Cardiovascular Diabetology最新文献

{"title":"Modulation of circulating levels of advanced glycation end products and its impact on intima-media thickness of both common carotid arteries: CORDIOPREV randomised controlled trial.","authors":"Francisco M Gutierrez-Mariscal, Alejandro Lopez-Moreno, Jose D Torres-Peña, Purificacion Gomez-Luna, Antonio P Arenas-de Larriva, Juan Luis Romero-Cabrera, Raul M Luque, Jaime Uribarri, Pablo Perez-Martinez, Javier Delgado-Lista, Elena M Yubero-Serrano, Jose Lopez-Miranda","doi":"10.1186/s12933-024-02451-4","DOIUrl":"https://doi.org/10.1186/s12933-024-02451-4","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD).</p><p><strong>Methods: </strong>1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal-MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention.</p><p><strong>Results: </strong>The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p < 0.001). The Mediterranean diet, but not the low-fat diet, produced an upregulation of AGE metabolism, with increased AGER1 and GloxI gene expression as well as increased GSH and sRAGE levels in Non-increased IMT-CC patients (all p < 0.05). Although the Mediterranean diet increased MG levels in Increased IMT-CC patients, this increment was lower compared to the low-fat diet (all p < 0.05).</p><p><strong>Conclusions: </strong>Our results suggest that an improvement in modulation of AGE metabolism, which facilitates better management of circulating AGE levels, may be one of the mechanisms through which the Mediterranean diet, compared to a low-fat diet, reduces the progression of atherosclerosis in patients with CHD. Trial registration https://clinicaltrials.gov/ct2/show/NCT00924937 , Clinicaltrials.gov number, NCT00924937.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"361"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11475769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458609","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 relationship between serum HDL-cholesterol, cardiovascular disease and mortality in community-based people with type 2 diabetes: the Fremantle Diabetes Study phase 2.","authors":"Timothy M E Davis, S A Paul Chubb, Wendy A Davis","doi":"10.1186/s12933-024-02447-0","DOIUrl":"https://doi.org/10.1186/s12933-024-02447-0","url":null,"abstract":"<p><strong>Background: </strong>Older general population-based studies found an inverse association between serum HDL-cholesterol and both cardiovascular disease (CVD) events and mortality, but more recent data have suggested a U-shaped relationship. Whether this applies to type 2 diabetes is uncertain. The aim of this study was to assess the prognostic significance of serum HDL-cholesterol concentrations in representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2).</p><p><strong>Methods: </strong>We followed 1,479 FDS2 participants with confirmed type 2 diabetes (713 females, mean age 65.6 years; 763 males, mean age 65.9 years) from entry (2008-2011) to death/end-2021. Major adverse cardiovascular events (non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular death; 3-point MACE), and all-cause mortality were ascertained from prospectively collected data and validated administrative databases. Independent associates of 3-point MACE by sex, excluding participants with prior MI/stroke, were assessed using Cox and competing risk models with sex-specific quintiles of HDL-cholesterol added to the most parsimonious models. Predictors of all-cause mortality were identified using Cox proportional hazards modelling.</p><p><strong>Results: </strong>In females, with baseline serum HDL-cholesterol quintile 2 (1.04-1.22 mmol/L) as reference, both quintiles 1 (< 1.04 mmol/L) and 5 (> 1.59 mmol/L) were significant independent predictors of 3-point MACE (P < 0.027) and all-cause death (P < 0.019) after adjustment for a full range of demographic, clinical and laboratory variables. In males, serum HDL-cholesterol quintile did not add to the most parsimonious model for 3-point MACE, but quintile 1 (< 0.90 mmol/L) was a significant predictor of death (P = 0.026 versus quintile 4 (1.15-1.31 mmol/L) as reference) after adjustment. Competing risk analyses for 3-point MACE showed similar results to the Cox models for both sexes.</p><p><strong>Conclusion: </strong>There was a significant U-shaped relationship between serum HDL-cholesterol and both 3-point MACE and all-cause death in females with type 2 diabetes after adjustment for confounders. There was no such relationship for 3-point MACE in males but a low HDL-cholesterol was associated with all-cause mortality. These data have sex-specific implications for assessment of serum lipid profiles in the clinical management of type 2 diabetes.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"362"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458625","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":"Multiple triglyceride-derived metabolic indices and incident cardiovascular outcomes in patients with type 2 diabetes and coronary heart disease.","authors":"Shiyi Tao, Lintong Yu, Jun Li, Li Huang, Tiantian Xue, Deshuang Yang, Xuanchun Huang, Chao Meng","doi":"10.1186/s12933-024-02446-1","DOIUrl":"https://doi.org/10.1186/s12933-024-02446-1","url":null,"abstract":"<p><strong>Background: </strong>Triglyceride (TG) and its related metabolic indices are recognized as important biomarker gauging cardiovascular diseases. This study aimed to explore the association between multiple TG-derived metabolic indices including the atherogenic index of plasma (AIP), triglyceride-glucose (TyG) index, triglyceride glucose-body mass index (TyG-BMI) and cardiovascular outcomes to identify valuable predictors for cardiovascular prognosis in patients with type 2 diabetes (T2DM) and coronary heart disease (CHD).</p><p><strong>Methods: </strong>Data of 1034 patients with T2DM and CHD from China-Japan Friendship Hospital between January 2019 and March 2022 were collected and analyzed. Multivariate Cox proportional hazards models and restricted cubic spline (RCS) analysis were conducted to examine the associations between AIP, TyG index, TyG-BMI and major adverse cardiac and cerebrovascular events (MACCEs). The area under the receiver operating characteristic (ROC) curve (AUC) was used to screen the most valuable predictor. Kaplan-Meier curve analysis was employed to examine the relationship between the predictor and prognosis. The goodness-of-fit of models was evaluated using the calibration curve and χ² likelihood ratio test. Subgroup analysis and interaction test were performed to control for confounding factors.</p><p><strong>Results: </strong>The overall incidence of MACCEs was 31.04% during a median of 13.3 months of follow-up. The results showed that AIP, TyG index and TyG-BMI were all positively correlated with the risk of MACCEs in patients with T2DM and CHD (P < 0.05). Furthermore, ROC (AUC = 0.899) suggested that AIP had the strongest ability to predict the risk of MACCEs, and the highest AIP values enhanced the risk by 83.5% in the population. RCS model demonstrated that AIP was nonlinearly associated with the incident cardiovascular outcomes (P for nonlinear = 0.0118). The Kaplan-Meier analysis for MACCEs grouped by the AIP tertiles indicated that the probability of cumulative incidences of MACCEs was significantly higher in patients with a higher AIP (all Log rank P < 0.001). Meanwhile, the calibration curve demonstrated an excellent goodness-of-fit of the multivariate model (χ² = 13.210, P = 0.105). Subgroup analysis revealed that the trend of positive association of AIP with cardiovascular risk was similar across subgroups except in non-hypertensive individuals.</p><p><strong>Conclusion: </strong>Our study, for the first time, may provide valuable information that multiple TG-derived metabolic indices play a crucial role in the risk of MACCEs and it is recommended to monitor the AIP for lipid management in patients with established T2DM and CHD.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"359"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458611","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 stress hyperglycemia ratio index and all-cause mortality in critically ill patients with atrial fibrillation: a retrospective study using the MIMIC-IV database.","authors":"Siyuan Cheng, Hui Shen, Yucheng Han, Shaojie Han, Yun Lu","doi":"10.1186/s12933-024-02462-1","DOIUrl":"https://doi.org/10.1186/s12933-024-02462-1","url":null,"abstract":"<p><strong>Background: </strong>The stress hyperglycemia ratio (SHR) was developed to mitigate the influence of long-term chronic glycemic factors on stress hyperglycemia levels, which are associated with adverse clinical events, particularly cardiovascular events. However, studies examining the SHR index and its prognostic significance in patients with atrial fibrillation (AF) are lacking. This study aims to evaluate the relationship between the SHR index and all-cause mortality in critically ill patients with AF upon Intensive Care Unit admission.</p><p><strong>Methods: </strong>The patients' data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. All patients were categorized into four groups based on the SHR index. The outcomes include both primary and secondary endpoints, with the primary endpoints being 30-day and 365-day all-cause mortality, and the secondary endpoints being 90-day and 180-day all-cause mortality. The SHR index was analyzed using quartiles, and the Kaplan-Meier curve was employed to compare the outcomes across groups. Cox proportional-hazards regression and restricted cubic splines (RCS) were used to assess the relationship between the SHR index and the outcomes.</p><p><strong>Results: </strong>Out of a total of 1,685 participants, the average age was 63.12 years (range: 40.17 to 101.49), with 1,004 (59.58%) being male. Higher levels of the SHR index were associated with an increased risk of all-cause mortality at 30 days, 90 days, 180 days, and 365 days, as indicated by the Kaplan-Meier curves (log-rank P < 0.01). Additionally, Cox proportional-hazards regression analysis revealed that the risk of mortality at these time points was significantly higher in the highest quartile of the SHR index. Restricted cubic splines (RCS) analysis demonstrated U-shaped relationships between the SHR index and all-cause mortality, with inflection points at 0.73 for 30-day mortality and 0.76 for 365-day mortality. Compared to patients with SHR levels below these inflection points, those with higher levels had a 69.9% increased risk for 30-day all-cause mortality (hazard ratio [HR] 1.699; 95% confidence interval [CI] 1.336 to 2.159) and a 61.6% increased risk for 365-day all-cause mortality (HR 1.616; 95% CI 1.345 to 1.942).</p><p><strong>Conclusion: </strong>In critically ill patients with AF, higher levels of the SHR index are significantly associated with an increased risk of all-cause mortality at 30 days, 90 days, 180 days, and 365 days. The SHR index may serve as a valid indicator for assessing the severity and guiding the treatment of AF patients in the ICU.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"363"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458606","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":"Correction to: Mortality and cardiovascular events in diabetes mellitus patients at dialysis initiation treated with glucagon-like peptide-1 receptor agonists.","authors":"Hsuan-Wen Lai, Chun Yin See, Jui-Yi Chen, Vin-Cent Wu","doi":"10.1186/s12933-024-02452-3","DOIUrl":"https://doi.org/10.1186/s12933-024-02452-3","url":null,"abstract":"","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"360"},"PeriodicalIF":8.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458607","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":"Spatial multiomics atlas reveals smooth muscle phenotypic transformation and metabolic reprogramming in diabetic macroangiopathy.","authors":"Yongjiang Qian, Shizheng Xiong, Lihua Li, Zhen Sun, Lili Zhang, Wei Yuan, Honghua Cai, Guoquan Feng, Xiaoguang Wang, Haipeng Yao, Yun Gao, Li Guo, Zhongqun Wang","doi":"10.1186/s12933-024-02458-x","DOIUrl":"https://doi.org/10.1186/s12933-024-02458-x","url":null,"abstract":"<p><strong>Background: </strong>Diabetic macroangiopathy has been the main cause of death and disability in diabetic patients. The mechanisms underlying smooth muscle cell transformation and metabolic reprogramming other than abnormal glucose and lipid metabolism remain to be further explored.</p><p><strong>Method: </strong>Single-cell transcriptome, spatial transcriptome and spatial metabolome sequencing were performed on anterior tibial artery from 11 diabetic patients with amputation. Multi-omics integration, cell communication analysis, time series analysis, network analysis, enrichment analysis, and gene expression analysis were performed to elucidate the potential molecular features.</p><p><strong>Result: </strong>We constructed a spatial multiomics map of diabetic blood vessels based on multiomics integration, indicating single-cell and spatial landscape of transcriptome and spatial landscape of metabolome. At the same time, the characteristics of cell composition and biological function of calcified regions were obtained by integrating spatial omics and single cell omics. On this basis, our study provides favorable evidence for the cellular fate of smooth muscle cells, which can be transformed into pro-inflammatory chemotactic smooth muscle cells, macrophage-like smooth muscle cells/foam-like smooth muscle cells, and fibroblast/chondroblast smooth muscle cells in the anterior tibial artery of diabetic patients. The smooth muscle cell phenotypic transformation is driven by transcription factors net including KDM5B, DDIT3, etc. In addition, in order to focus on metabolic reprogramming apart from abnormal glucose and lipid metabolism, we constructed a metabolic network of diabetic vascular activation, and found that HNMT and CYP27A1 participate in diabetic vascular metabolic reprogramming by combining public data.</p><p><strong>Conclusion: </strong>This study constructs the spatial gene-metabolism map of the whole anterior tibial artery for the first time and reveals the characteristics of vascular calcification, the phenotypic transformation trend of SMCs, and the transcriptional driving network of SMCs phenotypic transformation of diabetic macrovascular disease. In the perspective of combining the transcriptome and metabolome, the study demonstrates the activated metabolic pathways in diabetic blood vessels and the key genes involved in diabetic metabolic reprogramming.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"358"},"PeriodicalIF":8.5,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458624","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 relationship between repeated measurements of HbA_1c and risk of coronary events among the common haptoglobin phenotype groups: the Action for Health in Diabetes (Look AHEAD) study.","authors":"A S Carew, R A Warren, M P Bancks, M A Espeland, J L Bahnson, C L Lewis, A P Levy, J L Sapp, R Urquhart, J L Wang, E B Rimm, L E Cahill","doi":"10.1186/s12933-024-02448-z","DOIUrl":"10.1186/s12933-024-02448-z","url":null,"abstract":"<p><strong>Background: </strong>In the ACCORD study, participants with the haptoglobin (Hp) 2-2 phenotype and glycated hemoglobin (HbA_1c) ≥ 8.0% had a higher risk of coronary artery disease (CAD) compared to those with HbA_1c 7.0-7.9%. However, this association was not observed in participants without the Hp2-2 phenotype. The optimal glycemic target for CAD prevention for the Hp phenotypes remains uncertain and may vary based on demographic and clinical factors.</p><p><strong>Objective: </strong>To investigate how reaching clinically relevant HbA_1c targets relates to the risk of CAD in different Hp phenotype groups among a diverse cohort of individuals with T2DM (the Look AHEAD study, HbA_1c ≤ 11% at baseline).</p><p><strong>Methods: </strong>Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA_1c (< 6.5%, 6.5-6.9%, and ≥ 8.0% compared to 7.0-7.9%), updated at years 1-4, 6, 8, and 10, and incident CAD in the Hp2-2 (n = 1,587) and non-Hp2-2 (n = 2,944) phenotypes separately. Further pre-specified subgroup analyses by age, sex, history of cardiovascular disease (CVD), race, and diabetes duration were performed in each Hp phenotype group separately.</p><p><strong>Results: </strong>Compared with HbA_1c 7.0-7.9%, having HbA_1c < 6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 phenotype (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 phenotype who were male (0.60, 0.44-0.83), who did not have a history of CVD (0.65, 0.47-0.90), who were aged ≥ 65 years (0.64, 0.44-0.94), who were White (0.68, 0.51-0.91), or who had diabetes duration > 10 years (0.58, 0.35-0.95). HbA_1c ≥ 8.0% was associated with CAD risk only among participants with the Hp2-2 phenotype who had a history of CVD (1.79, 1.00-3.20). No associations were found between the other HbA_1c targets and CAD risk when participants with the Hp2-2 phenotype were grouped together or divided into subgroups.</p><p><strong>Conclusion: </strong>The differences in our results compared to our previous findings may be due to variations in the study populations and factors associated with weight loss, making it difficult to draw definitive conclusions. Our current findings should be considered in the context of hypothesis generation, and ideally, will encourage additional research in this field.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"356"},"PeriodicalIF":8.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11466022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388259","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":"External validation and calibration of risk equations for prediction of diabetic kidney diseases among patients with type 2 diabetes in Taiwan.","authors":"Hsuan-Yu Su, Thi Thuy Dung Nguyen, Wei-Hung Lin, Huang-Tz Ou, Shihchen Kuo","doi":"10.1186/s12933-024-02443-4","DOIUrl":"10.1186/s12933-024-02443-4","url":null,"abstract":"<p><strong>Background: </strong>Most existing risk equations for predicting/stratifying individual diabetic kidney disease (DKD) risks were developed using relatively dated data from selective and homogeneous trial populations comprising predominately Caucasian type 2 diabetes (T2D) patients. We seek to adapt risk equations for prediction of DKD progression (microalbuminuria, macroalbuminuria, and renal failure) using empiric data from a real-world population with T2D in Taiwan.</p><p><strong>Methods: </strong>Risk equations from three well-known simulation models: UKPDS-OM2, RECODe, and CHIME models, were adapted. Discrimination and calibration were determined using the area under the receiver operating characteristic curve (AUROC), a calibration plot (slope and intercept), and the Greenwood-Nam-D'Agostino (GND) test. Recalibration was performed for unsatisfactory calibration (p-value of GND test < 0.05) by adjusting the baseline hazards of risk equations to address risk variations among patients.</p><p><strong>Results: </strong>The RECODe equations for microalbuminuria and macroalbuminuria showed moderate discrimination (AUROC: 0.62 and 0.76) but underestimated the event risks (calibration slope > 1). The CHIME equation had the best discrimination for renal failure (AUROCs from CHIME, UKPDS-OM2 and RECODe: 0.77, 0.60 and 0.64, respectively). All three equations overestimated renal failure risk (calibration slope < 1). After rigorous updating, the calibration slope/intercept of the recalibrated RECODe for predicting microalbuminuria (0.87/0.0459) and macroalbuminuria (1.10/0.0004) risks as well as the recalibrated CHIME equation for predicting renal failure risk (0.95/-0.0014) were improved.</p><p><strong>Conclusions: </strong>Risk equations for prediction of DKD progression in real-world Taiwanese T2D patients were established, which can be incorporated into a multi-state simulation model to project and differentiate individual DKD risks for supporting timely interventions and health economic research.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"357"},"PeriodicalIF":8.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388258","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":"Exposure of cumulative atherogenic index of plasma and the development of prediabetes in middle-aged and elderly individuals: evidence from the CHARLS cohort study.","authors":"Yang Zou, Song Lu, Dongdong Li, Xin Huang, Chao Wang, Guobo Xie, Lihua Duan, Hongyi Yang","doi":"10.1186/s12933-024-02449-y","DOIUrl":"10.1186/s12933-024-02449-y","url":null,"abstract":"<p><strong>Background: </strong>The impact of dynamic changes in the degree of atherosclerosis on the development of prediabetes remains unclear. This study aims to investigate the association between cumulative atherogenic index of plasma (CumAIP) exposure during follow-up and the development of prediabetes in middle-aged and elderly individuals.</p><p><strong>Methods: </strong>A total of 2,939 prediabetic participants from the first wave of the China Health and Retirement Longitudinal Study (CHARLS) were included. The outcomes for these patients, including progression to diabetes and regression to normal fasting glucose (NFG), were determined using data from the third wave. CumAIP was calculated as the ratio of the average AIP values measured during the first and third waves to the total exposure duration. The association between CumAIP and the development of prediabetes was analyzed using multivariable Cox regression and restricted cubic spline (RCS) regression.</p><p><strong>Results: </strong>During a median follow-up period of 3 years, 15.21% of prediabetic patients progressed to diabetes, and 22.12% regressed to NFG. Among the groups categorized by CumAIP quartiles, the proportion of prediabetes progressing to diabetes gradually increased (Q1: 10.61%, Q2: 13.62%, Q3: 15.65%, Q4: 20.95%), while the proportion regressing to NFG gradually decreased (Q1: 23.54%, Q2: 23.71%, Q3: 22.18%, Q4: 19.05%). Multivariable-adjusted Cox regression showed a significant positive linear correlation between high CumAIP exposure and prediabetes progression, and a significant negative linear correlation with prediabetes regression. Furthermore, in a stratified analysis, it was found that compared to married individuals, those who were unmarried (including separated, divorced, widowed, or never married) had a relatively higher risk of CumAIP-related diabetes.</p><p><strong>Conclusion: </strong>CumAIP is closely associated with the development of prediabetes. High CumAIP exposure not only increases the risk of prediabetes progression but also hinders its regression within a certain range. These findings suggest that monitoring and maintaining appropriate AIP levels may help prevent the deterioration of blood glucose levels.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"355"},"PeriodicalIF":8.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342134","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":"N⁶-Methyladenosine-mediated phase separation suppresses NOTCH1 expression and promotes mitochondrial fission in diabetic cardiac fibrosis.","authors":"Zhi-Yan Liu, Li-Chan Lin, Zhen-Yu Liu, Kai Song, Bin Tu, He Sun, Yang Zhou, Sui Mao, Ye Zhang, Rui Li, Jing-Jing Yang, Jian-Yuan Zhao, Hui Tao","doi":"10.1186/s12933-024-02444-3","DOIUrl":"https://doi.org/10.1186/s12933-024-02444-3","url":null,"abstract":"<p><strong>Background: </strong>N⁶-methyladenosine (m⁶A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m⁶A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive.</p><p><strong>Methods: </strong>Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1^flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings.</p><p><strong>Results: </strong>In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m⁶A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m⁶A demethylation in the 3'UTR of Notch1 mRNA and elevated m⁶A mRNA levels. These elevated m⁶A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m⁶A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis.</p><p><strong>Conclusions: </strong>We identified a novel epitranscriptomic mechanism by which m⁶A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis.</p>","PeriodicalId":9374,"journal":{"name":"Cardiovascular Diabetology","volume":"23 1","pages":"347"},"PeriodicalIF":8.5,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342146","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}