Cardiovascular Diabetology最新文献

Research has shown that diabetes mellitus is not just a disorder of blood sugar, but a complex metabolic imbalance that also profoundly involves lipid metabolism. Patients with diabetes often show alterations in their lipid profile, which contribute to the risk of cardiovascular complications. The EmDia clinical trial, a randomized, placebo-controlled study, has investigated the impact of empagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i), on the plasma lipidome in patients with type 2 diabetes (T2DM). The goal was to identify molecular alterations that could explain the drug's cardiovascular and renal benefits, which extend beyond simple glucose reduction. Using an untargeted lipidomics approach and advanced statistical techniques like sparse group LASSO regression, the study identified significant and reproducible alterations in specific lipid classes, most notably lysophosphatidylcholines (LPCs), after one and twelve weeks of treatment. These changes in the lipid profile correlated with clinical parameters such as estimated glomerular filtration rate (eGFR), uric acid, and blood pressure, suggesting that LPCs could serve as biomarkers of drug response. The discovery of LPCs as potential markers of empagliflozin's effect opens new avenues for developing pharmacodynamic biomarkers and understanding the metabolic mechanisms of action, including the relationship between lipid metabolism and kidney health.

Cardiovascular disease is a leading cause of morbidity and mortality in individuals with type 2 diabetes. This population faces an increased risk of coronary artery disease due to accelerated atherosclerosis, endothelial dysfunction and chronic inflammation. A substantial proportion of cases remain clinically silent, with coronary artery disease often undetected until the occurrence of acute events. This silent progression poses a significant challenge for timely diagnosis and prevention. This review explores the prevalence, mechanisms, and prognosis of asymptomatic coronary artery disease in type 2 diabetes, focusing on current strategies for cardiovascular risk assessment and screening. While traditional risk factors such as hypertension, dyslipidemia, and hyperglycemia remain central to clinical evaluation, they often fail to fully capture the residual cardiovascular risk in diabetic patients. Advances in imaging, particularly coronary calcium scoring and computed tomography angiography, allow for the direct visualization of total plaque burden, providing a more refined assessment of risk. Functional tests and novel biomarkers, including high-sensitivity C-reactive protein and lipoprotein(a), further enhance the precision of risk stratification. Despite these advances, the clinical value of routine screening in asymptomatic diabetic individuals remains controversial. Evidence suggests that a selective, risk-based approach to screening may be more effective than universal testing, identifying high-risk patients who could benefit from more intensive preventive therapies. Emerging technologies, such as artificial intelligence and machine learning, promise to improve risk prediction by integrating clinical, imaging, and biomarker data into personalized care pathways. The review emphasizes the need to move from a reactive approach, based on symptom-driven evaluation, to a proactive strategy aimed at early identification of subclinical disease. By combining advanced imaging techniques, biomarker profiling, and updated risk algorithms, clinicians can better tailor preventive interventions, reduce adverse cardiovascular outcomes, and optimize long-term care. Further prospective studies are required to define the most effective and cost-efficient screening protocols for asymptomatic coronary artery disease in individuals with diabetes.

Background: Heart failure (HF) is a major complication of type 2 diabetes (T2D), with HF with preserved ejection fraction (HFpEF) now representing the most frequent phenotype. However, its clinical profile, prognosis, and treatment patterns compared with HF with reduced ejection fraction (HFrEF) remain insufficiently characterized.

Objectives: To compare characteristics, outcomes, and longitudinal management of HFpEF versus HFrEF in T2D patients.

Methods: This prespecified subanalysis of the nationwide, prospective DIABET-IC cohort included 1517 patients with T2D recruited across 58 Spanish centers and followed for three years. HF phenotypes were defined according to the 2016 ESC guidelines criteria. Baseline characteristics, outcomes (mortality, hospitalizations, and progression), and therapeutic patterns were assessed.

Results: At baseline, 490 patients had HF (50.2% HFrEF, 30.6% HFpEF, 19.2% HFmrEF). HFpEF patients were older, more often female, and had higher prevalence of obesity, hypertension, and metabolic syndrome, whereas HFrEF was more strongly associated with ischemic heart disease, prior ST-elevation myocardial infarction (STEMI), and conduction disturbances. During follow-up, HFpEF was the predominant incident phenotype (46.6% of new cases), and 4.7% progressed to HFrEF. Mortality was similarly elevated in both phenotypes; HF hospitalizations tended to be higher in HFrEF, while acute coronary syndromes were more frequent in HFpEF. HFrEF patients more often received guideline-directed therapies, whereas the pre-guideline era for HFpEF, with greater uptake of SGLT2 inhibitors over time, limited used of GLP-1 receptor agonists. Notably, > 20% of HFpEF patients had natriuretic peptide levels below diagnostic thresholds, highlighting underdiagnosis.

Conclusions: HFpEF is the most frequent HF phenotype in the T2D population, with outcomes comparable to HFrEF yet frequently underdiagnosed and undertreated. Improved screening strategies and broader adoption of evidence-based therapies-particularly SGLT2 inhibitors-are urgently needed for this high-risk population.

Background: Both glucagon-like peptide 1 receptor agonist (GLP1RA) and pioglitazone are associated with cardiovascular and hepatic benefits in patients with type 2 diabetes (T2D). However, studies that directly compare their cardio-hepatic effects are lacking. We emulated a target trial to compare their effects on adverse liver and cardiovascular outcomes in T2D patients.

Methods: We adopted an "active comparator, new user" design involving T2D patients newly prescribed GLP1RA or pioglitazone between January 2008 and December 2022. The primary outcomes were major adverse liver outcomes (MALO) and cardiovascular events (MACE), with their individual outcomes and heart failure (HF) as secondary outcomes. Cox proportional hazards models were used to estimate hazard ratios (HRs) via intention-to-treat (ITT) and per-protocol (PP) analyses.

Results: A total of 8922 patients (N = 4461 each group) were included. Compared to pioglitazone users, GLP1RA users had comparable risks of incident MALO (ITT: HR 0.94, 95% CI 0.66-1.34; PP: HR 1.13, 95% CI 0.60-2.15) and MACE (ITT: HR 0.99, 95% CI 0.80-1.22; PP: HR 1.10, 95% CI 0.77-1.58). The risk of HF was significantly lower in GLP1RA users in ITT analysis (HR 0.65, 95% CI 0.51-0.83). The results were consistent across most subgroup and sensitivity analyses.

Conclusions: The effects on incident major adverse liver and cardiovascular outcomes were comparable between GLP1RA and pioglitazone, although the risk of incident HF was lower with GLP1RA. Treatment decisions for T2D patients at risk of adverse cardio-hepatic events should be individualized, considering HF risk and the need for weight loss, which if present, GLP1RA may be preferred.

Background: Diabetes mellitus is a civilisation disease that can cause damage to tissues and organs as well as affects the biological properties of cells isolated from these tissues. In recent years, there has been increasing interest in cell-based therapies, including the use of mesenchymal stem/stromal cells (MSCs). Therefore, the aim of the current study was to compare the biological potential of adipose tissue-derived MSCs (AT-MSCs) from healthy and diabetic donors under in vitro conditions and to clarify the implications for cell-based medicinal product development. Biological potential of both populations of AT-MSCs was also investigated in the relation to their major therapeutic mechanisms of action-we focused on the chondrogenic and osteogenic differentiation capacity of AT-MSCs and their pro-angiogenic potential.

Methods: Human AT-MSCs derived from healthy and type 2 diabetes (T2D) donors underwent biological characterization including assessment of: morphology, viability, antigenic profile, proliferation, presence of senescent cells and oxidative stress, pro-angiogenic properties of AT-MSC secretome as well as trilineage differentiation potential in vitro. AT-MSCs were cultured under the control and diabetes mimicking culture conditions.

Results: We observed no significant differences in morphology, viability, expression of MSC markers, proliferation rate, concentration of oxidative stress marker (8OHdG) and content of senescent cells between AT-MSCs from healthy and T2D donors under control culture conditions. The conditioned medium from a culture of diabetic AT-MSCs was found to improve the pro-angiogenic potential of human umbilical vein endothelial cells (HUVECs), compared with the medium from healthy AT-MSCs. HUVECs that were incubated in conditioned media collected from healthy AT-MSCs from diabetic culture conditions, exhibited greater potential to form capillary-like structures. Furthermore, diabetic culture conditions induced the oxidative stress in healthy AT-MSCs. Diabetic AT-MSCs exhibited greater chondrogenic differentiation capacity along with lower adipogenic differentiation potential and comparable osteogenic differentiation capacity when compared to healthy donor-derived AT-MSCs.

Conclusions: The present study provides evidence of the biological potential of AT-MSCs from diabetic donors, which can be used as an active substance in the development of cell-based autologous advanced therapy medicinal products (ATMPs) dedicated for the treatment of e.g. osteoarthritis or myocardial infarction. Diabetic AT-MSCs in the used culture conditions are functional cells with greater chondrogenic and pro-angiogenic potential when compared to AT-MSCs from healthy donors. This increases the possibility of treating diabetic patients using their own cells.

Background: The triglyceride-glucose (TyG) related indices are simple biomarkers of insulin resistance and are associated with metabolic syndrome (MetS) and atrial fibrillation (AF). However, whether TyG-related indices are linked to all-cause and cardiovascular mortality in individuals with coexisting AF and MetS remains unclear.

Methods: We included 2535 participants with both AF and MetS from the UK Biobank. TyG-related indices, including TyG, TyG combined with body mass index (TyG-BMI), TyG combined with waist circumference (TyG-WC), and TyG combined with the waist-to-height ratio (TyG-WHtR), were calculated. The study endpoints were all-cause and cardiovascular mortality. Participants were followed until death or December 31, 2023, whichever occurred first. Associations between TyG-related indices and mortality outcomes were assessed using Cox proportional hazards models and restricted cubic spline (RCS) analyses.

Results: Over a mean follow-up period of 12.7 years (IQR: 11.8‒15.2), 956 all-cause deaths and 385 cardiovascular deaths were documented. Kaplan‒Meier survival analyses revealed the highest incidence of all-cause mortality in the fourth quartile of TyG (log-rank P < 0.001). Compared with individuals in the second quartile, individuals in the highest quartile had a significantly increased risk of all-cause mortality (TyG: hazard ratio (HR) 1.36, 95% confidence interval (CI): (1.14‒1.64); TyG-BMI: 1.31, 1.10‒1.56; TyG-WC: 1.41, 1.18‒1.68; TyG-WHtR: 1.56, 1.3‒-1.86). Moreover, TyG, TyG-BMI, and TyG-WHtR were significantly associated with cardiovascular mortality (TyG: HR 1.47, 95% CI 1.10‒1.95; TyG-WC: 1.41, 1.03‒1.93; TyG‒WHtR: 1.35, 1.01‒1.80). RCS analyses revealed nonlinear association between TyG and mortality and between TyG-BMI and all-cause mortality (all P < 0.05). The results of the sensitivity and subgroup analyses were consistent with those of the primary analyses.

Conclusions: This study demonstrateed the prognostic value of TyG-related indices in individuals with AF and MetS. These indices may serve as practical surrogate markers for risk stratification and the prevention of adverse outcomes.

Aim: Sarcopenia is common in heart failure (HF) patients; however, there are no data regarding the possible long-term prognostic role of sarcopenia in younger adults with chronic HF without malnutrition. The aim of this study was to examine the long-term prognostic role of sarcopenia in predicting major adverse cardiac events (MACE) in outpatients with chronic HF.

Methods: In the present retrospective analysis, 670 subjects with HF were enrolled. MACE (non-fatal ischemic stroke, non-fatal myocardial infarction, cardiac revascularization or coronary bypass surgery, and cardiovascular death) and total mortality occurrence were evaluated during a mean follow-up of 4.7 years.

Results: In the entire population, 340 patients were sarcopenic and 330 were not sarcopenic. In patients without sarcopenia, the observed MACE were 2.1 events/100 patient-year; while in the sarcopenic group there were 13.3 events/100 patient-year (p < 0.001). The multivariate analysis model confirmed that sarcopenia increase the risk of MACE by a factor of 8.6. Patients with sarcopenia had also a higher incidence of total mortality (p < 0.001) than patients without sarcopenia.

Conclusions: Patients with chronic HF that suffered from sarcopenia show a higher risk of MACE and total mortality, independently by their chronological age.

Background: The stress hyperglycemia ratio (SHR) has been reported to be closely associated with various diseases and prognoses. However, the relationship between SHR and elevated blood pressure (EBP) in adolescents aged 12-17 remains unclear.

Methods: This cross-sectional study included U.S. adolescents from the 1999-2016 National Health and Nutrition Examination Survey (NHANES). The primary outcome was EBP. SHR was calculated by the formula [FPG (mmol/L)] / [1.59 × HbA1c (%) - 2.59]. Patients were divided into SHR quartiles. Weighted multivariable logistic regression models, subgroup analysis, restricted cubic spline (RCS) and receiver operating characteristic (ROC) curves, sensitivity analyses were used to evaluate the associations.

Results: A total of 3676 participants were included. Among them, 543 participants had EBP. In the fully adjusted model (Model 3), per SD increase in SHR was associated with a 17% higher odds of EBP (aOR 1.17, 95%CI 1.04-1.32, p = 0.009). Compared with the lowest quartile, participants in the highest quartile had a 95% higher odds of EBP (aOR 1.90, 95%CI 1.29-2.79, p for trend < 0.001). RCS analysis revealed a significant linear association between SHR and EBP (p for non-linearity > 0.05). ROC curves indicated that SHR had modest predictive performance for EBP in adolescents (AUC 0.723, 95%CI 0.699-0.747).

Conclusions: This study suggests that higher SHR levels are positively associated with the prevalence of EBP among U.S. adolescents aged 12-17.