SS/SL 16%, p = 0.006) but not in women (LL 15.7% vs. SS/SL 14.9%, p = 0.657). For the -413A/T SNP, men with the AA genotype experienced ischemic cardiac events more frequently (21.0% vs. 17.4%, p = 0.044), but no differences were found for women or for men and women together. There were no differences between different genotypes of the + 99G/C variant regarding cardiovascular complications. Also, there was no difference in HO-1 serum concentrations between different genotypes (GTn repeat, -413A/T or + 99G/C). Men had higher HO-1 serum concentrations compared to women (3.12 ± 1.23 ng/ml vs. 2.64 ± 1.04 ng/ml, p < 0.001). In women, higher HO-1 serum concentrations were associated with cardiovascular disease and need for antihypertensive and lipid lowering medications.</p><p><strong>Conclusions: </strong>The LL genotype of the HMOX1 GTn repeat and the AA genotype of -413A/T SNP were associated with ischemic cardiac complications and all-cause mortality in men, but not in women. Thus, the HMOX1 genotype may influence the development of cardiovascular complications in individuals with T1D in a sex-dependent manner.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"339"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871578","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 levels and statin treatment related to dementia and cognitive decline in individuals with type 2 diabetes: an observational analysis from the ADVANCE study.","authors":"Peder Af Geijerstam, John Chalmers, Miriam Pikkemaat, Ruth Peters, Michel Marre, Giuseppe Mancia, Mark Woodward, Katie Harris","doi":"10.1186/s12933-025-02894-3","DOIUrl":"10.1186/s12933-025-02894-3","url":null,"abstract":"<p><strong>Introduction: </strong>Studies on the association between lipid levels and lipid-lowering treatment and the risk of dementia and/or cognitive decline (CD) have shown conflicting results and are few in individuals with type 2 diabetes (T2D). The aim was to evaluate the relationship of baseline LDL cholesterol levels and statin treatment with the development of dementia/CD in patients with T2D from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation trial.</p><p><strong>Methods: </strong>Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and CD was defined as at least a 3-point decrement in the Mini Mental State Examination score. Exposures were baseline LDL cholesterol levels, statin treatment at baseline, and statin treatment initiation during the first 18 months of follow-up. Multinomial logistic regression was used to estimate the odds ratio (OR) and 95% CI for the composite of dementia/CD.</p><p><strong>Results: </strong>Of 11,140 participants, 1827 (16.4%) developed dementia/CD over the 5-year follow up. The OR (95% CI) of dementia/CD were 1.06 (1.00-1.14) per standard deviation higher in baseline LDL cholesterol and 0.90 (0.79-1.03) for participants with vs without statin treatment.</p><p><strong>Conclusion: </strong>We observed an association between LDL levels, but not statin treatment, and incident dementia/CD. Although causality cannot be determined by our study, the results are in line with multiple randomised controlled trials. However, to understand the long-term effects of lipid levels and statin treatment on dementia/CD, studies of longer follow-up are still needed.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"340"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871579","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":"Predictive value and robustness of the stress hyperglycemia ratio combined with hypertension for stroke risk: evidence from the CHARLS cohort.","authors":"Yaxuan He, Yu Cao, Rong Xiang, Fang Wang","doi":"10.1186/s12933-025-02898-z","DOIUrl":"10.1186/s12933-025-02898-z","url":null,"abstract":"<p><strong>Background: </strong>Stroke remains a major cause of death and long-term disability worldwide, particularly in low- and middle-income countries. Early identification of individuals at high risk is essential for prevention. The stress hyperglycemia ratio (SHR), a novel indicator integrating acute and chronic glycemic states, has shown prognostic value in acute illness. However, its association with stroke risk in community populations and its potential interaction with hypertension remain unclear.</p><p><strong>Methods: </strong>This retrospective cohort study included 9682 stroke-free participants aged ≥ 45 years from the 2011 baseline of the China Health and Retirement Longitudinal Study (CHARLS), followed through 2020. SHR was calculated using fasting blood glucose and glycated hemoglobin. Participants were categorized by median SHR and hypertension status into four groups. Cox proportional hazards models were used to assess associations with incident stroke over a median follow-up of 8.43 years. Subgroup, stratified, and sensitivity analyses were performed. Predictive performance was evaluated using receiver operating characteristic (ROC) curve analysis.</p><p><strong>Results: </strong>During 81,601 person-years of follow-up, 764 incident stroke cases were documented, with an overall incidence of 9.36 per 1000 person-years. Compared to the reference group (low SHR without hypertension), those with high SHR and hypertension had the highest stroke risk (hazard ratio: 2.94, 95% confidence interval: 2.38-3.64). SHR and hypertension were independently associated with stroke risk, and their combination demonstrated a dose-response relationship. Subgroup analyses confirmed consistent findings across sex and age strata. The combined SHR-hypertension model showed improved discriminative ability (area under the ROC curve: 0.653). Sensitivity analyses confirmed the robustness of the results.</p><p><strong>Conclusions: </strong>Elevated SHR is independently associated with an increased risk of stroke, and its predictive value is enhanced when combined with hypertension. SHR may serve as an integrated metabolic marker reflecting both acute stress and chronic risk burden. Incorporating SHR into stroke risk assessment tools may improve early identification and enable more targeted prevention strategies, particularly in hypertensive populations.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"336"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871580","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":"The dual GLP-1 and GIP receptor agonist tirzapetide provides an unintended interaction with the β-adrenoceptors and plays a role in glucose metabolism in hyperglycemic or senescent cardiac cells.","authors":"Dunya Aydos, Zeynep Busra Aksoy, Mehmet Altay Unal, Kamil Can Akcali, Ceylan Verda Bitirim, Belma Turan","doi":"10.1186/s12933-025-02828-z","DOIUrl":"10.1186/s12933-025-02828-z","url":null,"abstract":"<p><strong>Background: </strong>A dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1) receptor agonist, tirzepatide (TZPD), is a novel cardioprotective agent, particularly in metabolic disturbances-related co-morbidities, however, there is no exact study to emphasize its possible unintended action in cardiac cells.</p><p><strong>Objective: </strong>Considering a relationship between the trafficking of incretin receptors in a manner not anticipated by the standard way of cAMP as a primary actor in TZPD action, together with the role of cAMP depression in cardiac dysfunction, here, we aimed to elucidate a pattern of unintended receptor interactions of TZPD and molecular processes underlying the pleiotropic effects of TZPD through modulation of the β-adrenoceptors (β-ARs) signaling in cardiomyocytes.</p><p><strong>Methods: </strong>To establish the multifaceted cardioprotective function and underlying mechanisms of TZPD against hyperglycemia (HG)-or senescence (SC)-induced cardiac dysfunction, H9c2 cells were treated with and without TZPD. We also used β₃-ARs overexpressed H9c2 cells (β3OE) for comparisons.</p><p><strong>Results: </strong>The TZPD intervention ameliorated the HG or SC phenotypes in the cardiac cells via alleviation in protein levels of GLP-1R and GIP-R as well as production of cAMP or cGMP, even in the presence of these receptor antagonisms. TZPD also increased the levels of β₁- and β₂-ARs while significantly decreasing activated β₃-ARs and PKG, being parallel to normalizations in the cAMP and cGMP in the presence of the antagonisms of these receptors. The therapeutic effects of TZPD on similar parameters of the β3OE group of cells can strongly verify its unintended action among multifaceted effects in either HG or SC cells. In addition, molecular dynamics simulations indicated that TZPD binds with the highest affinity to GLP-1R and β₃-ARs rather than GIP-R and then relatively lower but almost similar affinities to β₁- and β₂-ARs. Furthermore, mechanistically, the cardioprotective effect of TZPD includes significant regulation of the cellular Ca²⁺, at most, modulating the proteins in β-ARs signaling pathways. Moreover, TZPD could significantly increase not only the depressed protein level but also the translocation of GLUT4 on the sarcolemma, promoting glucose uptake in the HG or SC groups independent of its receptor actions.</p><p><strong>Conclusions: </strong>Our findings indicate that TZPD, with its multifaceted role, has beneficial effects on cardiac cells by positively modulating β-ARs signaling and glucose metabolism rather than on-target receptor action. Furthermore, we demonstrated how TZPD can engage the different targets with distinct signaling motifs at the sarcolemma.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"338"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871603","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":"Prognostic value of triglyceride-glucose index combined with stress hyperglycemia ratio for all-cause mortality in critically ill patients with stroke.","authors":"Tengli Li, Zhiheng Yi, Yangshen Huang, Yuhan Tan, Shan Gao, Tingting Wang, Shaowei Guo","doi":"10.1186/s12933-025-02901-7","DOIUrl":"10.1186/s12933-025-02901-7","url":null,"abstract":"<p><strong>Background: </strong>The triglyceride-glucose (TyG) index and stress hyperglycemia ratio (SHR) are emerging biomarkers in cerebrovascular diseases, but their combined prognostic value for mortality in patients with critically ill stroke remains unexplored. This study, based on a cohort of critically ill patients with stroke, aims to investigate the prognostic value of the combined TyG index and SHR in predicting all-cause mortality at multiple time points in this high-risk population.</p><p><strong>Methods: </strong>Based on the Medical Information Mart for Intensive Care (MIMIC)-IV database, 2998 critically ill patients with stroke requiring intensive care unit (ICU) admission were included. Patients were stratified into 8 groups based on the median of the TyG index and the quartiles of the SHR. The primary outcomes were 30-day and 365-day all-cause mortality; the secondary outcomes included 90-day and 180-day mortality. Cox proportional hazards regression models, restricted cubic splines (RCS) curves, subgroup analyses, and mediation analyses were employed to assess associations between the combined TyG index and SHR with all-cause mortality.</p><p><strong>Results: </strong>The cohort had a median age of 72.63 years (IQR 61.27-82.69 years), with 51.33% male (1539/2998). Fully adjusted Cox proportional hazards models showed that compared to the reference group (TyG < 8.72 and SHR < 0.86), patients with TyG ≥ 8.72 and SHR ≥ 1.18 had the highest mortality risk (30-day HR 2.481, 95% CI 1.767-3.485; 365-day HR 1.954, 95% CI 1.532-2.493). RCS analysis confirmed linear positive correlations between the TyG index, SHR, and mortality at all time points (all P for non-linearity > 0.05). Subgroup analyses further demonstrated consistent associations between the combined TyG index and SHR on 30-day and 365-day all-cause mortality. Mediation analysis revealed that the highest SHR significantly mediated the association between high TyG and mortality in these patients (30-day mediation proportion: 48.82%, P = 0.024; 365-day: 22.93%, P = 0.004).</p><p><strong>Conclusion: </strong>The combination of high TyG (≥ 8.72) and elevated SHR (≥ 1.18) is significantly associated with increased short- and long-term mortality in critically ill patients with stroke. Integrated metabolic monitoring and early intervention targeting at these biomarkers may improve their prognosis.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"337"},"PeriodicalIF":10.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12362854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871602","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 of circulating metabolites and polygenic risk score with incident type 2 diabetes: a prospective community-based cohort study.","authors":"Masato Takase, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Kotaro Nochioka, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Seizo Koshiba, Kazuki Kumada, Ikuko Motoike, Eiji Hishinuma, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Ippei Takahashi, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Koichi Matsuda, Yoko Izumi, Kinuko Ohneda, Kengo Kinoshita, Atsushi Hozawa, Masayuki Yamamoto","doi":"10.1186/s12933-025-02849-8","DOIUrl":"10.1186/s12933-025-02849-8","url":null,"abstract":"<p><strong>Background: </strong>No previous studies have explored metabolites associated with both genetic predispositions to type 2 diabetes (T2DM) and T2DM onset. Therefore, we aimed to explore metabolic profiles using genetic risk to identify pathways for tailored T2DM prevention strategies.</p><p><strong>Methods: </strong>This prospective community-based cohort study in Japan included a total of 12,461 participants aged ≥ 20 years. Genetic predictors were genome-wide and pathway-based polygenic risk scores (PRSs). We quantified 43 metabolites using nuclear magnetic resonance spectroscopy. T2DM was defined as a non-fasting glucose level of ≥ 200 mg/dL, glycated hemoglobin level ≥ 6.5%, or self-reported T2DM treatment. A modified Poisson regression model was used to examine the associations of PRSs and metabolites with T2DM incidence. Linear associations were tested using the restricted cubic spline, and mediation analysis was conducted to assess the mediating effect of metabolites on the association between PRSs and T2DM incidence.</p><p><strong>Results: </strong>During the 4.3-year median follow-up period, 354 T2DM cases were identified. A higher PRS was associated with incident T2DM (relative risk [RR] 2.09, 95% confidence interval [CI], 1.68-2.60, P < 0.001, 1-standard deviation [SD] increment). The nitrogen compound transport pathway PRS was associated with incident T2DM (RR 1.32, 95% CI 1.03-1.70, P < 0.001, 1-SD increment). Fourteen metabolites like glucose, 2-ketoisocaproic acid, glutamic acid, leucine, 2-aminobutyric acid, 2-hydroxybutyric acid, valine, 3-methyl-2-oxobutyric acid, alanine, 3-hydroxybutyric acid, 3-methyl-2-oxiovaleric acid, formic acid, arginine, and tyrosine were positively associated with the risk of T2DM. Only glycine was inversely associated with the risk of T2DM. Among 43 metabolites, 14 metabolites were positively associated with PRS (P for linear trend < 0.05). 3-hydroxyisobutyric-acid, 2-Aminobutyric acid, 2-ketoisocaproic acid, 2-hydroxybutyric acid, leucine, glycine, and glucose mediated the association between PRS and incident T2DM.</p><p><strong>Conclusions: </strong>Several metabolites were found to mediate the association between PRS and incident T2DM. These findings may contribute to a better understanding of the metabolic pathways involved in genetic susceptibility to T2DM.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"335"},"PeriodicalIF":10.6,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854652","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":"Mitochondrial ultrastructural pathology in diabetic cardiomyopathy: integrated analysis via scanning electron microscopy and 3D visualization imaging.","authors":"Bo Wang, Linghao Dai, Haowei Liang, Jiayu He, Jiayi Zhou, Yang Guan, Hui Wang","doi":"10.1186/s12933-025-02884-5","DOIUrl":"10.1186/s12933-025-02884-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mitochondrial dysfunction plays a pivotal role in the onset and progression of diabetic cardiomyopathy (DCM). It is hypothesized that ultrastructural mitochondrial abnormalities, molecular dynamics imbalance, and bioenergetic impairments collectively contribute significantly to cardiac dysfunction. Consequently, investigating mitochondrial ultrastructural changes and metabolic disturbances is crucial for elucidating the mechanistic underpinnings of DCM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to comprehensively characterize alterations in mitochondrial ultrastructure and energy metabolism in DCM and examine the interplay between these two factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;High glucose-treated H9c2 cardiomyocytes and DCM model mice were analyzed via scanning electron microscopy (SEM) and 3D imaging. Three-dimensional morphometric parameters-such as Length3D, Thickness3D, Width3D, Area3D, Volume3D, Anisotropy, Flatness, and Elongation-were quantified to evaluate mitochondrial architecture. At the two-dimensional (2D) level, mitochondria-associated membrane (MAM) parameters were analyzed. Further, detailed statistical analysis was conducted on mitochondrial cristae, including cristae scores, count, width, gap size, and junction widths in myocardial tissues. Mitochondrial dynamics and autophagy-related protein expression (Mfn1, Mfn2, Opa1, p-Drp1(ser616), PINK1, Parkin1) in myocardial tissues were assessed by Western blot. Mitochondrial bioenergetics were measured by ATP content, membrane potential, mtDNA copy number, SOD levels, mitochondrial Ca&lt;sup&gt;2+&lt;/sup&gt; levels, and oxidative phosphorylation (OXPHOS) activity across Complexes I-V in myocardial tissue. Additionally, the oxygen consumption rate (OCR) of viable H9c2 cells was measured using the O2k system.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;3D reconstruction revealed key myocardial ultrastructures-including T-tubules, sarcoplasmic reticulum (SR), intercalated discs, and mitochondria-and demonstrated significant differences in mitochondrial morphology and 3D morphometric parameters across subpopulations. Under high glucose (HG) conditions, in vitro analysis showed a reduction in mitochondrial Length3D and Anisotropy in H9c2 cells, accompanied by increases in Thickness3D, Width3D, Flatness, and Elongation. HG exposure also led to an increase in the length of MAM contact sites and the MAM-to-mitochondria perimeter ratio. In vivo, the DCM group exhibited decreased 2D morphometric parameters (length, width, area, perimeter, and shape AP), as well as reductions in 3D measurements (Thickness3D, Width3D, and Volume3D) compared to controls. No significant differences were observed in Length3D, Area3D, Anisotropy, Flatness, and Elongation between groups. 3D surface analysis revealed rough mitochondrial surfaces in the DCM group, while controls displayed smooth surfaces. Control mitochondria exhibited well-aligned, well-defined cristae, whereas DCM mitochondria sh","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"331"},"PeriodicalIF":10.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844513","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 autonomic neuropathy defined by indices of heart rate variability is associated with cardiovascular disease: a longitudinal cohort study of participants with type 1 diabetes.","authors":"Barbara H Braffett, Laure El Ghormli, Catherine Martin, Neil H White, Irl B Hirsch, Anne Bantle, Anders Carlson, Ellen Leschek, Rose Gubitosi-Klug, Elsayed Z Soliman, Adrian Vella, Bruce A Perkins, Ionut Bebu, Rodica Pop-Busui","doi":"10.1186/s12933-025-02856-9","DOIUrl":"10.1186/s12933-025-02856-9","url":null,"abstract":"<p><strong>Background: </strong>To describe longitudinal prevalence and risk factors associated with cardiovascular autonomic neuropathy (CAN), defined by heart rate variability (HRV) indices, and evaluate the impact of CAN on cardiovascular disease (CVD), in adults with type 1 diabetes (T1D) from the Epidemiology of Diabetes Interventions and Complications (EDIC) study.</p><p><strong>Methods: </strong>Standard resting electrocardiogram (ECG) recordings were obtained annually in 997 participants (mean ± SD age 56.2 ± 6.8 years; T1D duration 34.7 ± 7.9 years; 48% female) between 2015 and 2022. The standard deviation of normally conducted R-R intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) were used to define CAN using previously validated cut-offs in this cohort from gold-standard cardiovascular reflex tests (CARTs). Generalized estimating equation models were used to evaluate the association of ECG-derived CAN with individual risk factors over repeated time points. Kaplan-Meier estimates were used to describe the cumulative incidence of the first occurrence of any-CVD and of MACE by ECG-derived CAN status, and Cox proportional hazards regression models were used to estimate the effect of ECG-derived CAN adjusted for age and HbA1c.</p><p><strong>Results: </strong>The prevalence of ECG-derived CAN (~ 64%) was stable. Higher pulse rate (OR [95% CI] 1.08 [1.07,1.10] per 1 bpm) and HbA1c (1.43 [1.29,1.58] per 1%) were the most significant risk factors for CAN, followed by older age, male sex, higher albumin excretion rate, and hypertension history. The cumulative incidence of first occurrence of any-CVD over 7 years of follow-up was significantly higher in participants with vs. without CAN (HR [95% CI] any-CVD 2.37 [1.43,3.94]), which remained significant adjusting for mean HbA1c and age, but was attenuated with further adjustment for other factors.</p><p><strong>Conclusions: </strong>The prevalence of and risk factors for standard resting ECG-derived CAN were similar to previously reported estimates from CARTs. CVD risk was significantly higher in those with vs. without CAN. These data support future studies examining the diagnostic utility of HRV indices at the point of care for risk stratification.</p><p><strong>Trial registration: </strong>clinicaltrials.gov NCT00360815 and NCT00360893.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"334"},"PeriodicalIF":10.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844511","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":"The predictive value of atherogenic index of plasma and clonal hematopoiesis of indeterminate potential among patients with STEMI-from a prospective cohort study.","authors":"Xiaoxiao Zhao, Jiannan Li, Runzhen Chen, Nan Li, Linghan Xue, Shaodi Yan, Chen Liu, Peng Zhou, Yi Chen, Hongbing Yan, Yu Tan, Hanjun Zhao, Li Song","doi":"10.1186/s12933-025-02877-4","DOIUrl":"10.1186/s12933-025-02877-4","url":null,"abstract":"<p><strong>Background: </strong>Acute coronary syndrome (ACS) remains a leading global cause of mortality despite advances in revascularization therapies.</p><p><strong>Methods: </strong>This prospective cohort study investigated the synergistic prognostic impact of clonal hematopoiesis of indeterminate potential (CHIP) and atherogenic index of plasma (AIP) in 1396 ACS patients undergoing primary percutaneous coronary intervention at Fuwai Hospital (2017-2020). Using deep targeted sequencing (42 genes, median depth 14,219 ×), we identified CHIP mutations (VAF ≥ 2%) in 14.5% of participants, with DNMT3A (23.7%), TET2 (2.8%), and ASXL1 (1.9%) being most prevalent.</p><p><strong>Results: </strong>High-AIP patients stratified by cutoff value were younger (57.8 vs. 63.2 years), had elevated hs-CRP (7.2 vs. 5.8 mg/L), and higher smoking rates, suggesting accelerated atherosclerosis. Multivariable Cox regression revealed that in patients with AIP ≥ cutoff, CHIP carriers exhibited significantly higher all-cause mortality, particularly for TET2 mutations (HR 5.20, CI 95%: 1.75-15.41; p = 0.003) and TET2/ASXL1 co-mutations (HR 5.5, CI 95%: 2.02-13.15; p = 0.001). Among individuals in the high AIP group, any CHIP (Fig. 3A, HR 2.38, 95% CI 1.18-4.81; P log-rank = 0.015) and common CHIP (Fig. 3B, HR 2.74, 95% CI 1.30-5.08; P log-rank = 0.008) mutation experienced a higher risk of mortality than individuals absence of CHIP mutation.</p><p><strong>Conclusion: </strong>These findings establish AIP as a critical modifier of CHIP-related cardiovascular risk, potentially through enhanced inflammatory pathways in younger ACS populations. The study highlights the clinical utility of combining lipid-based (AIP) and genetic (CHIP) biomarkers for precision prognostication, though validation in larger cohorts and mechanistic investigations of the AIP-CHIP interplay are warranted to guide targeted therapies.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"24 1","pages":"333"},"PeriodicalIF":10.6,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12351917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144844514","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}