Objectives: This study aimed to investigate the impact of hepatic steatosis on cardiometabolic outcomes in young adults with prediabetes.
Methods: A nationwide cohort study was conducted with 896,585 young adults under 40 years old without diabetes or previous history of cardiovascular disease. Hepatic steatosis was identified using a fatty liver index of ≥ 60. The outcomes of this study were incident diabetes (DM) and composite major adverse cardiovascular events (MACE), including myocardial infarction, stroke, or cardiovascular death.
Results: During a median follow-up of 11.8 years, 27,437 (3.1%) incident DM cases and 6,584 (0.7%) MACE cases were recorded. Young adults with prediabetes had a significantly higher risk of incident DM (hazard ratio [HR]: 2.81; 95% confidence interval [CI]: 2.74-2.88; P-value: <0.001) and composite MACE risk (HR: 1.10; 95% CI: 1.03-1.17; P-value: 0.003) compared to individuals with normoglycemia, after adjusting for relevant covariates. Stratification based on hepatic steatosis showed that the combination of prediabetes and hepatic steatosis posed the highest risk for these outcomes, after adjusting for relevant covariates. For incident DM, the HRs (95% CI; P-value) were: 3.15 (3.05-3.26; <0.001) for prediabetes without hepatic steatosis, 2.89 (2.78-3.01; <0.001) for normoglycemia with hepatic steatosis, and 6.60 (6.33-6.87; <0.001) for prediabetes with hepatic steatosis. For composite MACE, the HRs (95% CI; P-value) were 1.05 (0.97-1.13; 0.235) for prediabetes without hepatic steatosis, 1.39 (1.27-1.51; <0.001) for normoglycemia with hepatic steatosis, and 1.60 (1.44-1.78; <0.001) for prediabetes with hepatic steatosis.
Conclusions: Prediabetes and hepatic steatosis additively increased the risk of cardiometabolic outcomes in young adults. These findings hold significance for physicians as they provide insights into assessing high-risk individuals among young adults with prediabetes.
Background: A substantial number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) experience adverse events after TAVI, with health care expenditure. We aimed to investigate cardiac remodeling and long-term outcomes in diabetic patients with severe AS, left ventricular ejection fraction (LVEF) < 50%, and extra-valvular cardiac damage (EVCD) undergoing TAVI treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus other glucose-lowering strategies (no-SGLT2i users).
Methods: Multicenter international registry of consecutive diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI. Based on glucose-lowering therapy at hospital discharge, patients were stratified in SGLT2i versus no-SGLT2i users. The primary endpoint was a composite of all-cause death and heart failure (HF)-hospitalization (major adverse cardiovascular events, MACE) at 2-year follow-up. Secondary outcomes included all-cause death, cardiovascular death, and HF hospitalization.
Results: The study population included 311 patients, among which 24% were SGLT2i users. Within 1-year after TAVI, SGLT2i users experienced a higher rate of LV recovery (p = 0.032), especially those with baseline LVEF ≤ 30% (p = 0.026), despite the lower baseline LVEF. Patients not treated with SGLT2i were more likely to progress to a worse EVCD stage over time (p = 0.018). At 2-year follow-up, SGLT2i use was associated with a lower rate of MACE, all-cause death, and HF hospitalization (p < 0.01 for all). After adjusting for confounding factors, the use of SGLT2i emerged as an independent predictor of reduced MACE (HR = 0.45; 95% CI 0.17-0.75; p = 0.007), all-cause death (HR = 0.51; 95% CI 0.25-0.98; p = 0.042) and HF-hospitalization (HR = 0.40; 95% CI 0.27-0.62; p = 0.004).
Conclusions: In diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI, the use of SGLT2i was associated with a more favorable cardiac remodeling and a reduced risk of MACE at 2-year follow-up.
Background: Insulin resistance coexist with many metabolic disorders, whether these disorders were promotors or pathway-factors for the association of insulin resistance and cardiovascular disease (CVD) remained unclear. We aimed to investigate the pathways related to elevated the triglyceride-glucose (TyG) index and pathways through elevated TyG index to the occurrence of CVD in Chinese adults.
Methods: A total of 96,506 participants were enrolled from the Kailuan study. Bayesian network model with the max-min hill climbing algorithm and maximum likelihood estimation was applied to identify factors and pathways related to the TyG index, and quantitatively infer the impact of associated factors on elevated TyG index and the occurrence of CVD by computing conditional probabilities.
Results: A final Bayesian network was constructed with 14 nodes and 25 arcs, creating 28 pathways related to elevated TyG index and 8 pathways from elevated TyG index to CVD. Elevated TyG index was causally associated with CVD, the condition probability was 11.9%. Pathways to elevated TyG index were mainly through unhealthy lifestyles and the subsequent increase in lipid profiles, especially smoking and low-density lipoprotein cholesterol. The most important pathway from elevated TyG index to CVD was through overweight/obesity, hypertension, and chronic kidney disease, with a condition probability of 18.5%. The maximum relative change rate related to elevated TyG index was observed for overweight/obesity (64.3%).
Conclusions: Elevated TyG index was causally associated with the risk of CVD, a combined control of lifestyles and metabolic factors may contribute to the reduction of TyG index and the prevention of CVD.
Background: Diabetic heart disease may eventually lead to heart failure, a leading cause of mortality in diabetic individuals. The lack of effective treatments for diabetes-induced heart failure may result from a failure to address the underlying pathological processes, including chronic, low-grade inflammation. Previous studies have reported that lipoxin A4 (LXA4), known to promote resolution of inflammation, attenuates diabetes-induced atherosclerosis, but its impact on diabetic hearts has not been sought. Thus, we aimed to determine whether LXA4 therapeutic treatment attenuates diabetes-induced cardiac pathology.
Methods: Six-week-old male apolipoprotein E-deficient (ApoE-/-) mice were followed for 16 weeks after injection of streptozotocin (STZ, 55 mg/kg/day, i.p. for 5 days) to induce type-1 diabetes (T1DM). Treatment with LXA4 (5 μg/kg, i.p.) or vehicle (0.02% ethanol, i.p.) was administered twice weekly for the final 6 weeks. One week before endpoint, echocardiography was performed within a subset of mice from each group. At the end of the study, mice were euthanized with sodium pentobarbital (100 mg/kg i.p.) and hearts were collected for ex vivo analysis, including histological assessment, gene expression profiling by real-time PCR and protein level measurement by western blot.
Results: As expected diabetic mice showed a significant elevation in plasma glycated hemoglobin (HbA1c) and glucose levels, along with reduced body weight. Vehicle-treated diabetic mice exhibited increased cardiac inflammation, macrophage content, and an elevated ratio of M1-like to M2-like macrophage markers. In addition, myocardial fibrosis, cardiomyocytes apoptosis and hypertrophy (at the genetic level) were evident, with echocardiography revealing early signs of left ventricular (LV) diastolic dysfunction. Treatment with LXA4 ameliorated diabetes-induced cardiac inflammation, pro-inflammatory macrophage polarization and cardiac remodeling (especially myocardial fibrosis and cardiomyocytes apoptosis), with ultimate improvement in cardiac function. Of note, this improvement was independent of glucose control.
Conclusions: These findings demonstrated that LXA4 treatment attenuated the extent of cardiac inflammation in diabetic hearts, resulting in limited cardiac remodeling and improved LV diastolic function. This supports further exploration of LXA4-based therapy for the management of diabetic heart disease. The recent development of stable LXA4 mimetics holds potential as a novel strategy to treat cardiac dysfunction in diabetes, paving the way for innovative and more effective therapeutic strategies.
Background: Both insulin resistance and hyperglycemia are important risk factors for atherosclerosis. While the characteristics of atherosclerosis are obviously different according to established diabetes, little has been known regarding the risk of coronary artery calcification (CAC) progression related to the biomarkers of atherogenic index of plasma (AIP), triglyceride glucose (TyG) index, and hemoglobin A1C (HbA1C) in conditions with and without diabetes.
Methods: We analyzed 12,326 asymptomatic Korean adults (mean age 51.7 ± 8.5 years; 84.2% males; 15.8% with diabetes) over a median follow-up period of 3.0 years. AIP was defined as the base-10 logarithm of the ratio of triglyceride concentration (mmol/L) to high-density lipoprotein cholesterol (mmol/L). The TyG index was calculated as ln (fasting triglycerides [mg/dL] × fasting glucose [mg/ dL]/2). CAC progression was defined using the SQRT method, as a difference of ≥ 2.5 between the square roots (√) of baseline and follow-up coronary artery calcium scores (CACS) (Δ√transformed CACS). Logistic regression models adjusted for interscan periods were used to estimate the odds ratio (OR).
Results: The levels of AIP, TyG index, and HbA1C were significantly higher in diabetics than in non-diabetics. CAC progression was more frequently observed in diabetics (46.9%) than in non-diabetics (28.0%). After adjusting for age, sex, hypertension, hyperlipidemia, obesity, current smoking status, serum creatinine levels, baseline CACS, and interscan period, AIP (per-0.1 unit increase) was associated with CAC progression in only non-diabetics (OR: 1.04, 95% confidence interval [CI]: 1.02 - 1.06; P < 0.001). In contrast, HbA1C level (per-1% increase) was significantly associated with CAC progression in only diabetics (OR: 1.19, 95% CI: 1.08 - 1.32; P = 0.001). The TyG index (per-1 unit increase) was associated with CAC progression in both non-diabetics (OR: 1.32, 95% CI: 1.19 - 1.46; P < 0.001) and diabetics (OR: 1.33, 95% CI: 1.10 - 1.60; P = 0.003).
Conclusions: The associations between AIP, TyG index, and HbA1C levels with CAC progression vary according to established diabetes. Of these biomarkers, TyG index is independently associated with CAC progression irrespective of established diabetes.
Background: Individuals with type 1 diabetes are at increased risk of accelerated atherosclerosis, causing coronary artery disease (CAD). The underlying mechanisms remain unclear, but new theories proposed are damage of gut mucosa causing leakage and translocation of gut microbiota products into the circulation, leading to inflammatory responses and atherosclerosis. We therefore aimed to study the associations between gut related inflammatory biomarkers and coronary atherosclerosis in individuals with long-term type 1 diabetes.
Methods: In this cross-sectional, controlled study of 102 participants with type 1 diabetes and 63 control subjects, we measured circulating levels of intestinal fatty acid binding protein (I-FABP), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP) and interleukin 18 (IL-18) by enzyme-linked immunosorbent assay (ELISA), and further gene expression of CD14 and toll-like receptor 4 (TLR4) by real time PCR in circulating leukocytes and peripheral blood mononuclear cells (PBMCs). The participants had either established coronary heart disease (CHD) or underwent computed tomography coronary angiography (CTCA) to assess for coronary atherosclerosis, including total, calcified and soft/mixed plaque volumes.
Results: In the diabetes group, the levels of I-FABP were significantly higher in participants with established CHD or significant stenosis on CTCA compared to the participants with normal arteries or non-significant stenosis, with median 1.67 ng/ml (interquartile range [IQR] 1.02-2.32) vs. median 1.09 ng/ml (IQR 0.82-1.58), p = 0.003. I-FABP was associated with significant coronary artery stenosis by CTCA (> 50%) or previously established CHD in the adjusted analysis (odds ratio [OR] = 2.32, 95% confidence interval [CI]: 1.09-4.95; p = 0.029). The levels of I-FABP correlated also to total coronary plaque volume (r = 0.22, p < 0.05). This association remained significant after adjusting for age, sex, persistent albuminuria, eGFR, statin treatment, diabetes duration and mean time-weighted variables; HbA1c, LDL-cholesterol and systolic blood pressure (OR = 1.97, 95% CI: 1.28-3.01; p = 0.002).
Conclusions: In this cohort of individuals with long-term type 1 diabetes I-FABP associated significantly with coronary artery stenosis, suggesting a potential role of gut mucosa damage in the process of atherosclerosis in type 1 diabetes.
The article by Wang et al. titled "Exploring the mortality and cardiovascular outcomes with SGLT-2 inhibitors in patients with T2DM at dialysis commencement: a health global federated network analysis" demonstrated that new SGLT-2i use in T2DM patients at the onset of dialysis was associated with a reduced long-term risk of all-cause mortality and MACE over a median follow-up duration of 2.0 years. However, the hemodialysis dose and frequency, which are significant confounding factors, were not included in the study's subgroup analysis. We raise concerns about this limitation, which may affect the study's findings.
Background: Metabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients.
Methods: One hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS-) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain.
Results: Compared to MetS(CAS-), MetS(NOCAS+) showed a significantly increased LV mass index (p < 0.05). Global longitudinal peak strain was decreased gradually from MetS(CAS-) through MetS(NOCAS+) to MetS(OCAS+) (- 13.02 ± 2.32% vs. - 10.34 ± 4.05% vs. - 7.55 ± 4.48%, p < 0.05). MetS(OCAS+) groups showed significantly decreased LV global peak strain (GPS), PSSR and PDSR in radial and circumferential directions compared with MetS(NOCAS+) (all p < 0.05). The degree of CAS was independently associated with impaired global radial peak strain (GRPS) (β = - 0.289, p < 0.001) and global longitudinal peak strain (GLPS) (β = 0.254, p = 0.004) in MetS patients. The ROC analysis showed that the degree of CAS can predict impaired GRPS (AUC = 0.730) and impaired GLPS (AUC = 0.685).
Conclusion: Besides traditional biochemical indicators, incorporating CAS assessment and CMR assessment of the LV into routine evaluations ensures a more holistic approach to managing MetS patients. Timely intervention of CAS is crucial for improving cardiovascular outcomes in this high-risk population.
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：