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Background and Objectives: Metabolic-dysfunction-associated steatotic liver disease or MASLD is the main cause of chronic liver diseases in children, and it is estimated to affect 35% of children living with obesity. This study aimed to identify metabolic phenotypes associated with two advanced stages of MASLD (hepatic steatosis and hepatic steatosis plus fibrosis) in Mexican children with obesity. Materials and Methods: This is a cross-sectional analysis derived from a randomized clinical trial conducted in children and adolescents with obesity aged 8 to 16 years. Anthropometric and biochemical data were measured, and targeted metabolomic analyses were carried out using mass spectrometry. Liver steatosis and fibrosis were estimated using transient elastography (Fibroscan® Echosens, Paris, France). Three groups were studied: a non-MASLD group, an MASLD group, and a group for MASLD + fibrosis. A partial least squares discriminant analysis (PLS-DA) was performed to identify the discrimination between the study groups and to visualize the differences between their heatmaps; also, Variable Importance Projection (VIP) plots were graphed. A VIP score of >1.5 was considered to establish the importance of metabolites and biochemical parameters that characterized each group. Logistic regression models were constructed considering VIP scores of >1.5, and the receiver operating characteristic (ROC) curves were estimated to evaluate different combinations of variables. Results: The metabolic MASLD phenotype was associated with increased concentrations of ALT and decreased arginine, glycine, and acylcarnitine (AC) AC5:1, while MASLD + fibrosis, an advanced stage of MASLD, was associated with a phenotype characterized by increased concentrations of ALT, proline, and alanine and a decreased Matsuda Index. Conclusions: The metabolic MASLD phenotype changes as this metabolic dysfunction progresses. Understanding metabolic disturbances in MASLD would allow for early identification and the development of intervention strategies focused on limiting the progression of liver damage in children and adolescents.
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Fígado Gorduroso , Adolescente , Humanos , Criança , Estudos Transversais , Obesidade/complicações , Cirrose Hepática/complicações , FenótipoRESUMO
BACKGROUND: Patients with obesity have an increased risk for adverse COVID-19 outcomes. Body mass index (BMI) does not acknowledge the health burden associated this disease. The performance of the Edmonton Obesity Staging System (EOSS), a clinical classification tool that assesses obesity-related comorbidity, is compared with BMI, with respect to adverse COVID-19 outcomes. METHODS: 1071 patients were evaluated in 11 COVID-19 hospitals in Mexico. Patients were classified into EOSS stages. Adjusted risk factors for COVID-19 outcomes were calculated and survival analysis for mechanical ventilation and death was carried out according to EOSS stage and BMI category. RESULTS: The risk for intubation was higher in patients with EOSS stages 2 and 4 (HR 1.42, 95% CI 1.02-1.97 and 2.78, 95% CI 1.83-4.24), and in patients with BMI classes II and III (HR 1.71, 95% CI 1.06-2.74, and 2.62, 95% CI 1.65-4.17). Mortality rates were significantly lower in patients with EOSS stages 0 and 1 (HR 0.62, 95% CI 0.42-0.92) and higher in patients with BMI class III (HR 1.58, 95% CI 1.03-2.42). In patients with a BMI ≥ 25 kg/m2, the risk for intubation increased with progressive EOSS stages. Only individuals in BMI class III showed an increased risk for intubation (HR 2.24, 95% CI 1.50-3.34). Mortality risk was increased in EOSS stages 2 and 4 compared to EOSS 0 and 1, and in patients with BMI class II and III, compared to patients with overweight. CONCLUSIONS: EOSS was associated with adverse COVID-19 outcomes, and it distinguished risks beyond BMI. Patients with overweight and obesity in EOSS stages 0 and 1 had a lower risk than patients with normal weight. BMI does not adequately reflect adipose tissue-associated disease, it is not ideal for guiding chronic-disease management.
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COVID-19 , Obesidade , Adulto , Idoso , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/mortalidade , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To describe a third-degree polynomial function (hysteresis) of the effect size of age, obesity, and insulin sensitivity over the carotid intima-media thickness (c-IMT), in the pediatric and adult groups. METHODS: A quasi-experimental study with fixed factor analysis of age (children aged 8-12 years, n = 73; adults aged 21-45 years, n = 82) and obesity (yes, n = 76; no, n = 79) was conducted to analyze the effect on the c-IMT and Matsuda insulin sensitivity index values. This quasi-experimental design was analyzed with robust regression modeling. RESULTS: The additive effect of obesity, independent of age, was evident in the case of the c-IMT values. There was no interaction effect, but a significant difference between participants with normal weight and those with obesity was found (P < .0001). The difference between adults and children was also significant, but the effect size was smaller. A model was created based on age, Tanner stage, and obesity using the c-IMT and Matsuda insulin sensitivity index values. A linear function fit as R2, and the cubic function estimated parameters like a polynomial model. CONCLUSION: This practical study design showed that children with obesity displayed the same levels of carotid intima-media abnormalities as adults with obesity. The polynomial shape of the model suggests potentially poor outcomes that resemble the hysteresis process and may predict chronic cardiometabolic events during early adulthood.
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Espessura Intima-Media Carotídea , Resistência à Insulina , Obesidade , Adulto , Fatores Etários , Artérias Carótidas/diagnóstico por imagem , Criança , Humanos , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/complicações , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD. METHODS: We included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender. RESULTS: The mean age was 10.64±2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR=2.39; 95%CI=1.10-5.19; p=0.025). For girls, NAFLD was significantly associated with triglycerides (p=0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p=0.048), and the visceral adiposity index (VAI) (p=0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p=0.001), waist circumference (WC) (p<0.001), HDL cholesterol (p=0.021), alanine aminotransferase (ALT) (p<0.001), and aspartate aminotransferase (AST) (p=0.002). CONCLUSIONS: In our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5U/L in females and 27.5U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.
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Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , México/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sobrepeso/metabolismo , Obesidade Infantil/metabolismo , Prevalência , Distribuição por Sexo , Fatores Sexuais , UltrassonografiaRESUMO
BACKGROUND: In high-fat diet-fed mice, interleukin-1 beta (IL-1 beta) has been shown to play a key role in hepatic steatosis. However, it remains unknown whether IL-1 beta could be associated with different grades of steatosis in obese humans. MATERIALS AND METHODS: Morbidly obese patients (n = 124) aged 18-65 years were divided into four groups: no steatosis (controls), mild steatosis, moderate steatosis, and severe steatosis using abdominal ultrasound. IL-1 beta serum levels and liver function tests were measured and significant differences were estimated by one-way ANOVA followed by Tukey test. RESULTS: IL-1 beta serum levels significantly increased in morbidly obese patients with mild (11.38 ± 2.40 pg/ml), moderate (16.72 ± 2.47 pg/ml), and severe steatosis (23.29 ± 5.2 pg/ml) as compared to controls (7.78 ± 2.26 pg/ml). Liver function tests did not significantly change among different grades of steatosis. CONCLUSION: IL-1 beta serum levels associate better with steatosis degree than liver function tests in morbidly obese population.
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BACKGROUND: Childhood obesity is a significant public health concern in Mexico, with far-reaching implications for the nation's healthcare system and economy. In light of this challenge, our study sought to validate the Childhood Family Mealtime Questionnaire (CFMQ) in Mexican adolescents living with obesity and their primary caregivers. METHODS: A sample of 56 adolescents ages 13 to 17 years and their primary caregivers from one pediatric obesity clinic participated in the study. We conducted a comprehensive assessment of the CFMQ's consistency, reliability, and construct validity among all participants. Internal consistency was determined using Cronbach's α, and the questionnaire's reliability was assessed through test-retest and intraclass correlation coefficients. Construct validity was assessed through an exploratory factor analysis. RESULTS: Our findings confirmed strong internal consistency and reliability for both adolescents and caregivers. Construct validity was established through exploratory factor analysis, refining the questionnaire while preserving its original seven dimensions. This validation of the CFMQ highlights its applicability in evaluating family mealtime experiences in this context, providing valuable insights into the dynamics that influence adolescent nutrition and health. CONCLUSION: The CFMQ proves to be a reliable tool for assessing family mealtime experiences in Mexican adolescents living with obesity and their caregivers who seek care at third-level public hospitals.
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Obesidade Infantil , Adolescente , Humanos , Criança , Cuidadores , México , Reprodutibilidade dos Testes , Inquéritos e Questionários , Refeições , Psicometria/métodosRESUMO
The COVID-19 lockdown caused health system issues, including the need for long-term care for patients with conditions like childhood obesity. We wanted to know how the lockdown had changed our patients' health and which variables had greater influence in preventing and managing overweight and obesity in kids and teens during and after the lockdown. METHODS: Our study comprised two phases. The initial descriptive cross-sectional phase included surveys of children who are overweight or obese and their parents/guardians from the Pediatric Obesity Clinic at the Child Welfare Unit (UBI, acronym in Spanish) in the Hospital General de México "Dr. Eduardo Liceaga" (n = 129). The participants were studied to explore changes in lifestyle, physical activity, sleep patterns, eating behaviors, food consumption, anxiety, and depression. In the second phase, the biochemical, body composition, and anthropometric parameters of 29 pre-COVID-19 patients were compared before and after the lockdown. RESULTS: The survey showed more moderate anxiety and depression, alterations in sleep, physical inactivity, and an increase in the consumption of animal products, fruits, cereals, tubers, sugary drinks, and ultra-processed food. In the study's comparative phase, we observed a substantial increase in BMI z-score (p = 0.01), waist circumference (p < 0.001), fat mass (p < 0.001), percentage of adiposity (p = 0.002), and basal glucose (p = 0.047) and a drop in lean mass (p = 0.008). CONCLUSIONS: The pandemic led to a loss of routines and socioeconomic changes that made it difficult to address weight and obesity in young people. The results show that managing obesity in our patients involves considering both lifestyle and the social environment. This encourages us to consider a comprehensive and personalized approach.
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COVID-19 , Obesidade Infantil , Animais , Humanos , Criança , Adolescente , Sobrepeso , Obesidade Infantil/epidemiologia , Obesidade Infantil/terapia , Estudos Transversais , México/epidemiologia , Índice de Massa Corporal , COVID-19/epidemiologia , Controle de Doenças TransmissíveisRESUMO
The differential contribution of monocyte subsets expressing the C-C chemokine receptor 2 (CCR2) to subclinical atherosclerosis in girls and boys is unclear. In this pilot study, we compared classical, intermediate, and nonclassical monocyte subsets expressing CCR2 in 33 obese children of both sexes aged 8 to 16 divided by carotid intima-media thickness (IMT), considering values above the 75th percentile (p75) as abnormally high IMT. Obesity was defined as body mass index above the 95th percentile according to age and sex. Flow cytometry analyses revealed that boys but not girls with IMT ≥ p75 displayed increased CCR2+ cell percentage and CCR2 expression in the three monocyte subsets, compared to boys with IMT < p75. The CCR2+ cell percentage and CCR2 expression in the three monocyte subsets significantly correlated with increased IMT and insulin resistance in boys but not girls, where the CCR2+ nonclassical monocyte percentage had the strongest associations (r = 0.73 and r = 0.72, respectively). The role of CCR2+ monocyte subpopulations in identifying an abnormally high IMT shows a marked sexual dimorphism, where boys seem to be at higher subclinical atherosclerosis risk than girls.
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Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic hepatic disorder in the pediatric population and has grown along with the obesity pandemic in which we live today. Adipose tissue storage in the upper body segment has been positively correlated with visceral adiposity and metabolic disease, which suggests that neck circumference could represent an easily accessible and replicable anthropometric measurement to identify patients with a higher risk of developing NAFLD. The main purpose of this study is to determine if there is an association between neck circumference and NAFLD. The secondary objectives are to establish cutoff values based on gender and puberty staging. Methods We included a sample pediatric population of 112 patients diagnosed with obesity aged between 6 and 18 years. We performed anthropometric and metabolic measurements on every patient, and NAFLD diagnosis was determined with hepatic ultrasound. Results The neck circumference was larger in NAFLD pediatric patients compared to those without NAFLD (p = 0.001). In a multivariate analysis, the neck circumference was associated with NAFLD as an independent risk factor (odds ratio [OR] = 1.172; 95% CI = 1.008-1.362; p = 0.038). Tanner 2-3 = 35 cm and Tanner 4-5 = 38 cm were established as risk cutoff values to develop NAFLD in the male adolescent population. Conclusions There is an association between the neck circumference and NAFLD in pediatric patients with obesity, particularly in the male population.
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Biomarcadores/análise , Índice de Massa Corporal , Pescoço/patologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade Infantil/complicações , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , México/epidemiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Prevalência , Prognóstico , Fatores de RiscoRESUMO
OBJECTIVE: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules. METHODS: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test. RESULTS: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions. CONCLUSIONS: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/antagonistas & inibidores , Ácido Graxo Sintases/antagonistas & inibidores , Glucose/efeitos adversos , Hepatócitos/efeitos dos fármacos , Hormônio do Crescimento Humano/farmacologia , Lipogênese , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Células Hep G2 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Edulcorantes/efeitos adversosRESUMO
The main complication associated with renal graft loss is immune rejection. The gold standard for the diagnosis of renal graft rejection is percutaneous renal biopsy, which is expensive and can lead to complications. Inflammation is one of the main pathogenic pathways in allograft rejection, and urine samples seem to be efficient windows to explore the allograft condition with a high cost-benefit ratio. This study aimed to evaluate the messenger ribonucleic acid (mRNA) profile expression pattern for interleukin (IL) 2, IL-4, IL-6, IL-8, and IL-10; tumor necrosis factor alfa; gamma interferon; and transforming growth factor ß1 in the urine renal cells of patients with a diagnosis of humoral rejection and patients with a diagnosis of normal biopsy. METHODS: An observational, cross-sectional analytical study was performed. All kidney transplants were performed at the Organ Transplant Department between 2018 and 2019. Also, a healthy control with a normal blood test and no apparent infection was included. mRNA from urine samples and biopsies was isolated, and the expression of interleukins was analyzed in PCR real time. Data were analyzed by Shapiro-Wilk and Kruskal-Wallis tests. RESULTS: The proinflammatory IL expression pattern in urine samples of kidney rejection group showed overexpression for IL-8 (P = .0001). No differences were observed in the rest of the interleukins analyzed. When we compared the results in the rejected versus not rejected transplanted patients with a group of apparently healthy subjects, the difference remains consistent. Thus, mRNA of IL-8 could function as a diagnostic tool in cases of chronic damage secondary to fibrosis.