Obese Prepubertal Children Research Articles

Could Receptors for Advanced Glycation End Products Be Considered Cardiovascular Risk Markers in Obese Children?

Early development of increased cardiovascular risk in obese children and the possible related cardiovascular diseases into adulthood have been shown; however, the underling pathogenetic mechanisms implicated are not yet completely defined. Receptors for advanced glycation end products (RAGE) pathway play a pivotal role in the genesis of abnormality of arterial wall. However, whether obese prepubertal children present impaired levels of endogenous and soluble secretory receptor for advanced glycation end products (esRAGE/sRAGE) and whether an association exists between RAGE levels and carotid intima media thickness (cIMT) are not yet evaluated in this age group. We note that esRAGE and sRAGE were significantly lower in obese children than controls and were independently related to cIMT. Our findings lead to the hypothesis that RAGE system seems to be related to the development of atherosclerosis even in obese prepubertal children.

Thyroid dysfunction in obese pre-pubertal children: Oxidative stress as a potential pathogenetic mechanism

Although a relationship between obesity and hyperthyrotropinemia has been hypothesized in obese children, the underlying pathogenesis is not completely known. In the current cross-sectional study, we evaluated the thyroid function in a group of 80 obese pre-pubertal children compared to 41 healthy normal weight peers, exploring the possible association between hyperthyrotropinemia and oxidative stress. In all children, thyrotropin (TSH), free T4 (fT4), free T3 (fT3) and anti-thyroid antibodies were evaluated. Homeostatic model assessment of insulin resistance (HOMA-IR) level was evaluated as index of insulin resistance. We measured the endogenous secretory receptor for advanced glycation end products (esRAGE) and soluble RAGE (sRAGE) and the urinary prostaglandin F2α (PGF-2α) as markers of oxidative stress. We found that TSH levels were significantly higher in obese children than controls. TSH significantly correlated with body mass index-standard deviation score (BMI-SDS), HOMA-IR, PGF-2α, esRAGE and sRAGE. The multiple linear regression showed that in obese children HOMA-IR, PGF-2α, esRAGE and sRAGE were significantly related to TSH, independently of BMI-SDS, age and gender. In obese children, hyperthyrotropinemia could be detected already in pre-pubertal age. The increased oxidative stress might represent one of the key regulators of TSH levels, early in life.

Breakfast skipping in prepubertal obese children: hormonal, metabolic and cognitive consequences

Skipping breakfast influences cognitive performance. The aim of our study was to investigate the relationship between the variation of hormonal and metabolic postprandial parameters induced by breakfast consumption or fasting and cognitive performance in obese children. Cross-sectional study for repeated measures. Memory and attention assessment tests, hormones and nutrient oxidation were measured before and after consuming breakfast vs fasting in 10 prepubertal obese children. Fasting induced a significant (P<0.05) increase of the Overall Index of the Continuous Performance Test II (a global index of inattention) and the Test of Memory and Learning Word Selective Reminding (a test of verbal memory), whereas no changes were found after breakfast. Fasting was associated with a reduction of insulin and an increase in glucagon, with no changes in glucose. The increase in inattention was associated with a reduction of carbohydrate oxidation (ρ=-0.66, P<0.05). We found no difference in the area under the curve of peptide YY and glucagon-like peptide-1 after breakfast or fasting, whereas Ghrelin was significantly lower. No association between postprandial hormone variation and cognitive performance was found. Attention and visual memory performance in the morning were reduced when the children skipped breakfast. No association was found with hormones or metabolic changes, but we did find an association with a reduction of carbohydrate oxidation. Nevertheless, these preliminary findings need confirmation in larger sample size.

Effects of a psychomotor education program on body Mass index (bMI) in a group of school- aged Italian children

Many studies report that a corrected and systematic motor activity may represent a valid and therapeutic approach for preventing and treating overweight and obesity in pre-pubertal children [1]. In this context a psychomotor activity, aimed mainly to improve the functional pre-requisites [2], could play a key role, in particular in helping to perceive properly the own body image often misrepresented among obese children. The aim of this study was to evaluate the effects of a psychomotor education program (focused on the training of global and segmentary coordination, static and dynamic equilibrium, as well as spatio-temporal cognition) for a period of two years, on body mass index (BMI) an anthropometric parameter easily obtainable from weight and height and commonly utilized as index of obesity [3], in a group of 489 eight year- old children living in Florence (Italy).Comparing the BMI values recorded in children before and after the psycomothor activity we found a significant decrease of weight excess (approximately 17.6% vs 27.6%). Moreover we also found that the mean increase of BMI was less than that of the Italian population of the same age (approximately 0.55 vs 1.2), suggesting a beneficial effects of the psychomotor activity.

Implications of gastrointestinal hormones in the pathogenesis of obesity in prepubertal children

There is a worsening high prevalence of global obesity. Special attention has been paid to the gut-endocrine system, represented by the regulators of appetite. In particular, it has been suggested that ghrelin ("hunger" peptide), and obestatin and glucagon-like peptide-1 (GLP-1) ("satiety" peptides) could play important roles in the pathogenesis of obesity. The aims of this study were to compare fasting plasma ghrelin, obestatin, and GLP-1 levels between obese and nonobese prepubertal children, and to assess their relations with fatness indexes and insulin resistance (IR). Fifty-two prepubertal obese children and 22 controls were enrolled. Fasting levels of gastrointestinal hormones (ghrelin, obestatin, and GLP-1), glucose, and insulin were evaluated. IR was assessed using the homeostasis model assessment of IR (HOMA-IR) index. Analysis was performed by Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation. Obese prepubertal children and normal-weight controls had similar age distribution. Obese children were more insulin resistant when compared to controls (HOMA-IR: p < 0.01 ). GLP-1 levels were significantly lower in obese children than in controls (p < 0.01). Obestatin was significantly higher in obese than normal-weight children (p < 0.01), while ghrelin was not different. There was a negative correlation between GLP-1 and standard deviation score-body mass index (r = -0.36, p = 0.009) and between GLP-1 and waist circumference (r = -0.45, p = 0.001), while no association was observed with HOMA-IR. GLP-1 levels have been shown to be correlated with adiposity indexes, but not with HOMA-IR, suggesting that this hormone could play an important role in the early development of obesity.

Expression profiling based on coexpressed modules in obese prepubertal children

The aim of this study was to identify related genes and the underlying molecular mechanisms in obese patients who show a series of clinical and metabolic abnormalities known as metabolic syndrome. We identified expression profiles through a coexpression network. In addition, a similarity matrix and expression modules were constructed based on domain and pathway enrichment analysis. The genes in module 1 were mainly involved in the metabolism of xenobiotics by cytochrome P450, aldosterone-regulated sodium reabsorption, and focal adhesion owing to the presence of aldo/ketoreductase, basic helix-loop-helix, von Willebrand factor, Frizzled-related domain, and other domains. The genes in module 3 may be involved in cell cycle (hsa04110) and DNA replication (hsa03030) pathways through mini-chromosome maintenance, serine/threonine protein kinase, the protein kinase domain, and other domains. We analyzed the published molecular mechanisms of obesity and found many genes and pathways that have not been given enough attention and require further confirmation.

Impact of childhood obesity treatment on body composition and metabolic profile

Childhood obesity is associated with adverse changes in cardiometabolic risk factors. A family-oriented group program stressing a health-promoting lifestyle has been more effective than routine counselling in the treatment of obesity in school children. The aim of the present study was to compare the impact of group program and routine councelling on body composition and metabolic profile, and to evaluate the associations of changes in adiposity with levels of cardiometabolic risk factors. Seventy obese prepubertal children were randomized into family-oriented group program (15 sessions for parents and children) and routine counselling (2 appointments for children). Body mass index (BMI), body composition and different metabolic risk factors were assessed before and after the 6-month intervention. Waist/height decreased more in the children attending the group treatment, but there were no significant differences between treatment arms in the changes of metabolic risk factors. When the arms were analyzed as combined, serum triglycerides decreased significantly if BMI standard deviation score (BMI-SDS) decreased ≥ 0.5. Serum fasting insulin decreased if BMISDS decreased ≥ 0.25. Obesity-related metabolic risk factors reduced in prepubertal children if BMI-SDS decreased substantially. This result was not dependent on which intervention, family-oriented group program or routine counselling, was used.

Elevated circulating levels of the serum acute-phase protein YKL-40 (chitinase 3-like protein 1) are a marker of obesity and insulin resistance in prepubertal children

YKL-40 (chitinase 3-like protein 1) is a newly recognized protein that is secreted by activated macrophages and neutrophils and expressed in a broad spectrum of inflammatory conditions and cancers. It has also been associated with endothelial dysfunction and diabetes in adults. Its role in childhood obesity has not been evaluated yet. Our aim was to evaluate the associations of serum YKL-40 levels with markers of obesity, inflammation, and insulin resistance in children. Forty-one obese prepubertal children and 41 age- and sex-matched lean controls were included, and serum YKL-40 levels were determined. Body mass index (BMI), blood pressure (BP), body fat percentage, fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR) index, whole-body insulin sensitivity index, lipids, white blood cell (WBC) count, C-reactive protein, and fibrinogen levels were also assessed. Obese children had higher YKL-40 levels compared with controls (P = .003). Insulin-resistant individuals showed higher YKL-40 compared with non–insulin-resistant individuals after adjusting for age and BMI (adjusted P = .039). Serum YKL-40 levels were positively correlated with age, BMI, body fat percentage, fasting glucose and insulin, HOMA-IR index, whole-body insulin sensitivity index, systolic BP, mean BP, and WBC count (P < .05). After adjustment for age, sex, BMI, WBC count, and systolic BP, HOMA-IR index remained significantly associated with YKL-40 levels (P < .001). The study suggests that YKL-40 levels are elevated in obese youth and represent a marker of insulin resistance even in childhood. Prospective studies are needed to determine whether children with elevated YKL-40 levels are at higher risk for future cardiovascular disease.

Presence of the Metabolic Syndrome in Obese Children at Prepubertal Age

Background/Aims: There is a strong debate on the diagnosis and early phenotypic expression of the metabolic syndrome in children. The aim of the present study was to examine the frequency of the metabolic syndrome using various definitions in obese prepubertal and pubertal children. Methods: 478 (213 females and 265 males) obese children were recruited in three provinces of Spain. Blood pressure (BP), waist circumference, and weight and height were measured, and body mass index was calculated. Glucose, insulin, high-density lipoprotein cholesterol and triacylglycerols were determined. We classified the children according to seven different proposed definitions of the metabolic syndrome. Results: Regardless of the definition used, the prevalence of the metabolic syndrome (8.3–34.2%) was relatively high in obese children in the prepubertal period as well as in pubertal children (9.7–41.2%). We performed a principal-factor analysis to explain correlations among features of the metabolic syndrome and found that glucose metabolism (factor 1), dyslipidemia (factor 2) and obesity/BP (factor 3) explained 72% of the total variance. Conclusion: Irrespective of the classification used, the metabolic syndrome is not only present in pubertal but also in prepubertal children. International definitions of the metabolic syndrome should also consider criteria specific for children in the prepubertal period, i.e. children aged <10 years.

Early-Onset Metabolic Syndrome in Prepubertal Obese Children and the Possible Role of Alanine Aminotransferase as Marker of Metabolic Syndrome

Introduction: Obesity is often associated with increased serum alanine aminotransferase (ALT), and elevation of ALT is a marker of non-alcoholic fatty liver disease which is caused in part by insulin resistance, the essential characteristic of metabolic syndrome (MS). We evaluated the prevalence of MS in prepubertal obese children and the usefulness of ALT as an MS marker. Patients: 120 obese children (6.3 ± 1.6 years old) and 50 normal-weight controls (5.3 ± 2.0 years old) were included. Patients were classified as having MS if they met ≧3 of the following criteria: body mass index >97th percentile, triglycerides >95th percentile, high-density lipoprotein cholesterol <5th percentile, systolic (SBP) and/or diastolic (DBP) blood pressure >95th percentile, fasting blood glucose 100 mg/dl and/or impaired insulin sensitivity with homeostasis model assessment for insulin resistance >97.5th percentile. ALT levels were also evaluated. Results: MS occurred in 16.6% of obese patients. Significant differences were present in body mass index (p < 0.001), SBP (p = 0.002) and DBP (p < 0.001) between non-MS and MS obese patients; laboratory data, except total cholesterol, were significantly different in the two groups. The strongest association with MS (as evaluated by the c-statistic) was found for insulin and homeostasis model assessment for insulin resistance (c = 0.92 and 0.91, respectively); also, DBP and SBP showed good discrimination ability (c = 0.73 and 0.72, respectively). ALT levels in the MS group were higher than in the non-MS group (p = 0.02) and associated with MS (p = 0.001; c = 0.69). Conclusion: MS is a consequence of obesity already in very young children. Also, pathological serum ALT levels were significantly correlated with MS and might be considered a marker for defining MS, though confirmation in a longitudinal study is called for.

Osteocalcin-insulin relationship in obese children: a role for the skeleton in energy metabolism

Osteocalcin is a bone-specific protein secreted by osteoblasts and often used as a bone formation biomarker. Rodent studies have reported a hormonal role of osteocalcin on glucose metabolism, increasing insulin secretion and sensitivity and increasing energy expenditure. However, it is unknown whether osteocalcin fulfils the same function in humans. We investigated the relationship between serum osteocalcin and insulin concentrations in 27 prepubertal obese children (9-12 years old) randomly divided into two groups, one of which entered a physical training programme, and 16 nonobese control children. Whole body bone mineral density (WB-BMD), serum osteocalcin, circulating insulin and adiponectin were measured at baseline and after 6 months. Trained and untrained obese children had higher WB-BMD than controls at baseline. Trained children also displayed a significant insulin increase and a significant adiponectin decrease while osteocalcin was increased compared to untrained obese children. Significant linear correlations between WB-BMD and adiponectin, delta BMD (variation between baseline and after-training values) and delta adiponectin, insulin and osteocalcin, delta insulin and delta osteocalcin, delta insulin and delta under-carboxylated osteocalcin were found only in trained obese children with no significant relationship in control and untrained obese children. In trained obese children, correlations indicate that when BMD is increased, osteocalcin is increased and insulin lowered. This suggests that increased BMD is associated with increased energy metabolism and a decreased level of insulin. We thus report statistically significant relationships between the skeleton (osteocalcin) and energy metabolism (insulin), suggesting a regulatory hormonal loop including osteocalcin and insulin.

Commentaries on Viewpoint: Can muscle size fully account for strength differences between children and adults?

# {#article-title-2} to the editor: As comprehensively explained in their Viewpoint article ([1][1]), the answer to the question posed in the title has received conflicting answers. Since the contractile machinery in children is the same as that in adults, there is no reason to believe that

Lumbar spine bone mineral density is influenced by bone age but not by weight loss in prepubertal obese children

Lumbar spine bone mineral density is influenced by bone age but not by weight loss in prepubertal obese children

Effect Of A Fruit And Vegetable Juice Concentrate (FVJC) Vs. Medical Nutrition Therapy Alone On Metabolic Syndrome Components In Obese Children: A 6 Month Pilot Double Blind Placebo‐Controlled Study

Epidemiologic studies report lower β‐carotene (BC) and retinol (ROL) in obese vs. non obese children, and suggest this likely predisposes to the metabolic syndrome (MS). We determined the effect of a 6‐month FVJC vs. Medical Nutrition Therapy (MNT) on the prevalence of MS based on 4 different criteria (MS1–Cook; MS2 and MS3‐Lambert; MS4‐de Ferranti) in 11 normal weight, 6 overweight and 22 obese pre pubertal children in a prospective randomized placebo‐controlled trial. Waist circumference, fasting glucose, insulin, triglyceride, HDL and systolic blood pressure (SBP) for age, sex and height (NHPBEP) were determined. Daily total kilocalories and average intake of vitamin A in retinol equivalents (VARE) or BC were derived from FFQ. ROL, BC, HOMA‐IR and QUICKI were determined at 0, 3 and 6 months. The prevalence of MS (MS4 criteria) decreased by 16 % at 3‐months (χ2 =6.004 p=0.014) in the FVJC vs. MNT but this effects was lost at 6 months; no significant change in HOMA‐IR or QUICKI; BC but not ROL correlated with a decrease in HOMA‐IR (χ2 = −0.393 p= 0.03) and an increase in QUICKI (χ2 =0.550 p=0.002), no correlation between intakes of VARE or BC and BC. Taken together, the increase in BC and reduction in MS (MS4 criteria) in FVJC vs. MNT suggest a potential role for BC in the regulation of insulin sensitivity in obese children. Population‐wide studies are warranted to determine the significance of this association.

Parent Diet Modification, Child Activity, or Both in Obese Children: An RCT

Outcomes of childhood obesity interventions are rarely reported beyond 1 year. We hypothesized that the impact on the BMI z score from a child-centered physical-activity program in combination with a parent-centered dietary-modification program would be greater than either program conducted alone at 24 months' after baseline. A total of 165 overweight prepubertal children (68 boys, aged 5.5-9.9 years, mean BMI z score: 2.8) were randomly assigned to either a child-centered physical-activity program, a parent-centered dietary-modification program, or both conducted together in an assessor-blinded 6-month intervention. Using linear mixed models, all groups reduced their mean (95% confidence interval) BMI z score at 24 months from baseline (P < .001) (the activity and diet group: -0.24 [-0.35 to -0.13]; the diet-only group: -0.35 [-0.48 to -0.22]; activity-only group -0.19 [-0.30 to -0.07]). There was a significant group-by-time interaction (P = .04) with the activity + diet and the diet-only groups showing a greater reduction than the activity-only group. For waist z score and waist-to-height ratio, there was a significant time effect (P < .0001) at 24 months but no between-group differences (P > .05). Some metabolic outcomes improved at 24 months, although there were no between-group differences (P > .05). A reduction in BMI z score was sustained at 24 months by treatment with either program combination. The greatest effects were achieved through inclusion of a parent-centered diet program, indicating the importance of targeting parents within treatment and the possibility of targeting them exclusively in treating obese prepubertal children.

Feeding frequency and appetite in lean and obese prepubertal children.

To determine the effect of feeding frequency on appetite in normal weight (NW) and obese (OB) prepubertal children, we carried out a prospective, randomized interventional study of 18 NW and 17 OB children ages 6-10. Children received three or five feedings in random order on separate days. Total calories, carbohydrate, protein, and fat composition on each day were equal. Two hours following the last feeding, children were offered ice cream ad lib. The major outcome variable was kilocalories ice cream consumed. A visual analog scale to assess fullness was also administered before consumption of ice cream. We observed that OB children consumed 73.0 ± 37.4 kcal more after five feedings than after three feedings whereas the NW children consumed 47.1 ± 27.8 kcal less. There was significant interaction between meal pattern and weight group indicating that this change in ice cream consumption differed significantly between groups (P = 0.014 by two-factor analysis). Ice cream intake/kg was less in OB compared to NW subjects (P = 0.012). Fullness ratings before ice cream did not differ by meal pattern or weight group. However, pre-ice cream fullness predicted ice cream intake in NW but not OB children. In summary, OB and NW children differed in appetite response to meal frequency. Our data suggest that: (i) satiety in OB children is related more to proximity of calories (larger supper) than to antecedent distribution of calories and; (ii) NW children may be more prone to restrict intake based on subjective fullness.

A Parent-Led Family-Focused Treatment Program for Overweight Children Aged 5 to 9 Years: The PEACH RCT

To evaluate a healthy lifestyle intervention to reduce adiposity in children aged 5 to 9 years and assess whether adding parenting skills training would enhance this effect. We conducted a single-blinded randomized controlled trial of prepubertal moderately obese (International Obesity Task Force cut points) children, aged 5 to 9 years. The 6-month program targeted parents as the agents of change for implementing family lifestyle changes. Only parents attended group sessions. We measured BMI and waist z scores and parenting constructs at baseline, 6, 12, 18, 24 months. Participants (n = 169; 56% girls) were randomized to a parenting skills plus healthy lifestyle group (n = 85) or a healthy lifestyle-only group (n = 84). At final 24-month assessment 52 and 54 children remained in the parenting skills plus healthy lifestyle and the healthy lifestyle-only groups respectively. There were reductions (P < .001) in BMI z score (0.26 [95% confidence interval: 0.22-0.30]) and waist z score (0.33 [95% confidence interval: 0.26-0.40]). There was a 10% reduction in z scores from baseline to 6 months that was maintained to 24 months with no additional intervention. Overall, there was no significant group effect. A similar pattern of initial improvement followed by stability was observed for parenting outcomes and no group effect. Using approaches that specifically target parent behavior, relative weight loss of ∼10% is achievable in moderately obese prepubertal children and can be maintained for 2 years from baseline. These results justify an investment in treatment as an effective secondary obesity-prevention strategy.

Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism

To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

What Is the Significance of Soluble and Endogenous Secretory Receptor for Advanced Glycation End Products in Liver Steatosis in Obese Prepubertal Children?

The endogenous secretory receptor for advanced glycation end products (esRAGE) and soluble RAGE (sRAGE) have been shown in human plasma and have emerged as reliable biomarkers of several pathological conditions, including insulin resistance and liver injury. We examined esRAGE and sRAGE levels in obese prepubertal children with and without liver steatosis. esRAGE and sRAGE levels were significantly lower in obese prepubertal children affected by liver steatosis and were independently related to liver steatosis. These findings suggest that AGE-RAGE pathway plays an independent role in the development of liver injury already present in this age group.

Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance

We compared the fasting serum proinsulin levels in lean, overweight, and obese prepubertal children with normal glucose tolerance (NGT). We also evaluated the relationship between fasting proinsulin level and indices of insulin resistance (IR). One hundred nine prepubertal children (mean age, 8.6 yr) with NGT were included. The indices of IR included the homeostasis model assessment of IR (HOMA-IR) and adiponectin level. We recorded the presence of one or more of the following metabolic derangements: triglycerides ≥ 150 mg/dL, HDL-cholesterol < 35 mg/dL, and hypertension. Fasting proinsulin levels significantly increased with body mass index (BMI) category from lean (n = 52, 7.22 ± 3.01 pmol/L) to overweight (n = 14, 12.31 ± 2.91 pmol/L) to obese (n = 43, 16.51 ± 7.27 pmol/L) (p < 0.001), after controlling for HOMA-IR. The ratio of the fasting levels of proinsulin to insulin did not differ significantly between the three groups. Both BMI z-score and HOMA-IR were significant independent factors related to the fasting proinsulin level (p < 0.001 for each). A significant inverse association was found between fasting proinsulin level and adiponectin level (r = -0.464, p < 0.001). Children with NGT who had at least one metabolic derangement had higher proinsulin levels than those without metabolic derangement. Obesity itself or obesity-related IR may independently impose β-cell overload on prepubertal children with NGT, leading to hyperproinsulinemia without causing failure to convert proinsulin to insulin when some degree of IR and metabolic derangement appears.