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Objective: To compare the prevalence of mildly reduced estimated glomerular filtration rate (MRGFR) (eGFR >60 and < 90 mL/min/1.73 m 2 ), calculated by two creatinine-based equations, and its association with cardiometabolic risk factors (CMRF) in youth with overweight (OW)/obesity (OB)., Methods: This is a multicenter cross-sectional study involving university and non-university hospital pediatrics departments. We enrolled 3,118 youth with OW/OB (5-14 years) and 286 healthy normal weight (NW) youth. eGFR was calculated using bedside Schwartz equation (eGFRBSE) and Full Age Spectrum equation (eGFRFAS). In OW/OB group we analyzed the association between eGFR calculated by both equations and CMRF. Uric acid (UA) and birth weight were available in 2,135 and in 1,460 youth., Results: The prevalence of MRGFR was 3.8% in NW versus 7.8% in OW/OB (P = .016) by eGFRBSE, and 8.7% in NW versus 19.4% in OW/OB (P < .0001) by eGFRFAS. eGFRBSE and eGFRFAS identified 242 and 605 young people with OW/OB with MRGFR, respectively. Individuals with MRGFR according with both equations showed lower birth weight, younger age, higher BMI-SDS, non-high-density lipoprotein-cholesterol and UA as compared to those with normal eGFR. To examine whether the eGFRFAS was associated with a worse CMR profile also in the range of normal eGFRBSE, we reclassified young people with normal eGFRBSE (n = 2,876) according with eGFRFAS. Out of youth with normal eGFRBSE, 366 (12.7%) presented MRGFR by eGFRFAS and had lower age, higher BMI-SDS, BP and UA than the remaining youth reclassified as normal eGFRFAS., Conclusion: MRGFR is associated with an altered CMR profile in a large sample of young people with overweight (OW)/obesity (OB). The eGFRFAS equation identifies a higher prevalence of youth with MRGFR, compared to eGFRBSE equation., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Recent evidence linked early menarche to a higher risk of insulin-resistance (IR) and nonalcoholic fatty liver disease (NAFLD) in adulthood. We aimed to evaluate the impact of early menarche on glucose derangements and NAFLD in a sample of Italian adolescents with obesity., Methods: Anthropometric and biochemical evaluations were conducted in all the enrolled 318 obese patients (mean age 12.31 ± 2.95 years). NAFLD was defined by the presence of ultrasound detected liver steatosis and/or alanine transaminase (ALT) levels >40 IU/L., Results: Patients with early menarche showed both higher homeostasis model assessment of insulin-resistance (HOMA-IR) (p=0.008) and ALT (p=0.02) values, an increased prevalence of NAFLD (p=0.001), and lower Matsuda and Insulinogenic Index (IGI) values than the other obese patients. The association between early menarche and both ALT and Matsuda Index remained significant in General Linear Models (GLMs) in which respectively body mass index standard deviation score (BMI-SDS) and Matsuda Index, and BMI-SDS were included as covariates. Patients with early menarche also showed a higher risk of both HOMA-IR>3 (OR 1.69, CI 1.05-2.70, p=0.02) and NAFLD (OR 1.10, CI 1.01-1.21, p=0.03)., Conclusions: Girls with obesity presenting early menarche showed higher HOMA-IR levels, lower Matsuda Index and IGI values, and higher risk of NAFLD compared to girls without early menarche., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphism influences estimated glomerular filtration rate (eGFR) in adults without diabetes and without obesity. We aimed exploring the impact of this polymorphism on eGFR in children with obesity with and without non-alcoholic fatty liver disease (NAFLD)., Methods: We genotyped 531 children with obesity for TM6SF2 E167K polymorphism. NAFLD was defined by ultrasound detected liver steatosis and/or ALT > 40 IU/L., Results: Patients carrying the TM6SF2 167K allele showed higher eGFR levels compared with E167 homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with TM6SF2 genotype both in patients with and without NAFLD. This association, however, was stronger in patients with NAFLD., Conclusions: Children with obesity carrying the TM6SF2 167K allele show higher eGFR levels compared with E167 allele homozygous subjects, independently of NAFLD. A major effect of this polymorphism in the presence of NAFLD was captured.

Background: PNPLA3 I148M polymorphism has an effect on modulation of estimated glomerular filtration rate (eGFR) in nonobese nondiabetic adults and in children with histologically confirmed nonalcoholic fatty liver disease (NAFLD)., Objectives: The objective of the study is to explore the impact of PNPLA3 I148M polymorphism on eGFR in children with obesity with and without NAFLD., Methods: We genotyped 591 patients with obesity for PNPLA3 I148M polymorphism. Anthropometrical, biochemical, and instrumental data were collected. NAFLD was defined by the presence of ultrasound-detected liver steatosis and/or ALT levels greater than 40 IU/L., Results: Patients with NAFLD showed significantly lower eGFR levels compared with subjects without NAFLD. Children with PNPLA3 MM genotype showed lower eGFR levels compared with those with either PNPLA3 IM or II genotypes both in the presence and absence of NAFLD. A general linear model for eGFR variance, including gender, duration of obesity, PNPLA3 genotypes, HOMA, BMI-SDS, LDL-C, and triglycerides as covariates, confirmed an inverse association between eGFR and PNPLA3 genotype only in the presence of NAFLD., Conclusions: Children with obesity and PNPLA3 MM genotype show lower eGFR levels compared with other genotypes, with a major effect of this polymorphism in the presence of NAFLD., (© 2019 World Obesity Federation.)

Asthma is the most frequent chronic disease in childhood. Chest tightness, cough, wheezing and dyspnoea during or after exercise may be unique manifestations of asthma in up to 90% of subjects. Physical activity may be reduced by uncontrolled asthma symptoms and parental beliefs, impairing physical fitness of asthmatic children. Clinicians working in the field of allergy are aware of evidence supporting the benefits of physical activity for patients with asthma. Treatment of asthma is required in order to obtain its control and to avoid any limitation in sports and active play participation. As exercise performance in children with controlled asthma is not different from that of healthy controls, any exercise limitation cannot be accepted. Overweight and obesity may interfere with asthma and exercise, leading to dyspnoea symptoms. Evidences on the effect of insulin resistance on airway smooth muscle and on bronchial hyperactivity are presented. CONCLUSION: Exercise is part of the strategy to obtain the best control of asthma in childhood, but we have to optimise the asthma control therapy before starting exercise programming. Furthermore, it is crucial to give best attention on the effects of obesity and insulin resistance, because they could in turn influence patients' symptoms., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Obesity is an increasing health problem worldwide. Its related comorbidities imply a high cost for the National Health System and diminish a patient's life quality. Adipose tissue is composed of three types of cells. White adipocytes are involved in fat storage and secretion of hormones. Brown adipocytes are involved in thermogenesis and caloric expenditure. Beige adipocytes are transitional adipocytes that in response to various stimuli can turn from white to brown and could be protective against the obesity, enhancing energy expenditure. The conversion of white in beige adipose tissue is a potential new therapeutic target for obesity. Cannabinoid receptors (CB) regulate thermogenesis, food intake and inflammation. CB1 ablation or inhibition helps reducing body weight and food intake. Stimulation of CB2 limits inflammation and promotes anti-obesity effects by reducing food intake and weight gain. Its genetic ablation results in adiposity development. CB receptors are also responsible for transforming white adipose tissue towards beige or brown adipocytes, therefore their modulation can be considered potential anti-obesity target. CB1 principal localization in central nervous system represents an important limit. Stimulation of CB2, principally localized on peripheral cells instead, should facilitate the anti-obesity effects without exerting remarkable psychotropic activity.

Background: The rs641738 polymorphism in the membrane-bound O-acyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD)., Objectives: To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin-like phospholipase domain-containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms., Methods: One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated., Results: Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3-5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43-4.83, P = 0.0018) compared with those belonging to lower genetic risk score group., Conclusions: We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.

Background: Youth exposed to antipsychotics may experience several metabolic consequences that often limit the effectiveness of this class of drugs., Objectives: The aim of this study was to compare several metabolic markers between subjects who experienced antipsychotic-induced weight gain and untreated obese patients., Methods: Nineteen non-diabetic youth (mean age 159 months, mean body mass index z-score 1.81) experiencing antipsychotic-induced weight gain and an age-, sex-, and body mass index-matched group of non-diabetic obese patients with no record of treatment (n = 19, mean age 147 months, mean body mass index z-score 2) were compared for a wide range of metabolic factors using a Bioplex Multiplex system., Results: C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin were significantly higher in the antipsychotic-induced weight gain group, whereas visfatin was significantly higher in the untreated obese patients. When age, sex, pubertal status, and body mass index were controlled, C-peptide, glucose-dependent insulinotropic polypeptide, and visfatin remained significant, whereas adipsin fell slightly below the threshold of statistical significance. No other statistically significant difference emerged., Conclusions: Antipsychotic-induced weight gain and untreated obesity showed some similarities, confirming that levels of some hormones, such as leptin and ghrelin, are related to body mass index rather than to antipsychotic exposure. Some differences were also noted; for example, the antipsychotic-induced weight gain group displayed higher C-peptide, glucose-dependent insulinotropic polypeptide, and adipsin, which may reflect β-cell stress and may suggest susceptibility to insulin resistance and lower visfatin, possibly indicating a lower inflammatory status.

Objectives: To assess cytokine and chemokine levels in youth experiencing antipsychotic-induced weight gain (AIWG) compared to obese patients, hypothesizing a different "immune signature" between the two kinds of obesity., Methods: We compared a group of youth experiencing AIWG (N 19, mean age 159 months, mean body mass index [BMI] z-score 1.81) and an age-, gender-, and BMI-matched group of untreated obese patients (N 19, mean age 147 months, mean BMI z-score 2) for a wide range of cytokines and chemokines by using a multiplex ELISA test., Results: Platelet-derived growth factor (PDGF), interleukin (IL)1-β, IL4, IL8, IL9, IL12, IL 17, eotaxin, FGF, GMCSF, IP10, MIP1b, and vascular-endothelial growth factor (VEGF) were significantly lower in the AIWG group, whereas IL13 and RANTES were significantly higher. Controlling for age, sex, and BMI, PDGF, IL4, IL8, IL13, IL17, eotaxin, fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GMCSF), IP10, MIP1b, and VEGF remain significantly different., Conclusion: A clearly different pattern of cytokines distinguishes the two kinds of obesity, suggesting a different immune signature. Interestingly, most of the cytokines and chemokines bearing proinflammatory effects resulted decreased in the AIWG group, whereas IL-13, which holds an immune-modulatory effect, resulted increased.

Background: The N-acetyltransferase 2 ( NAT2 ) A803G polymorphism has been associated with decreased insulin sensitivity in a large adult population with the A allele associated with insulin-resistance-related traits., Objective: Evaluate the association of this polymorphism with anthropometric and metabolic parameters in obese children and adolescents., Subjects: A total of 748 obese children and adolescents were enrolled., Methods: Anthropometric and laboratory data were collected. During oral glucose tolerance test, the presence of a possible exaggerated plasma glucose excursion at 1 h (1HPG) or impaired glucose tolerance (IGT) was considered. Homeostasis model assessment, oral disposition index (oDI) and insulinogenic index (IDI) were calculated. Patients were genotyped for the NAT2 A803G polymorphism., Results: The prevalence of both IGT and elevated-1HPG was higher in children carrying the A803 allele (P = .02 and P = .03). Moreover, this allele was associated with both oDI and IGI reduction (P = .01). No differences among the NAT2 A803G genotypes for the other parameters were shown. Children homozygous for the A allele presented an odds ratio (OR), to show IGT of 4.9 (P = .01). Children both homozygous and heterozygous for the A allele had higher risk to show elevated-1HPG (OR of 2.7, P = .005; and OR = 2.3, P = .005) compared with patients homozygous for the NAT2 803G allele., Conclusions: NAT2 A803 allele seems to play a role in worsening the destiny of obese children carrying it, predisposing them to elevated-1HPG and IGT and then to a possible future type 2 diabetes mellitus throughout an impairment of pancreatic β-cellular insulin secretion as suggested by oDI and IGI reduction., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Context: Obesity is associated with a low-grade inflammatory state and adipocyte (ADP) hyperplasia/hypertrophy. Obesity inhibits the "browning" of white adipose tissue. Cannabinoid receptor 2 (CB2) agonists reduce food intake and induce antiobesity effect in mice. A common missense CB2 variant, Q63R, causes CB2-reduced function., Objective: To evaluate the influence of CB2 receptor on the modulation of childhood obesity and of ADP activity and morphology., Design: CB2-Q63R variant was analyzed in obese Italian children. The effects of an inflammatory stimulus and those of drugs selectively acting on CB2 were investigated on in vitro ADPs obtained from mesenchymal stem cells of adult healthy donors or from sc adipose biopsies of adult nonobese and obese subjects., Setting: Department of Women, Child and General and Specialist Surgery of the Second University of Naples., Patients or Other Participants: A total of 501 obese Italian children (age 11 ± 2.75). Twelve healthy bone marrow donors (age 36.5 ± 15); and 17 subjects, 7 lean (age 42 ± 10) and 10 obese (age 37.8 ± 12) underwent sc adipose tissue biopsies., Main Outcome Measures: Effects of CB2 stimulation on adipokine, perilipin, and uncoupling protein-1 expression., Results: The less-functional CB2-R63 variant was significantly associated with a high z-score body mass index. CB2 blockade with AM630 reverse agonist increased inflammatory adipokine release and fat storage and reduced browning. CB2 stimulation with JWH-133 agonist reversed all of the obesity-related effects., Conclusion: CB2 receptor is a novel pharmacological target that should be considered for obesity.

Background: The ovary is an important site where gene variants modulate pubertal timing. The cannabinoid receptor 2 (CB2) is expressed in the ovary, plays a role in folliculogenesis and ovulation, and can be modulated by estrogens. Obesity is strictly associated with early menarche and is characterized by sex hormone and endocannabinoid derangement., Aim: In this study, we investigated the role of the CB2 receptor in determining the age at menarche in obese girls., Methods: We studied a cohort of 240 obese girls (age 11.9±3 years; BMI z-score 2.8±0.8). The age at menarche (if it had already occurred) was recorded at the time of the visit or via phonecall. The CNR2 rs35761398 polymorphism, which leads to the CB2 Q63R variant, was detected by the TaqMan assay., Results: In total, 105 patients were homozygous for the R63-coding allele (RR), 113 were QR and 22 were QQ. Variance analysis revealed a significantly earlier age of menarche in subjects carrying the Q63 allele, which was also found after adjusting for BMI z-score (11±1.2 vs. 11.6±1.2 years, p = 0.0003). Logistic regression analysis demonstrated that patients homozygous for the Q allele had a 2.2-fold higher risk (odds ratio = 2.2; CI1.1-3.4; p = 0.02) of presenting with an early menarche (age at menarche <12 years)., Conclusion: We demonstrated for the first time the association between the CB2 Q63R functional variant and the age at menarche in a cohort of Italian obese girls.

Background: The prevalence of obesity is increasing among children/adolescents. Subtle cardiovascular abnormalities, responsible for a higher mortality later in life, have been reported in obese children/adolescents. The aims of the study were to evaluate cardiovascular autonomic regulation, by means of spectrum analysis of R-R interval variability, and myocardial function, by means of standard and tissue Doppler echocardiography, in a group of non-hypertensive asymptomatic obese children and adolescents; furthermore, the influence of insulin resistance was tested., Subjects and Methods: R-R interval variability was analyzed during both the 70° head-up tilt and 24-hour electrocardiographic holter monitoring. Spectrum analysis of R-R interval variability provided the indices of sympathetic (low frequency [LFRR]) and vagal (high frequency [HFRR]) modulation of the sinoatrial node. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to classify obese children/adolescents (n=72) as insulin resistant (n=37) and non-insulin resistant (n=35)., Results: In obese subjects: a) left ventricular mass was significantly (p<0.05) increased, whereas both the e/a ratio and the e'/a' ratio were decreased; b) at rest, HFRR was lower, and the LFRR/HFRR ratio was higher; c) during tilting, magnitude of tilt-induced inhibition of HFRR was lower; d) during 24-hour electrocardiographic holter monitoring, LFRR and the LFRR/HFRR ratio were higher, whereas HFRR was lower; e) HOMA-IR inversely correlated with both the e'/a' ratio (r=-0.655; p<0.001) and the tilt-induced LFRR/HFRR ratio (r=-0.933; p<0.001); and, f) the e'/a' ratio correlated with the tilt-induced LFRR/HFRR ratio (r=0.501; p<0.001). Moreover, HFRR at rest, magnitude of tilt-induced HFRR reduction, and the e'/a' ratio in insulin resistant obese children/adolescents were markedly lower when compared with the remaining subjects., Conclusions: Subclinical abnormalities of myocardial function and of cardiac autonomic regulation were closely associated in obese children/adolescents and both correlated with the degree of insulin resistance.

Objective: To assess the accuracy of body mass index (BMI), Z score of the BMI, waist circumference, and waist-to-height ratio in selecting obese children with fasting metabolic impairments or impaired glucose tolerance., Study Design: In a cohort of 883 obese children and adolescents (age 8-18 years), we assessed the associations of anthropometric indices with traditional metabolic complications of obesity (impaired fasting glucose, impaired glucose tolerance, hypertension, high triglycerides, low high-density lipoprotein-cholesterol). The accuracy of anthropometric indices as markers of metabolic impairment was assessed by receiver operating characteristic analysis and the areas under the receiver operating characteristics curves (AUROCs) of anthropometric indices were compared with each other by the DeLong test., Results: BMI, Z score of the BMI, waist circumference, and waist-to-height ratio were associated with metabolic impairments but showed low to moderate accuracy in discriminating both single and clustered metabolic impairments. The AUROCs ranged from 0.55-0.70. The 4 anthropometric indices did not show significantly different AUROCs as predictors of clustered metabolic risk factors (all P values of DeLong tests: >.05)., Conclusions: Commonly used anthropometric indices are not satisfactory markers of metabolic comorbidity among obese children and adolescents and should not be adopted as screening tools for the metabolic assessment of this category of patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Obesity in children/adolescents has been associated with subtle cardiac abnormalities, including myocardial dysfunction and cardiac autonomic dysregulation at rest, both likely responsible for a higher mortality in adulthood. Food intake induces remarkable adjustments of cardiovascular autonomic activity in healthy subjects., Objective: The objective of the study was to evaluate in obese children/adolescents meal-induced cardiac autonomic response and the role played by insulin resistance., Design and Setting: Sixty-eight obese and 30 matched normal-weight children/adolescents underwent blood sampling and cardiovascular autonomic analysis while recumbent and 20 minutes after a mixed meal ingestion. Spectrum analysis of the R-R interval and systolic blood pressure (SBP) variability provided the indices of sympathetic [low frequency (LFRR)] and vagal [high frequency (HFRR)] modulation of the sinoatrial node and the low frequency component of SBP. The homeostasis model assessment of insulin resistance served to separate insulin resistant (n = 35) from non insulin resistant (n = 33) obese children/adolescents., Results: At baseline, C-reactive protein, the LFRR to HFRR ratio, SBP, and low frequency oscillatory component of SBP variability in obese children/adolescents were significantly (P < .05) greater than in referent subjects, whereas high-density lipoprotein cholesterol and HFRR were lower; meal-induced increase in the LFRR to HFRR ratio was significantly less than in controls and exaggeratedly scanty (or opposite) among insulin resistant subjects. The homeostasis model assessment of insulin resistance index strongly and inversely correlated (r = -0.871; P < .001) with meal-induced changes in the LFRR to HFRR ratio among obese subjects., Conclusions: Autonomic modulation of the heart was impaired after eating in obese children/adolescents. This abnormality was exaggerated among insulin resistant subjects and strongly correlated with the degree of insulin resistance.

Objective: To verify in obese children whether or not the presence of (i) high waist-to-height ratio (WHtR), (ii) family history for type 2 diabetes (T2D) and (iii) acanthosis nigricans (AN), singularly or together, might predict the occurrence of metabolic syndrome or prediabetes., Methods: 1,080 Italian obese children (567 females) were enrolled. Blood pressure, fasting plasma glucose, insulin, and lipids were measured, and oral glucose tolerance test (OGTT) was performed. The WHtR was calculated, family history for T2D was assessed, and the presence of AN was noticed. The odds ratios for showing metabolic syndrome and/or prediabetes according to the presence of these features were calculated., Results: The prevalence of metabolic syndrome was 29.2%. AN (OR1.81; p = 0.002) and WHtR higher than 0.60 (OR 2.24; p < 0.0001) were the clinical signs linked to higher risk for showing metabolic syndrome, and the odds raised significantly when these elements occurred simultaneously (OR 3.34; p < 0.0001). T2D family history (OR 2.36; p = 0.01) and WHtR higher than 0.60 (OR 2.32; p = 0.009) were the two features associated with increased odds of showing prediabetes., Conclusions: Three simple actions, i.e., looking at the patient, asking about T2D family history, and measuring WHtR, may represent a powerful tool in the hands of pediatricians to identify obese children with high cardiovascular and metabolic risk., (Copyright © 2013 S. Karger GmbH, Freiburg)

Context: Several studies demonstrated that obese children have higher TSH than normal-weight children. The polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene showed an association with TSH., Objectives: i) To assess the effect of PDE8B on TSH in obese children; ii) to dissect the role of obesity degree in modulating this association; and iii) to stratify the individual risk to show hyperthyrotropinaemia according to PDE8B genotype., Methods: Eight hundred and sixty-seven Italian obese children were investigated. Clinical data and thyroid hormones were evaluated and the PDE8B rs4704397 was genotyped., Results: PDE8B A/A homozygous subjects showed higher TSH (P=0.0005) compared with A/G or G/G. No differences were found for peripheral thyroid hormones. Among A/A children, 22% had hyperthyrotropinaemia, compared with 11.6% of heterozygotes and 10.8% of G/G (P=0.0008). Consistently, A/A had an odds ratio (OR) to show abnormal TSH level of 2.25 (P=0.0004). Body mass index (BMI) appeared correlated with TSH (P=0.0001), but the strength of the effect of PDE8B on TSH was independent of BMI (P=0.1). Children were subdivided into six groups according to obesity degree and genotypes. PDE8B A/A with BMI SDS above 3 had the highest OR (OR 2.6, P=0.0015) to have hyperthyrotropinaemia, whereas G/G with BMI SDS below 3 showed the lowest possibilities (OR 0.3, P=0.005)., Conclusions: We have shown: i) in obese children, PDE8B is associated with TSH; ii) the interaction between adiposity and PDE8B on TSH is not synergistic, but follows an additive model; and iii) impact of this association in the stratification of individual risk to have hyperthyrotropinaemia.

Obese children have a great risk of hypertension and cardiovascular morbidity in adults. The insulin-like growth factor type II (IGF-II) regulates glucose homeostasis, cardiovascular functions, and lipid metabolism. IGF2 gene variants have shown a strong association with weight, body mass index (BMI), and metabolic profile in adults. We performed the molecular screening of two IGF2 polymorphisms (6815 A/T, 820 G/A), in 227 obese children to evaluate the potential association between IGF2 variants with either obesity or high blood pressure (assessed with a 24-h holter system) or both. A second cohort of age-, sex-, and BMI-matched children were enrolled to confirm any eventual association. We observed a significant association between the 6815 A/T IGF2 gene variant and high systolic blood pressure in obese children. Homozygote subjects for the T6815 allele showed, even in 24-h measurements, a higher risk to develop hypertension than those carrying the A6815 allele (OR = 3.7, 95% CI: 1.59-8.66). This result was confirmed in the second cohort (OR = 4.1, 95% CI: 1.41-6.50). Any statistically significant difference in terms of BMI between the genotype groups was observed. Our results suggest that IGF2 gene variants are involved in the blood pressure regulation in obese children.

Context: Obesity and iron deficiency are two of the most common nutritional disorders worldwide. Several studies found higher rates of iron deficiency in obese than in normal-weight children. Hepcidin represents the main inhibitor of intestinal iron absorption, and its expression is increased in adipose tissue of obese patients. Leptin is able, in vitro, to raise hepcidin expression., Objectives: Aims of this work were 1) to assess the association between poor iron status and obesity, 2) to investigate whether iron homeostasis of obese children may be modulated by serum hepcidin variations, and 3) to assess the potential correlation between leptin and serum hepcidin variations., Methods: Iron status and absorption as well as hepcidin, leptin, and IL-6 levels were studied in 60 obese children and in 50 controls., Results: Obese children showed lower iron and transferrin saturation (both P < 0.05) and higher hepcidin levels (P = 0.004) compared with controls. A direct correlation between hepcidin and obesity degree (P = 0.0015), and inverse correlations between hepcidin and iron (P = 0.04), hepcidin and transferrin saturation (P = 0.005), and hepcidin and iron absorption (P = 0.003) were observed. A correlation between leptin and hepcidin (P = 0.006) has been found. The correlation remained significant when adjusted for body mass index, sex, pubertal stage, and IL-6 values., Conclusions: We propose that in obese patients, increased hepcidin production, at least partly leptin mediated, represents the missing link between obesity and disrupted iron metabolism.

Background: Melanocortin-4-receptor (MC4R) mutations represent the most frequent genetic cause of non-syndromic early onset obesity. Children carrying MC4R mutations seem to show a particular phenotype characterized by early onset, severe obesity and high stature. To verify whether MC4R mutations are associated with this particular phenotype in the Italian pediatric population, we decided to screen the MC4R gene in a group of obese children selected on the basis of their phenotype., Methods: To perform this study, a multicentric approach was designed. Particularly, to be enrolled in the study subjects needed to meet the following criteria: Body mass index > or = 3 deviation scores according to age and sex, familiar history of obesity (at least one parent obese), obesity onset before the 10 years old, height > or = 2 deviation scores. The coding region of MC4R gene was screened in 240 obese children (mean age 8.3 +/- 3.1, mean BMI 30.8 +/- 5.4) and in 200 controls (mean age 8.1 +/- 2.8; mean BMI 14.2 +/- 2.5)., Results: Three mutations have been found in five obese children. The S127L (C380T), found in three unrelated children, had been described and functionally characterized previously. The Q307X (C919T) and the Y332H (T994C) mutations were found in two patients. Functional studies showed that only Q307X impaired protein function., Conclusion: The low prevalence of MC4R mutations (1.6%) in this group of obese children selected according to the obesity degree, the tall stature and the family history of obesity was similar to the prevalence observed in previous screenings performed in obese adults and in not phenotypically selected obese children.

Context: Variants on the nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1) gene have been associated with obesity and insulin resistance. Because insulin resistance is a pivotal factor in the development of metabolic syndrome (MS) and impaired glucose tolerance (IGT), we aimed to test the association between the K121Q and rs997509 ENPP-1 variants with obesity, MS and IGT in obese children and adolescents., Methods: We screened 809 children, 409 obese and 400 lean controls. Obese subjects underwent a standard oral glucose tolerance test, whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) were calculated., Results: No difference in prevalence for K121Q and rs997509 polymorphisms between obese and controls (P > 0.05) were observed. Obese children carrying the rs997509 rare allele showed higher insulin (P = 0.001), HOMA (P < .001) and lower WBISI values (P = 0.04) compared with common allele homozygous. A similar observation was done for K121Q variant, with 121Q allele carriers showing higher insulin (P = 0.03) and HOMA (P = 0.04) values than 121K homozygotes. Moreover, subjects carrying the rs997509 rare allele had higher risk of MS (odds ratio 2.4, 95% confidence interval: 1.3-4.3) and IGT (odds ratio 4.7, 95% confidence interval: 1.9-11.4) than common allele homozygotes. Evaluating combined effects of both polymorphisms, which are in strong linkage disequilibrium, we showed that the effect on insulin sensitivity was due to the rs997509 T variant., Conclusion: We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.

Objective: To verify whether peptide YY (PYY) and its Y2 receptor (Y2R) gene variants can be associated with obesity or hypertension or both in a cohort of obese children and adolescents., Patients and Methods: Two hundred and twenty-nine obese children (105 girls, mean z-score BMI 5.1 +/- 2.4; mean age 10.5 +/- 2.9 years) and 250 age and sex-matched lean controls (130 women, mean z-score BMI 0.5 +/- 1.1; mean age 10.3 +/- 2.8) were enrolled in the study. Height, weight, BMI, waist circumference and 24-h systolic and diastolic blood pressure were measured. Night-time, day-time and 24-h systolic and diastolic blood pressures were evaluated by 24 h ambulatory blood pressure measurement, and appropriate standard deviation scores according to sex, age and height were calculated. Molecular screening of the PYY and Y2R genes was performed., Results: No new mutations were found. We observed three previously described polymorphisms: G767C on PYY and T585C and T936C on Y2R. An association study was carried out in obese patients. No associations were found between the PYY genotypes and the studied phenotypes. The Y2R gene variants, T585C and T936C, which are in almost complete linkage disequilibrium, were found to be associated with night-time, day-time and 24-h systolic and diastolic blood pressures. In particular, subject homozygotes for the T allele showed lower systolic and diastolic blood pressure values compared with the other genotypes. Moreover, obese children homozygous for the T585 allele showed a lower risk of developing hypertension than patients carrying the CC and CT genotypes (chi 6.9; df = 1, P = 0.03; odds ratio = 0.5, 95% confidence interval: 0.27-0.88)., Conclusion: Our results suggest that Y2R gene variants are involved in blood pressure regulation in obese children and adolescents.

According to the World Health Organization, obesity is one of the most common nutritional problem among children. The major determinant of this enormous increase in obesity prevalence is modern lifestyle and the consumption of very caloric foods such as fast-food products. Actually, there is a strong relationship between obesity and hypertension, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, and orthopedic problems. The aim of this review is to discuss the main mechanisms that link obesity to cardiovascular disease.

Objective: In search of functional polymorphisms associated with the genetics of insulin resistance, we studied a variant in the promoter of PIK3CB, the gene coding for the catalytic p110beta subunit of phosphatidylinositol (PI) 3-kinase, a major effector of insulin action., Research Design and Methods: The rs361072 C/T variant was selected among single nucleotide polymorphisms of the PIK3CB region because we suspected that its common C allele (allelic frequency approximately 50% in Europeans) could create a GATA-binding motif and was genotyped in five cohorts of obese (n = 1,876) and two cohorts of nonobese (n = 1,490) European children. To estimate insulin resistance in these children, the homeostasis model assessment for insulin resistance (HOMA-IR) index was measured in strict nutritional conditions. GATA-binding and functional effects of rs361072 were explored in transfected cell lines and in lymphocytes from obese children., Results: The rs361072 C/T variant was associated with HOMA-IR in the obese children cohorts (1.7 x 10(-12) < P < 2 x 10(-4) for C/C vs. T/T using regression analysis). HOMA-IR averaged 3.3 +/- 0.1 in C/C and 4.5 +/- 0.2 in T/T obese children (P = 4.5 x 10(-6) by ANOVA). C/T patients had intermediate values. As shown by the interaction between BMI and genotype (P = 2.1 x 10(-9)), the association of rs361072 with HOMA-IR depended on BMI and was only marginal in nonobese children (P = 0.04). At the molecular level, the C allele of rs361072 was found to create a GATA-binding site able to increase transcription of PIK3CB., Conclusions: We postulate that the C allele of rs361072 is a causal variant capable of attenuating insulin resistance in obese children through increased expression of p110beta.

Background: Obesity in adulthood is associated with a higher occurrence of atrial arrhythmias. Obese children, without arterial hypertension, may be a unique clinical opportunity to evaluate the effect of obesity, per se, on atrial myocardial function, excluding the influence of possible comorbidities. We sought to define the preclinical effects of obesity on the atrial function of healthy children with excess weight who have no other clinically appreciable cause of heart disease, by using the more sensitive ultrasonic-derived strain (S) and S rate imaging., Methods: We studied 320 children divided into two groups: obese children (group O; n = 160; age 12 +/- 3 years); and healthy lean children, comparable for age, sex, and pubertal stage (referents; n = 160; mean age 12 +/- 3 years)., Results: Systolic blood pressure (BP) and diastolic BP, as well as 24-hour systolic BP and 24-hour diastolic BP were comparable between groups. Left ventricular mass/height(2.7) and left atrial dimensions were increased (P < .0001) in group O (46 +/- 12 g/m(2.7)) compared with referents (31 +/- 14 g/m(2.7)). Standard echocardiographic indices of global left ventricular systolic function were similar in the two groups. Obese children showed atrial peak systolic S rate (2.5 +/- 1.2 (s-1)) values lower (P < .0001) than that of referents (4.9 +/- 1.6(s-1)) in both left and right atria. In multivariable analysis, average peak systolic atrial S was significantly correlated with glycemia (P < .05, coefficient -0.23), body mass index (P < .01, coefficient -0.19), and left ventricular mass (P < .05, coefficient -0.17)., Conclusions: Our study demonstrated that obesity, in absence of hypertension, is associated with reduced atrial myocardial deformation properties already in childhood involving both right and left atria.

Background: The central melanocortin system is critical for the long-term regulation of energy homeostasis. Melanocortin-3 receptor (MC3R) knock-out mice, despite being hypophagic, have increased fat mass and higher feed efficiency than do their wild-type littermates., Objective: The aim was to evaluate whether, in childhood obesity, MC3R variants are associated with changes in fatness reduction as a consequence of a weight-reduction program., Design: Molecular screening of the MC3R coding region in 184 obese children, 77 girls and 107 boys [x (+/-SEM) body mass index (BMI; in kg/m(2)) z score: 3.3 +/- 2.3; age 9.2 +/- 2 y], was performed. BMI was evaluated at baseline and after 6 and 12 mo of the weight loss program., Results: No new mutations were found. Two previously described polymorphisms, C17A (Thr6Lys) and G241A (Val81Ile), were observed in 20 patients in almost complete linkage disequilibrium. No significant differences in BMI z scores were observed at baseline of the weight-loss program between the genotypes; however, at follow-up, heterozygotes showed a significantly higher BMI z score (P = 0.03). When the patients were divided according to the amount of weight lost, a higher prevalence of heterozygotes was observed among subjects who lowered their BMI z score <1.5 (P = 0.03)., Conclusion: These results suggest a gene-diet interaction between the MC3R C17A and G241A variants and a weight loss program for the ability to lose weight in childhood obesity.

Aims: The prevalence of obesity is increasing among children in the developed world. The association of obesity and abnormal cardiac function is still debated. The reported changes may reflect the role of comorbidities that contribute to ventricular dysfunction. Obese children, without arterial hypertension, may be a unique clinical opportunity to evaluate the effect of obesity, per se, on myocardial function, excluding the influence of possible comorbidities. We sought to define the preclinical effects of obesity on the cardiovascular system, of healthy children with excess weight who have no other clinically appreciable cause of heart disease, using the more sensitive ultrasonic-derived strain and strain rate (SR) imaging., Methods and Results: We studied 300 subjects divided into two groups: (i) obese children (Group O: n=150; age, 12+/-3 years); (ii) healthy lean children comparable for age, sex, and pubertal stage (Referents: n=150; mean age, 12+/-3 years). Systolic (SBP) and diastolic blood pressure (DBP), as well as 24 h-SBP and 24 h-DBP were comparable between groups. Left ventricular (LV) mass/height(2.7) was increased (P<0.0001) in Group O (46+/-12 g/m(2.7)) when compared with Referents (31+/-14 gm(2.7)). Standard echocardiographic indices of global systolic function were similar in the two groups. Intima-media thickness measured at the common carotid artery was not significantly different (P=0.4) in obese children (0.46+/-0.09 mm) when compared with Referents (0.45+/-0.07 mm). Obese children showed regional longitudinal peak systolic myocardial deformation properties (SR=-1.4+/-0.7 s(-1)) lower (P<0.0001) than those of Referents (SR=-2.2+/-0.5) in both left and right ventricle. In multivariable analysis, average peak systolic SR was significantly correlated with homeostasis model assessment of insulin resistance (P<0.01; coefficient, 0.02; SE, 0.011), and insulin serum concentration (P<0.01; coefficient, 0.05; SE, 0.023). Average LV peak systolic strain was significantly correlated with body mass index (P=0.0001; coefficient, 0.06; SE, 0.016), LVM/H(2.7) (P=0.006; coefficient, 0.016; SE, 0.018)., Conclusions: Our study demonstrated that obesity, in absence of hypertension, is associated with significant reduction in systolic myocardial deformation properties already in childhood involving both right and left ventricle. Obesity not only is a risk factor for later cardiovascular disease, but also is associated with contemporaneous and significant impairment of longitudinal myocardial deformation properties.

Objective: The insulin variable number of tandem repeats (VNTR) polymorphism located in the insulin gene promoter (INS VNTR) has been associated with insulin levels in obese children. Hyperinsulinemia is a pivotal factor in the development of metabolic syndrome, an emerging complication in childhood obesity. With the present study, we aimed to test the associations between INS VNTR and the metabolic syndrome in juvenile-onset obesity., Subjects and Methods: We screened for the INS VNTR in 320 obese children (152 girls; mean age, 11.2 +/- 2.3 yr; mean z-score body mass index, 3.6 +/- 1.1). All of them underwent a standard oral glucose tolerance test; baseline measurements included blood pressure and plasma lipid and fasting insulin levels. By using the data derived from the oral glucose tolerance test, the whole-body insulin sensitivity and the insulinogenic index were calculated., Results: The prevalence of metabolic syndrome reached 39%. No differences in INS VNTR genotype distribution were observed between obese subjects and 200 lean, age- and sex-matched children (P = 0.7). Among obese subjects, the prevalence of the metabolic syndrome was significantly higher in subjects with the I/I genotype (P = 0.006); the risk for developing the metabolic syndrome was significantly higher in subjects carrying the I/I genotype (odds ratio, 2.5; 95% confidence interval, 1.5-3.9). Obese subjects homozygous for the class I allele showed higher insulin levels and insulinogenic index but lower whole-body insulin sensitivity., Conclusions: We conclude that the I variant of the insulin promoter, when expressed in homozygotes, can predispose obese children to develop the metabolic syndrome.

Background and Purpose: To assess the presence of sleep-disordered breathing (SDB) in a population of obese children and adolescents and to investigate the role of fat distribution in predicting SDB., Patients and Methods: One hundred and thirty-two obese children and adolescents, aged 5.0-14.2 years, were consecutively referred to the Department of Pediatrics of the Second University of Naples for screening of obesity. The control group consisted of 453, sex- and age-matched lean subjects selected from local schools in Campania region. The sleep disturbances scale for children (SDSC) questionnaire was used to evaluate SDB prevalence. In all subjects, waist circumference, triceps and sub-scapular skin folds were measured, and Z-scores were calculated., Results: Obese subjects showed significantly higher SDB and sleep hyperhydrosis (SHY) scores than controls. The Z-score of waist circumference correlated with SDB (r=0.32; P=0.006) and SHY factor scores (r=0.37; P=0.005), while the Z-score of body mass index (BMI), triceps and sub-scapular skin folds were not correlated with any SDSC factor scores. Subjects in the higher tertile for Z-score of waist circumference had a significantly higher risk for developing SDB (OR 1.9; 95% IC 1.8-3.2) and SHY (OR 2.1; 95% IC 2.0-4.5)., Conclusions: Waist circumference is a more reliable index than total adiposity and subcutaneous fat in predicting the risk of obese children to develop SDB.

Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART.

Lines of evidence show a role of the melanocortinergic system in the regulation of glucose metabolism in obese subjects. The aim of this study was to investigate the influence of proopiomelanocortin (POMC) in the variability of insulin levels in early-onset obesity. To address this issue, an association study using a 9-bp insertional polymorphism, AGC AGC GGC, between nucleotides 6979 and 6998 of the POMC gene, was performed in 380 (185 girls) Italian obese children and adolescents. Allelic frequencies were comparable in our patients (0.053) and in 300 lean controls of Mediterranean descent (0.045). Interestingly, we showed that this polymorphism, in the obese patients, was associated with differences in fasting insulin levels; this finding persisted after correction for age, sex, and pubertal stage. Heterozygotes had 24% higher mean insulin levels than those homozygous for the wild allele and showed a stronger correlation between insulin and body mass index (P < 0.001). These findings support the hypothesis that the melanocortin pathway may modulate glucose metabolism in obese subjects and suggest that this common POMC variant may be involved in the natural history of polygenic obesity in late adolescence and adulthood, contributing to the link between type 2 diabetes and obesity.

The role of obesity as a risk factor for chronic kidney disease (CKD) in adulthood has been well established. Over the last years, kidney damage (KD) has emerged as a significant consequence of obesity since childhood. Indeed, a complex interplay of metabolic factors, including insulin resistance (IR), hypertension, oxidative stress, adipose tissue dysfunction, and systemic inflammation, might affect renal hemodynamics, contributing to CKD development over time in at-risk young patients. As the prevalence of pediatric obesity continues to rise globally, understanding the implications for kidney health in terms of early intervention is of paramount importance. Careful monitoring of kidney function within a multidisciplinary approach in children with obesity is crucial for detecting early KD, allowing for timely lifestyle modifications and treatment. In this framework, continued research is essential to further elucidate mechanisms linking obesity and KD and to explore not only effective preventive strategies but also the long-term impact of obesity on kidney health in children with obesity. Given the intimate link of KD with the metabolic milieu in children with obesity, we aimed to provide a comprehensive and insightful overview on KD and its implications in pediatric obesity by reviewing the most recent literature in the field. [ABSTRACT FROM AUTHOR]

Background: Pediatric obesity treatment is based on high-intensity lifestyle counseling. However, high dropout rates and low effectiveness have been reported, even in specialized centers. Mobile health technologies have been used to overcome these limits with contrasting results. This study aims at evaluating the effectiveness of a six-month intervention with a mobile app for the treatment of pediatric obesity at 6 and 12 months of follow-up. Methods: Seventy-five patients were randomly assigned to standard care or standard care plus mobile app (2:1) using an online randomizer system. The mobile app delivered high-intensity lifestyle counseling for diet and physical activity. Results: At six months of follow-up, the M-App group showed significantly lower dropout rates compared to standard care (p = 0.01). The risk of dropout was significantly higher in controls compared to the intervention group (OR 3.86, 95% C.I. 1.39–10.42, p = 0.01). After one year, we observed lower albeit non-statistically significant dropout rates in the M-App compared to the standard care group (p = 0.24). No differences were observed in z-score BMI and percentage of BMI reduction between the two groups. Conclusions: Our findings suggest that the mobile app might help in the clinical management of children and adolescents with obesity in terms of dropout reduction. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between HDL-Cholesterol (HDL-C), hypertension, and left ventricular hypertrophy (LVH) in a large sample of Caucasian youths with overweight/obesity (OW/OB). A cross-sectional multicenter study was performed in 1469 youths (age 6–16 years) with OW/OB observed in the period 2016–2020. An additional independent sample of 244 youths with an echocardiographic evaluation, observed in a single center was analyzed. The sample was divided in six quantiles (Q) of HDL-C: Q1: >56, Q2: ≤56 > 51, Q3: ≤51 > 45, Q4: ≤45 > 41, Q5: ≤41 > 39, Q6: <39 mg/dL. The nadir of the relationship was identified in youths in the first quantile. Among HDL-Cholesterol quantiles the distribution of hypertension was non-linear with a percentage of 25.0%, 40.1%, 33.6%, 31.3%, 35.2% and 39.7% in the six quantiles, respectively. The percentage of LVH was 21.8%, 43.6%, 48.8%, 35.5%, 38.5% and 52.0% in the six quantiles, respectively. The highest odds [95%Cl] of hypertension were 2.05 (1.33–3.16) (P < 0.01) in Q2, 1.67 (1.10–2.55) (P < 0.05) in Q3 and 1.59 (1.05–2.41) (P < 0.05) in Q6 vs Q1. The odds of LVH were 3.86 (1.15–10.24) (P < 0.05) in Q2, 4.16 (1.58–10.91) (P < 0.05) in Q3 and 3.60 (1.44–9.02) (P < 0.05) in Q6 vs Q1, independently by centers, age, sex, prepubertal stage, and body mass index. Contrary to the common belief, the present study shows that high levels of HDL-C may be not considered a negative predictor of hypertension and LVH, two risk factors for future CV disease. • Association between HDL-Cholesterol and cardiovascular risk is non-linear in adults. • Whether a similar slope is present in youths with obesity is unexplored. • 1469 youths with obesity were stratified across six quantiles of HDL-Cholesterol. • A U-shaped curve between HDL-Cholesterol quantiles and hypertension was found. • Targeting only low HDL-Cholesterol as a risk factor may be misleading. [ABSTRACT FROM AUTHOR]

As the pediatric obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in childhood. Pediatric NAFLD pathophysiology is tangled and still unclear, but insulin resistance (IR), genetics, epigenetics, oxidative stress, and inflammation act as key players. Due to the increased cardiometabolic risk of these patients, several biomarkers have been proposed for early NAFLD identification, but their clinical utility is poor. Recently, hepatic dysregulation of microRNAs (miRNAs) has been linked to metabolic dysfunction, which in turn implied in NAFLD development. Evidence on the intriguing role of miRNAs in NAFLD pathogenesis has emerging especially in at-risk children such as those with obesity. However, pediatric evidence supporting their potential use as early noninvasive NAFLD tools is still limited but promising. We provided an overview on the emerging role of miRNAs in pediatric NAFLD by addressing some issues regarding their pathophysiological link with the metabolic milieu and their role as reliable NAFLD markers in children with obesity. Strong evidence supports a potential role of miRNAs as early biomarkers of NAFLD in children with obesity. They might represent a valid diagnostic and targeted therapeutic tool due to its close pathogenic link with the metabolic milieu. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones (TH) play multiple effects on glucose metabolism. Some recent studies carried out in adult patients suggested an association between altered sensitivity to TH and type 2 diabetes, obesity, and metabolic syndrome. No studies are currently available on the presence of altered sensitivity to the action of TH in youths with prediabetes. Objective: To evaluate the relationship between sensitivity to TH and impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or glycosylated hemoglobin (HbA1c) ≥ 5.7% in youths with overweight/obesity (OW/OB). Materials and methods: This cross-sectional study included 805 Caucasian youths with OW or OB (aged 6-18 years) recruited at seven Italian centers for the care of OW/OB. Individuals with TH out of the normal range of TH in each center were excluded. The fT3/fT4 ratio was evaluated to assess peripheral sensitivity, while TSH index (TSHI), Thyrotroph T4 Resistance Index (TT4RI), Thyroid Feedback Quantile-based Index (TFQI) and Parametric TFQI were calculated to assess central sensitivity. Results: Youths with IGT (n =72) showed higher levels of TSH (3.08 ± 0.98 vs 2.68 ± 0.98 mIU/L, P =0.001), TSHI (3.06 ± 0.51 vs 2.85 ± 0.53, P =0.001), TT4RI (46.00 ± 17.87 vs 38.65 ± 16.27, P <0.0001), TFQI [1.00 (0.97-1.00) vs 1.00 (0.99-1.00)], P=0.034), PTFQI (0.67 ± 0.20 vs 0.60 ± 0.22, P =0.007) compared to youths without IGT (n =733), independently of centers and age. No differences were observed for fT3/fT4-ratio. The others phenotypes of prediabetes were not associated with altered sensitivity to TH. Odds ratio of IGT raised of 1-7-fold for each increase of 1 mIU/L in TSH (P =0.010), 1 unit in TSH Index (P =0.004), TT4RI (P =0.003) or PTFQI (P =0.018), independently of centers, age, and prepubertal stage. Conclusion: IGT was associated with a reduced central sensitivity to TH in youths with OW/OB. Our finding suggests that IGT phenotype, known to be associated with an altered cardiometabolic risk profile, might also be associated with an impaired TH homeostasis in youths with OW/OB. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic changed adults and children's lifestyle. We focused our attention on children affected by chronic kidney disease (CKD) due to congenital abnormalities of kidney and urinary tract (CAKUT) and their behavior during the lockdown. Our aims were to evaluate the incidence of CKD progression within 6 months after the end of the first Italian lockdown and the factors associated to it. CKD progression was defined by the transition to higher CKD stage or by the drop in estimated glomerular filtration rate by a 25% or more for patients belonging to CKD stages 1 and 2. We retrospectively selected 21 children with CAKUT and CKD ≥ stage 1 observed within 3 months before and 6 months after the first Italian lockdown. We called them by phone and asked them about their lifestyle before and during lockdown focusing on physical activity, screen time, sweet/candies/sugar-sweetened beverages eaten/drunk and adherence to the Mediterranean diet (MD) (through KIDMED questionnaire). We calculated and analyzed the delta between the pre- and post- lockdown observation of all collected parameters (clinical and biochemical parameters and questionnaires scores). Analyzing the overall cohort, we found significantly increased mean BMI and mean screen time and significantly lower mean physical activity time in post- compared with pre-lockdown observations. Eleven out of twenty-one patients (52.4%) had a worsening of CKD. These patients presented higher delta of levels of uric acid and microalbuminuria and showed minor adherence to the MD and declared to have consumed more sweets or candies or sugar-sweetened beverages/week during the lockdown with a tendentially major increment of BMI compared with patients not presenting CKD progression. In conclusion, the lockdown for COVID-19 pandemic determined increase of BMI in all enrolled patients due to a "forced" negative lifestyle. About half of these patients presented CKD progression. This progression was associated to less adherence to the MD and major consumption of sweets or candies or sugar-sweetened beverages. [ABSTRACT FROM AUTHOR]

Aims: To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). Materials and Methods: Cross‐sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5–17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high‐density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. Results: The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06–1.68) for MetS (p = 0.02), 3.19 (2.51–4.05) for HUA (p < 0.0001) and 3.72 (2.65–5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. Conclusions: HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study. [ABSTRACT FROM AUTHOR]

Pediatric obesity is associated with an increased risk of morbidity during childhood. Alongside the well-known metabolic syndrome, during the last decades scientific research has deeply investigated the risk of sleep breathing disorders. Among them, obstructive sleep apnea (OSA) commonly affects children with obesity. The presence of OSA heightens the risk of metabolic impairment and weight gain. Therefore, it deserves specific treatment. However, polysomnography (PSG) is not always available in clinical settings, and alternative diagnostic tools are needed. This study aimed to investigate the predictivity of the pediatric sleep questionnaire (PSQ) for moderate-to-severe OSA diagnosis. Children and adolescents with obesity and suspected OSA with available full-night cardiorespiratory PSG were retrospectively enrolled. Receiver operating curve analysis was performed to test the ability of PSQ in predicting moderate-to-severe OSA (AHI > 5 episode/h). The final sample included 60 children and adolescents. The PSQ showed a good area under the curve (AUC) of 0.88 (95% CI 0.78–0.98, p < 0.0001). Moreover, a value above or equal to 0.65 showed an 80% sensitivity and 100% specificity for moderate and severe OSA. These findings suggest that PSQ might be used in clinical settings with limited access to PSG for stratifying disease severity and for selecting children with urgent need of sleep study. [ABSTRACT FROM AUTHOR]

The epidemic spread of childhood obesity in Western society has interested many researchers, who agree in defining it as a multifactorial disease in which not only eating habits and sedentary lifestyle play a role, but also genetic predisposition. The aim of this study was to analyze the personality profile of a group of mothers of children with obesity and to compare this profile to that of a group of mothers of children without obesity. A total of 258 mothers participated in the study (126 mothers of children with obesity and 132 mothers of children without obesity). Weight and height were measured and the body mass index was calculated. The Minnesota Multiphasic Personality Inventory second edition (MMPI-2), evaluating personality and psychological disorders, was used to evaluate the personality profile. The results suggested that mothers of children with obesity score higher than the mothers of children without obesity in all MMPI-2 subscales. In most of these subscales, the differences between the two groups of mothers were statistically significant and with a medium to high effect size. These data suggest a new perspective on childhood obesity, identifying it as a multifactorial pathology that requires a multimodal and multidisciplinary approach that also takes care of caregivers to ensure optimal therapeutic efficacy. [ABSTRACT FROM AUTHOR]