Cardiovascular Diabetology最新文献

Cardiovascular-Kidney-Metabolic (CKM) syndrome progresses through distinct stages, from early metabolic risk factors to advanced cardiovascular disease and kidney dysfunction. Across these stages, exercise remains a central yet underutilized intervention, offering physiological adaptations that address metabolic dysregulation, vascular dysfunction, and inflammation. This review evaluates the stage-specific effects of moderate-intensity continuous exercise (MICE), high-intensity interval exercise (HIIE), and resistance training (RT) on CKM syndrome. In Stage 0, exercise augments insulin sensitivity, endothelial function, and mitochondrial biogenesis, preserving optimal health in individuals without metabolic risk factors. Stage 1, marked by excess adiposity, sees structured exercise regimens effectively reducing visceral fat, improving lipid profiles, and enhancing glucose regulation. During Stage 2, encompassing metabolic risk factors and early chronic kidney disease (CKD), aerobic and resistance exercise improve endothelial responsiveness, glycemic control, and renal outcomes. In Stage 3, subclinical cardiovascular disease, targeted exercise interventions strengthen vascular integrity, boost cardiac efficiency, and enhance metabolic resilience. Finally, Stage 4 entails clinical CVD, where exercise-based rehabilitation programs (e.g., moderate-intensity continuous training [MICT], high-intensity interval training [HIIT]) raise functional capacity, improve quality of life, and support favorable prognosis. Sex differences in exercise adaptations underscore the importance of individualized prescriptions. Emphasizing a multidisciplinary strategy that integrates lifestyle modifications and clinical measures can mitigate CKM-associated morbidity and mortality. Future research should investigate long-term exercise adherence, sex-specific responses, and the role of digital health tools to optimize CKM management and patient outcomes.

Background: Prior studies have suggested an association between estimated glucose disposal rate (eGDR) and the risk of incident stroke in nondiabetic populations. However, evidence regarding the impact of long-term cumulative exposure to eGDR on stroke risk remains limited. This study aimed to investigate whether cumulative eGDR levels are independently associated with incident stroke among adults aged 50 years and older without diabetes.

Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS) and included 3,808 participants aged 50 years or older with no history of diabetes. Cumulative eGDR was calculated as the sum of the products of the average eGDR between consecutive survey waves and the corresponding time interval in years. The primary outcome was incident stroke. Associations between cumulative eGDR and stroke risk were assessed using Cox proportional hazards regression and restricted cubic spline (RCS) models. Discriminatory performance was assessed using receiver-operating characteristic (ROC) curves.

Results: The median age at baseline was 61 years, and 48.7% of participants were men. RCS analyses revealed a significant inverse and nonlinear association between cumulative eGDR and incident stroke (P < 0.001; P for nonlinearity = 0.021). After adjustment for potential confounders, higher cumulative eGDR was independently associated with a reduced risk of stroke (per standard deviation increase: HR: 0.69; 95% CI, 0.60-0.80; P < 0.001). Quartile-based analysis of cumulative eGDR further demonstrated that, compared with participants in the lowest quartile, those in the second quartile (Q2: HR: 0.63; 95% CI, 0.46-0.88; P = 0.006), third quartile (Q3: HR: 0.41; 95% CI, 0.28-0.60; P < 0.001) and fourth quartile (Q4: HR: 0.35; 95% CI, 0.23-0.52; P < 0.001) had significantly lower risks of incident stroke.

Conclusions: Among adults aged 50 years or older without diabetes, lower cumulative eGDR levels were significantly associated with an increased risk of incident stroke.

Background: Type 2 diabetes mellitus (T2DM) is associated with arterial diseases; particularly, the incidence of atherosclerotic conditions is increased among patients with diabetes. Basement membrane (BM) protein levels are increased in the artery wall of T2DM patients, but the underlying mechanisms and potential consequences remain elusive. This study aimed to identify putative connections between the level of arterial BM components, clinical characteristics, all-cause mortality and major adverse events (MACE) in groups of patients with and without T2DM.

Methods: Internal thoracic artery samples from 668 patients undergoing coronary artery bypass graft surgery at Odense University Hospital, Denmark, from 2008 to 2018 were included, of which 27% were diagnosed with T2DM. Seventeen vascular proteins were quantified using liquid chromatography tandem mass spectrometry.

Results: Levels of BM components-collagen IV, laminin, and perlecan-were significantly elevated in T2DM patients compared to non-diabetic controls. In the diabetic group, we found strong correlations between collagen IV and laminin levels and hemoglobin A1c, whereas correlations with plasma lipids, blood pressure, and body mass index (BMI) were weak or absent. Moreover, collagen IV and laminin were associated with both all-cause mortality and major adverse cardiovascular events (MACE) up to 14 years after surgery after adjustment for age, sex, and comorbidities.

Conclusions: We demonstrate that arterial basement membrane protein accumulation is related to glycemic status in T2DM. Furthermore, the observed associations between collagen IV and laminin levels and clinical outcomes support the notion that generalized alterations in arterial basement membranes may contribute to the development of cardiovascular disease.

Background: Patients with type 2 diabetes mellitus (T2DM) who are obese have increased risk of cardiovascular events. This study aimed to investigate the impact of obesity on myocardial interstitial fibrosis and its association with subclinical left ventricular (LV) systolic dysfunction in patients with T2DM.

Methods: Eighty-one T2DM patients without obesity, 48 patients with obesity and 40 matched lean healthy controls were prospectively recruited and underwent cardiac magnetic resonance imaging. Extracellular volume (ECV), 3-D feature tracking strain including LV radial (GRS), circumferential (GCS) and longitudinal (GLS) peak strains were evaluated from T1 mapping and cine images, and compared among the groups.

Results: Compared with controls, the LV GRS and GLS were significantly lower and ECV significantly higher in T2DM patients without obesity, and they were even lower or higher in patients with obesity than in both controls and patients without obesity. The LV GCS was significantly lower in patients with obesity than that in controls. Multivariable linear regression analyses demonstrated that obesity was independently associated with ECV (β = 2.147, p = 0.006), LV GRS and GLS (β = - 3.427 and 1.408, p = 0.019 and = 0.001, respectively) in patients with T2DM. When ECV was included in the regression analyses, both obesity and ECV were independently associated with LV GLS (β = 1.540 and 0.118, p < 0.001 and = 0.019, respectively).

Conclusions: In patients with T2DM, there was more severe myocardial interstitial fibrosis and subclinical LV systolic dysfunction in patients with obesity, and increased myocardial fibrosis is independently associated with impaired LV systolic function. These results indicate the potential clinical significance of weight management in T2DM patients with obesity.

Background: Stroke is a leading contributor to the high disease burden in low- and middle-income countries, making early prevention essential for risk reduction. The triglyceride-glucose (TyG) index and the estimated glucose disposal rate (eGDR) are surrogate markers of insulin resistance, and both have been associated with cardiometabolic risk. However, the predictive utility of their combined use for stroke risk across different glucose metabolism states remains unclear.

Methods: This prospective cohort study enrolled 5789 stroke-free participants aged ≥ 45 years, including 3490 with abnormal glucose regulation(AGR) and 2296 with normal glucose regulation(NGR). The TyG-eGDR index was dichotomised as TyG × eGDR. The TyG + eGDR combination was further partitioned into 12 strata defined by TyG tertiles crossed with eGDR quartiles. We evaluated the relationship between theseTyG, eGDR, TyG-eGDR and TyG + eGDR categories and incident stroke using cox proportional-hazards models, mediation analysis, restricted cubic splines, receiver-operating-characteristic curves, and subgroup analyses Query.

Results: Among 5789 participants followed for incident stroke, 460 new events were documented, corresponding to an overall incidence of 9.93 per 1000 person-years. We observed a negative association between lower eGDR index (OR = 0.70, 95% CI 0.62-0.79) and lower TyG-eGDR index (OR = 0.72, 95% CI 0.63-0.81) with stroke risk across all populations, while in the AGR subgroup, a higher TyG index (OR = 1.24, 95% CI 1.11-1.37) was associated with a higher risk of stroke. Compared to the reference group (low TyG and high eGDR), the combination of high TyG (≥ 8.90) and low eGDR (< 7.09) conferred the highest stroke hazard (HR = 3.75, 95% CI 2.29-6.15, p = 1.6 × 10⁻⁷), and this pattern was consistent in both AGR and NGR sub-cohorts. However, the TyG + eGDR combination exerted a stronger influence on stroke risk within the AGR group. RCS showed non-linear dose-response for TyG and TyG-eGDR with stroke (p < 0.05), but linear for eGDR. The TyG + eGDR composite model achieved superior discrimination (area under the ROC curve: 0.71). Mediation analysis indicated that eGDR accounted for 29.99% of the association between TyG and stroke risk, while TyG explained 5.81% of the association between eGDR and stroke risk; comparable mediation patterns were observed in the AGR population but not in the NGR population.

Conclusions: Low eGDR and a low TyG-eGDR product independently predict a higher stroke risk, whereas elevated TyG predominantly increases stroke risk in individuals with AGR. Combining TyG and eGDR markedly improves stroke discrimination beyond either metric alone. Routine integration of these two inexpensive indices permits earlier, more precise risk stratification and can inform targeted interventions that substantially reduce stroke incidence.

Background: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The atherogenic index of plasma (AIP) reflects atherogenic dyslipidemia and triglyceride-glucose (TyG) index is a surrogate of insulin resistance (IR). Evidence on their combined value for CVDs risk stratification remain limited. In this study, the associations between baseline levels and longitudinal changes of the composite TyG-AIP index and the incidence of CVDs were evaluated among middle-aged and older adults.

Methods: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS). A total of 6,986 participants were included in the baseline analysis(2012-2020), and 4,134 participants with repeated biomarker measurements in 2012 and 2015 were included in the longitudinal trajectory analysis. Multivariable cox proportional hazards models and restricted cubic spline(RCS) were applied to evaluate the associations of TyG, AIP, TyG&AIP and TyG-AIP with the incidence of CVDs (stroke and heart disease). K-means clustering characterized longitudinal TyG-AIP patterns. Discrimination was assessed with nomograms and receiver operating characteristic (ROC) curves.

Results: A total of 6,986 participants were included and followed for a median of 8.0 years, during which 1,752 incident CVDs occurred, including 1,343 cases of heart disease and 614 cases of stroke. Across tertiles of the TyG-AIP index, the risk of CVDs increased progressively, with adjusted HRs of 1.16 (95% CI: 1.03-1.31) for T2 and 1.25 (95% CI: 1.10-1.41) for T3 compared with T1. For stroke, the associations were higher in magnitude, with adjusted HRs of 1.40 (95% CI: 1.14-1.74) in T2 and 1.52 (95% CI: 1.23-1.88) in T3. TyG-AIP showed modest but superior discrimination versus TyG or AIP alone (AUC: 0.611 for CVDs; 0.631 for stroke; 0.605 for heart disease). NRI and IDI analyses demonstrated that adding TyG-AIP significantly improved risk reclassification for CVDs (NRI, 0.036-0.054, P < 0.001) and stroke (NRI, 0.096-0.114, P < 0.001). In longitudinal analyses (N = 4,134), participants in the cluster with persistently high and rising TyG-AIP values exhibited the highest risks of CVDs (adjusted HR 1.25, 95% CI: 1.04-1.51), stroke (HR 1.43, 95% CI: 1.05-1.95), and heart disease (HR 1.25, 95% CI: 1.01-1.54).

Conclusion: Both baseline and longitudinal changes of TyG-AIP were independently associated with the risk of developing CVDs, especially stroke, in middle-aged and older Chinese adults. Repeated assessment of TyG-AIP captured cardiometabolic deterioration over time and improved identification of individuals at elevated cardiovascular risk. Incorporating long-term monitoring of TyG-AIP into routine health evaluations may enhance population-level CVDs risk prediction and support more effective prevention strategies.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, evidence on proteomic mechanisms linking MASLD to ASCVD is limited. This study aims to identify proteomic signatures of MASLD and ASCVD subtypes (ischemic heart disease [IHD], peripheral artery disease [PAD], and stroke), evaluate mediating effects of proteins, and develop a proteomic-based ASCVD risk prediction model in MASLD patients. Among 40,913 UK Biobank participants (median follow-up 13.42 years [interquartile range, 12.52-14.22]), 14,425 (35.26%) had MASLD at baseline, and 6,014 (14.70%) developed ASCVD during follow-up (4,420 IHD, 866 PAD, and 1,767 stroke events; subtypes not mutually exclusive). We constructed a binary variable representing proteomics-inferred MASLD (cProMASLD) from MASLD-associated proteins. Two-step Mendelian randomization was applied to assess the mediating effects of proteins associated with MASLD and ASCVD subtypes. Furthermore, we integrated the all shared proteins associated with both MASLD and ASCVD subtypes into the conventional SCORE2 model to develop a prediction model specifically for ASCVD subtypes in the MASLD population, named Pro-SCORE2. Both MASLD and cProMASLD were significantly associated with an increased risk of ASCVD subtypes, with stronger associations observed for cProMASLD (IHD: HR 1.50 [95% CI 1.41-1.60] vs. 1.58 [1.48-1.68]; PAD: 1.25 [1.09-1.44] vs. 1.43 [1.24-1.64]; stroke: 1.19 [1.08-1.31] vs. 1.21[1.10-1.34]). After adjusting for MASLD, cProMASLD remained positively associated with ASCVD risk. This suggests that cProMASLD may capture MASLD-related physiological heterogeneity beyond clinical MASLD classification. We found 15, 3, and 3 proteins mediating the associations of MASLD with IHD, PAD, and stroke, respectively, including FABP4 (MASLD-IHD, mediation proportion: 15.12%), IL7R (MASLD-PAD, 7.45%), and EDA2R (MASLD-stroke, 9.24%). The Pro-SCORE2 significantly improved ASCVD risk prediction in the MASLD population, with a c-index increase of 7.5-9.6% and a 10-year AUC increase of 5.8-9.2% compared to SCORE2. These findings may offer new insights for risk stratification and potential therapeutic targets for ASCVD in MASLD patients.

Background: Insulin resistance and muscle loss are interrelated processes linked to cardiovascular disease (CVD), but they are rarely assessed together. We investigated the association between a novel integrated biomarker-triglyceride-glucose muscle-loss index (TyG-MLI)-and incident CVD in a large prospective cohort.

Methods: A total of 277,418 UK Biobank participants free of CVD at baseline were included. TyG-MLI was calculated as ln[(triglycerides × fasting glucose)/2] × (cystatin C/creatinine). Incident CVD was identified through hospital admissions and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Over a median follow-up of 15.1 years, 40,398 participants developed CVD. Crude CVD incidence increased steadily across TyG-MLI quartiles, and the cumulative incidence curves demonstrated clear separation on Kaplan-Meier analysis (log-rank p < 0.001). Higher TyG-MLI was independently associated with greater CVD risk when modeled either continuously (per 1-SD: HR 1.17; 95% CI 1.16-1.18) or categorically (Q4 vs. Q1: HR 1.48; 95% CI 1.44-1.53). Restricted cubic spline analyses demonstrated a non-linear association across the TyG-MLI distribution. Sensitivity analyses yielded consistent results. In body mass index-stratified analyses, TyG-MLI showed stronger associations with CVD than TyG index, particularly among normal-weight and underweight individuals.

Conclusions: TyG-MLI, a composite marker reflecting insulin resistance and muscle loss, was independently associated with incident CVD in this large population-based cohort. These findings suggest that TyG-MLI captures cardiometabolic risk beyond traditional measures and may be particularly informative in individuals without obesity.

Intracellular calcium (Ca²⁺) homeostasis is a central determinant of cardiometabolic physiology, integrating excitation-contraction coupling, metabolic signaling, and stress adaptation across multiple organs. The sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), regulated by the micropeptides phospholamban (PLN) and dwarf open reading frame (DWORF), governs ER/SR Ca²⁺ reuptake and thereby shapes Ca²⁺-dependent signaling dynamics. Dysregulation of the SERCA-PLN-DWORF axis is increasingly recognized as a shared pathogenic mechanism in type 2 diabetes-related complications, including diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF), where reduced SERCA2a activity prolongs diastolic Ca²⁺ clearance and promotes calcineurin-NFAT activation and mitochondrial Ca²⁺ overload. In the liver, loss of SERCA2b activity promotes chronic ER stress, Ca²⁺-phosphoinositide complex formation, insulin resistance, and fibrotic activation, thereby linking Ca²⁺ dysregulation to progressive metabolic liver injury in metabolic dysfunction-associated fatty liver disease (MAFLD) and steatohepatitis (MASH). These observations position Ca²⁺ dysregulation as a unifying mechanism across the cardiometabolic disease continuum, spanning myocardial dysfunction, systemic insulin resistance, and progressive fatty liver disease. Therapeutic strategies targeting the SERCA-PLN-DWORF axis, including SERCA activators, PLN-directed antisense oligonucleotides, DWORF gene therapy, and CRISPR-based modulation, have demonstrated efficacy in preclinical models by improving Ca²⁺ handling and alleviating metabolic or contractile stress. Further studies are required to determine the translational feasibility, long-term safety, and optimal patient subsets for SERCA-targeted interventions in cardiometabolic disease.

Objective: The triglyceride-glucose (TyG) index, a measure of insulin resistance, has been confirmed to be associated with adverse clinical outcomes. A new composite indicator, the TyG-A body type index (TyG-ABSI), was developed by integrating the TyG index and the A body type index. This study aimed to thoroughly investigate the association between the TyG-ABSI and the risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with normoglycemia, dysglycemia, and diabetes.

Methods: Participants from the UK Biobank were included and categorized into 3 groups: normoglycemia, dysglycemia (prediabetes), and diabetes. The primary study outcome was the incidence of all-cause ASCVD. Cox regression and restricted cubic spline (RCS) analyses were performed to evaluate the linear and nonlinear associations between the TyG-ABSI and ASCVD. Furthermore, time-dependent receiver operating characteristic (ROC) curves were constructed to evaluate the discriminative performance of the TyG-ABSI and other indices. Additional analyses, including Kaplan-Meier survival curves, subgroup analyses, and sensitivity analyses, were conducted to assess robustness. A mediation analysis was performed to identify potential biomarkers.

Results: During an average follow-up of 14.8 years, a total of 29,680 ASCVD events were documented. The results indicated that elevated TyG-ABSI values were positively associated with the risk of ASCVD in the population with normoglycemia (nonlinear, P for nonlinear < 0.001) and diabetes (linear, P for nonlinear = 0.96) (HR = 1.07, 95% CI: 1.05-1.09; HR = 1.10, 95% CI: 1.06-1.14, respectively). No significant associations were detected in the dysglycemia group. Compared with the TyG index and other TyG-derived metrics, the TyG-ABSI demonstrated superior predictive performance (e.g., 10-year AUC = 0.634 in the normoglycemia group). Subgroup analyses and sensitivity analyses confirmed the robustness of our findings. Moreover, the results of the mediation analysis demonstrated that white blood cell (WBC) count (mediation proportions: 3.74-9.73%) and C-reactive protein (CRP) level (mediation proportions: 9.96-26.89%) significantly mediated the association between the TyG-ABSI and ASCVD.

Conclusions: In the normoglycemia subgroup, the association between the TyG-ABSI and ASCVD was nonlinear. Moreover, the TyG-ABSI was linearly associated with an increased risk of ASCVD in the diabetes subgroup but not in the dysglycemia subgroup. The predictive value of the TyG-ABSI across different glycemic statuses provides new evidence for medical practice. Furthermore, the TyG-ABSI may serve as a useful tool for identifying high-risk individuals within the seemingly low-risk normoglycemic population and for further risk identification among diabetic patients.