Publications by authors named "Jack A Yanovski"

238 Publications

Osteogenesis Imperfecta: The Impact of Genotype and Clinical Phenotype on Adiposity and Resting Energy Expenditure.

J Clin Endocrinol Metab 2021 Sep 14. Epub 2021 Sep 14.

Section on Heritable Disorders of Bone and Extracellular Matrix, National Institutes of Health, Bethesda, MD.

Context: Mutations in type I collagen or collagen-related proteins cause Osteogenesis Imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility, or intrinsic defects in osteoblast differentiation increasing adipocyte development.

Objective: Compare adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences.

Design/setting/participants: We studied 90 participants, 30 with OI (13 COL1A1 Gly, 6 COL1A2 Gly, 3 COL1A1 non-Gly, 2 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy X-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates to examine the relationship of OI genotypes and phenotypic Types.

Results: FM% did not differ significantly in all patients with OI versus HC (OI: 36.6±1.9%, HC: 32.7±1.2%, p =0.088). FM% was, however, greater than HC for those with non-COL variants (p=0.018). FM% did not differ from HC among OI Types (p's>0.05). Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5±44.7 kcal/d, healthy controls: 1377.0±96 kcal/d p=0.345). However, those with non-COL variants (p=0.034) and Type VI OI (p=0.04) had significantly lower REE than HC.

Conclusions: Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.
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http://dx.doi.org/10.1210/clinem/dgab679DOI Listing
September 2021

Associations of sleep with food cravings and loss-of-control eating in youth: An ecological momentary assessment study.

Pediatr Obes 2021 Sep 8:e12851. Epub 2021 Sep 8.

Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Division of Intramural Research, National Institutes of Health (NIH), Bethesda, Maryland, USA.

Background: Inconsistent sleep patterns may promote excess weight gain by increasing food cravings and loss-of-control (LOC)-eating; however, these relationships have not been elucidated in youth.

Objective: We tested whether sleep duration and timing were associated with food cravings and LOC-eating.

Method: For 14 days, youths wore actigraphy monitors to assess sleep and reported severity of food cravings and LOC-eating using ecological momentary assessment. Generalized linear mixed models tested the associations between weekly and nightly shifts in facets of sleep (i.e., duration, onset, midpoint, and waketime) and next-day food cravings and LOC-eating. Models were re-run adjusting for relevant covariates (e.g., age, sex, adiposity).

Results: Among 48 youths (12.88 ± 2.69 years, 68.8% female, 33.3% with overweight/obesity), neither weekly nor nightly facets of sleep were significantly associated with food cravings (ps = 0.08-0.93). Youths with shorter weekly sleep duration (est. ß = -0.31, p = 0.004), earlier weekly midpoints (est. ß = -0.47, p = 0.010) and later weekly waketimes (est. ß = 0.49, p = 0.010) reported greater LOC-eating severity; findings persisted in adjusted models.

Conclusions: In youth, weekly, but not nightly, shifts in multiple facets of sleep were associated with LOC-eating severity; associations were not significant for food cravings. Sleep should be assessed as a potentially modifiable target in paediatric LOC-eating and obesity prevention programs.
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http://dx.doi.org/10.1111/ijpo.12851DOI Listing
September 2021

Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic.

Front Genet 2021 11;12:697549. Epub 2021 Aug 11.

Division of Pediatric Endocrinology Rutgers Robert Wood Johnson Medical School Child Health Institute of New Jersey, New Brunswick, NJ, United States.

Purpose: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.

Methods: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) ( = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups.

Results: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology ( mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, = 0.01).

Conclusion: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.
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http://dx.doi.org/10.3389/fgene.2021.697549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386283PMC
August 2021

Changes in adiposity among children and adolescents in the United States, 1999-2006 to 2011-2018.

Am J Clin Nutr 2021 10;114(4):1495-1504

Division of Health and Nutrition Examination Surveys, National Center for Health Statistics, CDC, Hyattsville, MD, USA.

Background: Data from the NHANES indicate that BMI has increased in some subgroups of children and adolescents in the United States over the past 20 y; however, BMI is an indirect measure of body fatness.

Objectives: We assessed changes in DXA-derived measures of adiposity in a nationally representative population of US children and adolescents aged 8-19 y from 1999-2006 to 2011-2018.

Methods: Using data from the NHANES, we compared the means and distributions of DXA-derived percentage body fat (%BF) and fat mass index (FMI; fat mass/height2 in kg/m2) between 1999-2006 (n = 10,231) and 2011-2018 (n = 6923) among males and females by age group, race and Hispanic origin, and BMI categories. Estimates were standardized by age and race and Hispanic origin.

Results: From 1999-2006 to 2011-2018, mean %BF increased from 25.6% to 26.3% (change in %BF: 0.7%; 95% CI: 0.2%, 1.2%; P < 0.01) among all males, whereas mean %BF increased from 33.0% to 33.7% (change in %BF: 0.7%; 95% CI: 0.2%, 1.2%; P = 0.01) and mean FMI increased from 7.7 to 8.0 fat mass kg/m2 (change in FMI: 0.3 fat mass kg/m2; 95% CI: 0.0, 0.6 fat mass kg/m2; P = 0.02) among all females. Changes were not consistent across all age, race and Hispanic origin, and BMI categories. Both %BF and FMI increased among Mexican-American children and adolescents, but not other race and Hispanic origin groups.

Conclusions: Among US children and adolescents, DXA-derived measures of adiposity increased from 1999-2006 to 2011-2018, albeit not consistently in every age, race and Hispanic origin, and BMI subgroup. These data reinforce the need to consider other measures, besides BMI categories, when studying adiposity in children and adolescents.
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http://dx.doi.org/10.1093/ajcn/nqab237DOI Listing
October 2021

Shifts in the Skin Bacterial and Fungal Communities of Healthy Children Transitioning through Puberty.

J Invest Dermatol 2021 Jul 10. Epub 2021 Jul 10.

Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:

Previous cross-sectional studies have shown that skin microbiomes in adults are distinct from those in children. However, the human skin microbiome in individuals as they sexually mature has not been studied as extensively. We performed a prospective, longitudinal study to investigate the puberty-associated shifts in skin microbiota. A total of 12 healthy children were evaluated every 6-18 months for up to 6 years. Using 16S ribosomal RNA (V1-V3) and internal transcribed spacer 1 amplicon sequencing analyzed with Divisive Amplicon Denoising Algorithm 2, we characterized the bacterial and fungal communities of five different skin and nares sites. We identified significant alterations in the composition of skin microbial communities, transitioning toward a more adult microbiome, during puberty. The microbial shifts were associated with Tanner stages (classification method for the degree of sexual maturation) and showed noticeable sex-specific differences. Over time, female children demonstrated a predominance of Cutibacterium with decreasing diversity. Among fungi, Malassezia predominated at most skin sites in more sexually mature subjects, which was more pronounced in female children. The higher relative abundances of these lipophilic taxa-C. acnes and M. restricta-were strongly associated with serum sex hormone concentrations with known influence on sebaceous gland activity. Taken together, our results support the relationship between sexual maturation, skin physiology, and the skin microbiome.
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http://dx.doi.org/10.1016/j.jid.2021.04.034DOI Listing
July 2021

Progress in Pharmacotherapy for Obesity.

JAMA 2021 07;326(2):129-130

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1001/jama.2021.9486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277731PMC
July 2021

The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alström syndrome: Phase 3 trial design.

Contemp Clin Trials Commun 2021 Jun 3;22:100780. Epub 2021 May 3.

Rhythm Pharmaceuticals, Inc, Boston, MA, USA.

Background: A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alström syndrome. Here, we present the study design of an ongoing, randomized, double-blind, placebo-controlled, phase 3 trial to assess the long-term efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS or Alström syndrome (ClinicalTrials.gov identifier: NCT03746522).

Methods: It was initially planned that ~30 participants aged ≥6 years with a clinical diagnosis of BBS or Alström syndrome would be enrolled. Participants with obesity as defined by a body mass index ≥30 kg/m (in those aged ≥16 years) or a weight >97th percentile (in those aged 6-15 years) are included. Participants are initially randomized in a 1:1 ratio to receive setmelanotide or placebo for 14 weeks (period 1). Following period 1, all participants receive 38 weeks of open-label treatment with setmelanotide (period 2). In each treatment period, setmelanotide is administered at 3 mg once a day following completion of dose escalation. The primary endpoint is the proportion of participants aged ≥12 years achieving a clinically meaningful reduction from baseline (≥10%) in body weight after ~52 weeks (eg, following period 2). Safety and tolerability are assessed by frequency of adverse events.

Conclusions: This pivotal trial is designed to evaluate the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS and Alström syndrome.

Submission Category: Study Design, Statistical Design, Study Protocols.
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http://dx.doi.org/10.1016/j.conctc.2021.100780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114053PMC
June 2021

Food cravings and loss-of-control eating in youth: Associations with gonadal hormone concentrations.

Int J Eat Disord 2021 08 4;54(8):1426-1437. Epub 2021 May 4.

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Objective: Among youth with overweight, food cravings (FC) are associated with loss-of-control (LOC)-eating, but the impact of sex-associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC-eating severity among healthy boys and girls across the weight strata in natural and laboratory environments.

Method: Using ecological momentary assessment (EMA), FC, and LOC-eating severity were reported 3-5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC-eating, and rated LOC-eating severity during the meal.

Results: Eighty-seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC-eating severity (ps < .01), with no differences by sex (ps = .21-.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC-eating such that general FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC-eating severity (ps = .36-.97). At the test meal, pre-meal FC were positively related to LOC-eating severity (p < .01), without sex or hormonal moderation (ps = .20-.64).

Discussion: FC were related to LOC-eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys. The mechanisms through which gonadal hormones might affect the relationship between FC and LOC-eating warrant investigation.
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http://dx.doi.org/10.1002/eat.23530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355041PMC
August 2021

Associations between weight-based teasing and disordered eating behaviors among youth.

Eat Behav 2021 04 29;41:101504. Epub 2021 Mar 29.

Section on Growth and Obesity, Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), 10 Center Drive, Bethesda, MD 20892, USA.

Weight-based teasing (WBT) is commonly reported among youth and is associated with disinhibited and disordered eating. Specifically, youth who experience WBT may engage in disordered eating behaviors to cope with the resultant negative affect. Therefore, we examined associations between WBT and disordered eating behaviors among youth and assessed whether negative affect mediated these relationships. Two hundred one non-treatment seeking youth (8-17y) completed questionnaires assessing WBT, disinhibited eating, depression, and anxiety. Disordered eating and loss-of-control (LOC) eating were assessed via semi-structured interview. Analyses of covariance were conducted to examine relationships between WBT and eating-related variables, and bootstrapping mediation models were used to evaluate negative affect (a composite of depressive and anxiety symptoms) as a mediator of these associations. All models were adjusted for sex, race, age, and adiposity. Among 201 participants (13.1 ± 2.8y; 54.2% female; 30.3% Black; 32.8% with overweight/obesity), WBT was associated with emotional eating, eating in the absence of hunger, and disordered eating attitudes and behaviors (ps ≤ 0.02). These associations were all mediated by negative affect. WBT was also associated with a threefold greater likelihood of reporting a recent LOC eating episode (p = .049). Among boys and girls across weight strata, WBT was associated with multiple aspects of disordered eating and these relationships were mediated by negative affect. Longitudinal studies are needed to clarify the directionality of these associations and to identify subgroups of youth that may be particularly vulnerable to WBT and its sequelae.
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http://dx.doi.org/10.1016/j.eatbeh.2021.101504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131258PMC
April 2021

The NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty: Protocol and rationale for methods and measures.

Neuroimage 2021 07 24;234:117970. Epub 2021 Mar 24.

Section on Integrative Neuroimaging, Clinical & Translational Neuroscience Branch, National Institute of Mental Health, Bethesda, MD USA.

Delineating the relationship between human neurodevelopment and the maturation of the hypothalamic-pituitary-gonadal (HPG) axis during puberty is critical for investigating the increase in vulnerability to neuropsychiatric disorders that is well documented during this period. Preclinical research demonstrates a clear association between gonadal production of sex steroids and neurodevelopment; however, identifying similar associations in humans has been complicated by confounding variables (such as age) and the coactivation of two additional endocrine systems (the adrenal androgenic system and the somatotropic growth axis) and requires further elucidation. In this paper, we present the design of, and preliminary observations from, the ongoing NIMH Intramural Longitudinal Study of the Endocrine and Neurobiological Events Accompanying Puberty. The aim of this study is to directly examine how the increase in sex steroid hormone production following activation of the HPG-axis (i.e., gonadarche) impacts neurodevelopment, and, additionally, to determine how gonadal development and maturation is associated with longitudinal changes in brain structure and function in boys and girls. To disentangle the effects of sex steroids from those of age and other endocrine events on brain development, our study design includes 1) selection criteria that establish a well-characterized baseline cohort of healthy 8-year-old children prior to the onset of puberty (e.g., prior to puberty-related sex steroid hormone production); 2) temporally dense longitudinal, repeated-measures sampling of typically developing children at 8-10 month intervals over a 10-year period between the ages of eight and 18; 3) contemporaneous collection of endocrine and other measures of gonadal, adrenal, and growth axis function at each timepoint; and 4) collection of multimodal neuroimaging measures at these same timepoints, including brain structure (gray and white matter volume, cortical thickness and area, white matter integrity, myelination) and function (reward processing, emotional processing, inhibition/impulsivity, working memory, resting-state network connectivity, regional cerebral blood flow). This report of our ongoing longitudinal study 1) provides a comprehensive review of the endocrine events of puberty; 2) details our overall study design; 3) presents our selection criteria for study entry (e.g., well-characterized prepubertal baseline) along with the endocrinological considerations and guiding principles that underlie these criteria; 4) describes our longitudinal outcome measures and how they specifically relate to investigating the effects of gonadal development on brain development; and 5) documents patterns of fMRI activation and resting-state networks from an early, representative subsample of our cohort of prepubertal 8-year-old children.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159875PMC
July 2021

MRI measures of hypothalamic injury are associated with glucagon-like peptide-1 receptor agonist treatment response in people with hypothalamic obesity.

Diabetes Obes Metab 2021 07 29;23(7):1532-1541. Epub 2021 Mar 29.

Seattle Children's Research Institute, Seattle, Washington, USA.

Aim: To evaluate whether neuroimaging-delineated regions of hypothalamic injury are associated with a differential treatment response to a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with hypothalamic obesity (HO).

Materials And Methods: We performed a prespecified secondary analysis of a randomized, multicentre, double-blind, placebo-controlled trial of people aged 10-25 years with hypothalamic injury and HO randomized to the GLP-1RA exenatide once-weekly (ExQW) or placebo for 36 weeks. Subjects underwent MRI prior to enrolment and the degree of hypothalamic damage was assessed using an integrative hypothalamic lesion score (HLS). Mammillary body (MB) damage was specifically determined. The main clinical endpoints were % change in body mass index (BMI) and change in % body fat. Nested ANCOVA models including a treatment × imaging measure interaction were compared using partial F-tests to assess whether the effect of ExQW treatment differed by severity of hypothalamic damage.

Results: Complete data were available in 35/42 randomized participants (placebo, n = 15; ExQW, n = 20). ExQW-treated patients with worse HLS or bilateral MB damage had greater reductions in % body fat at 36 weeks (interaction coefficient estimates for HLS: -0.9%, 95% CI -1.6% to -0.2%, p = .02; for MB damage: -7.4%, 95% CI -10.1% to -4.7%, p < .001, respectively) but not for BMI % change. Similarly, patients with more damaged and smaller MB cross-sectional areas had greater reductions in % body fat following ExQW (interaction coefficient estimate 0.3%, 95% CI 0.2%-0.4%, p < .001).

Conclusions: In people with HO, greater hypothalamic damage as determined by MRI, in particular MB injury, is associated with greater reductions in adiposity following GLP-1RA treatment.
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http://dx.doi.org/10.1111/dom.14366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353597PMC
July 2021

Bridging executive function and disinhibited eating among youth: A network analysis.

Int J Eat Disord 2021 05 27;54(5):721-732. Epub 2021 Jan 27.

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, USA.

Objective: Poorer executive function (EF) has been linked to disinhibited eating in youth, suggesting poor EF predisposes toward obesity, yet the specific nature and extent of interconnections between facets of these domains is unclear. Network analysis provides a promising framework for elucidating the relationship between poor EF and disinhibited eating, and offers insights into potential maintenance processes.

Method: Among youth ages 8-17 years, a regularized partial correlation network of EF and disinhibited eating facets was estimated to examine expected influence centrality and bridge expected influence. Computerized neurocognitive tasks assessed EF variables, including decision-making, general and food-related inhibitory control, delayed gratification, cognitive flexibility, and working memory. Disinhibited eating variables included total carbohydrate-fat intake at a laboratory test meal and self-reported eating in the absence of hunger, emotional eating, and loss-of-control eating severity.

Results: In the current sample (N = 248; M = 12.5; 54.8% female; 43.5% non-Hispanic White; 25.8% non-Hispanic Black; BMI %ile = 65.8 ± 27.8), emotional eating in response to depressive symptoms emerged as a central symptom in the network. Carbohydrate-fat intake had the highest bridge expected influence and was most strongly connected to general inhibitory control (part r = .14).

Discussion: The link between general inhibitory control and objective palatable food intake may be particularly salient in maintaining maladaptive eating behavior. Interventions targeting behavioral disinhibition may disrupt associations among a network of disinhibited eating facets in youth and should be targets for longitudinal research.
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http://dx.doi.org/10.1002/eat.23476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119329PMC
May 2021

Weight-Based Teasing and Metabolic Syndrome Components among Adolescent Military Dependents at Risk for Adult Obesity.

Child Obes 2021 03 12;17(2):116-124. Epub 2021 Jan 12.

Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Among adults, weight stigma is associated with markers of poor cardiometabolic health. Although weight-based teasing (WBT) is common among youth with high body weight, few studies have examined its associations with cardiometabolic markers. Owing to unique stressors (, parental deployment and frequent moves), military-dependent youth may be at particularly high risk for obesity, WBT, and poor cardiometabolic health. We, therefore, assessed associations between WBT and cardiometabolic health markers among adolescent military dependents presenting for a weight gain prevention trial. Participants underwent fasting phlebotomy; had fasting weight, height, and waist circumference measured; and completed assessments of WBT, anxiety, and loss-of-control eating. Multivariate analysis of covariance, adjusting for relevant covariates including demographics and body composition, was used to examine differences in metabolic syndrome (MetS) components (waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, triglycerides, and glucose) between youth reporting WBT and youth reporting no WBT. Bootstrapped models examined whether WBT mediated the relationship between BMI and MetS components. Data from 142 youth (57.7% female; 14.4 ± 1.6 years; 51.2% non-Hispanic White, 20.9% non-Hispanic Black; BMI: 1.9 ± 0.4) were analyzed. WBT was not significantly associated with any MetS component. Relationships were observed between BMI and all MetS components (except systolic blood pressure and glucose), although WBT did not significantly mediate these relationships (s > 0.05). This study did not find support for a relationship between WBT and MetS components in adolescent military dependents at risk for adult obesity. Prospective research is needed to determine whether associations between WBT and adverse cardiometabolic outcomes emerge primarily in adulthood.
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http://dx.doi.org/10.1089/chi.2020.0256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984651PMC
March 2021

Permanent change of station moves and disordered-eating attitudes and behaviors in prevention-seeking adolescent military-dependents.

Eat Behav 2021 01 26;40:101470. Epub 2020 Dec 26.

Department of Medicine, Uniformed Services University of the Health Sciences (USU), 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Military Cardiovascular Outcomes Research (MiCOR), USU, 4301 Jones Bridge Road, Bethesda, MD 20814, USA; Section on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, 10 Center Drive, Bethesda, MD 20892, USA; Department of Medical and Clinical Psychology, USU, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Electronic address:

Objective: Military-dependent youth appear to be at greater risk for disordered-eating than their civilian counterparts. Permanent change of station moves (PCS-moves), typically occurring every 2-3 years, are commonly experienced by adolescent military-dependents. However, the links between PCS-moves and disordered-eating in this population have not been explored. We hypothesized that stress arising from PCS-moves may contribute to the development and/or exacerbation of disordered-eating.

Methods: One-hundred-forty-nine adolescent military-dependents with overweight or obesity (59.7% female; 46.3% non-Hispanic White; 14.4±1.5 years; BMI-z: 1.9±0.4) completed measures before commencing an adulthood obesity and binge-eating disorder prevention trial for adolescents at-risk for both conditions due to BMI percentile ≥85th and loss-of-control (LOC)-eating and/or elevated anxiety symptoms. Disordered-eating attitudes and LOC-eating were assessed by semi-structured interview, and emotional eating was self-reported. Adjusting for relevant covariates, multiple linear regressions examined the unique association of PCS-move frequency with disordered-eating attitudes and disinhibited-eating behaviors.

Results: PCS-move frequency was not significantly associated with either LOC-eating frequency (β = 0.09, p = .27) or emotional eating (β = -0.04, p = .62). However, PCS-move frequency was positively associated with disordered-eating attitudes (β = 0.17, p = .04), which appeared to be primarily driven by shape concerns (β = 0.21, p = .01).

Discussion: Findings indicate that frequency of PCS-moves is related to disordered-eating attitudes, but not behaviors. Longitudinal research is needed to understand if PCS-moves prospectively relate to the onset and/or exacerbation of disordered-eating, and the relevance of disordered-eating attitudes as opposed to disinhibited-eating behaviors.
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http://dx.doi.org/10.1016/j.eatbeh.2020.101470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906934PMC
January 2021

Characterization of the adiponectin promoter + Cre recombinase insertion in the Tg(Adipoq-cre)1Evdr mouse by targeted locus amplification and droplet digital PCR.

Adipocyte 2021 12;10(1):21-27

Section on Growth and Obesity and Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health , Bethesda, MD, USA.

The Tg(Adipoq-cre)1Evdr mouse has become an important tool in adipose tissue biology. However, the exact genomic transgene integration site has not been established. Using Targeted Locus Amplification (TLA) we found the transgene had integrated on mouse chromosome 9 between exons 6 and 7 of . We detected transgene-transgene fusion; therefore, we used droplet digital polymerase chain reaction to identify copy number. In two separate experiments, we digested with BAMHI and with HindIII to separate potentially conjoined sequences. We found one copy of intact present in each experiment, indicating transgene-transgene fusion in other parts of the BAC that would not contribute to tissue-specific expression. copy number for Tg(Adipoq-cre)1Evdr mice can be potentially used to identify homozygous mice.
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http://dx.doi.org/10.1080/21623945.2020.1861728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781622PMC
December 2021

A Pilot Feasibility Study of Interpersonal Psychotherapy for the Prevention of Excess Weight Gain Among Adolescent Military-dependent Girls.

Mil Med 2021 02;186(3-4):344-350

Department of Medical and Clinical Psychology, Uniformed Services University of the Health Sciences (USU), Bethesda, MD 20814, USA.

Introduction: Adolescent military-dependents face unique psychosocial stressors due to their parents' careers, suggesting they may be particularly vulnerable to excess weight gain and symptoms of depression and anxiety. Despite these risk factors, there is a lack of tested preventative interventions for these youths. Given the transient nature of military family deployments, research may be hindered due to difficulty in collecting long-term prospective outcome data, particularly measured height and weight. The primary aim of this study was to examine the feasibility and acceptability of collecting body mass index (BMI, kg/m2) outcome data up to 2 years following a randomized controlled pilot trial of an adapted interpersonal psychotherapy (IPT) program aimed at preventing excess weight gain and improving psychological functioning for adolescent military-dependents. In exploratory analyses, patterns in body composition over time were examined.

Materials And Methods: Twenty-seven adolescent military-dependent girls (baseline: Mage: 14.4 ± 1.6 years; MBMI: 30.7 ± 4.9 kg/m2; MBMI-z: 1.9 ± 0.4) participated in this study. After a baseline assessment, utilizing a computerized program to create a randomization string, girls were assigned to either an IPT or a health education (HE) program. Participants completed three follow-up visits (posttreatment, 1-year follow-up, and 2-year follow-up). Girls completed a Treatment Acceptability Questionnaire at posttreatment; at all time points, height and fasting weight were collected. For the primary aim, Fisher's exact tests examined the rate of obtained follow-up data and lost to follow-up status between the two groups, Mann-Whitney U tests examined the session attendance between groups, and treatment acceptability ratings were compared between the two groups at posttreatment using an independent samples t-test. For the exploratory aim, one-way analyses of covariance (ANCOVAs) examined the group differences in BMI at each time point, adjusting for baseline values, and paired samples t-tests examined the within-group differences at each time point relative to baseline. Using imputed data in the full intent-to-treat sample, mixed model ANCOVAs were conducted to examine the group differences over time.

Results: Across both groups, girls attended an average of 72.0% of sessions. At least partial data were collected at posttreatment, 1-year follow-up, and 2-year follow-up for 96.3%, 85.2%, and 74.1% of the participants, respectively. There were no significant group differences in follow-up data collection rates, follow-up status, number of sessions attended, or treatment acceptability. BMI-z stabilized across groups, and there were no group differences in BMI-z. In adjusted ANCOVA models with imputed data, no significant group-by-time effects emerged.

Conclusions: For this randomized controlled prevention trial, long-term outcome data collection of measured BMI was possible in adolescent military-dependents and IPT was an acceptable and feasible intervention. An adequately powered trial is required to assess the efficacy of this intervention among military-dependents for obesity prevention and improvements in BMI.
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http://dx.doi.org/10.1093/milmed/usaa514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909453PMC
February 2021

Cross-Sectional and Longitudinal Examination of Insulin Sensitivity and Secretion across Puberty among Non-Hispanic Black and White Children.

Endocrinol Metab (Seoul) 2020 12 18;35(4):847-857. Epub 2020 Nov 18.

Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Background: Few studies using criterion measures of insulin sensitivity (SI) and insulin secretory capacity (ISC) have been conducted across puberty to adulthood. We examined how SI and ISC change from pre-puberty through adulthood.

Methods: Hyperglycemic clamp studies were performed in a convenience sample of non-Hispanic Black (NHB) and White children evaluated at age 6 to 12 years and at approximately 5-year intervals into adulthood (maximum age 27 years). SI and ISC (first-phase and steady-state insulin secretion) were determined cross-sectionally in 133 unique participants across puberty and in adulthood. Additionally, longitudinal changes in SI and ISC were compared at two timepoints among three groups defined by changes in pubertal development: pre-pubertal at baseline and late-pubertal at follow-up (n=27), early-pubertal at baseline and late-pubertal at follow-up (n=27), and late-pubertal at baseline and adult at follow-up (n=24).

Results: Cross-sectionally, SI was highest in pre-puberty and early puberty and lowest in mid-puberty (analysis of covariance [ANCOVA] P=0.001). Longitudinally, SI decreased from pre-puberty to late puberty (P<0.001), then increased somewhat from late puberty to adulthood. Cross-sectionally, first-phase and steady-state ISC increased during puberty and decreased in adulthood (ANCOVA P<0.02). Longitudinally, steady-state and first-phase ISC increased from pre-puberty to late puberty (P<0.007), and steady-state ISC decreased from late puberty to adulthood. The NHB group had lower SI (P=0.003) and greater first-phase and steady-state ISC (P≤0.001), independent of pubertal development.

Conclusion: This study confirms that SI decreases and ISC increases transiently during puberty and shows that these changes largely resolve in adulthood.
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http://dx.doi.org/10.3803/EnM.2020.771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803592PMC
December 2020

Weight-based teasing in youth: Associations with metabolic and inflammatory markers.

Pediatr Obes 2021 03 15;16(3):e12729. Epub 2020 Oct 15.

Section on Growth and Obesity, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Division of Intramural Research, National Institutes of Health (NIH), Bethesda, Maryland, USA.

Background: Research among adults suggests that weight stigma is associated with worsened cardiometabolic health. However, these relationships have not been examined among youth.

Objective: Assess associations between weight-based teasing (WBT) and metabolic and inflammatory markers among two samples of youth: (1) a non-treatment-seeking sample and (2) a weight loss treatment-seeking sample with obesity.

Method: Weight, height, adiposity, waist circumference and blood pressure were measured. Fasting blood samples were collected for metabolic (triglycerides, glucose, high-density lipoprotein cholesterol) and inflammatory analytes (high-sensitivity C-reactive protein in Study 1 and erythrocyte sedimentation rate in both studies). Youths completed the Perception of Teasing Scale, a measure of WBT. Metabolic and inflammatory indices were compared between those with and without teasing, adjusting for demographics and body composition.

Results: Study 1 enrolled 201 non-treatment-seeking youth (M = 13.1y; 54.2% female; 44.8% non-Hispanic White; 32.8% with overweight/obesity); 15.4% reported WBT. Study 2 enrolled 111 treatment-seeking adolescents with obesity (M = 14.0y; 66.7% female; 37.8% non-Hispanic White); 73.0% reported WBT. Adjusting for covariates, WBT was not associated with cardiometabolic risk factors in either study.

Conclusions: WBT was not associated with worsened cardiometabolic health. Longitudinal research is needed to elucidate associations between WBT and health in youth.
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http://dx.doi.org/10.1111/ijpo.12729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209784PMC
March 2021

A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity.

Diabetes Obes Metab 2021 02 25;23(2):363-373. Epub 2020 Oct 25.

McNeely Pediatric Diabetes Center and Endocrinology Clinic, Children's Minnesota, St. Paul, Minnesota.

Aim: To evaluate the efficacy, safety and tolerability of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with hypothalamic obesity (HO).

Materials And Methods: A two-arm, randomized, multicentre, double-blind, placebo-controlled trial was conducted in 10- to 25-year-olds with hypothalamic injury following intracranial tumour and HO. Participants were randomized to once-weekly subcutaneous injections of a GLP-1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint was 36-week % change in body mass index (BMI). Secondary outcomes included change in body composition (by dual energy x-ray absorptiometry).

Results: Forty-two participants were randomized to ExQW (n = 23) or placebo (n = 19). Participants were 5 ± 2 years (mean ± SD) postdiagnosis and development of HO (BMI 37.3 ± 7.1 kg/m ). In intention-to-treat analysis, the effect of 36-week ExQW vs. placebo on % Δ BMI was not significant (estimated treatment difference -1.7 ± 1.8%, 95% CI -4.1 to 0.6%, P = .40); however, total body fat mass was reduced (estimated treatment difference -3.1 ± 1.4 kg, 95% CI -5.7 to -0.4 kg, P = .02). There was a significant reduction in waist circumference (estimated effect of treatment -3.5 [95% CI -5.5 to -1.6] cm, P = .004). All patients treated with placebo increased % of adipose tissue, while 50% treated with ExQW had reductions (P < .001). Mean HbA1c, glucose tolerance and serum lipids did not change significantly with therapy. ExQW was well tolerated. The most frequent adverse events were transient gastrointestinal disturbances (ExQW vs. placebo: nausea 6/23 vs. 3/18, vomiting 4/23 vs. 4/18 and diarrhoea 7/23 vs. 3/18).

Conclusions: GLP-1 RAs are a promising and safe treatment to improve or stabilize HO in children and young adults.
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http://dx.doi.org/10.1111/dom.14224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821019PMC
February 2021

Inhibitory control and negative affect in relation to food intake among youth.

Appetite 2021 01 4;156:104858. Epub 2020 Sep 4.

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), USA.

Negative affect and poor inhibitory control are related to disinhibited eating behaviors in youth and may contribute to the development and/or maintenance of obesity. Although few studies have jointly examined these constructs in youth, it has been theorized that poor inhibitory control may be driven by negative affect. If supported, impaired inhibitory control, driven by negative affect, could represent a modifiable neurocognitive treatment target for disinhibited eating. The current study examined whether inhibitory control mediates the relationship between negative affect and eating among youth. Youth (8-17 years) participated in a Food Go/No-Go neurocognitive task to measure inhibitory control as the percentage of commission errors. A composite negative affect score was created from self-report measures of anxiety and depression. A laboratory buffet meal modeled to simulate disinhibited eating was used to measure total and snack food intake. Cross-sectional mediation models with bias-corrected bootstrap confidence intervals (CI) were conducted using negative affect as the independent variable, inhibitory control as the mediator, and intake patterns as dependent variables. One-hundred-eighty-one youths (13.2 ± 2.7y; 55% female; BMIz 0.6 ± 1.0) were studied. Total Go/No-Go commission errors mediated the relationship between negative affect and total intake (95%CI = [0.3, 31.6]), but not snack intake (95%CI = [-2.5, 7.3]). Commission errors for Food-Go blocks significantly mediated the relationship between negative affect and total intake (95%CI = [7.7, 44.4]), but not snack intake (95%CI = [-3.4, 9.5]). Commission errors on Neutral-Go blocks did not significantly mediate any of these relationships. Negative affect may lead to poorer inhibitory control as well as a stronger approach tendency toward food, increasing the likelihood of engaging in disinhibited eating. Future research should determine if, in combination with approaches to reduce negative affect, improved inhibitory control could help prevent overeating in youths with depressive or anxiety symptoms.
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http://dx.doi.org/10.1016/j.appet.2020.104858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7669609PMC
January 2021

Associations of GlycA and high-sensitivity C-reactive protein with measures of lipolysis in adults with obesity.

J Clin Lipidol 2020 Sep - Oct;14(5):667-674. Epub 2020 Aug 4.

Section on Growth and Obesity, Division of Intramural Research (DIR), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA; Johns Hopkins Community Physicians at Howard County General Hospital, Johns Hopkins Medicine, Columbia, MD, USA; Department of Endocrinology, Diabetes and Metabolism, Johns Hopkins School of Medicine, Baltimore, MD, USA. Electronic address:

Background: Obesity-associated inflammation promotes metabolic dysfunction. However, it is unclear how different inflammatory biomarkers predict dysregulation in specific tissues/organs, particularly adipose tissue.

Objective: The aim of our study was to examine whether GlycA, a nuclear magnetic resonance-measured biomarker of inflammation, is a better predictor of insulin-suppressible lipolysis and other measures of metabolic dysfunction compared with high-sensitivity C-reactive protein (hsCRP) in human obesity.

Methods: This was a cross-sectional study of 58 nondiabetic adults with obesity (body mass index: 39.8 ± 7.0 kg/m, age 46.5 ± 12.2 years, 67.2% female) who underwent a frequently sampled intravenous glucose tolerance test in the fasted state. Noninsulin-suppressible (l), insulin-suppressible (l), and maximal (l+l) lipolysis rates, as well as insulin sensitivity and acute insulin response to glucose, were calculated by minimal model analysis. Nuclear magnetic resonance was used to measure GlycA. Body composition was determined by dual-energy X-ray absorptiometry.

Results: GlycA was strongly correlated with hsCRP (r = +0.46; P < .001). GlycA and hsCRP were positively associated with l, l+l, and fat mass (Ps < .01). In linear regression models accounting for age, race, sex, and fat mass, GlycA remained significantly associated with l and l+l (Ps < .05), whereas hsCRP did not (Ps ≥ .20). Neither GlycA nor hsCRP was associated with l insulin sensitivity, or acute insulin response to glucose.

Conclusions: GlycA was associated with elevated lipolysis, independent of adiposity, in adults with obesity. Our findings suggest that GlycA and hsCRP have distinct inflammation-mediated metabolic effects, with GlycA having a greater association with adipose tissue dysfunction. Further studies are warranted to investigate the mechanisms underlying these associations.
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http://dx.doi.org/10.1016/j.jacl.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642018PMC
September 2021

Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

Int J Obes (Lond) 2020 08 27;44(8):1793-1799. Epub 2020 May 27.

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892-1103, USA.

Objective: Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS).

Methods: Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6 mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing.

Results: At baseline, age (48.0 ± 13.8 vs. 44.7 ± 10.3 years) and BMI (39.8 ± 6.4 vs. 41.8 ± 8.2 kg/m) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis.

Conclusions: In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.
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http://dx.doi.org/10.1038/s41366-020-0598-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253147PMC
August 2020

Exceptional Reported Effects and Data Anomalies Merit Explanation from "A randomized controlled trial of coordination exercise on cognitive function in obese adolescents" by.

Psychol Sport Exerc 2020 Jan 20;46. Epub 2019 Oct 20.

Department of Epidemiology and Biostatistics, Indiana University School of Public Health-Bloomington, Bloomington, IN, USA.

We read the recent article in Psychology of Sport and Exercise by Liu et al. ("A randomized controlled trial of coordination exercise on cognitive function in obese adolescents") with great interest. Our interest in the article stemmed from the extraordinary differences in obesity-related outcomes reported in response to a rope-jumping intervention. We requested the raw data from the authors to confirm the results and, after the journal editors reinforced our request, the authors graciously provided us with their data. We share our evaluation of the original data herein, which includes concerns that weight and BMI loss by the intervention appears extraordinary in both magnitude and aspects of the distributions. We request that the authors address our findings by providing explanations of the extraordinary data or correcting any errors that may have occurred in the original report, as appropriate.
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http://dx.doi.org/10.1016/j.psychsport.2019.101604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189777PMC
January 2020

DLG2 variants in patients with pubertal disorders.

Genet Med 2020 08 28;22(8):1329-1337. Epub 2020 Apr 28.

Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Purpose: Impaired function of gonadotropin-releasing hormone (GnRH) neurons can cause a phenotypic spectrum ranging from delayed puberty to isolated hypogonadotropic hypogonadism (IHH). We sought to identify a new genetic etiology for these conditions.

Methods: Exome sequencing was performed in an extended family with autosomal dominant, markedly delayed puberty. The effects of the variant were studied in a GnRH neuronal cell line. Variants in the same gene were sought in a large cohort of individuals with IHH.

Results: We identified a rare missense variant (F900V) in DLG2 (which encodes PSD-93) that cosegregated with the delayed puberty. The variant decreased GnRH expression in vitro. PSD-93 is an anchoring protein of NMDA receptors, a type of glutamate receptor that has been implicated in the control of puberty in laboratory animals. The F900V variant impaired the interaction between PSD-93 and a known binding partner, Fyn, which phosphorylates NMDA receptors. Variants in DLG2 that also decreased GnRH expression were identified in three unrelated families with IHH.

Conclusion: The findings indicate that variants in DLG2/PSD-93 cause autosomal dominant delayed puberty and may also contribute to IHH. The findings also suggest that the pathogenesis involves impaired NMDA receptor signaling and consequently decreased GnRH secretion.
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http://dx.doi.org/10.1038/s41436-020-0803-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510947PMC
August 2020

Sex differences in metabolic syndrome components in adolescent military dependents at high-risk for adult obesity.

Pediatr Obes 2020 08 14;15(8):e12638. Epub 2020 Apr 14.

Department of Medicine, Uniformed Services University of the Health Sciences (USU), Bethesda, Maryland, USA.

Background: Metabolic syndrome in adolescence has been associated with adverse cardiometabolic outcomes in adulthood. Preliminary data suggest that boys may have worsened metabolic syndrome components compared to girls. Yet, little is known about the physical health of military dependents, a potentially at-risk population.

Objective: Examine sex differences in metabolic syndrome components in a sample of adolescent military dependents.

Methods: Participants were adolescents (N = 139; 14.4 ± 1.6 years; 45.3% male; 41.0% non-Hispanic White, 19.4% non-Hispanic Black; BMI-z: 1.9 ± 0.4) at-risk for adult obesity and binge-eating disorder due to an age- and sex-adjusted BMI ≥85th percentile and loss-of-control eating and/or elevated anxiety. A multivariate analysis of covariance was conducted to compare objectively measured metabolic syndrome components across boys and girls. Covariates were age, race, loss-of-control eating status, anxiety symptoms, and BMI-z.

Results: Metabolic syndrome components differed by sex (P = .01). Boys had higher systolic blood pressure (P = .049), lower high-density lipoprotein cholesterol (P = .01), and higher glucose (P = .001) than girls. Waist circumference, diastolic blood pressure, and triglycerides did not differ between boys and girls (P > .05).

Conclusions: Future research should prospectively examine these relationships into adulthood. If the current findings are supported, prevention programs should consider targeting cardiometabolic health particularly among male adolescent military dependents.
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http://dx.doi.org/10.1111/ijpo.12638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183113PMC
August 2020

Bacitracin attenuates haemolysis-induced insulin degradation during insulin sensitivity testing: Repurposing an old drug for use in metabolic research.

Diabetes Obes Metab 2020 08 20;22(8):1469-1473. Epub 2020 Apr 20.

Section on Growth and Obesity, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Haemolysis of serially collected insulin serum samples frequently causes falsely-low measured concentrations because of the release of intracellular insulin degrading enzyme (IDE). We investigated if bacitracin, an in vitro IDE inhibitor, could prevent haemolysis-induced insulin degradation during insulin sensitivity testing. Blood samples were collected from adults undergoing serial sampling for insulin sensitivity. A dose-finding study measured insulin from experimentally haemolysed samples containing five bacitracin concentrations (0-2.5 g/L) and from non-experimentally haemolysed samples. To confirm the utility of bacitracin in the clinical setting, we compared insulin in samples collected with and without 1 g/L bacitracin from a frequently sampled intravenous glucose tolerance test (FSIVGTT), where haemolysis often occurs accidentally. In the dose-finding study, bacitracin 0.25, 1 and 2.5 g/L all maximally prevented insulin degradation in experimentally haemolysed samples. Among FSIVGTT unintentionally haemolysed samples, insulin concentrations from bacitracin-containing samples were significantly higher than from those without bacitracin (P < .01), and not different from non-haemolysed samples obtained simultaneously from a second intravenous catheter (P = .07). Bacitracin did not significantly alter insulin concentrations in non-haemolysed samples. Bacitracin attenuates haemolysis-associated insulin degradation in clinical samples, enabling a more accurate assessment of insulin sensitivity and glucose homeostasis.
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http://dx.doi.org/10.1111/dom.14038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405941PMC
August 2020

Assessment of loss-of-control eating in healthy youth by interview and questionnaire.

Int J Eat Disord 2020 05 23;53(5):510-519. Epub 2020 Mar 23.

Section on Growth and Obesity, Division of Intramural Research Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.

Objective: The aim of this study is to evaluate two questionnaires, an updated youth version of the questionnaire on eating and weight patterns (Questionnaire on Eating and Weight Patterns-5 Children/Adolescent [QEWP-C-5]) and the Loss-of-Control (LOC) Eating Disorder Questionnaire (LOC-ED-Q), against the Eating Disorder Examination (EDE) interview to assess the presence of LOC-eating among youth.

Method: Two-hundred and eighteen youths (12.8 ± 2.7 years) completed the QEWP-C-5, LOC-ED-Q, and EDE, depressive and anxiety questionnaires, and adiposity assessment. Sensitivity, specificity, positive-predictive value, negative-predictive value, and diagnostic accuracy were calculated; Cochran's Q and McNemar's tests were used to compare measures. Receiver operating characteristic area under the curve (AUC) analyses were performed. Mood and adiposity based on LOC-eating presence and absence based on each measure were examined.

Results: The QEWP-C-5 and LOC-ED-Q demonstrated poor sensitivity (33%; 30%) and high specificity (95%; 96%) compared with the EDE. The AUCs suggested neither the QEWP-C-5 (0.64) nor the LOC-ED-Q (0.62) demonstrated acceptable diagnostic accuracy. Comparing distributions of LOC-eating presence between assessments, the QEWP-C-5 and EDE did not differ significantly (p = .10), while the LOC-ED-Q and EDE had significantly different distributions (p = .03). LOC-eating presence was associated with higher depressive and anxiety symptoms across all measures (ps < .02). Greater adiposity (ps < .02) was associated with LOC-eating presence on the EDE and LOC-ED-Q, and higher BMI z-score (p = .02) on the LOC-ED-Q.

Discussion: Neither the QEWP-C-5 nor the LOC-ED-Q was sensitive for identifying LOC-eating presence as determined by the EDE, although both were associated with greater mood symptoms. Research is needed to improve self-report questionnaires to better screen for LOC-eating presence among pediatric populations.
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http://dx.doi.org/10.1002/eat.23262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217739PMC
May 2020

The Effects of Interrupting Sitting Time on Affect and State Anxiety in Children of Healthy Weight and Overweight: A Randomized Crossover Trial.

Pediatr Exerc Sci 2020 05 12;32(2):97-104. Epub 2020 Mar 12.

University of Southern California.

Purpose: Sedentary time relates to higher anxiety and more negative affect in children. This study assessed whether interrupting sitting over 3 hours is sufficient to influence state anxiety, positive affect, or negative affect, and tested weight status as a moderator.

Methods: Analyses were the second (preplanned) purpose of a larger study. Children (N = 61; age: mean [SD] = 9.5 [1.3]; 43% healthy weight) completed 2 experimental conditions: continuous sitting for 3 hours and sitting for 3 hours interrupted with walking for 3 minutes in every 30 minutes. State anxiety, positive affect, and negative affect were reported at pretest and posttest. Multilevel models for repeated measures assessed whether experimental condition predicted posttest scores.

Results: Experimental condition was unrelated to posttest state anxiety or positive affect. Weight status moderated how experimental condition influenced posttest negative affect (P = .003). Negative affect was lower in the children of healthy weight after interrupted sitting (vs continuous sitting; β = -0.8; 95% confidence interval, -1.5 to 0.0, P = .05), but it was higher in the children with overweight/obesity after interrupted sitting (vs continuous sitting; β = 0.6; 95% confidence interval, 0.0 to 1.2, P = .06).

Conclusions: Interrupting sitting acutely reduced negative affect in children of healthy weight, but not in children with overweight. Further research is needed to better understand the potential emotional benefits of sitting interruptions in youth.
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http://dx.doi.org/10.1123/pes.2019-0169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785062PMC
May 2020

Associations between latent trait negative affect and patterns of food-intake among girls with loss-of-control eating.

Int J Eat Disord 2020 04 27;53(4):618-624. Epub 2020 Feb 27.

Department of Medical and Clinical Psychology and Medicine, Uniformed Services University of the Health Sciences (USU), Bethesda, Maryland, USA.

Objective: Momentary negative affect (NA) has been shown to predict eating patterns in the laboratory, yet, more stable mood states have not been studied in relation to eating patterns in the laboratory among youth at high risk for binge-eating disorder and obesity.

Method: One-hundred-eight adolescent girls (14.5 ± 1.7 years) with BMI between the 75th-97th percentile who reported loss-of-control (LOC)-eating completed measures of trait anxiety and depressive symptoms. Food-intake patterns were measured from a laboratory test meal (9,385 kcal). Latent factor analysis of depressive symptoms and trait anxiety was used to compute latent trait NA. Multivariate general linear models predicted total energy, snacks, and macronutrient intake from trait NA, adjusting for age, race, height, lean-mass, and percentage fat-mass.

Results: Trait NA was significantly positively related to total energy-intake, and, specifically, snacks, sweet snacks, and percentage sweet fats (ps ≤ .03), and negatively related to percentage protein consumed (p = .04).

Discussion: Expanding on affect theory, trait NA may relate to palatable food-intake among girls with LOC-eating. Further data are needed to determine whether those with LOC-eating and trait NA are at heightened risk for the development of binge-eating disorder and obesity.
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http://dx.doi.org/10.1002/eat.23253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190819PMC
April 2020
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