European Journal of Clinical Investigation最新文献

Objective: Despite growing evidence, the mechanisms connecting adipose tissue (AT) function to type 2 diabetes (T2DM) remain incompletely understood. A detailed analysis of AT transcriptomes could offer valuable insights into this relationship. Here, we examined gene expression patterns in bulk subcutaneous AT, focusing on biological pathways and cellular composition associated with glycated haemoglobin (HbA1c) levels.

Methods: A transcriptomic dataset was obtained from subcutaneous AT samples of 901 adults collected during elective surgical procedures. We characterized cellular composition within subcutaneous AT in association with blood HbA1c levels by performing bulk adipose transcriptomes cell deconvolution analysis. We also conducted differential gene expression and overrepresentation analyses. We validated our cross-sectional study using two independent validation cohorts, performing further downstream analyses.

Results: Subcutaneous AT from subjects with increased HbA1c had lower adipocytes, smooth muscle, pericytes and other endothelial cell numbers. Pathways associated with HbA1c levels included cellular senescence and telomere-related pathways and extracellular matrix organisation. We identified the expression of RHO GTPases associated with HbA1c not previously linked to glucose homeostasis, with a possible sexual dimorphism shaped by the obesity state. The findings were confirmed in both longitudinal cohorts. At the gene level, HLA-DR, CCL13, and S100A4 mRNA levels were strongly correlated with HbA1c levels.

Conclusions: This study underscores the utility of AT transcriptome analysis in unravelling T2DM complexities. Our findings enhance knowledge of glucose homeostasis' molecular and cellular underpinnings, paving the way for potential therapeutic targets to mitigate the impact of AT dysfunction in metabolic diseases.

Background: The prevalence of metabolic syndrome (MetS) is increasing worldwide. The change in nutrition and eating patterns contributes partly to this rise. On the other hand, increased sodium intake is common in most of the world. There are some studies showing that increased sodium intake may be associated with MetS.

Methods: To provide an overview of the current evidence regarding the relationship between excess sodium/salt intake and MetS, we performed a literature search of PubMed/Medline, Web of Science and Google Scholar until October 2024 to recruit studies examining the relationship between sodium/salt intake and MetS.

Results: Our review showed that most but not all cross-sectional studies have shown that excess sodium/salt intake is associated with the presence of MetS. Additionally, few longitudinal studies also demonstrated that excess sodium intake is related with the development of new MetS. These studies are mostly observational, and mechanistic studies explaining underlying mechanisms are lacking. The most correlated components of MetS associated with high salt intake were blood pressure and waist circumference, while the correlations between HDL-C, TG and FG were variable.

Conclusions: These findings suggest that excess sodium/salt intake may be a risk factor for the development of MetS.

Background: The validation of a combination of plasma biomarkers and demographic variables is required to establish reliable cut-offs for Alzheimer's disease diagnosis (AD).

Methods: Plasma biomarkers (Aβ42/Aβ40, p-Tau181, t-Tau, NfL, GFAP), ApoE genotype, and demographic variables were obtained from a retrospective clinical cohort of cognitive disorders (n = 478). These patients were diagnosed as AD (n = 254) or non-AD (n = 224) according to cerebrospinal fluid (CSF) Aβ42/Aβ40 levels. An analysis using a Ridge logistic regression model was performed to predict the occurrence of AD. The predictive performance of the model was assessed using the observations from a training set (70% of the sample) and validated using a test set (30% of the sample) in each group. Optimum cutoffs for the model were evaluated.

Results: The model including plasma Aβ42/Aβ40, p-Tau181, GFAP, ApoE genotype and age was optimal for predicting CSF Aβ42/Aβ40 positivity (AUC .91, sensitivity .86, specificity .82). The model including only plasma biomarkers (Aβ42/Aβ40, p-Tau181, GFAP) provided reliable results (AUC .88, sensitivity .83, specificity .78). Also, GFAP, individually, showed the best performance in discriminating between AD and non-AD groups (AUC .859). The established cut-offs in a three-range strategy performed satisfactorily for the validated predictive model (probability) and individual plasma GFAP (concentration).

Conclusions: The plasma GFAP levels and the validated predictive model based on plasma biomarkers represent a relevant step toward the development of a potential clinical approach for AD diagnosis, which should be assessed in further research.

Background & aims: Sleeve gastrectomy (SG) and gastric plication (GP) are two widely performed bariatric techniques reducing the size of the stomach. The improvements observed following these procedures are not fully explained only by caloric restriction. Thus, we aimed at the analysis of adiposity and metabolism modifications in diet-induced obesity (DIO) rats submitted to SG or GP and correlate the changes with total ghrelin concentrations and its two different ghrelin isoforms.

Materials and methods: Adiposity, lipolysis and circulating ghrelin isoforms were determined in 191 male Wistar rats submitted to surgery: sham (SO), SG, or GP. Results were compared with pair-fed (PF) controls fed either a normal diet (ND) or a high-fat diet (HFD).

Results: DIO rats submitted to SG had significantly lower (p < .05) levels of desacyl ghrelin (DAG) and total ghrelin compared with SO and PF ones. Furthermore, they achieved a greater weight loss, adiposity and improvement in glucose and lipid metabolism, as well as brown adipose tissue mitochondrial morphology. No decrease in ghrelin concentrations was observed in GP.

Conclusions: The differential effect on circulating ghrelin concentrations of SG and GP, despite both procedures reducing actual stomach size, probably underlies the better outcomes on weight control and lipolysis of the SG due to the fundus removal, the main site of ghrelin-producing cells.

Background: Anti-neutrophil cytoplasmic antibodies (ANCA), a hallmark of systemic vasculitis (SV), have been reported in patients with idiopathic interstitial pneumonia (IIP). However, the clinical significance of ANCA in IIP remains unclear.

Methods: We retrospectively studied 101 IP patients diagnosed by pneumologists as idiopathic interstitial pneumonia (IIP,64) and IP with autoimmune features (IPAF,37). ANCA, anti-myeloperoxidase and anti-proteinase-3 were tested by immunofluorescence and ELISA. Chest HRCT patterns, pulmonary function tests (PFTs) and the evolution to SV during a 12-month follow-up were assessed. Multivariable regression analysis was performed to assess the association of baseline covariates with SV. The proximity of patients with close characteristics was investigated by cluster analysis.

Results: Twenty-one patients (20.8%) were ANCA+, similarly distributed between IPAF and IIP. ANCA+ patients were more likely to have NSIP (p = .02) and bronchiectasis (p = .02) on HRCT, less impaired 6MWD (p = .02), higher CRP (p = .02) and more arthralgias (p < .001) than ANCA- patients. During follow-up, 9 (43%) p-ANCA+ patients, but no ANCA- patients, developed SV (p = .001). p-ANCA+ IP had 26.3 OR (95% CI 3.20-36.8) to evolve to SV within 12 months (p < .0001). Cluster analysis identified one group of 25 patients with significantly higher baseline NSIP (88%), p-ANCA+ (48%), arthralgias (32%), and SV (24%) at 12 months. Nevertheless, 12 p-ANCA+ IP patients never developed SV.

Conclusions: ANCA+ IP patients had a high risk of developing SV and need close monitoring and prompt immunotherapy. ANCA+ IP patients not evolving to SV had a diagnosis of IIP or IPAF. These patients need longer observational studies to investigate if they represent a distinct ILD entity.

Background: Kidney transplant recipients (KTRs) are at high risk for cardiovascular disease due to the long-term use of immunosuppressive therapy. This study aims to evaluate the long-term impact of sirolimus on cardiovascular outcomes in Korean KTRs.

Methods: From a cohort of 7180 eligible KTRs identified from 2010 to 2021, 387 KTRs who received sirolimus were included. To control for confounding variables, propensity score matching was applied, and the landmark method was used to address immortal time bias. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, coronary revascularization, ischaemic stroke and all-cause mortality.

Results: The analysis showed no significant difference in MACE between the sirolimus-treated and untreated groups (hazard ratio, 1.40; 95% confidence interval, .77-2.55), despite a higher incidence of dyslipidaemia in the sirolimus-treated group. However, subgroup analysis revealed an increased MACE risk in KTRs with pre-transplant congestive heart failure (CHF) who were treated with sirolimus (hazard ratio, 6.22; 95% confidence interval, 1.78-21.74), while no significant differences were found in other subgroups.

Conclusions: These findings suggest that while sirolimus can be a viable option for immunosuppression, it should be used cautiously in those with pre-existing CHF.

Myocardial perfusion imaging (MPI) is widely adapted as a noninvasive technique to assess the presence and extent of ischemia in patients with symptoms suggestive of obstructive coronary artery disease (CAD). However, as CAD advances, several factors can complicate the interpretation of MPI, subsequently impacting clinical decision-making. This review focuses on the utility of MPI by means of cardiac magnetic resonance (CMR) imaging, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in patients with advanced CAD-the latter characterized by documented CAD (i.e. prior myocardial infarction [MI] and/or percutaneous coronary intervention [PCI]), prior coronary artery bypass grafting (CABG) or the presence of a chronic total occlusion (CTO). It will discuss factors impacting the interpretation of MPI, the diagnostic performance for detecting obstructive CAD and coronary microvascular dysfunction (CMD), as well as the role of MPI in guiding revascularization.

Background: Exercise is a well-known strategy for the prevention and treatment of cardiovascular diseases; however, the potential additional benefits of hypoxic exercise on cardiovascular function in comparison to normoxic exercise are still unknown. This study aimed to synthesize the hypoxic exercise protocols of application and to comparatively determine the effects of hypoxic versus normoxic exercise on cardiovascular function (i.e. haemoglobin concentrations, arterial oxygen saturation %, maximal heart rate, blood pressure at rest and blood lactate levels) in people without cardiovascular diseases.

Methods: We systematically searched five databases, from inception to September 2023, and selected randomized controlled trials (RCTs) comparing the effects of chronic hypoxic exercise versus normoxic exercise on cardiovascular function in people without cardiovascular diseases. A random effects meta-analysis with both the Dersimonian-Laird and the Hartung-Knapp-Sidik-Jonkman methods was conducted to estimate the pooled standardized mean differences (SMDs) and their 95% confidence intervals (95% CIs) of the hypoxic exercise effectiveness on each of the included outcomes related to cardiovascular function. We performed meta-regression models-considering total sample size, age, BMI, length of intervention and FiO₂ percentages-to determine their influence on the estimated effect. Subgroup analyses based on age, gender, type of exercise and health status of participants were conducted.

Results: A total of 31 RCTs involving 910 individuals were included. None of the pooled SMDs comparing hypoxic versus normoxic exercise were statistically significant. Subgroup analyses were only significant for lactate in people under 30 years of age and healthy and/or athletic individuals (.59; 95% CI .11, 1.06).

Conclusions: Our data suggest that there were no additive benefits of performing hypoxic exercise on the cardiovascular function parameters explored for up to 7 weeks when compared to normoxic exercise in people without cardiovascular disease, except for a moderate increase in blood lactate levels in young healthy and/or athletic individuals.