Cardiometabolic Risk in Children and Adolescents: The Paradox between Body Mass Index and Cardiorespiratory Fitness. / Risco Cardiometabólico em Crianças e Adolescentes: O Paradoxo entre Índice de Massa Corporal e Aptidão Cardiorrespiratória.

BACKGROUND: Cardiometabolic risk has been shown to be inversely associated with cardiorespiratory fitness (CRF) and positively associated with body mass index (BMI). OBJECTIVE: Our objective was to analyze the association of cardiometabolic risk factors with combined BMI and CRF in schoolchildren from a city in southern Brazil. METHODS: Cross-sectional study with a sample of 1252 schoolchildren aged seven to 17 years. Total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG), systolic (SBP) and diastolic blood pressure (DBP) were evaluated. CRF and BMI were grouped into one variable and the schoolchildren were classified as eutrophic/fit, eutrophic/unfit, overweight-obese/fit, and overweight-obese/unfit. Crude and adjusted analyzes were performed using Poisson Regression and an alpha of 0.05 was adopted. RESULTS: Overweight-obese and fit schoolchildren showed a prevalence ratio (PR) of 1.50 (1.04 - 2.16) for altered TG, 3.05 (2.05 - 4.54) for elevated SBP, and 2.70 (1.87 - 3.88) for elevated DBP. Overweight-obese and unfit schoolchildren showed a PR for high TC of 1.24 (1.11 - 1.39) and 1.51(1.11 - 2.04) for low HDL levels. In addition, they had a risk of 2.07 (1.60 - 2.69) for altered TG, 3.36 (2.31 - 4.60) for elevated SBP and 2.42 (1.76 - 3.32) for altered DBP. CONCLUSION: BMI played a central role in the association with risk and CRF was shown to attenuate the association between risk factors and obesity. Overweight-obese children and adolescents had a higher cardiometabolic risk, but the effect size was larger among the unfit.

FUNDAMENTO: Foi demonstrado que o risco cardiometabólico está inversamente associado à aptidão cardiorrespiratória (APCR) e positivamente associado ao índice de massa corporal (IMC). OBJETIVO: Analisar a associação de fatores de risco cardiometabólicos com IMC e APCR combinados em escolares de um município do sul do Brasil. MÉTODOS: Estudo transversal com uma amostra de 1252 escolares de sete a 17 anos. Foram avaliados colesterol total (CT), HDL-c, LDL-c, triglicerídeos (TG), pressão arterial sistólica (PAS) e diastólica (PAD). APCR e IMC foram agrupados em uma variável e os escolares classificados como eutróficos/aptos, eutróficos/inaptos, excesso de peso/aptos e excesso de peso/inaptos. Análises foram realizadas por meio de Regressão de Poisson e uma alfa de 0,05 foi adotado. RESULTADOS: Escolares classificados com excesso de peso/aptos demonstraram uma razão de prevalência (RP) de 1,50 (1,04 ­ 2,16) para TG alterado, 3,05 (2,05 ­ 4,54) para PAS e 2,70 (1,87 ­ 3,88) para PAD elevada. Escolares com excesso de peso/ inaptos apresentaram RP para CT alto de 1,24 (1,11 ­ 1,39) e 1,51 (1,11 ­ 2,04) para baixos níveis de HDL. Além disso, apresentaram um risco de 2,07 (1,60 ­ 2,69) para TG alterado, 3,26 (2,31 ­ 4,60) para PAS e 2,42 (1,76 ­ 3,32) para PAD elevada. CONCLUSÃO: O IMC apresentou um papel central na associação com o risco e a APCR demonstrou atenuar a associação entre fatores de risco e excesso de peso. Escolares com excesso de peso apresentaram um risco cardiometabólico mais elevado, mas o tamanho do efeito foi maior entre os inaptos.

Risco Cardiometabólico em Crianças e Adolescentes: O Paradoxo entre Índice de Massa Corporal e Aptidão Cardiorrespiratória / Cardiometabolic Risk in Children and Adolescents: The Paradox between Body Mass Index and Cardiorespiratory Fitness

Resumo Fundamento Foi demonstrado que o risco cardiometabólico está inversamente associado à aptidão cardiorrespiratória (APCR) e positivamente associado ao índice de massa corporal (IMC). Objetivo Analisar a associação de fatores de risco cardiometabólicos com IMC e APCR combinados em escolares de um município do sul do Brasil. Métodos Estudo transversal com uma amostra de 1252 escolares de sete a 17 anos. Foram avaliados colesterol total (CT), HDL-c, LDL-c, triglicerídeos (TG), pressão arterial sistólica (PAS) e diastólica (PAD). APCR e IMC foram agrupados em uma variável e os escolares classificados como eutróficos/aptos, eutróficos/inaptos, excesso de peso/aptos e excesso de peso/inaptos. Análises foram realizadas por meio de Regressão de Poisson e uma alfa de 0,05 foi adotado. Resultados Escolares classificados com excesso de peso/aptos demonstraram uma razão de prevalência (RP) de 1,50 (1,04 - 2,16) para TG alterado, 3,05 (2,05 - 4,54) para PAS e 2,70 (1,87 - 3,88) para PAD elevada. Escolares com excesso de peso/ inaptos apresentaram RP para CT alto de 1,24 (1,11 - 1,39) e 1,51 (1,11 - 2,04) para baixos níveis de HDL. Além disso, apresentaram um risco de 2,07 (1,60 - 2,69) para TG alterado, 3,26 (2,31 - 4,60) para PAS e 2,42 (1,76 - 3,32) para PAD elevada. Conclusão O IMC apresentou um papel central na associação com o risco e a APCR demonstrou atenuar a associação entre fatores de risco e excesso de peso. Escolares com excesso de peso apresentaram um risco cardiometabólico mais elevado, mas o tamanho do efeito foi maior entre os inaptos.

Abstract Background Cardiometabolic risk has been shown to be inversely associated with cardiorespiratory fitness (CRF) and positively associated with body mass index (BMI). Objective Our objective was to analyze the association of cardiometabolic risk factors with combined BMI and CRF in schoolchildren from a city in southern Brazil. Methods Cross-sectional study with a sample of 1252 schoolchildren aged seven to 17 years. Total cholesterol (TC), HDL-c, LDL-c, triglycerides (TG), systolic (SBP) and diastolic blood pressure (DBP) were evaluated. CRF and BMI were grouped into one variable and the schoolchildren were classified as eutrophic/fit, eutrophic/unfit, overweight-obese/fit, and overweight-obese/unfit. Crude and adjusted analyzes were performed using Poisson Regression and an alpha of 0.05 was adopted. Results Overweight-obese and fit schoolchildren showed a prevalence ratio (PR) of 1.50 (1.04 - 2.16) for altered TG, 3.05 (2.05 - 4.54) for elevated SBP, and 2.70 (1.87 - 3.88) for elevated DBP. Overweight-obese and unfit schoolchildren showed a PR for high TC of 1.24 (1.11 - 1.39) and 1.51(1.11 - 2.04) for low HDL levels. In addition, they had a risk of 2.07 (1.60 - 2.69) for altered TG, 3.36 (2.31 - 4.60) for elevated SBP and 2.42 (1.76 - 3.32) for altered DBP. Conclusion BMI played a central role in the association with risk and CRF was shown to attenuate the association between risk factors and obesity. Overweight-obese children and adolescents had a higher cardiometabolic risk, but the effect size was larger among the unfit.

Combination of sleep duration, TV time and body mass index is associated with cardiometabolic risk moderated by age in youth.

OBJECTIVES: The combination of sleep duration, television (TV) time and body mass index (BMI) may be related to the alteration of cardiometabolic risk. However, there are few studies that use these variables grouped, and showing the moderating role of age. This study aimed to verify if the combination of sleep duration, TV time and BMI is associated with cardiometabolic risk and the moderating role of age in this relationship in youth. METHODS: Cross-sectional study conducted with 1411 adolescents (611 male), aged 10-17 years. Sleep duration, TV time and BMI were assessed and grouped into eight categories. Cardiometabolic risk was assessed by a continuous metabolic risk score, including the following variables: low HDL-cholesterol, elevated triglycerides, dysglycemia, high systolic blood pressure, high waist circumference and low cardiorespiratory fitness. Generalized linear models were used to test moderation of age in the relationship between the eight categories of sleep duration/television time/BMI with cardiometabolic risk. RESULTS: Cardiometabolic risk factor showed association with all overweight or obesity independent of sleep time and TV time. Age moderated the relationship between sleep duration/television time/BMI with cardiometabolic risk. This association was stronger in younger adolescents (11 and 13 years), indicating that individuals with inadequate sleep, prolonged TV time and overweight/obesity present higher cardiometabolic risk values when compared to 15-year-old adolescents. CONCLUSION: Overweight/obesity, independently of sleep duration and TV time, is the main risk factor for cardiometabolic disorders in adolescence. When moderated by age, younger adolescents that presented the combination of risk factors had higher cardiometabolic risk.

Potential Ameliorative Effects of Chromium Supplementation on Glucose Metabolism, Obesity, and Genomic Stability in Prediabetic Rat Model.

Chromium (III) (Cr(III)) effect on improving glucose, body mass loss, and genomic stability has been extensively studied in models of type 2 diabetes. However, there is a lack of studies evaluating its effect on prediabetes. Thus, this study evaluates the effects of Cr(III) as dietetic supplementation on glucose metabolism, obesity, and genomic stability on prediabetic rat model using high-invert sugar. Male Wistar rats were divided randomly into four treatment groups: (1) control, receiving standard diet (control); (2) prediabetic (PD), receiving a 32% of invert sugar; (3) Cr(III), receiving chromium (III) chloride (CrCl3•6H2O) (58.4 mg/L); and (4) Cr(III) + PD, receiving CrCl3•6H2O in combination with high-invert sugar. Cr(III) supplementation significantly reduced blood glucose (123.00 ± 8.29 mg/dL vs. 115.30 ± 9.31 mg/dL, p = 0.015) and partially reduced area under the 120-min blood glucose response curve (AUC) in PD rats (p = 0.227). Moreover, Cr(III) attenuated weight gain (187.29 ± 38.56 g vs. 167.22 ± 29.30 g, p = 0.004), significantly reducing body mass index (0.68 ± 0.04 g/cm2 vs. 0.63 ± 0.04 g/cm2, p < 0.001), Lee index (0.30 ± 0.01 vs. 0.28 ± 0.01, p < 0.001), and peritoneal fat (p < 0.001). Regarding genomic stability, high-invert sugar, Cr(III), or the combination of both did not produce changes in oxidative stress, DNA damage in pancreas, or cytotoxicity markers. These data suggest that Cr(III) supplementation improved partially glucose metabolism and reduced obesity in rat model PD due to high-invert sugar without influence in genomic stability.

Invert sugar induces glucose intolerance but does not cause injury to the pancreas nor permanent DNA damage in rats.

The high consumption of sugars is linked to the intermediate hyperglycemia and impaired glucose tolerance associated with obesity, inducing the prediabetes. However, the consequences of excessive invert sugar intake on glucose metabolism and genomic stability were poorly studied. The aim of this study was to evaluate the effects of invert sugar overload (32%) in rats, analyzing changes in obesity, glucose tolerance, pancreatic/hepatic histology and primary and permanent DNA damage. After 17 weeks, the rats became obese and had an excessive abdominal fat, as well as presented impaired glucose tolerance, caused by higher sugar caloric intake. Primary DNA damage, evaluated by the comet assay, was increased in the blood, however not in the pancreas. No protein carbonylation was seen in serum. Moreover, no increase in permanent DNA damage was seen in the bone marrow, evaluated using the micronucleus test. Some rats presented liver steatosis and that the pancreatic islets were enlarged, but not significantly. In this study, invert sugar altered the glucose metabolism and induced primary DNA damage in blood, but did not cause significant damage to the pancreas or liver, and neither changes in the levels of oxidative stress or permanent DNA damage.

Metabolic risk associated with liver enzymes, uric acid, and hemoglobin in adolescents.

BACKGROUND: The associations of renal, hepatic, and hematologic markers with metabolic risk (MR) have already been shown in adolescents. However, it is still controversial which marker best predicts metabolic changes in youth. The aim of this study was to verify the association of MR with alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid, and hemoglobin (Hb) in adolescents. METHODS: We evaluated 1713 Brazilian adolescents aged 10 to 17 years. MR was calculated using a continuous metabolic risk score, including the sum of Z-scores of waist circumference, systolic blood pressure, fasting glucose, high-density lipoproteins, triglycerides, and cardiorespiratory fitness. Cutoff points were set for MR prediction for five metabolic components (ALT, AST, AST/ALT ratio, uric acid, and Hb). RESULTS: MR was strongly associated with increased uric acid (odds ratio [OR]: 2.50; 95% confidence interval [CI]: 1.74-3.59), ALT (OR: 2.64; 95% CI: 1.63-4.27), and AST levels (OR: 2.53; 95% CI: 1.24-5.18). Uric acid was shown to be the best predictor for MR (sensitivity: 55.79%; specificity: 61.35%; area under the curve: 0.616). CONCLUSION: Elevated hepatic, renal, and hematological markers were associated with MR in adolescents, especially ALT, AST, and uric acid levels. IMPACT: Elevated hepatic, renal, and hematological markers were associated with metabolic risk in adolescents, especially ALT, AST, and uric acid levels. It is still controversial which marker best predicts metabolic changes in adolescents. In addition, association of Hb with metabolic risk is under-studied in this population. It is important to further investigate the relationship between elevated Hb and hepatic markers, since there are key aspects not addressed yet. Our results highlight the importance of creating public health policies aimed to child and adolescent population, to prevention of metabolic disorders from an early age.

Periodontitis: Genomic instability implications and associated risk factors.

Periodontitis is a bacterial infection characterized by the presence of a dense inflammatory infiltrate, which may result in increased DNA damage and other nuclear/cellular abnormalities. Therefore, it is important to evaluate the periodontal diseases influence on DNA damage and other nuclear/cellular abnomalies formation as cancer risk markers. Thus, the aim of this study was to evaluate the periodontal diseases effect, according to its severity, on the occurrence of DNA damage and other nuclear/cellular abnormalities. This is a cross-sectional study with 77 subjects from the dentistry clinic of the University of Santa Cruz do Sul, Brazil, divided in control group (26 subjects), moderate periodontal disease group (26 subjects) and severe periodontal disease group (25 subjects). All subjects answered self-referenced questionnaires, underwent periodontal clinical examinations and allowed the collection of oral mucosa cells for the BMCyt. In relation to DNA damage biomarkers (micronuclei (MN) and/or nuclear buds (NBUD)), our results indicated no increase in MN frequencies (p > 0.05), however it indicated significant difference in NBUD frequencies between groups (p < 0.024). This result suggests that the periodontal disease status may influence DNA damage. Regarding the other nuclear/cellular abnormalities, was observed a significant difference in the binucleated (BN) frequencies between groups (p < 0.05). Moreover, the periodontitis severity was associated to an increase in the combined (summed) frequency of cells with different levels of DNA damage (MN and/or NBUD), cytokinetic defects (BN cells) and/or cell death (karyorrhexis, pyknotic and karyolytic cells) (r = 0.235; p = 0.040). Periodontal disease depending on its severity, induces nuclear anomalies in buccal cells.

Overweight and Obesity in Schoolchildren: Hierarchical Analysis of Associated Demographic, Behavioral, and Biological Factors.

Studies focused on the mechanisms involved in the development of obesity in children and adolescents have reported associations between this condition and birth weight, sedentary lifestyle, and hereditary conditions. However, few studies have simultaneously evaluated these factors. This cross-sectional study aims to identify demographic, behavioral, and biological factors associated with overweight/obesity in children and adolescents. 381 schoolchildren aged seven to 17 years were included in the study to evaluate the associations between overweight/obesity and biological factors (including family history of obesity, birth weight, and the fat mass and obesity-associated (FTO) rs9939609 polymorphism), demographic variables (including gender and age), and behavioral variables (including physical activity and/or sports participation). The results of this study showed that there was a lower prevalence of obesity in schoolchildren aged 11-17 years (PR: 0.89; p=0.004). Obesity was more prevalent in children whose father (PR: 1.24; p < 0.001) and maternal grandmother (PR: 1.16; p=0.019) were obese. Higher prevalence rates of obesity were also identified in schoolchildren who were overweight at birth (PR: 1.18; p=0.002) and carriers of the obesity risk genotype (PR: 1.13; p=0.016). Biological factors, such as family history of obesity, overweight at birth, and the presence of the fat mass and obesity-associated rs9939609 polymorphism were associated with the prevalence of obesity in children and adolescents.

Influence of hesperidin and vitamin C on glycemic parameters, lipid profile, and DNA damage in rats treated with sucrose overload.

We evaluated the influence of hesperidin and vitamin C (VitC) on glycemic parameters, lipid profile, and DNA damage in male Wistar rats treated with sucrose overload. Rats were divided into six experimental groups: I-water control; II-sucrose control; III-hesperidin control; IV-VitC control; V-co-treatment of sucrose plus hesperidin; VI-co-treatment of sucrose plus VitC. We measured the levels of triglycerides, total cholesterol, HDL-c, LDL-c, fasting glucose, and glycated hemoglobin (A1C). DNA damage was evaluated in blood and brain cells using the comet assay and the micronucleus test was used to evaluate chromosomal damages in the rat bone marrow. Co-treatment with VitC, but not with hesperidin, normalized the serum glucose. No effect of co-treatments was observed on A1C. The co-treatment with VitC or hesperidin did not influence the lipid profile (p>0.05). Rats co-treated with hesperidin had a significantly lower DNA damage level in blood (p<0.05) and brain (p<0.05). Rats treated with VitC only, but not those co-treated with VitC plus sucrose, had significantly higher DNA damage in brain (p<0.05). No significant differences were observed in the results of micronucleus test (p>0.05). Hesperidin and VitC showed different effects on sucrose and DNA damage levels. While VitC lowered the serum glucose, hesperidin reduced the DNA damage.

High consumption of sucrose induces DNA damage in male Wistar rats.

The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

High consumption of sucrose induces DNA damage in male Wistar rats

ABSTRACT The purpose of this study was to determine the effects of the high consumption of sucrose on the levels of DNA damage in blood, hippocampus and bone marrow of rats. Male Wistar rats were treated for 4 months with sucrose (10% for 60 initial days and 34% for the following 60 days) in drinking water, and then, glycemia and glycated hemoglobin (A1C) were measured. Levels of DNA damage in blood and hippocampus were evaluated by the comet assay. The micronucleus test was used to evaluate chromosomal damages in the bone marrow. The sucrose treatment significantly increased (p<0.01) the serum glucose levels (~20%) and A1C (~60%). The level of primary DNA damage was significantly increased (p<0.05) in hippocampal cells (~60%) but not in peripheral blood leukocytes (p>0.05). Additionally, it was observed a significative increase (p<0.05) in the markers of chromosomal breaks/losses in bone marrow, as indicated by the micronucleus test. This is the first study that evaluated DNA damage induced by high sucrose concentration in the hippocampus and bone marrow of rats. Sucrose-induced DNA damage was observed in both tissues. However, the mechanism of sucrose toxicity on DNA remains unknown.

Biological functions of selenium and its potential influence on Parkinson's disease.

Parkinson's disease is characterized by the death of dopaminergic neurons, mainly in the substantia nigra, and causes serious locomotor dysfunctions. It is likely that the oxidative damage to cellular biomolecules is among the leading causes of neurodegeneration that occurs in the disease. Selenium is an essential mineral for proper functioning of the brain, and mainly due to its antioxidant activity, it is possible to exert a special role in the prevention and in the nutritional management of Parkinson's disease. Currently, few researchers have investigated the effects of selenium on Parkinson´s disease. However, it is known that very high or very low body levels of selenium can (possibly) contribute to the pathogenesis of Parkinson's disease, because this imbalance results in increased levels of oxidative stress. Therefore, the aim of this work is to review and discuss studies that have addressed these topics and to finally associate the information obtained from them so that these data and associations serve as input to new research.

Recognition memory and DNA damage in undernourished young rats.

This study evaluated the recognition memory and the levels of DNA damage (blood and hippocampus) in undernourished young Wistar rats. The experiment was conducted along 14-week with rodents divided in control group (CG, n=8) and undernourished group (UG, n=12) which was submitted to caloric restriction. Nutritional status for undernutrition was defined by Body Mass Index (BMI) ≤0.45g/cm2 and by weighting the organs/tissue (liver, spleen, intestine, peritoneal fat, kidney and encephalon). The Novel Object Recognition Test assessed recognition memory and the Comet Assay evaluated the levels of DNA damage. Student t test, 2-way ANOVA and Pearson's correlation analysis were used and the significance level was of p<0.05. The UG showed lower BMI and organ/tissue weights than CG (p<0.001). In short-term memory, the recognition rate was higher in the UG (p<0.05), only after 4 weeks. In the long-term memory, again recognition rate was higher in the UG than the CG, after 4 weeks (p<0.001) and 14 weeks (p<0.01). The UG showed decreased levels of DNA damage in the blood (p<0.01) and increased levels in the hippocampus (p<0.01). We concluded in this study that the undernutrition by caloric restriction did not cause impairment in recognition memory, however induced DNA damage in the hippocampus.

DNA damage in children and adolescents with cardiovascular disease risk factors.

The risk of developing cardiovascular disease (CVD) is related to lifestyle (e.g. diet, physical activity and smoking) as well as to genetic factors. This study aimed at evaluating the association between CVD risk factors and DNA damage levels in children and adolescents. Anthropometry, diet and serum CVD risk factors were evaluated by standard procedures. DNA damage levels were accessed by the comet assay (Single cell gel electrophoresis; SCGE) and cytokinesis-blocked micronucleus (CBMN) assays in leukocytes. A total of 34 children and adolescents selected from a population sample were divided into three groups according to their level of CVD risk. Moderate and high CVD risk subjects showed significantly higher body fat and serum CVD risk markers than low risk subjects (P<0.05). High risk subjects also showed a significant increase in DNA damage, which was higher than that provided by low and moderate risk subjects according to SCGE, but not according to the CBMN assay. Vitamin C intake was inversely correlated with DNA damage by SCGE, and micronucleus (MN) was inversely correlated with folate intake. The present results indicate an increase in DNA damage that may be a consequence of oxidative stress in young individuals with risk factors for CVD, indicating that the DNA damage level can aid in evaluating the risk of CVD.

Desferoxamine reverses neonatal iron-induced recognition memory impairment in rats.

We have previously demonstrated that rats given iron neonatally presented memory deficits. The aim of the present study was to evaluate the effect of desferoxamine, a metal chelating agent, on memory deficits in an iron overload model in rats. Male rats received vehicle or iron orally at postnatal days 12-14 and desferoxamine (30 or 300 mg/kg) in the adulthood. After desferoxamine treatment, they were trained in a novel-object recognition task. Iron-treated rats showed recognition memory impairments when compared to controls. Iron-treated rats that received desferoxamine 300 mg/kg, showed normal recognition memory, suggesting that desferoxamine can reverse recognition memory deficits associated with iron accumulation. Further research is required to examine whether the findings from animal models of iron overload have implications for humans.