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Background. Adipose tissue is a key factor during metabolic dysregulation, whereas adipose tissue dysfunction is promoted if enlarged adipocytes, impaired adipocyte differentiation, inflammation, remodeling and/or fibrosis. As evidenced by in vitro studies and animal models, adipocyte hypertrophy alone is sufficient to impair glucose uptake, probably explained by changes of cell distribution of Glucose Transporter 4 (GLUT4) and trafficking, reflecting a new potential regulatory pathway. Patients with obesity can be subclassified into cardiometabolic risk phenotypes, with significant difference in adipose tissue characteristics and glucose uptake. Therefore, GLUT4 distribution in adipocytes from the so known: 1) metabolic healthy obese (MHO) and 2) metabolic unhealthy obese (MUO), may help to understand cardiometabolic risk differences between them. Objectives. To analyze GLUT4 distribution in adipocytes from MHO vs MUO phenotypes. Subjects and Methods. Cross-sectional observational study. Patients programmed for bariatric surgery were included. Patients were classified as MHO or MUO according to NCEP-ATPIII criteria. Samples from subcutaneous (SAT) and visceral adipose tissue (VAT) were obtained during bariatric surgery. GLUT4 expression and distribution in adipocytes were evaluated by immunofluorescence and image analysis. Results. GLUT4 molecules showed a lower number and more spared distribution in adipocytes from MUO phenotype. Likewise, GLUT4 distribution was related to insulin resistance in both metabolic phenotypes, with differences between VAT and SAT. Conclusion. GLUT4 expression pattern in adipocytes was related with the type of adipose tissue, the cardiometabolic risk and insulin resistance, suggesting potential and specific regulatory role.

Introduction. The metabolic syndrome (MS) has been related to the unbalance between pro- and anti-inflammatory cytokines; where adiponectin, an anti-inflammatory adipokine, is considered to play a key metabolic role. The consumption of certain micronutrients has been claimed to modify pro- and anti-inflammatory cytokines. Aim. To explore whether dietary micronutrients are related with plasma adiponectin in patients with MS. Methods. Cross-sectional analysis. Quartiles of dietary bioactive compounds were compared according to values of plasma adiponectin. Interquartile variation (IQV) and correlation analyses were performed. Results. There was a significant IQV of dietary unsaturated fatty acids (between -50% to -66% of change, p25 vs p75, pConclusion. Dietary amounts of unsaturated fatty acids inversely related to plasma adiponectin in patients with MS.

Alcohol withdrawal syndrome (AWS) represents an adverse consequence of chronic alcohol use that may lead to serious complications. Therefore, AWS requires timely attention based on its early recognition, where easy-to-apply diagnostic tools are desirable. Our aim was to characterize the performance of a short-scale AST (Anxiety, Sweats, Tremors) in patients from public general hospitals. We conducted a cross-sectional study of patients attended at the Emergency Department diagnosed with AWS. Three scales were applied: CIWA-Ar (Clinical Institute Retirement Assessment Scale-Revised), GMAWS (Glasgow Modified Alcohol Withdrawal Syndrome) and AST. Cronbach’s alpha and Cohen’s kappa tests were used for reliability and concordance. Factorial analysis and diagnostic performance including ROC curve were carried out. Sixty-eight males with a mean age of 41.2 years old, with high school education and robust alcohol consumption, were included. Mean scores for CIWA-Ar, GMWAS and AST were 17.4 ± 11.2, 3.9 ± 2.3 and 3.8 ± 2.6, respectively, without significant differences. The AST scale showed an acceptable reliability and concordance (0.852 and 0.439; p < 0.0001) compared with CIWA-Ar and GMAWS. AST component analysis evidenced tremor (77.5% variance), sweat (12.1% variance) and anxiety (10.4% variance). Diagnostic performance of the AST scale was similar to the GMAWS scale, evidencing a sensitivity of 84%, specificity of 83.3% and Area Under the Curve (AUC) of 0.837 to discriminate severe AWS, according to CIWA-Ar. The performance of the AST scale to evaluate AWS is comparable with the commonly used CIWA-Ar and GMAWS scales. AST further represents an easy-to-apply instrument.

Morphological characteristics and source of adipose tissue as well as adipokines may increase cardiometabolic risk. This study aimed to explore whether adipose tissue characteristics may impact metabolic and atherogenic risks. Subcutaneous Adipose Tissue (SAT), Visceral Adipose Tissue (VAT) and peripheral blood were obtained from obese patients submitted to bariatric surgery. Adipose tissue (morphometry), plasma adiponectin, TNF-α, resistin (multiplexing) and biochemical chemistry were analyzed; as well as endothelial dysfunction (Flow Mediated Dilation, FMD) and atherogenesis (Carotid Intima Media Thickness, CIMT). Subgroups divided by adipocyte size and source were compared; as well as correlation and multivariate analysis. Sixty patients 36.6% males, aged 44 years-old, BMI 46.7 kg/m2 were included. SAT’s adipocytes showed a lower range of size expandability than VAT’s adipocytes. Independent from their source, larger adipocytes were associated with higher glucose, lower adiponectin and higher CIMT. Particularly, larger adipocytes from SAT were associated with higher blood pressure, lower insulin and HDL-cholesterol; and showed positive correlation with glucose, HbA1c, systolic/diastolic values, and negatively correlated with insulin and adiponectin. VAT’s larger adipocytes particularly associated with lower resistin and lower FMD values. Gender and Diabetes Mellitus significantly impacted the relation of adipocyte size/source with the metabolic and atherogenic risk. Multivariable analysis suggested hypertension-resistin-HbA1c interactions associated with SAT’s larger adipocytes; whereas potential insulin-adiponectin associations were observed for VAT’s larger adipocytes. Adipocyte morphology and source are differentially related with cardiometabolic and atherogenic risk in population with obesity, which are potentially affected by gender and Diabetes Mellitus.

Critical limb ischemia (CLI) represents an advanced stage of the peripheral arterial disease. Angioplasty improves the blood flow to the lower limb; however, some patients irreversibly progress to limb amputation. The extent of vascular damage and the mechanisms of vascular repair are factors affecting post-angioplasty outcome. Mononuclear Progenitor Cells (MPCs) are reactive to vascular damage and repair, with the ability to reflect vascular diseases. The present protocol describes quantification of MPCs obtained from blood circulation from vessel close to the angioplasty site, as well as its relationship with endothelial dysfunction and its predictive ability for limb amputation in the next 30 days after angioplasty in patients with CLI.

The present study aimed to compare echocardiography measurements of epicardial adipose tissue (EAT) thickness and other risk factors regarding their ability to predict adverse cardiovascular outcomes in patients with coronary artery disease (CAD). Outcomes of 107 patients (86 males, 21 females, mean age 63.6 years old) submitted to diagnostic echocardiography and coronary angiography were prospectively analyzed. EAT (measures over the right ventricle, interventricular groove and complete bulk of EAT) and left ventricle ejection fraction (LVEF) were performed by echocardiography. Coronary complexity was evaluated by Syntax score. Primary endpoints were major adverse cardiovascular events (MACE’s), composite of cardiovascular death, myocardial infarction, unstable angina, intra-stent re-stenosis and episodes of decompensate heart failure requiring hospital attention during a mean follow up of 15.94 ± 3.6 months. Mean EAT thickness was 4.6 ± 1.9 mm; and correlated with Syntax score and body mass index; negatively correlated with LVEF. Twenty-three cases of MACE's were recorded during follow up, who showed higher EAT. Diagnostic ability of EAT to discriminate MACE's was comparable to LVEF (AUROC > 0.5); but higher than Syntax score. Quartile comparison of EAT revealed that measurement of the complete bulk of EAT provided a better discrimination range for MACE's, and higher, more significant adjusted risk (cutoff 4.6 mm, RR = 3.91; 95% CI 1.01–15.08; p = 0.04) than the other risk factors. We concluded that echocardiographic measurement of EAT showed higher predicting ability for MACE’s than the other markers tested, in patients with CAD. Whether location for echocardiographic measurement of EAT impacts the diagnostic performance of this method deserves further study.

Background. The metabolic syndrome (MS) is associated with an increased production of nitrogen metabolites and elevated oxidative stress, which favor the development and progression of non-alcoholic fatty liver disease (NAFLD). Subjects with the phenotype known as metabolically unhealthy obese (MUO) meet most of the MS cardiometabolic risk criteria and show a higher prevalence of NAFLD and fibrosis progression risk, compared to the so-known as metabolically healthy obese (MHO). The present study aimed to explore whether liver-specific biomarkers of nitrogen metabolism and oxidative stress, measured in both plasma and in liver tissue, may relate to NAFLD severity and/or metabolic phenotype. Methods. This observational, cross-sectional study included candidates for bariatric surgery with biopsy-proven NAFLD diagnosis and staging. For comparison, the study population was divided according to NAFLD progression (steatohepatitis F0-F1 vs F2-F4) and metabolic phenotype (MHO vs MUO, based on the MS criteria). Hepatic and plasma concentrations of nitrogen metabolites and oxidative stress biomarkers were determined by enzymatic kinetics assays, ELISA and Griess reaction. Results. The study population consisted of 28 patients with obesity and higher prevalence of dyslipidemia, diabetes mellitus and hypertension. NAFLD progression was related with the metabolic phenotype. According to plasma biomarkers, MUO phenotype was related to higher cardiometabolic risk; while NAFLD severity progression was related to higher Hb A1c and triglycerides. Elevated hepatic concentrations of ammonium, nitrites, arginine and citrulline were found in MUO phenotype, but only higher plasma concentration of MDA was found as specifically related to NAFLD progression. Conclusions. Circulating biomarkers of redox state were selectively related with NAFLD progression, supporting prognostic and therapeutic potential target. Hepatic concentrations of nitrogen metabolism biomarkers may be more related to cardiometabolic risk.

ObjectiveTo evaluate the relationship between pro-atherogenic biomarkers and epicardial adipose tissue (EAT) thickness in patients with cardiovascular risk factors.MethodsPlasma nitric oxide (NO), soluble intercellular adhesion molecule-1 and malondialdehyde (MDA) levels, EAT thickness, flow-mediated dilation (FMD) and carotid intima media thickness (CIMT) were determined in patients aged >18 years who were referred for echocardiography for heart ischemia or non-ischemic diseases. Cardiovascular risk factors (Framingham score [FS] ≥ 20) were weighted.ResultsHypertension, dyslipidaemia and type 2 diabetes mellitus were prevalent (≥55% of 40 patients). Patients with FS ≥ 20 ( n = 21) showed significantly higher EAT and CIMT values. Globally, MDA, CIMT, age, waist circumference, high-density lipoprotein cholesterol (HDL-C) and FS were associated with EAT thickness. EAT was significantly associated with NO in patients with FS ≥ 20. Significant differences in EAT thickness were found between patients stratified by NO value, FMD, age, smoking status, dyslipidaemia, type 2 diabetes mellitus and FS. An EAT-associated atherogenic risk (CIMT ≥ 1 mm) model was statistically significant when MDA and type 2 diabetes mellitus were included.ConclusionEAT thickness was associated with MDA, CIMT, age, waist circumference, HDL-C and FS globally, but with NO only in patients with FS≥20. EAT may be used to identify vascular damage stage, possibly influenced by MDA and type 2 diabetes mellitus.

Atherosclerosis represents a cardiovascular risk. Chronic inflammation is a key factor for atherogenic progression. Neutrophil-to-lymphocyte ratio (NLR) has been proposed as a novel biomarker for cardiovascular risks. We aimed to explore whether NLR was related to surrogate pro-atherogenic promoters driving atherogenic progression, as measured by carotid intima-media thickness (CIMT).Thirty-one patients with obesity candidates for bariatric surgery were recruited from Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City. The results are part of the "CROP" study (NCT03561987). NLR was calculated from routine complete blood count, and its relation with plasma pro-inflammatory mediators (hsCRP, TNF-α and IL-1β), adipokines (adiponectin and leptin), adiposity markers (visceral adipose tissue [VAT] determined from CT scan image and VAT individual adipocyte area at histological sample) and CIMT were determined.Neutrophil-to-lymphocyte ratio correlated with hsCRP (Spearman's r = 0.70 [95% CI 0.46 to 0.85], P 0.01), TNF-α (r = 0.69 [0.44 to 0.84], P 0.0001) and adiponectin (r = -0.69 [-0.84 to -0.45], P 0.03), as well as with VAT individual adipocyte area (r = 0.64 [0.37 to 0.81], P 0.0001) and with VAT area (r = 0.43; [0.07 to 0.68], P 0.01). Leptin and adiponectin showed further independent association with higher NLR (multivariate regression analysis OR 7.9 [95% CI 1.1 to 56.2] P = 0.03 and 0.1 [0.01 to 1.0] P = 0.05, respectively). Moreover, NLR distribution significantly varied between subgroups divided according to progressive CIMT (P = 0.05); whereas adiponectin and VAT adipocyte area associated with CIMT 0.9 mm (univariate analysis OR 0.1 [0.01 to 1.0] P = 0.05 and 13.1 [1.4 to 126.3] P = 0.03, respectively).Neutrophil-to-lymphocyte ratio was related to pro-inflammatory, adiposity biomarkers and progressive subclinical atherogenesis.

Background Alpha1 anti-trypsin (α1-AT), a serine protease inhibitor synthesized in the liver, is a major circulating antiprotease that provides defense against proteolytic damage in several tissues. Its deficiency is associated with airflow obstruction. The present study aimed to explore the role of α1-AT as a biomarker of airflow performance in chronic liver disease (CLD). Material/Methods Serum α1-AT levels and lung function (spirometry) were evaluated in non-primary α1-AT-deficient, alcoholic CLD patients without evident respiratory limitations. Results Thirty-four patients with airflow obstruction (n=11), airflow restriction (n=12), and normal airflow (n=11, age-matched controls) were eligible. α1-AT was decreased in the airflow obstruction group. ROC-cutoff α1-AT=24 mg/dL effectively discriminated airflow obstruction (AUC=0.687) and was associated with a 10-fold higher risk (p=0.0007). Conclusions Lower α1-AT increased the risk of airflow obstruction in CLD patients without primary α1-AT deficiency.