Cardiovascular Diabetology最新文献

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2-4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions. However, their role in ischemic heart disease in DM remains poorly understood. We provide new insights into the lncRNA expression profile after ischemic heart disease in DM mice. We performed unbiased RNA sequencing of well-characterized type 2 DM model db/db mice or its control db/+ subjected to sham or MI surgery. Computational analysis of the RNA sequencing of these LV tissues identified several differentially expressed lncRNAs between (db/db sham vs. db/db MI) including Gm19522 and Gm8075. lncRNA Gm-19522 may regulate DNA replication via DNA protein kinases, while lncRNA Gm-8075 is associated with cancer gene dysregulation and PI3K/Akt pathways. Thus, the downregulation of lncRNAs Gm19522 and Gm8075 post-MI may serve as potential biomarkers or novel therapeutic targets to improve cardiac repair/recovery in diabetic ischemic heart disease.

Background: Cardiovascular disease (CVD), particularly ischemic heart disease, remains the leading cause of death and morbidity in patients with type 1 diabetes. Detecting subclinical atherosclerosis could enhance cardiovascular risk stratification and enable individualised therapies. The aim of this study is to investigate the prevalence and predictors of subclinical atherosclerosis in patients with type 1 diabetes without overt cardiovascular disease (CVD) and to assess its impact on patient survival over a follow-up period of at least 5 years.

Methods: This observational study included 507 patients treated at the Diabetes Unit of the Hospital of Girona Doctor Josep Trueta between 2015 and 2023. The inclusion criteria for patients were as follows: those aged 18 and older with diabetes for a minimum of 10 years or those aged 40 and older with a diabetes for at least 5 years. Subclinical atherosclerosis was identified via ultrasound imaging of the carotid and femoral arteries. Clinical and biochemical evaluations were also conducted. Major cardiovascular events (MACE) and deaths from other causes were monitored, and survival analysis was performed using Kaplan‒Meier methods.

Results: Subclinical atherosclerosis was detected in 218 patients (43%). Multivariate analysis revealed that the male sex, diabetic nephropathy, tobacco exposure, higher HbA1c levels, older age, and longer diabetes duration were significant predictors. During a mean follow-up of 70.64 ± 27.08 months, 19 patients experienced MACE, and 13 died from any cause. The probability of MACE or death was greater in patients with subclinical atherosclerosis, with a hazard ratio (HR) of 25.1 (95% CI 5.81-108, p < 0.001) for MACE and an odds ratio (OR) of 7.57 (95% CI 1.97-53.9, p = 0.004) for death.

Conclusion: Subclinical atherosclerosis is independently associated with increased overall mortality and MACE in patients with type 1 diabetes. Identifying clinical predictors can improve risk stratification and personalised therapeutic strategies to prevent MACEs in this high-risk population.

Background: The association between changes in insulin resistance, reflected by the triglyceride-glucose (TyG) index, and mortality remains unclear. This study investigated whether longitudinal trajectories of TyG index changes are associated with all-cause and cardiovascular disease (CVD) mortality.

Methods: This retrospective cohort study analyzed data from 233,546 adults aged ≥ 19 years from the Korea National Health Insurance Service-National Sample Cohort. Participants were categorized as having increasing, stable, or decreasing TyG index changes during a 4-year exposure period (2009-2014). Mortality outcomes were assessed during an 8.13-year follow-up period (2015-2021). Cox proportional hazards regression and competing risk analysis were used to evaluate all-cause and CVD mortality.

Results: A total of 7918 mortality events, including 651 CVD deaths, were recorded. Compared with the stable group, adjusted hazard ratios for all-cause mortality were 1.09 (95% CI 1.03-1.15) in the increasing group and 1.23 (95% CI 1.01-1.50) for CVD mortality. An increased TyG index was significantly associated with all-cause mortality in individuals aged < 50 years; men; and individuals with obesity, hypertension, diabetes, and/or dyslipidemia. For CVD mortality, significant associations were found in individuals aged 50-69 years, with obesity, with diabetes, or without dyslipidemia.

Conclusion: An increasing TyG index from baseline during follow-up was independently associated with higher risks of all-cause and CVD mortality. Serial monitoring of TyG index changes could enhance risk stratification and inform targeted interventions to reduce insulin resistance, and ultimately lower mortality risk.

Background: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.

Background: 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.

Method: 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.

Result: 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.

Conclusion: 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.

Background: 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.

Objective: 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).

Methods: 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.

Results: 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.

Conclusion: 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.