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Objective: The increasing prevalence of and inequities in childhood obesity demand improved access to effective treatment. The SmartMoves curriculum used in Bright Bodies, a proven-effective, intensive health behavior and lifestyle treatment (IHBLT), was disseminated to ≥30 US sites from 2003 to 2018. We aimed to identify barriers to and facilitators of IHBLT implementation/sustainment., Methods: We surveyed and interviewed key informants about experiences acquiring/implementing SmartMoves. In parallel, we analyzed and then integrated survey findings and themes from interviews using the constant comparative method., Results: Participants from 16 sites (53%) completed surveys, and 12 participants at 10 sites completed interviews. The 11 sites (63%) that implemented SmartMoves varied in both use of training opportunities/materials and fidelity to program components. In interviews, demand for obesity programming, organizational priorities, and partnerships facilitated implementation. Seven sites discontinued SmartMoves prior to the COVID-19 pandemic. Funding insecurity and insufficient staffing emerged as dominant barriers to implementation/sustainment discussed by all interviewees, and some also noted participants' competing demands and the program's fit with population as challenges., Conclusions: System- and organizational-level barriers impeded sustainment of an evidence-based IHBLT program. Adequate funding could enable sufficient staffing and training to promote fidelity to the intervention's core functions and adaptation to fit local populations/context., (© 2024 The Obesity Society.)

Objective: The main objective of this study is to better understand the effects of diet-induced weight loss on brain connectivity in response to changes in glucose levels in individuals with obesity., Methods: A total of 25 individuals with obesity, among whom 9 had a diagnosis of type 2 diabetes, underwent functional magnetic resonance imaging (fMRI) scans before and after an 8-week low-calorie diet. We used a two-step hypereuglycemia clamp approach to mimic the changes in glucose levels observed in the postprandial period in combination with task-mediated fMRI intrinsic connectivity distribution (ICD) analysis., Results: After the diet, participants lost an average of 3.3% body weight. Diet-induced weight loss led to a decrease in leptin levels, an increase in hunger and food intake, and greater brain connectivity in the parahippocampus, right hippocampus, and temporal cortex (limbic-temporal network). Group differences (with vs. without type 2 diabetes) were noted in several brain networks. Connectivity in the limbic-temporal and frontal-parietal brain clusters inversely correlated with hunger., Conclusions: A short-term low-calorie diet led to a multifaceted body response in patients with obesity, with an increase in connectivity in the limbic-temporal network (emotion and memory) and hormone and eating behavior changes that may be important for recovering the weight lost., (© 2024 The Obesity Society.)

Aims: Previous work found poor reproducibility for measures of glycemia in individuals at risk for dysglycemia. Differences between youth and adults have not been assessed. Using youth and adults in the Restoring Insulin Secretion Study, we tested variability and classification concordance for hemoglobin A1C (HbA1c), fasting and 2-hour glucose from oral glucose tolerance tests (OGTTs)., Methods: HbA1c and glucose on repeated samples obtained ∼6 weeks apart were compared in 66 youth (mean age 14.2 years) and 354 adults (52.7 years). Changes, coefficient of variation (CV), and concordance of diagnostic categories between the 2 visits were compared., Results: Mean difference between the 2 visits in HbA1c was higher in youth than adults (P < .001), while fasting glucose was similar and 2-hour glucose was lower in youth (P = .051). CV was smallest for HbA1c compared to fasting and 2-hour glucose. For HbA1c, youth had higher CV (P < .001); whereas CV for 2-hour glucose was lower for youth (P = .041). Classification concordance by HbA1c was lower in youth (P = .004). Using OGTT or HbA1c for classification, intervisit variability produced discordant classification in 20% of youth and 28% of adults. Using both fasting glucose and HbA1c, intervisit variability reduced discordant classification to 16% of adults while not improving classification in youth., Conclusions: Poor reproducibility and lack of classification concordance highlight the limitations of one-time testing, with important implications for assessing eligibility in clinical trials. Consideration should be given to using more than a single parameter for screening and diagnosis, especially when classification category is important., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To estimate the cost and cost-effectiveness of Bright Bodies, a high-intensity, family-based intervention that has been demonstrated to improve body mass index (BMI) among children with obesity in a randomized controlled trial., Methods: We developed a microsimulation model to project 10-year BMI trajectories of 8 to 16-year-old children with obesity, using data from the National Longitudinal Surveys and Centers for Disease Control and Prevention growth charts, and we validated the model using data from the Bright Bodies trial and a follow-up study. We used the trial data to estimate the average reduction in BMI per person-year over 10 years and the incremental costs of Bright Bodies, compared with the traditional clinical weight management (control), from a health system's perspective in 2020 US dollars. Using results from studies of Medical Expenditure Panel Survey data, we projected the long-term obesity-related medical expenditure., Results: In the primary analysis, assuming depreciating effects postintervention, Bright Bodies is expected to reduce a participant's BMI by 1.67 kg/m 2 (95% uncertainty interval 1.43-1.94) per year over 10 years as compared with control. The incremental intervention cost of Bright Bodies was $360 ($292-$421) per person compared with the clinical control. Nevertheless, savings in obesity-related healthcare expenditure offset these costs and the expected cost-savings of Bright Bodies is $1126 ($689-$1693) per person over 10-years. The projected time to achieve cost-savings compared with clinical control was 3.58 (2.63-5.17) years., Conclusions: Although resource-intensive, our findings suggest that Bright Bodies is cost-saving compared to the clinical control by averting future obesity-related healthcare costs among children with obesity., (Copyright © 2023. Published by Elsevier Inc.)

Objective: This study aimed to examine the extent to which Bright Bodies, a high-intensity, family-based pediatric weight management intervention, improved BMI for participants since publication of the randomized controlled trial establishing efficacy in 2007 and to describe adaptations to the program., Methods: For participants enrolled from 2008 to 2018, linear mixed-effects models were used to estimate monthly change in BMI expressed as percentage of the 95th percentile (%BMIp95) during participants' first beginner-level program., Results: The sample included 396 youth individuals (mean age: 11.7  [SD 2.8] years, 61.6% female, 37.1% non-Hispanic Black, 26.3% Hispanic or Latino, 53.8% with public insurance, 80.1% with severe obesity). Across the 11 years, participants' %BMIp95 reduced on average by 1.63% (95% CI: 1.44%-1.82%) per month during their first program (mean duration: 10 weeks) after adjusting for age, sex, season and year, starting %BMIp95, race and ethnicity, and insurance category. Greater reduction in %BMIp95 was associated with male versus female sex, spring/fall versus winter seasons, enrollment in 2008 to 2018 versus 2015 to 2018, and higher starting %BMIp95 (p value for all <0.001). Adaptations since 2007 included pragmatic changes to increase engagement and address funding shortages., Conclusions: These results suggest sustained clinical effectiveness of Bright Bodies in the context of real-world adaptations., (© 2022 The Obesity Society.)

Objectives: To assess changes in weight-related health behaviors and social determinants of health (SDoH) among youth with overweight/obesity during the coronavirus disease 2019 (COVID-19) pandemic. Methods: We assessed weight-related health behaviors (physical activity, screen time, sleep, and diet) and SDoH (food insecurity, income/childcare, and caregivers' perceived stress) before vs. during the pandemic with a survey administered August-October 2020 to caregivers of 2-17-year olds and adolescents 13-17 years old with BMI ≥85th percentile seen in clinic within 6 months prepandemic. We analyzed changes in continuous variables using paired t -tests and categorical variables with McNemar's or Fisher's exact tests, and the influence of social determinants on behavior change using multivariable regression models. Results: A total of 129 caregivers and 34 adolescents completed surveys. Compared with prepandemic, caregivers reported youth decreased moderate/vigorous physical activity (-87.4 [205.7] minutes/week, p  < 0.001) and increased recreational screen time (2.5 [2.1] hours/day, p  < 0.001). Fewer had regular bedtimes (before: 89% and during: 44%, p  < 0.001) and more ate most meals with television (before: 16% and during: 36%, p  < 0.001). Food insecurity increased from 27% to 43% ( p  < 0.001), 45% reported reduced household income, and caregivers with moderate/high perceived stress scale scores increased from 43% to 64% ( p  < 0.001). Moderate/high caregiver stress and food insecurity were associated with greater magnitudes of adverse behavior change. Conclusion: Alarming changes in health behaviors among youth with overweight/obesity, particularly among those with stressed caregivers and food insecurity, may increase prevalence of obesity-related comorbidities and exacerbate health disparities. There is an urgent need to expand access to effective interventions for overweight/obesity that address psychosocial stressors.

Aim: To examine the determinants and metabolic impact of the reduction in fasting and postload insulin levels after a low n-6 to n-3 polyunsaturated fatty acid (PUFA) ratio diet in obese youth., Materials and Methods: Insulin secretion and clearance were assessed by measuring and modelling plasma insulin and C-peptide in 17 obese youth who underwent a nine-point, 180-minute oral glucose tolerance test (OGTT) before and after a 12-week, eucaloric low n-6:n-3 polyunsaturated fatty acid (PUFA) ratio diet. Hepatic fat content was assessed by repeated abdominal magnetic resonance imaging., Results: Insulin clearance at fasting and during the OGTT was significantly increased after the diet, while body weight, glucose levels, absolute and glucose-dependent insulin secretion, and model-derived variables of β-cell function were not affected. Dietary-induced changes in insulin clearance positively correlated with changes in whole-body insulin sensitivity and β-cell glucose sensitivity, but not with changes in hepatic fat. Subjects with greater increases in insulin clearance showed a worse metabolic profile at enrolment, characterized by impaired insulin clearance, β-cell glucose sensitivity, and glucose tolerance, and benefitted the most from the diet, achieving greater improvements in glucose-stimulated hyperinsulinaemia, insulin resistance, and β-cell function., Conclusions: We showed that a 12-week low n-6:n-3 PUFA ratio diet improves hyperinsulinaemia by increasing fasting and postload insulin clearance in obese youth, independently of weight loss, glucose concentrations, and insulin secretion., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims/hypothesis: We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1 H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA 1c normalise intracerebral glucose levels., Methods: Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m 2 and HbA 1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1 H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist., Results: Following the intervention, mean ± SD HbA 1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA 1c (r = 0.71, p=0.048)., Conclusion/interpretation: These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control. Trial registration ClinicalTrials.gov NCT03469492., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Purpose: To examine youth and parent perspectives on the acceptability of Bright 1 Bodies, a group physical activity and coping intervention for adolescents with type 1 diabetes mellitus (T1DM)., Methods: Adolescents participated in 12 weekly sessions of moderate to vigorous physical activity and discussion with peers with T1DM. Adolescents completed an exit survey measuring satisfaction with the intervention on a 5-point Likert scale. Semistructured interviews were conducted with adolescents and at least one parent. Qualitative description was used to develop themes that summarize the acceptability of the intervention., Results: Mean scores for survey subscales were: 4.5 (SD = 0.39) for program components and strategies, 4.4 (SD = 0.44) for comfort with the intervention, and 4.3 (SD = 0.62) for instructors. Themes included: (1) adolescents and parents valued being around others with T1DM and their families, (2) the intervention helped adolescents gain knowledge and reinforce diabetes self-management behaviors, (3) challenges included convenience and sustaining participant engagement, and (4) adolescents intended to sustain physical activity and diabetes self-management behaviors after the intervention., Conclusions: Adolescents and parents viewed the intervention as acceptable across multiple domains. Participants valued the group aspect of the intervention, and future interventions would benefit from integrating social interactions with others with T1DM.

Background: Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth., Objectives: We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response., Methods: In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used., Results: Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time., Conclusions: These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background/objective: Many adolescents with type 1 diabetes do not achieve 60 minutes of daily moderate-to-vigorous intensity physical activity (MVPA). Recognizing the importance of peer influence during adolescence, we evaluated the feasibility and safety of a group MVPA intervention for this population., Methods: Eighteen adolescents with type 1 diabetes (age 14.1 ± 2 .3 years, female 67%, black or Latino 67%, median body mass index 92%'ile, A1c 79.9 ± 25.1 mmol/mol, 9.5 ± 2.3%). Intervention sessions (35 minutes MVPA and 45 minutes discussion) occurred 1×/week for 12 weeks. Feasibility and safety metrics were enrollment, completion of intervention and assessments, cost, and hypoglycemia rates. Participants completed MVPA (accelerometry), and exploratory nutritional, psychosocial, clinical, and fitness variable assessments at baseline, 3 months, and 7 months. Hedges' effect sizes were calculated., Results: Enrollment was 16%, and intervention completion was 56%. Assessment completion at 7 months was 67% for MVPA, nutrition, and fitness, 83% for psychosocial assessments, and 94% for clinical assessments. Cost was $1241 per completing participant. One episode of mild hypoglycemia occurred during the sessions (0.6%). Self-reported daily fruit/vegetable servings (d = -0.72) and diabetes self-management behaviors decreased over time (d = -0.40). In the 10 completers, endurance run score improved (d = 0.49) from low baseline levels, while systolic blood pressure decreased (d = -0.75) and low-density lipoprotein increased (d = 0.49) but stayed within normal ranges., Conclusions: The protocol for the group MVPA intervention was safe and had some feasibility metrics meriting further investigation. MVPA levels and glycemic control remained suboptimal, suggesting the need for more intensive interventions for this population., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the feasibility of engaging stressed, low-income parents with obesity in a novel mindfulness-based parent stress intervention aimed at decreasing the risk of early childhood obesity., Study Design: An 8-week mindfulness-based parent stress group intervention (parenting mindfully for health) plus nutrition and physical activity counseling (PMH+N) was developed for parents with obesity aimed at preventing obesity in their at-risk 2- to 5-year-old children. PMH+N was compared with a control group intervention (C+N), and improvement in parenting was assessed before and after the intervention using the laboratory-based toy wait task (TWT). In addition, nutrition, physical activity, and stress were assessed using a multimethod approach., Results: After establishing feasibility in 20 parent-child dyads (phase 1), 42 dyads were randomized to PMH+N vs C+N (phase 2). Compared with the C+N group, the PMH+N group demonstrated significantly better group attendance (P < .015), greater improvement in parental involvement (P < .05), and decreased parental emotional eating rating (P < .011). Furthermore, C+N, but not PMH+N, was associated with significant increases in child body mass index percentile during treatment (P < .03) when accounting for the TWT before and after changes in parenting scores., Conclusions: These findings suggest that a mindfulness-based parent stress intervention to decrease childhood obesity risk is feasible, requires further testing of therapeutic mechanisms in larger samples, and may be a potential way to attenuate the risk of childhood obesity., Trial Registration: ClinicalTrials.govNCT01974102., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Type 2 diabetes is preceded by a prediabetic stage of impaired glucose tolerance that affects 10-23% of youth and is expected to double over the next decade. The natural history of impaired glucose tolerance and the determinants of β-cell dynamic response have never been investigated longitudinally in young people. We aimed to investigate the clinical and metabolic determinants of longitudinal glucose tolerance changes and β-cell function in a multiethnic cohort of obese youth., Methods: We followed up prospectively a multiethnic cohort of overweight and obese (body-mass index >85th percentile) adolescents with baseline normal glucose tolerance (plasma glucose <140 mg/dL) or impaired glucose tolerance (plasma glucose 140-199 mg/dL) at the Yale Pediatric Obesity Clinic (CT, USA). All participants underwent a 3-h oral glucose tolerance test at baseline and after 2 years to estimate insulin secretion (oral disposition index) in the context of body insulin sensitivity. As part of standard care at the clinic, all participants received dietary advice and underwent dietary assessment every 5-6 months. No structured lifestyle or pharmacological intervention was administered., Findings: Between January, 2010, and December, 2016, 526 adolescents (mean age 12·7 years, range 10·6-14·2) were enrolled to our study. At baseline, 364 had normal and 162 had impaired glucose tolerance. Median follow-up was 2·9 years (IQR 2·7-3·1). 105 (65%) of 162 with impaired glucose tolerance at baseline reverted to normal glucose tolerance at follow-up, 44 (27%) had persistent impaired glucose tolerance, and 13 (8%) progressed to type 2 diabetes. A feature of reversion to normal glucose tolerance was a roughly four-fold increase in the oral disposition index (from median 0·94 [IQR 0·68-1·35] at baseline to 3·90 [2·58-6·08] at follow-up; p<0·0001) and a significantly higher oral disposition index at follow-up compared with participants who maintained normal glucose tolerance across the study period (median 3·90 [IQR 2·58-6·08] vs 1·59 [1·12-2·23]; p<0·0001). By contrast, a decrease in insulin secretion was seen in participants who had persistent impaired glucose tolerance (median 1·31 [IQR 1·01-1·85]; p<0·0001) or who progressed to type 2 diabetes (0·20 [0·12-0·58]; p<0·0001), compared with participants who maintained normal glucose tolerance across the study period. Non-Hispanic white ethnic origin conferred five times the odds of reversion to normal glucose tolerance compared with non-Hispanic black ethnic origin (OR 5·06, 95% CI 1·86-13·76; p=0·001), with a two times greater annual increase in the oral disposition index (β 2·32, 95% CI 0·05-4·60; p=0·045)., Interpretation: Impaired glucose tolerance is highly reversible in obese adolescents. Ethnic origin is the main clinical modifier of the dynamic β-cell response to prediabetic hyperglycaemia and, thus, determines the reversibility of impaired glucose tolerance, or its persistence. Therapeutic interventions for impaired glucose tolerance should target the specific mechanisms underpinning glucose tolerance changes in high-risk ethnic groups., Funding: National Institutes of Health (National Institute of Child Health and Human Development, National Center for Research Resources, and National Institute of Diabetes and Digestive and Kidney Diseases), American Diabetes Association, International Society for Pediatric and Adolescent Diabetes, Robert Leet Patterson and Clara Guthrie Patterson Trust, European Society for Pediatric Endocrinology, American Heart Association, and the Allen Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: An important area of research in childhood obesity is the identification of factors that predict or moderate the responses to obesity intervention programmes, yet few studies have examined the impact of self-esteem and family functioning on obesity treatment outcomes., Objectives: We sought to determine whether baseline self-esteem and family functioning predicted or moderated childhood obesity intervention outcomes at 6 months., Methods: From 2009 to 2011, seventy-five 10-16 year old, racially/ethnically diverse obese youths with abnormal glucose tolerance were randomized to 6 months of an intensive family-based obesity lifestyle intervention (Bright Bodies) or routine outpatient Clinic Care. We examined youth self-concept, parent-rated family functioning and 6-month outcomes (youths' glucose tolerance, weight, body mass index and percent fat). We set the significance threshold as P ≤ 0.05 for moderator and predictor analyzes., Results: Having poor family functioning and self-concept scores indicating high anxiety and low self-esteem at baseline predicted poor 6-month outcomes overall (Bright Bodies and Clinic Care groups combined). Additionally, baseline self-esteem and family functioning moderated treatment effects such that Bright Bodies outperformed Clinic Care in youths with low self-esteem and poorly functioning families, whereas youths with high self-esteem and high-functioning families did similarly well with either intervention., Discussion: Our findings suggest intensive family-based lifestyle programmes are particularly beneficial for youth with low self-esteem and poorly functioning families., (© 2016 World Obesity Federation.)

Objective: We aimed at determining the relationship of the gut microbiota and short chain fatty acids with obesity and fat partitioning and at testing potential differences in the ability of gut microbiota to ferment equal amounts of carbohydrates (CHO) between lean and obese youth., Research Design and Methods: We analyzed the gut microbiota of 84 youth in whom body fat distribution was measured by fast-magnetic resonance imaging, de novo lipogenesis (DNL) quantitated using deuterated water, and the capability of gut flora to ferment CHO was assessed by 13 C-fructose treatment in vitro., Results: A significant association was found between the Firmicutes to Bacteroidetes ratio, and the abundance of Bacteroidetes and Actinobacteria with body mass index, visceral and SC fat (all P < .05). Plasma acetate, propionate, and butyrate were associated with body mass index and visceral and SC fat (all P < .05) and with hepatic DNL (P = .01, P = .09, P = .04, respectively). Moreover, the rate of CHO fermentation from the gut flora was higher in obese than in lean subjects (P = .018)., Conclusions: These data demonstrate that obese youth show a different gut flora composition than lean and that short chain fatty acids are associated with body fat partitioning and DNL. Also, the gut microbiota of obese youth have a higher capability than the gut flora of lean to oxidize CHO.

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Unlabelled: We assessed the association between the single-nucleotide polymorphism (SNP) rs58542926 in the transmembrane 6 superfamily member 2 (TM6SF2) gene and fatty liver disease in obese youth. We genotyped the TM6SF2 rs58542926 SNP in a multiethnic cohort of 957 obese children and adolescents (42% Caucasians, 28% African Americans, 30% Hispanics). All underwent an oral glucose tolerance test, a liver panel, and a lipid profile. Of them, 454 children underwent a magnetic resonance imaging study to assess hepatic fat content and 11 underwent liver biopsy to assess the degree of disease severity. The minor allele of the rs58542926 SNP was associated with high hepatic fat content in Caucasians and African Americans (all P < 0.05), with high alanine aminotransferase levels in Hispanics (P < 0.05) and a more favorable lipoprotein profile (lower low-density lipoprotein, small dense low-density lipoprotein, and very small low-density lipoprotein) in Caucasians and Hispanics (all P < 0.05). The liver biopsy showed a higher prevalence of fibrosis (P = 0.04) and a higher nonalcoholic fatty liver disease activity score (P = 0.05) in subjects carrying the minor allele than in those homozygous for the common allele. Moreover, we observed a joint effect among the TM6SF2 rs58542926, the PNPLA3 rs738409, and the GCKR rs1260326 SNPs in determining intrahepatic fat accumulation (P < 0.05)., Conclusion: The rs58542926 SNP in the TM6SF2 gene is associated with pediatric nonalcoholic fatty liver disease but may confer protection against cardiovascular risk., (© 2015 by the American Association for the Study of Liver Diseases.)

Objective: This study's aim was to evaluate whether the GCKR rs1260326 variant increases hepatic de novo lipogenesis (DNL)., Setting and Design: To test this hypothesis, 14 adolescents, seven homozygous for the common allele (CC) and seven homozygous for the risk allele (TT), underwent measurement of hepatic DNL during the fasting state and after consumption of a carbohydrate (CHO) drink (75 g glucose and 25 g fructose). DNL was assessed through incorporation of deuterium in the palmitate contained in the very low-density lipoprotein., Results: Subjects with TT demonstrated higher fasting fractional DNL (P = .036) and a lower increase in fractional DNL after the CHO challenge (P = .016). With regard to absolute lipogenesis, TT subjects had both higher fasting rates (P = .015) and 44% greater area under the curve of absolute lipogenesis during the study (P = .016), compared to CC subjects. Furthermore, subjects carrying the TT genotype showed higher basal rates of glucose oxidation (P = .0028) and a lower ability than CC subjects to increase the rates of glucose oxidation after the CHO load (P = .054)., Conclusions: This study reports for the first time rates of DNL in obese adolescents and suggests that the GCKR rs1260326 gene variant, which is associated with greater glycolysis, increases hepatic DNL. These data highlight the role of glycolytic carbon flux in liver lipid synthesis and hypertriglyceridemia in these youngsters.

Objective: Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity., Methods: Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes., Results: Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose., Conclusions: Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating., (© 2015 The Obesity Society.)

Objective: In the U.S., an astonishing 12.5 million children and adolescents are now obese, predisposing 17% of our nation's youth to metabolic complications of obesity, such as type 2 diabetes (T2D). Adolescent obesity has tripled over the last three decades in the setting of food advertising directed at children. Obese adults exhibit increased brain responses to food images in motivation-reward pathways. These neural alterations may be attributed to obesity-related metabolic changes, which promote food craving and high-calorie food (HCF) consumption. It is not known whether these metabolic changes affect neural responses in the adolescent brain during a crucial period for establishing healthy eating behaviors., Research Design and Methods: Twenty-five obese (BMI 34.4 kg/m2, age 15.7 years) and fifteen lean (BMI 20.96 kg/m2, age 15.5 years) adolescents underwent functional MRI during exposure to HCF, low-calorie food (LCF), and nonfood (NF) visual stimuli 2 h after isocaloric meal consumption., Results: Brain responses to HCF relative to NF cues increased in obese versus lean adolescents in striatal-limbic regions (i.e., putamen/caudate, insula, amygdala) (P < 0.05, family-wise error [FWE]), involved in motivation-reward and emotion processing. Higher endogenous leptin levels correlated with increased neural activation to HCF images in all subjects (P < 0.05, FWE)., Conclusions: This significant association between higher circulating leptin and hyperresponsiveness of brain motivation-reward regions to HCF images suggests that dysfunctional leptin signaling may contribute to the risk of overconsumption of these foods, thus further predisposing adolescents to the development of obesity and T2D., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: The childhood obesity epidemic has been accompanied by an increasing prevalence of type 2 diabetes (T2D), particularly in minority children. Twenty to thirty percent of obese youth have "prediabetes," a precursor to diabetes marked by insulin resistance, β-cell dysfunction, and impaired glucose tolerance. The Diabetes Prevention Program demonstrated that T2D could be prevented/delayed by intensive lifestyle modification in adults with prediabetes, but efficacy of similar interventions in youth has not been established. Therefore, we evaluated the effects of the Bright Bodies (BB) Healthy Lifestyle Program on 2-h oral glucose tolerance test (OGTT) glucose in comparison with adolescents receiving standard of care., Research Design and Methods: A parallel-group randomized controlled trial comparing BB with standard clinical care (CC) in obese adolescents (10-16 years old, Tanner stage >2) with elevated OGTT 2-h blood glucose (130-199 mg/dL) from a racially/ethnically diverse population. OGTTs, including cardiovascular and anthropometric assessments, were conducted at baseline and 6 months. Children attended BB twice per week for exercise and nutrition/behavior modification, and the CC group received CC from their pediatrician. Primary outcome was change in 2-h OGTT glucose and percentage conversion from elevated 2-h blood glucose to nonelevated (<130 mg/dL) 2-h blood glucose. Changes in outcomes were compared between groups using an ANCOVA, with adjustment for baseline outcome and multiple imputation for missing data., Results: Reductions in 2-h glucose were more favorable in BB compared with CC (-27.2 vs. -10.1 mg/dL; difference = -17.1, 95% CI; P = 0.005). Moreover, greater conversion to <130 mg/dL 2-h glucose occurred in BB than CC (P = 0.003), and other insulin sensitivity indices were significantly improved., Conclusions: Compared with standard of care, the Yale BB Program is a more effective means of reducing the risk of T2D in obese adolescents with elevated 2-h glucose levels.

In this paper, we describe our efforts to integrate the Diabetes Prevention Program and the Bright Bodies program into a coordinated intensive lifestyle intervention program for families living in Fair Haven, an underserved Hispanic neighborhood in New Haven, Connecticut with high rates of obesity and prediabetes in adults and children.

Background: Reports of clinical rickets are particularly evident in minority infants and children, but only limited analyses of vitamin D are available in this demographic group., Objective: We sought to characterize circulating 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and their determinants, including circulating parathyroid hormone (PTH), total alkaline phosphatase activity (ALP), calcium, and phosphorus, in minority infants and children., Design: We obtained demographic information and blood samples for measurement of PTH, ALP, 25(OH)D, and 1,25(OH)(2)D in >750 6-mo- to 3-y-old children. Dietary intake data were obtained and analyzed., Results: The mean (±SD) 25(OH)D concentration was 66 ± 22 nmol/L (26.3 ± 8.7 ng/dL). A total of 15% of children had 25(OH)D concentrations less than the recommended target threshold of 50 nmol/L. Combined elevations of PTH and ALP occurred in only 2.5% of children. Determinants of 25(OH)D included vitamin D intake, age (decreasing with age), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), formula use (higher intakes), season (greater concentrations in the summer and fall than in the winter and spring), and, inversely, PTH. The mean 1,25(OH)(2)D concentration was 158 ± 58 pmol/L (60.6 ± 22.5 pg/mL), which was consistent with a reference range of 41-274 pmol/L or 15.7-105.5 pg/mL. Determinants for 1,25(OH)(2)D were age (decreasing with age), sex (greater concentrations in girls than in boys), skin type (greater concentrations in lighter-skinned children than in darker-skinned children), and, inversely, serum calcium and phosphorus., Conclusions: Although 15% of subjects were vitamin D insufficient, only 2.5% of subjects had elevations of both PTH and ALP. The greater 25(OH)D concentrations observed with formula use confirm that dietary vitamin D fortification is effective in this demographic group. Circulating 1,25(OH)(2)D is higher in infants than in older children and adults and, in contrast to 25(OH)D, is not directly correlated with nutrient intakes.

Background: A single nucleotide polymorphism (SNP), the rs738409, in the patatin like phospholipase 3 gene (PNPLA3) has been recently associated with increased hepatic steatosis and ALT levels in adults and children. Given the potential role of PNPLA3 in fatty liver development, we aimed to explore whether the influence of PNPLA3 genotype on hepatic fat in obese youth might be modulated by dietary factors such as essential omega polyunsaturated fatty acids (PUFA) intake., Materials and Methods: We studied 127 children and adolescents (56 boys, 71 girls; 58 Caucasians; 30 African Americans and 39 Hispanics; mean age 14.7±3.3; mean BMI 30.7±7.2). The dietary composition was assessed by the Nutrition Data System for Research (NDS-R version 2011). The patients underwent a MRI study to assess the liver fat content (HFF%), ALT measurement and the genotyping of the rs738409 SNP by automatic sequencing., Results: As previously observed, HFF% and ALT levels varied according to the genotype in each ethnicity. ALT levels and HFF% were significantly influenced by the interaction between genotype and omega-6/omega-3 PUFA ratio (n-6/n-3), p = 0.003 and p = 0.002, respectively. HFF% and ALT levels were, in fact, related to the n-6/n-3 consumption only in subjects homozygote for the G allele of the rs738409 (r2 = 0.45, p =  0.001 and r2 = 0.40, p = 0.006, respectively)., Conclusions: These findings suggest that the association of a high dietary n-6/n-3 PUFA with fatty liver and liver damage in obese youths may be driven by a predisposing genotype.

While outcome studies in pediatric obesity have received considerable attention, research on different components of effective interventions remains limited. Little is known which psychological method (i.e., behavior modification, cognitive behavior therapy and family therapy) is most useful or how the choice of program delivery (group/individual) influences the intervention outcomes. Group treatment is of particular interest for two reasons. First, motivation is important for behavior change; in group settings motivation can be increased in two ways: by the group leader and through the interaction with the group participants. Second, group treatment can be more cost-effective than individual approaches (i.e., it requires fewer staff resources and space). This paper aims to comment on the influence of the method choice and delivery in pediatric obesity interventions through discussion of the existing evidence on current programs. In addition, two examples of useful models will be described in more detail: the Yale Bright Bodies Weight Management Program and the Family Weight School. These are outpatients programs both targeting families with severely obese children but through different methodological approaches. Finally, directions for future research will be explored, particularly regarding how the selection of program delivery and psychological method affect treatment outcomes in various populations.

Objective: Hemoglobin A(1c) (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking., Research Design and Methods: We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of ∼2 years in 218 subjects., Results: At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C <5.7%), 21% at risk for diabetes (A1C 5.7-6.4%), and 1% with diabetes (A1C >6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% CI 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time., Conclusions: The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents.

Objective: To determine if beneficial effects of a weight-management program could be sustained for up to 24 months in a randomized trial in an ethnically diverse obese population., Patients and Methods: There were 209 obese children (BMI > 95th percentile), ages 8 to 16 of mixed ethnic backgrounds randomly assigned to the intensive lifestyle intervention or clinic control group. The control group received counseling every 6 months, and the intervention group received a family-based program, which included exercise, nutrition, and behavior modification. Lifestyle intervention sessions occurred twice weekly for the first 6 months, then twice monthly for the second 6 months; for the last 12 months there was no active intervention. There were 174 children who completed the 12 months of the randomized trial. Follow-up data were available for 76 of these children at 24 months. There were no statistical differences in dropout rates among ethnic groups or in any other aspects., Results: Treatment effect was sustained at 24 months in the intervention versus control group for BMI z score (-0.16 [95% confidence interval: -0.23 to -0.09]), BMI (-2.8 kg/m(2) [95% confidence interval: -4.0-1.6 kg/m(2)]), percent body fat (-4.2% [95% confidence interval: -6.4% to -2.0%]), total body fat mass (-5.8 kg [95% confidence interval: -9.1 kg to -2.6 kg]), total cholesterol (-13.0 mg/dL [95% confidence interval: -21.7 mg/dL to -4.2 mg/dL]), low-density lipoprotein cholesterol (-10.4 mg/dL [95% confidence interval: -18.3 mg/dL to -2.4 mg/dL]), and homeostasis model assessment of insulin resistance (-2.05 [95% confidence interval: -2.48 to -1.75])., Conclusions: This study, unprecedented because of the high degree of obesity and ethnically diverse backgrounds of children, reveals that benefits of an intensive lifestyle program can be sustained 12 months after completing the active intervention phase.

Impaired glucose tolerance (IGT) is a prediabetic state fueling the rising prevalence of type 2 diabetes mellitus (T2DM) in adolescents with marked obesity. Given the importance of insulin resistance, the poor β-cell compensation and the altered fat partitioning as underlying defects associated with this condition, it is crucial to determine the extent to which these underlying abnormalities can be reversed in obese adolescents. We tested, in a pilot study, whether rosiglitazone (ROSI) restores normal glucose tolerance (NGT) in obese adolescents with IGT by improving insulin sensitivity and β-cell function. In a small randomized, double-blind, placebo (PLA)-controlled study, lasting 4 months, 21 obese adolescents with IGT received either ROSI (8 mg daily) (n = 12, 5M/7F, BMI z-score 2.44 ± 0.11) or PLA (n = 9, 4M/5F, BMI z-score 2.41 ± 0.09). Before and after treatment, all subjects underwent oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, magnetic resonance imaging, and (1)H NMR assessment. After ROSI treatment, 58% of the subjects converted to NGT compared to 44% in the PLA group (P = 0.528). Restoration of NGT was associated with a significant increase in insulin sensitivity (P < 0.04) and a doubling in the disposition index (DI) (P < 0.04), whereas in the PLA group, these changes were not significant. The short-term use of ROSI appears to be safe in obese adolescents with IGT. ROSI restores NGT by increasing peripheral insulin sensitivity and β-cell function, two principal pathophysiological abnormalities of IGT.

Unlabelled: The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPLA3) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPARγ2(peroxisome proliferator-activated receptor gamma 2), SREBP1c(sterol regulatory element binding protein 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04)., Conclusion: A common variant of the PNPLA3 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size.

Background: Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors., Objective: We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences in the distributions of lipoprotein concentrations and sizes were associated with the hepatic fat fraction (HFF), VAT, or both., Design: In a multiethnic group of 33 white, 33 African American, and 33 Hispanic obese adolescents with normal glucose tolerance, we measured VAT and HFF by using magnetic resonance imaging. Fasting lipoprotein particle number and size were measured by using nuclear magnetic resonance spectroscopy. To assess the association between VAT and HFF, we categorized VAT into tertiles., Results: In each ethnic group, HFF values increased between successive tertiles of VAT. After multivariate adjustment and in comparison with the 2 other groups, African Americans showed lower triglyceride (P = 0.001) and higher HDL (P = 0.03) concentrations, lower concentrations of total (P = 0.007), large (P = 0.005), and medium (P lt 0.0001) VLDL, but higher concentrations of large HDL particles (P = 0.01) and larger HDL (P = 0.005). In multivariate linear models, independent of ethnicity, VAT was a significant predictor for large HDL (P = 0.003) and total small LDL (P = 0.001) concentrations, whereas HFF significantly predicted large VLDL (P = 0.03) concentrations., Conclusion: Liver fat accretion, independent of VAT, may play a role in the ethnic differences seen in large VLDL particles. This trial was registered at clinicaltrials.gov as NCT00536250.

Aim: Cross-sectional studies showed worsening of cardiovascular risk factors with increasing severity of childhood obesity. The aim of this study was to investigate the impact of obesity dynamics on cardiovascular risk factors and on the stability of the diagnosis of metabolic syndrome (MS) in obese youth., Methods and Results: A longitudinal assessment of components of the MS using two definitions was performed in 186 obese adolescents (106 females/80 males, age 13.1 +/- 2.5 yr). Components of the MS were assessed at baseline and after 19 +/- 7 months. We stratified the cohort into three categories based on the 25th and 75th percentile of body mass index (BMI) z-score change: category 1 reduced BMI z-score by 0.09 or more, category 2 had a BMI z-score change of between -0.09 and 0.12, and category 3 increased BMI z-score by >0.12. Subjects who reduced their BMI z-score significantly decreased their fasting and 2-h glucose levels and triglyceride levels and increased their high density lipoprotein cholesterol in comparison to subjects who increased their BMI z-score. BMI z-score changes negatively correlated with changes in insulin sensitivity (r = -0.36, p < 0.001). Among those with no MS at baseline (n = 119), 10 (8%), most of whom significantly increased their BMI z-score, developed MS. Of 67 who had MS at baseline, 33 (50%), most of whom decreased their BMI z-score, lost the diagnosis., Conclusions: Obesity dynamics, tightly linked to changes in insulin sensitivity, have an impact on each individual component of the MS and on the stability of the diagnosis of MS in obese youth.

Unlabelled: Fatty liver is increasingly common in obese adolescents. We determined its association with glucose dysregulation in 118 (37M/81F) obese adolescents of similar age and percent total fat. Fast-magnetic resonance imaging (MRI) and simple MRI were used to quantify hepatic fat content and abdominal fat distribution. All subjects had a standard oral glucose tolerance test. Insulin sensitivity was estimated by the Matsuda Index and homeostasis model assessment of insulin resistance. Baseline total and high molecular weight (HMW)-adiponectin and interleukin (IL)-6 levels were measured. The cohort was stratified according to tertiles of hepatic fat content. Whereas age and %fat were comparable across tertiles, ethnicity differed in that fewer Blacks and more Whites and Hispanics were in the moderate and high category of hepatic fat fraction (HFF). Visceral and the visceral-to-subcutaneous fat ratio increased and insulin sensitivity decreased across tertiles. Two-hour plasma glucose rose with increasing hepatic steatosis (P < 0.008). 73.7% of the subjects in the high HFF had the metabolic syndrome compared to 19.5% and 30.6%, respectively, in the low and moderate categories. Both total and HMW-adiponectin decreased, and IL-6 increased with increasing hepatic steatosis., Conclusion: In obese adolescents, independent of total fat, increasing severity of fatty liver is associated with glucose dysregulation, metabolic syndrome, and with a proinflammatory milieu.

Objective: To evaluate the impact on glucose metabolism of a lifestyle program (the Yale Bright Bodies Program) for obese children., Research Design and Methods: Thirteen Bright Bodies and ten clinic-care control subjects who were part of a large randomized clinical trial had 75-g oral glucose tolerance tests at the beginning and end of the 12-month study., Results: Bright Bodies subjects had significantly greater decreases in weight, BMI, and body fat than clinic-care subjects, and the Bright Body subjects' changes in body composition were accompanied by marked improvements in insulin sensitivity (P = 0.009) and glucose tolerance (P = 0.04)., Conclusions: An intensive lifestyle program that successfully reduces body weight and body fat can markedly improve insulin sensitivity and glucose metabolism in obese youth.

Objective: To explore whether an imbalance between the visceral and subcutaneous fat depots and a corresponding dysregulation of the adipokine milieu is associated with excessive accumulation of fat in the liver and muscle and ultimately with insulin resistance and the metabolic syndrome., Research Design and Methods: We stratified our multi-ethnic cohort of 118 obese adolescents into tertiles based on the proportion of abdominal fat in the visceral depot. Abdominal and liver fat were measured by magnetic resonance imaging and muscle lipid (intramyocellular lipid) by proton magnetic resonance spectroscopy., Results: There were no differences in age, BMI Z score, or fat-free mass across tertiles. However, as the proportion of visceral fat increased across tertiles, BMI and percentage of fat and subcutaneous fat decreased, while hepatic fat increased. In addition, there was an increase in 2-h glucose, insulin, c-peptide, triglyceride levels, and insulin resistance. Notably, both leptin and total adiponectin were significantly lower in tertile 3 than 1, while C-reactive protein and interleukin-6 were not different across tertiles. There was a significant increase in the odds ratio for the metabolic syndrome, with subjects in tertile 3 5.2 times more likely to have the metabolic syndrome than those in tertile 1., Conclusions: Obese adolescents with a high proportion of visceral fat and relatively low abdominal subcutaneous fat have a phenotype reminiscent of partial lipodystrophy. These adolescents are not necessarily the most severely obese, yet they suffer from severe metabolic complications and are at a high risk of having the metabolic syndrome.

Context: Pediatric obesity has escalated to epidemic proportions, leading to an array of comorbidities, including type 2 diabetes in youth. Since most overweight children become overweight adults, this chronic condition results in serious metabolic complications by early adulthood. To curtail this major health issue, effective pediatric interventions are essential., Objective: To compare effects of a weight management program, Bright Bodies, on adiposity and metabolic complications of overweight children with a control group., Design: One-year randomized controlled trial conducted May 2002-September 2005., Setting: Recruitment and follow-up conducted at Yale Pediatric Obesity Clinic in New Haven, Conn, and intervention at nearby school., Participants: Random sample of 209 overweight children (body mass index [BMI] >95th percentile for age and sex), ages 8 to 16 years of mixed ethnic groups were recruited. A total of 135 participants (60%) completed 6 months of study, 119 (53%) completed 12 months., Intervention: Participants were randomly assigned to either a control or weight management group. The control group (n = 69) received traditional clinical weight management counseling every 6 months, and the weight management group (n = 105) received an intensive family-based program including exercise, nutrition, and behavior modification. Intervention occurred biweekly the first 6 months, bimonthly thereafter. The second randomization within the weight management group assigned participants (n = 35) to a structured meal plan approach (dieting), but this arm of the study was discontinued while enrollment was ongoing due to a high dropout rate., Main Outcome Measures: Change in weight, BMI, body fat, and homeostasis model assessment of insulin resistance (HOMA-IR) at 6 and 12 months., Results: Six-month improvements were sustained at 12 months in weight management vs control, including changes in the following (mean [95% confidence interval]): weight (+0.3 kg [-1.4 to 2.0] vs +7.7 kg [5.3 to 10.0]); BMI (-1.7 [-2.3 to -1.1] vs +1.6 [0.8 to 2.3]); body fat (-3.7 kg [-5.4 to -2.1] vs +5.5 kg [3.2 to 7.8]); and HOMA-IR (-1.52 [-1.93 to -1.01] vs +0.90 [-0.07 to 2.05])., Conclusion: The Bright Bodies weight management program had beneficial effects on body composition and insulin resistance in overweight children that were sustained up to 12 months., Trial Registration: clinicaltrials.gov Identifier: NCT00409422.

The purpose of this pilot study was to determine the effects of the addition of coping skills training for obese multiethnic parents whose overweight children were attending a weight management program. At 6 months, parents in the experimental group had significantly lower body mass index (BMI) and body fat percentage (BFP) and higher numbers of pedometer steps compared with those in the control group. Parents in the experimental group also demonstrated significant improvement in interpersonal relationships, behavior control, and stress management compared with those in the control group. Children in the experimental group demonstrated trends toward decreased BMI and BFP and increased pedometer steps.