Cardiometabolic and Cardiovascular Complications of Obesity in Children

The rise in obesity in both children and adults has made obesity one of the biggest public health problems of this century. Obesity along with other factors such as hypertension, insulin resistance, dyslipidemia and diabetes mellitus are risk factors for the development of cardiovascular diseases. Overweight and/or obesity during childhood and its maintenance until adult life has been associated with early stages of cardiovascular disease. For this reason, the aim of this study is to revise the state of the art of cardiometabolic and cardiovascular complications related with overweight and/or obesity in children and adolescents. The first consequence of weight gain is an increase in adipose tissue, with different distribution depending on the sex. The excess of fat mass entails dysfunction of adipose tissue with an altered secretion of adipokines and instauration of a proinflammatory environment, which may derive in metabolic syndrome condition. The increase of adipose tissue along with an increase in sympathetic nervous system, triggers an increased left ventricular mass and with a reduced diastolic function. Therefore, obesity should be prevented from the early stages of life, in order to avoid obesity itself and the metabolic disturbances that could undermine quality of life further on

Cardiovascular risk biomarkers and metabolically unhealthy status in prepubertal children: Comparison of definitions

Background and aims: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers. Methods and results: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5–10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR. Conclusion: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations

Endometrial carcinoma: molecular alterations involved in tumor development and progression

In the western world, endometrial carcinoma (EC) is the most common cancer of the female genital tract. The annual incidence has been estimated at 10-20 per 100 000 women. Two clinicopathological variants are recognized: the estrogen related (type I, endometrioid) and the non-estrogen related (type II, non-endometrioid).The clinicopathological differences are paralleled by specific genetic alterations, with type I showing microsatellite instability and mutations in phosphatase and tensin homologue deleted on chromosome 70, PIK3CA, K-RAS and CTNNB1 (beta-catenin), and type II exhibiting TP53 mutations and chromosomal instability. Some non-endometrioid carcinomas probably arise from pre-existing endometrioid carcinomas as a result of tumor progression and, not surprisingly, some tumors exhibit combined or mixed features at the clinical, pathological and molecular levels. In EC, apoptosis resistance may have a role in tumor progression. Understanding pathogenesis at the molecular level is essential in identifying biomarkers for successful targeted therapies. In this review, the genetic changes of endometrial carcinogenesis are discussed in the light of the morphological features of the tumors and their precursors

Height-based equations as screening tools for high blood pressure in pediatric practice, the GENOBOX study

Due to the absence of easily applicable cut-off points to determine high blood pressure or hypertension in children, as in the adult population, blood pressure is rarely measured in the pediatrician''s clinical routine. This has led to an underdiagnosis of high blood pressure or hypertension in children. For this reason, the present study evaluate the utility of five equations for the screening of high blood pressure in children: blood pressure to height ratio, modified blood pressure to height ratio, new modified blood pressure to height ratio, new simple formula and height-based equations. The authors evaluated 1599 children between 5 and 18 years. The performance of the five equations was analyzed using the receiver-operating characteristics curves for identifying blood pressure above P90th according to the American Academy of Pediatrics Clinical Practice Guideline 2017. All equations showed an area under the curve above 0.882. The new modified blood pressure to height ratio revealed a high sensitivity whereas the height-based equations showed the best performance, with a positive predictive value above 88.2%. Finally, all equations showed higher positive predictive values in children with overweight or obesity. The height-based equation obtained the highest PPV values above 71.1% in children with normal weight and above 90.2% in children with overweight or obesity. In conclusions, the authors recommend the use of the height-based equations equation because it showed the best positive predictive values to identify children with elevated blood pressure, independently of their sex, pubertal and weight status. © 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC

EPD and Spark Plasma Sintering of bimodal alumina/titania concentrated suspensions

Alumina-aluminium titanate (A-AT) composites and laminates have been recently investigated because they can provide improved flaw tolerance and toughness associated to a microcracking mechanism. A-AT composites have been produced by slip casting and reaction sintering of submicron sized alumina and titania powders. This work deals with the preparation of thick self-sustained A-AT films from mixtures of submicron sized alumina and nanosized titania powders and further sintering by conventional and non-conventional (spark plasma sintering, SPS) methods. Suspensions were prepared in water to high solid loadings, up to 50 vol.%. Self-sustained films were obtained by aqueous electrophoretic deposition (EPD) using graphite substrates under constant current density conditions. The evolution of mass per unit area with current density and deposition time was recorded. The films were characterized in the green state and after sintering at different temperatures (1300-1400) degrees C. Fully dense A-AT reaction sintered materials were obtained at low temperature by SPSThis study has been supported by the Spanish Ministry of Science and Innovation MAT2009-14369-C02-01 and MAT2009-14144-C03-02. A. Borrell, acknowledges the Spanish Ministry of Science and Innovation for her Juan de la Cierva contract (JCI-2011-10498) and the Generalitat Valenciana for the BEST/2012/302 grant and the financial support for ACOMP/2012/166.Borrell Tomás, MA.; Salvador Moya, MD.; Rocha, VG.; Fernández, A.; Molina, T.; Moreno, R. (2013). EPD and Spark Plasma Sintering of bimodal alumina/titania concentrated suspensions. Journal of Alloys and Compounds. 577:195-202. https://doi.org/10.1016/j.jallcom.2013.04.175S19520257

Functional characterization of E- and P-cadherin in invasive breast cancer cells

Background: Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods: To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Results: Expression of either E-and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E-and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E-and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E-and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Conclusion: E-and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer

Evaluation of Sedentary Behavior and Physical Activity Levels Using Different Accelerometry Protocols in Children from the GENOBOX Study

Background Physical activity (PA) has acquired a significant relevance due to the health benefits associated with its practice. Accelerometers are an effective tool to assess PA; however, the diversity of cut-off points used to define different PA intensities through accelerometry could interfere in the interpretation of the findings among studies. Objectives The present study aimed to examine the sedentary behavior (SB) and physical activity (PA) levels in children using six selected accelerometry protocols based on diverse cut-off points. Methods Clinical examination, anthropometric measurements, and PA evaluation by accelerometry were assessed in 543 selected children (10 +/- 2.4 years old) from the Spanish GENOBOX study. The ActiLife data scoring program was used to determine daily min spent in SB, and light, moderate, vigorous and moderate-vigorous PA using six validated accelerometry protocols differing in their cut-off points. Results Very different estimations for SB and PA intensity levels were found in children, independently of the non-wear-time algorithm selected, and considering puberty stages, age and body mass index. The time spent in daily SB varied from 471 to 663.7 min, PA ranged from 141 to 301.6 min, and the moderate-vigorous PA was reported between 20.7 and 180.2 min. Conclusion The choice of a particular accelerometry protocol considering these factors is important to evaluate SB or PA intensities to suit the characteristics of the sample researched. It seems necessary to establish future lines of research that include different analytical approaches to measure SB and PA by accelerometry based on standardized and validated methodology

Modificaciones en variables antropométricas, analíticas de riesgo metabólico y composición corporal en pequeños para la edad gestacional en tratamiento con hormona de crecimiento

Introducción Los niños pequeños para la edad gestacional (PEG) sin crecimiento recuperador pueden beneficiarse del tratamiento con hormona de crecimiento (rhGH). Sin embargo, deben ser monitorizados de forma muy estrecha ya que son población de riesgo metabólico. Material y métodos Se han incluido 28 niños PEG, con una media de edad de 8, 79 años, sin crecimiento recuperador, tratados con rhGH. Hemos evaluado las modificaciones producidas en la antropometría, variables de riesgo metabólico y composición corporal durante 4 años de tratamiento. Resultados El tratamiento con rhGH se acompañó de un aumento de talla (–2, 76 ± 0, 11 DE hasta –1, 53 ± 0, 17 DE; p = 0, 000), peso (–1, 50 ± 0, 09 DE hasta –1, 21 ± 0, 13 DE; p = 0, 016) y velocidad de crecimiento (–1, 43 ± 0, 35 DE hasta 0, 41 ± 0, 41 DE; p = 0, 009), sin producir modificaciones en el índice de masa corporal (IMC). Se han visto aumentos significativos de la insulinemia (9, 33 ± 1, 93 mU/ml hasta 16, 55 ± 1, 72 mU/ml; p = 0, 044) y del índice HOMA (3, 63 ± 0, 76 hasta 6, 43 ± 0, 67; p = 0, 042), sin producirse modificaciones en el perfil lipídico. En el estudio de composición corporal se ha comprobado un aumento significativo de la masa magra (73, 19 ± 1, 26 hasta 78, 74 ± 1, 31; p = 0, 037) con una disminución de la masa grasa (26, 81 ± 1, 26 hasta 21, 26 ± 1, 31; p = 0, 021). Conclusión El tratamiento con rhGH se ha acompañado de una ganancia en la talla sin producir alteraciones en el IMC. Asimismo, se han observado cambios en la composición corporal, con un aumento de la proporción de masa magra a expensas de una disminución de la de masa grasa, que podrían conducir a un descenso del riesgo metabólico de estos pacientes. Sin embargo, se ha detectado cierta resistencia insulínica. Es importante continuar el seguimiento de estos niños para determinar las posibles repercusiones en la edad adulta. Introduction and objectives Small for gestational age (SGA) children without catch-up growth can benefit from treatment with growth hormone (rhGH). However, they should be monitored very closely because they are at increased risk of metabolic syndrome. Material and method A group of 28 SGA children with a mean age of 8.79 years and undergoing treatment with rhGH were selected for evaluation. Over the course of 4 years, an annual evaluation was performed on the anthropometric variables (weight, height, body mass index [BMI], growth rate, blood pressure and waist perimeter), metabolic risk variables (glycaemia, glycosylated haemoglobin, cholesterol ratio, insulinaemia, insulin-like growth factor 1[IGF1], IGF binding protein-3 [IGFBP-3], IGF1/IGFBP3 ratio, and HOMA index), and body composition variables. Results Treatment with rhGH was associated with a significant increase in height (–2.76 ± .11 SD to –1.53 ± .17 SD, P = .000), weight (–1.50 ± .09 SD to –1.21 ± .13 SD; P = .016), and growth rate (–1.43 ± .35 SD to .41 ± .41 SD; P = .009), without a corresponding change in the BMI. Insulinaemia (9.33 ± 1.93 mU/ml to 16.55 ± 1.72 mU/ml; P = .044) and the HOMA index (3.63 ± .76 to 6.43 ± .67; P = .042) increased, approaching insulin resistance levels. No changes were observed in the lipid profile. Body composition changes were observed, with a significant increase in lean mass (73.19 ± 1.26 to 78.74 ± 1.31; P = .037), and a reduction of fat mass (26.81 ± 1.26 to 21.26 ± 1.31; P = .021). Conclusion Treatment with rhGH is effective for improving anthropometric variables in SGA patients who have not experienced a catch-up growth. It also produces changes in body composition, which may lead to a reduction in risk of metabolic syndrome. However, some insulin resistance was observed. It is important to follow up this patient group in order to find out whether these changes persist into adulthood

The vitamin D decrease in children with obesity is associated with the development of insulin resistance during puberty: The PUBMEP study

Obesity and cardiometabolic risk have been associated with vitamin D levels even in children. The objective of the present study was to evaluate the association between insulin resistance (IR), cardiometabolic risk factors, and vitamin D in children from prepubertal to pubertal stages. A total of 76 children from the PUBMEP study, aged 4–12 years at baseline, were included. Children were evaluated in prepubertal and pubertal stages. Anthropometric measurements and selected cardiometabolic risk biomarkers, such as plasma glucose, blood lipids, insulin, adiponectin, leptin, and blood pressure, and serum 25-hydroxyvitamin D (25(OH)D) were determined. Children were categorized by obesity degree and IR status combined before and after puberty. Paired t-test and multivariate linear regression analyses were conducted. During puberty, the increase in triacylglycerols, insulin, and HOMA-IR and the decrease in QUICKI were significantly associated with the reduction in 25(OH)D (B = -0.274, p = 0.032; B = -0.219, p = 0.019; B = -0.250, p = 0.013; B = 1.574, p = 0.013, respectively) after adjustment by BMI-z, sex, and pubertal stage. Otherwise, prepubertal non-IR children with overweight/obesity that became IR during puberty showed a significant decrease in 25(OH)D and HDL-c, and an increase in waist circumference and triacylglycerol concentrations (p < 0.05 for all) over time. These results suggest that changes in IR seem to be associated with an effect on 25(OH)D levels during puberty, especially in children with overweight. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Dietary patterns and their association with body composition and cardiometabolic markers in children and adolescents: Genobox cohort

Diet is a key factor for obesity development; however, limited data are available on dietary cluster analysis in children with obesity. We aimed to assess the associations between dietary patterns and obesity and several cardiometabolic markers. Anthropometry, bioelectrical impedance, blood pressure and plasma biomarkers of oxidative stress, inflammation and endothelial damage were determined in 674 Caucasian children, aged 5–16, with normal or excess weight. Using a food frequency questionnaire and cluster analysis, two consistent dietary patterns were shown, labeled as health conscious (HC) and sweet and processed (SP). The HC pattern included a greater proportion of participants with overweight/obesity than the SP cluster (80.1% vs. 63.8%). However, children with obesity within the HC cluster, showed less abdominal fat, through waist to hip (0.93 vs. 0.94) and waist to height (0.61 vs. 0.63) indexes (p < 0.01). Univariate general models showed several additional differences in cardiometabolic risk biomarkers in the global and stratified analyses, with a healthier profile being observed mainly in the HC cluster. However, multivariate models questioned these findings and pointed out the need for further studies in this field. Anyhow, our findings support the benefits of a healthy diet and highlight the importance of dietary patterns in the cardiometabolic risk assessment of children with overweight/obesity, beyond weight control