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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 (PPPP=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.

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.

Allogeneic blood or marrow transplantation (BMT) is a potentially curative therapy for patients with primary immunodeficiency (PID). Safe and effective reduced-intensity conditioning (RIC) approaches that are associated with low toxicity, use alternative donors, and afford good immune reconstitution are needed to advance the field. Twenty PID patients, ranging in age from 4 to 58 years, were treated on a prospective clinical trial of a novel, radiation-free and serotherapy-free RIC, T-cell-replete BMT approach using pentostatin, low-dose cyclophosphamide, and busulfan for conditioning with post-transplantation cyclophosphamide-based graft-versus-host-disease (GVHD) prophylaxis. This was a high-risk cohort with a median hematopoietic cell transplantation comorbidity index of 3. With median follow-up of survivors of 1.9 years, 1-year overall survival was 90% and grade III to IV acute GVHD-free, graft-failure-free survival was 80% at day +180. Graft failure incidence was 10%. Split chimerism was frequently observed at early post-BMT timepoints, with a lower percentage of donor T cells, which gradually increased by day +60. The cumulative incidences of grade II to IV and grade III to IV acute GVHD (aGVHD) were 15% and 5%, respectively. All aGVHD was steroid responsive. No patients developed chronic GVHD. Few significant organ toxicities were observed. Evidence of phenotype reversal was observed for all engrafted patients, even those with significantly mixed chimerism (n = 2) or with unknown underlying genetic defect (n = 3). All 6 patients with pre-BMT malignancies or lymphoproliferative disorders remain in remission. Most patients have discontinued immunoglobulin replacement. All survivors are off immunosuppression for GVHD prophylaxis or treatment. This novel RIC BMT approach for patients with PID has yielded promising results, even for high-risk patients.

Few studies have assessed the accuracy of the FreeStyle Libre Pro (FLP) continuous glucose monitor for estimating plasma glucose (PG) in non-diabetic children. OBJECTIVE Determine the accuracy of FLP compared to PG during OGTT in healthy children. SUBJECTS Children (7-11.99 years) with healthy weight and overweight/obesity (n = 33; 52% male). METHODS Participants wore the FLP before and during a 2-hour OGTT; PG was measured at 30 minutes intervals. Potential systematic- and magnitude-related biases for FLP vs PG were examined. RESULTS FLP 15-minute averages and PG were correlated at most timepoints during OGTT (r2 = 0.35-0.69, P's

Recent studies examining the genetic underpinnings of obesity have suggested that the melanocortin 3 receptor (MC3R) plays a role in body composition and nutrient partitioning (Chen et al., 2000, Demidowich et al., 2017). In mice, inactivating Mc3r causes increased feeding efficiency leading to obesity with increased fat mass, but with reduced lean mass (Chen et al., 2000, Kumar et al., 2009, Butler et al., 2017, Renquist et al., 2011). The common minor human MC3R C17A+G241A haplotype, which leads to 2 amino acid substitutions Thr6Lys and Val81Ile in the protein translated from the first start site of the human gene, leads to a partially inactive protein transcript (Feng et al., 2005). In a large pediatric cohort, individuals homozygous for the MC3R C17A+G241A haplotype were reported to have greater BMI, body fat, plasma leptin, and insulin concentrations, with reduced lean mass when compared to those who were heterozygous (Het) for the C17A + G241A haplotype and homozygous for the wild-type MC3R gene (WT) (Feng et al., 2005). The greater adiposity and reduced signal transduction associated with homozygosity for the C17A+G241A haplotype has since been replicated in other pediatric cohorts (Savastano et al., 2009, Lee et al., 2007, Aris et al., 2015). Supportive data for the effects of this haplotype have also been reported in mice. When the murine Mc3r was replaced with the human MC3R C17A+G241A haplotype, homozygous knockin mice also displayed increased feeding efficiency, greater adiposity, and reduced lean mass (Lee et al., 2016). Among adult human cohorts, however, the MC3R C17A+G241A haplotype has not been associated with greater BMI (Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007, Calton et al., 2009, Matsuoka et al., 2007) and scant data exist for its effects on other anthropometric or metabolic parameters (Hani et al., 2001, Rutanen et al., 2007). A major limitation of most of these prior studies is the low number of homozygous participants (Calton et al., 2009, Li et al., 2000, Hani et al., 2001, Wong et al., 2002, Rutanen et al., 2007); consequently, many prior conclusions were based largely on the assumption that heterozygotes and homozygotes are phenotypically identical or there would be additive effects from each minor allele/haplotype. Although labelled as a common variant, the MC3R C17A+G241A haplotype is relatively rare in most races and ethnicities, with an estimated prevalence of homozygous individuals between 0.4–3.5% (Obregon et al., 2010, Lee et al., 2007, Rutanen et al., 2007, Hani et al., 2001). Individuals of predominately African ancestry are the exception, as over half carry at least one copy of the haplotype, and 12–16% are homozygous for C17A+G241A (Li et al., 2000, Feng et al., 2005, Savastano et al., 2009). As such individuals have been underrepresented in most adult cohort studies examining MC3R polymorphisms, it remains unclear if homozygous individuals have a different anthropometric and metabolic phenotype than Het or WT adults. To our knowledge, this is the first study of a large cohort of adults that has assessed the association of the MC3R C17A+G241A haplotype with body composition data such as fat mass and lean mass. Our primary hypothesis was that homozygosity for the MC3R C17A+G241A haplotype would be associated with greater BMI and fat mass in African American adults. We additionally hypothesized that this increase in adiposity would be associated with greater insulin resistance and inflammation in homozygous individuals as compared to Het and WT.

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 (Mage = 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 (Mage = 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.

Background Executive functioning (EF) difficulties may be associated with problems regulating eating behaviours. Few studies have evaluated this question in youth using diverse measures of EF or objective measures of energy intake. Methods The current study used neuropsychological tasks and a laboratory test meal to evaluate the links between EF and youth's disinhibited eating patterns. Two-hundred-five nontreatment seeking youth (M age = 13.1 ± 2.8 years; M BMIz = 0.6 ± 1.0; 33.2% overweight; 54.1% female) completed tasks measuring decision making, general and food-specific behavioural disinhibition, willingness to delay gratification for food and money, cognitive flexibility, and working memory. Age (children vs adolescents) was examined as a moderator. All analyses adjusted for demographic factors, pubertal status, lean mass (kg), fat mass (%), height, general intellectual functioning, and depressive symptoms. Results After adjusting for multiple comparisons, more general behavioural disinhibition was associated with greater total energy intake (P = .02), and poorer cognitive flexibility was associated with more fat intake (P = .03) across all ages. Poorer decision making in children (P = .04), but not adolescents (P = .24), was associated with greater fat intake. Food-specific behavioural disinhibition, the ability to delay gratification for both food and monetary rewards, and working memory were not significantly associated with youth's disinhibited eating patterns during a single meal. Conclusions Most domains of EF were not associated with youth's disinhibited eating. Significant associations may highlight the need to target specific cognitive processes, particularly behavioural disinhibition, decision making, and cognitive flexibility, in potential intervention strategies for children's disinhibited eating.

Objective Pediatric loss-of-control (LOC) eating is associated with, and predictive of, gains in adiposity and adverse metabolic outcomes. In addition, some preliminary data suggest that anxiety may exacerbate the relationship of LOC eating with weight and metabolic syndrome (MetS)-related measures. We therefore examined whether anxiety moderated the relationship between LOC eating and body mass index z (BMIz), adiposity, and MetS-related measures in youth. Methods A convenience sample of non-treatment-seeking boys and girls of varying weight strata were interviewed to determine the presence of LOC eating and completed a questionnaire assessing trait anxiety. BMIz and MetS-related measures (blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, glucose, and insulin) were measured after an overnight fast. Adiposity was assessed by air displacement plethysmography or dual-energy x-ray absorptiometry. Analyses adjusted for age, sex, race, height, fat mass, and depressive symptoms, as appropriate. Results In all, 379 youths (13.0 ± 2.8 years; 53% female; BMIz = 0.8 ± 1.1; 22% with LOC eating) were studied. Anxiety was not significantly related to BMIz, adiposity, or MetS-related measures. However, anxiety and LOC eating interacted such that only among youth with LOC eating, anxiety was positively associated with fasting insulin (p = .02) and insulin resistance (p = .01). The interaction of anxiety and LOC eating was not significantly related to BMIz, adiposity, or any other MetS-related measure (ps = ns). Conclusions Only among non-treatment-seeking youth with LOC eating, anxiety may be associated with increased insulin secretion and insulin resistance. Longitudinal studies are required to confirm these findings and explore mechanisms for these relationships.

Background Data on the link between anxiety and body composition in youth are mixed. Yet, anxiety and disordered eating are highly correlated. One pathway between anxiety and excess body weight and fat mass may be through loss of control (LOC) eating. We examined whether LOC eating mediated the relationship between anxiety and body composition in youth with and without overweight. Method Non-treatment-seeking youth (8–17 years) participated in studies examining weight and eating behaviors. Anxiety (child- and parent-report of child) and LOC eating were assessed by self-report questionnaires and interviews, respectively. Fat mass was assessed by dual-energy x-ray absorptiometry or air displacement plethysmography. Cross-sectional mediation models with bias-corrected bootstrap confidence intervals (CI) were conducted. Results 257 youth (12.91 ± 2.76 years; 52.5% female; BMI-z 0.93 ± 1.07) were studied. There was a significant indirect path between child-reported anxiety and both BMI-z (ab = .005, SE = 0.003, 95% CI = 0.001–0.01) and body fat mass (ab = 0.001, SE = 0.001, 95% CI ≤0.001–0.003) through the number of LOC episodes in the past month. No significant indirect paths through the number of LOC episodes was observed for parent-report of child anxiety on BMI-z (ab = 0.004, SE = 0.01, 95% CI = −0.01–0.03) or body fat mass (ab = 0.001, SE = 0.002, 95% CI = −0.002–0.01). No direct paths were observed between anxiety and body composition regardless of the informant. Discussion LOC eating appears to mediate the relationship of child-reported anxiety with body composition in non-treatment seeking boys and girls. Prospective data are needed to determine if anxiety promotes LOC eating that results in increased risk for excess body weight and fat gain.

BACKGROUND Resting energy expenditure (REE), adjusted for total lean mass (LM), is lower in African American (AA) than Caucasian American (CA) children. Some adult studies suggest that AA-CA differences in lean mass compartments explain this REE difference. Similar data are limited in children. OBJECTIVE To evaluate differences in compartment-specific lean mass between AA and CA children and examine the individual contributions of high-metabolic rate-at-rest trunk lean mass (TrLM) and low-metabolic-rate-at-rest appendicular lean mass (AppLM) for AA-CA differences in REE. METHODS We studied a convenience sample of 594 AA (n = 281) and CA (n = 313) children. REE was measured by using indirect calorimetry; dual-energy X-ray absorptiometry was used to assess body composition. ANCOVAs were performed to examine AA-CA differences in TrLM, AppLM and REE. After accounting for age, sex, height, pubertal development, bone mass and adiposity, REE was evaluated adjusting for total LM (model A) and separately adjusting for TrLM and AppLM (model B). RESULTS African American children had greater adjusted AppLM (17.8 ± 0.2 [SE] vs. 16.0 ± 0.2 kg, p

Objective The Eating Disorder Examination (EDE) was originally developed and validated in primarily white female samples. Since data indicate that eating pathology impacts black youth, elucidating the psychometric appropriateness of the EDE for black youth is crucial. Methods A convenience sample was assembled from seven pediatric obesity studies. The EDE was administered to all youth. Confirmatory factor analyses (CFA) were conducted to examine the original four-factor model fit and two alternative factor structures for black and white youth. With acceptable fit, multiple-group CFAs were conducted. For measurement invariant structures, the interactive effects of race with sex, BMIz, adiposity, and age were explored (all significance levels p

Loss of control (LOC) eating in youth is associated with excess body weight and adiposity. After adjusting for fat mass, youth with LOC eating have higher blood pressure and higher low-density lipoprotein cholesterol compared to youth without LOC eating. Increased inflammation may account for this relationship, although few data have examined this hypothesis. Therefore, this study explored the association between LOC eating and high-sensitivity C-reactive protein (hsCRP), a marker of inflammation.We investigated hsCRP concentrations in relation to LOC eating in a convenience sample of 194 youth (age 14.3 ± 2.1 years; 63.9% female; BMI-z 1.64 ± 1.06). The presence of LOC eating in the past month was assessed by the Eating Disorder Examination interview. Serum hsCRP was measured by enzyme-linked immunosorbent assay. Adiposity was measured by air displacement plethysmography or dual-energy x-ray absorptiometry. We compared hsCRP in those with and without LOC eating in analyses accounting for sex, adiposity, height, depressive symptoms, and eating psychopathology.Youth with LOC eating had significantly greater hsCRP than youth without LOC eating (p = 0.02), after accounting for all covariates. The number of LOC eating episodes in the past month was positively associated with hsCRP (p = 0.01). The relationship between LOC eating and hsCRP was not mediated by depressive symptoms or eating psychopathology (ps 0.05).Youth with disinhibited eating may manifest increased chronic inflammation. Those with LOC eating may be an important subgroup at risk for adverse health outcomes associated with both chronic inflammation and obesity. Future research should examine whether hsCRP concentrations mediate the relationship between LOC eating and its association with cardiometabolic risk.

Loss of control (LOC) eating in youth is associated with elevated fasting serum leptin, even after accounting for adiposity. Anxiety is closely linked to, and may exacerbate, LOC eating. Yet, it remains unclear how anxiety relates to leptin, or if the relationship is moderated by the presence of LOC eating. We examined whether self-reported trait anxiety interacted with LOC eating in relation to leptin in a convenience sample of youths (n = 592, 13.1 &plusmn, 2.7 years, body mass index z-score (BMIz) = 0.9 &plusmn, 1.1, 61.8% girls, 53.5% non-Hispanic White, 36.6% with LOC eating). LOC eating was assessed by interview. Leptin was measured after an overnight fast. Exploratory analyses were conducted to examine anxiety and LOC eating in relation to laboratory intake patterns in three sub-samples. In a generalized linear model adjusting for relevant covariates, anxiety significantly interacted with LOC eating in relation to leptin (p = 0.02), such that greater trait anxiety related to higher concentrations of leptin only among youth with LOC eating. Trait anxiety was not significantly related to fasting serum leptin independently in a generalized linear model adjusting for age, race, height, sex, study type, and fat mass (kg). Exploratory mechanistic analyses of food intake patterns did not identify consistent results for participants with both anxiety and LOC eating. Among youth with LOC eating, anxiety may be associated with higher serum leptin. Prospective data are required to elucidate the directionality and mechanisms of these relationships.

Insufficient average sleep duration has been inconsistently associated with poor diet and obesity risks in youth. Inconsistencies in findings across studies may be due to a general failure to examine associations in weekday versus weekend sleep. We hypothesized that greater variations in weekday and weekend sleep duration would be associated with more disinhibited eating behaviors, which, in turn, might be involved in the relationship between sleep and weight. We, therefore, examined, among healthy, non-treatment seeking youth, the associations of average weekly, weekend, and weekday sleep duration with eating in the absence of hunger (EAH), a disinhibited eating behavior associated with disordered eating and obesity. Sleep was assessed via actigraphy for 14 days. Participants completed a self-report measure of EAH. Adiposity was measured by dual-energy X-ray absorptiometry. Linear regressions were used to test the associations of sleep duration with EAH and the associations of sleep duration and EAH, with fat mass. Among 123 participants (8&ndash, 17 years, 52.0% female, and 30.9% with overweight), there was no significant association between average weekly sleep and EAH. Further, there was no significant association among average weekly sleep duration or EAH and fat mass. However, average weekday sleep was negatively associated, and average weekend sleep was positively associated, with EAH (ps &lt, 0.02). Weekend &ldquo, catch-up&rdquo, sleep (the difference between weekend and weekday sleep) was positively associated with EAH (p &lt, 0.01). Findings indicate that shorter weekday sleep and greater weekend &ldquo, sleep are associated with EAH, which may place youth at risk for the development of excess weight gain over time.

BACKGROUND: Ensuring children are fasting for blood draws is necessary to diagnose abnormalities in glucose homeostasis. We sought to determine if serum free fatty acid (FFA) concentrations might be a useful marker to differentiate the fed and fasted states among children. METHODS: A total of 442 inpatient (fasting) and 323 (postglucose load) oral glucose tolerance test samples of glucose, insulin, and FFA from children (age 5–18 years) who had healthy weight, overweight, or obesity were examined by receiver operating characteristic (ROC) curve analysis to identify a cut point for nonfasting. In a cross-sectional study, we compared mean FFA and percentage of FFA values below this cut point as a function of inpatient (n = 442) versus outpatient (n = 442) setting. RESULTS: The area under the curve of FFA was significantly better (P values < .001) than the area under the curve of glucose or insulin for identifying nonfasting. FFA CONCLUSIONS: Clinicians cannot assume that pediatric patients are adequately fasted on arrival for fasting blood work. On the basis of having significantly lower outpatient than inpatient FFA values and more frequently suppressed FFA, children appeared less likely to be fasting at outpatient appointments. FFA value

Background Youths with overweight and obesity report frequent instances of weight-based teasing. However, little is known about the prospective associations between weight-based teasing and changes in body composition among youth. Objective To assess associations between weight-based teasing and changes in body mass index (BMI) and fat mass in a longitudinal study of youths with, or at-risk for, overweight and obesity. Methods One hundred ten youths with, or at-risk for, overweight participated in a longitudinal observational study. The Perception of Teasing Scale was administered at baseline. Height, weight, and body composition were obtained at baseline and at follow-ups (range: 1-15 years). Results Mean age at baseline was 11.8 years; 53% had overweight/obesity; 36% were non-Hispanic Black; 55% were female; mean follow-up from baseline: 8.5 years. Adjusting for covariates and repeated measures of BMI or fat mass, linear mixed models revealed that weight-based teasing was associated with greater gain of BMI and fat mass across the follow-up period (ps ≤ .007). Adjusting for covariates, youths reporting high weight-based teasing (two standard deviations above the mean) experienced a 33% greater gain in BMI (an additional 0.20 kg/m2 ) and a 91% greater gain in fat mass (an additional 0.65 kg) per year compared with peers who reported no weight-based teasing. Conclusions Among youths with, and at-risk for, overweight and obesity, weight-based teasing was associated with greater weight and fat gain.

Introduction: Increased circulating free fatty acid (FFA) due to impaired control of adipocyte triglyceride lipolysis contributes to the development of obesity-related insulin resistance (IR). However, it is less clear whether there are differences in the relationship between lipolysis and skeletal muscle vs hepatic IR, or how these relationships are influenced by age, race, sex, body composition, or inflammation. We investigated the associations of lipolytic rate (LR) with skeletal muscle insulin sensitivity, as evidenced by insulin sensitivity index (SI), and hepatic IR, as measured by HOMA-IR. Methods: 46 healthy, non-diabetic adults with obesity (BMI 39.8±6.9 kg/m2) and 11 lean (BMI 25.6±2.1 kg/m2) adults (40% NHB, 20% HISP, 37% NHW, 3% Asian; 65% female; age 45.8±12.6y) underwent fasting blood draws and an insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT). LR was calculated by a mathematical minimal model that estimated basal lipolysis and insulin-mediated lipolysis stimulated by insulin modulation of FFA during the FSIVGTT; SI was derived from Bergman’s minimal model. Body composition was determined by DXA. Using ANCOVA, we examined how LR was related to SI and HOMA-IR, controlling for age, race, and sex. Secondary analyses examined if the differences seen could be accounted for by differences in total fat mass or hsCRP. Results: As expected, LR was significantly elevated in adults with obesity (Mean±SD: 0.069±0.047 vs. 0.0052±0.00084 mEq/L*min, p.05), LR remained correlated with SI (B= -.24, p.05). By contrast, for HOMA-IR, even after including total fat mass and hsCRP in the model, the effect of LR was still observed (B= +.30, p

Background Many studies show a correlation between short sleep duration and obesity/insulin resistance. One hypothesis for this association is that shortened sleep causes increased energy intake (EI). In some studies, experimentally reduced sleep duration has been found to increase total EI. There are mixed findings about the effects of habitual and acute short sleep on the macronutrient content of consumed meals. Additionally, there are few pediatric studies with objectively measured sleep duration (e.g. using actigraphy). Therefore, we aimed to determine if an acute sleep change was associated with greater total EI, altered macronutrient intake, or altered insulin sensitivity in children. Methods Healthy weight and overweight volunteers (n=18, 44% male), aged 7-11 years wore ActiGraph activity monitors for six consecutive 24 hour periods to determine nightly sleep duration. Volunteers were given no direction regarding sleep for the week. On day six, children underwent a standardized oral glucose tolerance test (OGTT) (1.75g/kg, max 75g) after which total EI (kcal) and macronutrient composition (% of total EI) were measured during a lunchtime laboratory test meal (>10,000 kcal; ~12% protein, 32% fat, 56% CHO). Subjects were directed to eat as much as they wanted. Acute change in sleep was calculated by subtracting each participant’s average nightly total sleep time over the entire week from their total sleep time on the fifth night (i.e., night before the test meal). Linear regressions examined associations of acute change in sleep with insulin AUC during OGTT, total EI, % CHO, % fat, and ratio of %CHO to %fat intake. Results Controlling for daily predicted energy needs and physical activity level, acute change in sleep (mean of 27.5 minutes less than average) was not significantly associated with total EI (p=0.58). However, the %CHO trended toward a significant negative correlation (r=-0.47, p=0.05) and %fat was positively associated (r=0.50, p=0.036) with acute change in sleep such that the %CHO to %fat intake ratio was greater in those with greater sleep deficit (p=0.039). Additionally, controlling for BMI-z score, basal insulin, and age, greater sleep deficit was associated with increased insulin AUC during the OGTT (p=0.001). Discussion Contrary to some previous experimental data, acute sleep deficit had no significant association with total EI; however, acute sleep deficit was associated with increased relative carbohydrate intake. Acute sleep deficit was also associated with decreased relative fat intake, a known satiating macronutrient. These data also suggest an acute decrease in insulin sensitivity associated with sleep deficit. All three mechanisms could explain or exacerbate the increased prevalence of obesity and metabolic abnormalities in children with short sleep duration and therefore, provide support for sleep-associated adjunctive treatment for such children.

Introduction: Low-grade chronic inflammation, due in part to activation of the NLRP3 inflammasome, increases with increasing adiposity and plays a significant role in the development of type 2 diabetes and cardiovascular disease. However, to date, the efficacy of anti-inflammatory medications to improve aspects of the metabolic syndrome (MetS) is not well established. As colchicine has been shown to prevent assembly of the NLRP3 inflammasome and ameliorate other inflammatory conditions, we aimed to evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in adults with obesity and MetS. Materials and Methods: We conducted a randomized, double-blind, placebo-controlled pilot trial in which 40 non-diabetic adults with obesity, MetS, and elevated high-sensitivity C-reactive protein (hsCRP≥ 2.0 mg/L) were randomized to colchicine 0.6 mg or placebo twice daily for three months. Fasting labs, insulin-modified frequently sampled intravenous glucose tolerance test (FSIVGTT), and body composition by DXA were performed at baseline and 3-month follow up. The primary outcome was change in FSIVGTT insulin sensitivity (SI) as measured by Bergman’s minimal model. Secondary outcomes included changes in other metabolic parameters and inflammatory markers. ANCOVA was used to examine differences between treatment arms, with age, sex, baseline body fat%, and Δbody fat% as covariates. Data were analyzed according to intention-to-treat and reported as mean±SD. Results: Colchicine significantly reduced inflammatory indices, including hsCRP (-2.8±2.9 vs. 0.4±2.8 mg/L, p=.002), ESR (-5.5±6.4 vs. 0.6±6.3 mm/hr, p=.007), white blood cell count (-1.09±1.23 vs. 0.29±1.16 K/µL, p=.002), and absolute neutrophil count (-1.06±1.05 vs. 0.12±0.93 K/µL, p

AIM To evaluate the efficacy and safety of colchicine for improving metabolic and inflammatory outcomes in people with obesity and metabolic syndrome (MetS). MATERIALS AND METHODS Adults with obesity and MetS, but who did not have diabetes, were randomized to colchicine 0.6 mg or placebo capsules twice daily for 3 months. The primary outcome was change in insulin sensitivity (SI ) as estimated by insulin-modified frequently sampled intravenous glucose tolerance tests. Secondary outcomes included changes in other metabolic variables and inflammatory markers. RESULTS Of 40 participants randomized (21 colchicine, 19 placebo), 37 completed the trial. Compared with placebo, colchicine significantly reduced C-reactive protein (P

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.

OBJECTIVE: Alexithymia, or the difficulty identifying or describing one’s own emotions, may be a risk factor for dysregulated eating and excess weight gain. However, the relationships between alexithymia and eating behaviors in community samples of non-clinical youth have not been well-characterized. We hypothesized that alexithymia would be positively associated with disordered and disinhibited eating in a community-based sample of boys and girls without an eating disorder. METHOD: Two hundred children (8–17 years old) across the weight spectrum completed an interview to assess loss of control (LOC) eating and eating-related psychopathology, a laboratory test meal designed to induce disinhibited eating, and questionnaires to assess alexithymia, eating in the absence of hunger, and emotional eating. Linear and logistic regressions were conducted to examine the relationship between alexithymia and eating variables, with age, sex, race, and fat mass as covariates. Test meal analyses also adjusted for lean mass. Given the overlap between alexithymia and depression, all models were repeated with depressive symptoms as an additional covariate. RESULTS: Alexithymia was associated with an increased likelihood of reporting LOC eating (p < .05). Moreover, alexithymia was positively associated with disordered eating attitudes, emotional eating, and eating in the absence of hunger (ps < .05). Greater alexithymia was associated with more carbohydrate and less fat intake at the test meal (ps < .05). After adjusting for depressive symptoms, alexithymia remained associated with eating in the absence of hunger and carbohydrate and fat intake (ps < .05). DISCUSSION: In healthy children, alexithymia is associated with some facets of eating behavior and food intake. If supported prospectively, these preliminary findings suggest alexithymia may be a modifiable risk factor to reduce disordered eating and excess weight gain in youth.

Objective: To evaluate the accuracy and practicality of the FreeStyle Libre Pro continuous glucose monitor (CGM) during oral glucose tolerance testing (OGTT) in a nondiabetic pediatric sample. Background: The FreeStyle Libre Pro CGM has been found, in adults, to have acceptable accuracy compared to lab-measured glucose without requiring individual patient calibrations. No studies have assessed lab-measured glucose accuracy for this CGM in children. Hypothesis: FreeStyle Libre Pro CGM glucose will not differ significantly from lab-measured plasma glucose during OGTT in youth. Methods: Healthy weight and overweight volunteers (n =8; 63% male), aged 7-11y wore FreeStyle Libre Pro Flash CGM for 6 days, with a 2-hour OGTT (1.75mg/kg, max 75g) on day 6. Laboratory (Cobas E6000, Roche) plasma glucose was measured at 30min intervals for 120min, and compared with the 15min average simultaneously obtained CGM glucose value. Glucose at each timepoint and Area Under the Curve (AUC) for CGM and lab-measured glucose were compared using paired t-tests. A correlation coefficient was calculated for each timepoint. Potential systematic errors were examined using Bland-Altman analyses. Results: AUC for CGM and lab glucose were well correlated (r= 0.91, p=0.006) and did not differ in mean value (p=0.84). CGM and lab glucose readings were not significantly different at any timepoint (all p’s>0.18). There were no significant systematic or magnitude errors as assessed by Bland-Altman analyses at any timepoint. No adverse events occurred with CGM use and all participants considered the device easy to wear. Conclusions: The Freestyle Libre Pro CGM device was well tolerated and, even without individual calibration, provided quantitatively similar glucose readings during OGTT for healthy weight and overweight children when compared to lab-measured glucose. If confirmed in larger studies, this CGM may provide adjunctive data during evaluations of glucose excursions that may be useful for pediatric clinical care and research. Disclosure N. Ghane: None. M. Broadney: None. S.M. Collins: None. E.K. Davis: None. S. Brady: None. J.A. Yanovski: Research Support; Self; Rhythm Pharmaceuticals Inc., Zafgen.

BackgroundPolycystic ovarian syndrome (PCOS) is the most common cause of female infertility and is associated with higher levels of circulating androgens. Exposure to higher levels of androgens in utero may be a risk factor for obesity among children of women with PCOS.MethodsWe examined whether maternal PCOS was associated with differences in offspring growth and obesity in the Upstate KIDS study, a prospective cohort study of infants born in New York State (excluding New York City) oversampled for fertility treatments and multiple births. Measurements of offspring length/height and weight were recorded at doctor’s visits through 3 years of age. PCOS diagnosis was self-reported by mothers at baseline. We used linear mixed models with robust SEs to estimate differences in growth by maternal PCOS exposure. We used logistic regression to examine whether infants experienced rapid weight gain at 4, 9 and 12 months. Growth measures were reported by 4098 mothers for 4949 children (1745 twins). Of these, 435 mothers (10.6%) had a diagnosis of PCOS.ResultsCompared with children born to mothers without PCOS, children of mothers with PCOS did not have significant differences in weight (4.81 g, 95% CI −95.1 to 104.7), length/height (0.18 cm, 95% CI −0.16 to 0.52) and body mass index (−0.14 kg/m2, 95% CI −0.30 to 0.01) through 3 years of age. We also observed no association between maternal PCOS and offspring rapid weight gain.ConclusionsOverall, we found little evidence to suggest that maternal PCOS influences early childhood growth in this large, prospective cohort study.

OBJECTIVESedentary children have greater risk of developing abnormalities in glucose homeostasis. We investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity. We hypothesized that interrupting sitting with short bouts of moderate-intensity walking would decrease insulin area under the curve (AUC) during an oral glucose tolerance test (OGTT) compared with uninterrupted sitting.RESEARCH DESIGN AND METHODSOverweight/obese (BMI ≥85th percentile) children 7–11 years of age underwent two experimental conditions in random order: prolonged sitting (3 h of continuous sitting) and interrupted sitting (3 min of moderate-intensity walking at 80% of ventilatory threshold every 30 min for 3 h). Insulin, C-peptide, and glucose were measured every 30 min for 3 h during an OGTT. Each session was followed by a buffet meal. Primary outcomes were differences in OGTT hormones and substrates and in buffet meal intake by condition.RESULTSAmong 35 children with complete data, mixed-model results identified lower insulin and C-peptide in the interrupted condition (P = 0.007 and P = 0.029, respectively); the intervention reduced insulin AUC by 21% (P < 0.001) and C-peptide AUC 18% (P = 0.001) and improved estimated insulin sensitivity (P = 0.013). Neither buffet total energy intake (1,262 ± 480 vs. 1,260 ± 475 kcal; P = 0.89) nor macronutrient composition of the meal (P values >0.38) differed between conditions significantly.CONCLUSIONSInterrupting sitting with brief moderate-intensity walking improved glucose metabolism without significantly increasing energy intake in children with overweight or obesity. Interrupting sedentary behavior may be a promising intervention strategy for reducing metabolic risk in such children.

Endocrine emergencies require prompt identification and intervention to prevent morbidity and mortality. This chapter addresses the presentation, diagnosis, initial management, and disposition of patients suffering the following endocrine emergencies: diabetic ketoacidosis, adrenal crisis, hypernatremia secondary to diabetes insipidus, thyroid storm, and hypoglycemia.

The authors describe the clinical investigation and progress of a 13-year-old girl diagnosed with hypertension 4 years prior to her admission. A thorough history was taken and physical examination performed. Laboratory analysis and relevant radiological evaluation were obtained in order to determine the etiology for suspected secondary hypertension, and later to differentiate between the possible causes of hyperreninemic hypertension. The patient had an accessory left renal artery, presumptively leading to renin secretion by the underperfused kidney. The patient was treated medically with spontaneous resolution of her hypertension and near normalization of plasma renin activity. On repeat imaging, the artery was not demonstrated. The authors concluded that the diagnosis of hyperreninemic hypertension in young ages should prompt investigation for the etiology. However, cautious observation is a valid option that might lead to spontaneous resolution.

BACKGROUND Self-reported short sleep duration is associated with greater risk for metabolic syndrome (MetS), obesity, and higher energy intake (EI). However, studies of these associations in children using objective methods are sparse. OBJECTIVES The study aims to determine the associations for sleep patterns with MetS indices, body composition, and EI using objective measures in children. METHODS Free-living sleep and physical activity were measured in 125 children (aged 8-17 years, BMI z = 0.57 ± 1.0, 55% female) using wrist-worn actigraphs for 14 nights. Blood pressure, fasting blood levels of lipids, insulin, glucose, waist circumference, and body composition (dual-energy X-ray absorptiometry [DXA]) were obtained during outpatient visits. EI was assessed during an ad libitum buffet meal. RESULTS Later weekday and weekend bedtimes were associated with higher systolic blood pressure (Ps

1. Miranda Broadney, MD, MPH* 2. Rajan Senguttuvan, MD† 3. Priti G. Patel, MD‡ 1. *National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD. 2. †Section of Pediatric Endocrinology, Department of Pediatrics, College of Medicine, The University of Arizona, Tucson, AZ. 3. ‡Pediatric Endocrinology, Texas Tech University Health Sciences Center, El Paso, TX. A previously healthy 3-year-old boy presents to the emergency department with a 5-day history of fever, sore throat, and progressive neck swelling despite treatment with antibiotics. Two days ago, he had presented to a community hospital emergency department for these symptoms and was prescribed azithromycin for presumed bacterial pharyngitis (no throat culture was obtained). Despite treatment, he now experiences a choking sensation and worsening pain in his neck. His vital signs are notable for a temperature of 98.2°F (36.8°C), blood pressure of 140/103 mm Hg, heart rate of 170 beats per minute, and respiratory rate of 20 breaths per minute. His physical examination reveals a teary boy because of pain with normal work of breathing. His oropharynx has no erythema, and the tonsils are normal in appearance. He has marked erythema of the anterior lower neck with an exquisitely tender, indurated area that measures 6 cm in diameter and extends laterally from midline to the left. There is no fluctuation. Respiratory examination reveals a hoarse voice without stridor and clear lung fields on auscultation. Cardiovascular examination findings are notable for moderate tachycardia. The remainder of the examination findings are unremarkable. Laboratory evaluation reveals a leukocyte count of …

Background/Objectives Maternal obesity may influence neonatal and childhood morbidities through increased inflammation and/or altered immune response. Less is known about paternal obesity. We hypothesized that excessive parental weight contributes to elevated inflammation and altered immunoglobulin (Ig) profiles in neonates. Subjects/Methods In the Upstate KIDS Study maternal pre-pregnancy body mass index (BMI) was obtained from vital records and paternal BMI from maternal report. Biomarkers were measured from newborn dried blood spots (DBS) among neonates whose parents provided consent. Inflammatory scores were calculated by assigning one point for each of 5 pro-inflammatory biomarkers above the median and one point for an anti-inflammatory cytokine below the median. Linear regression models and generalized estimating equations were used to estimate mean differences (β) and 95% confidence intervals (CI) in the inflammatory score and Ig levels by parental overweight/obesity status compared to normal weight. Results Among 2974 pregnancies, 51% were complicated by excessive maternal weight (BMI>25), 73% by excessive paternal weight, and 28% by excessive gestational weight gain. Maternal BMI categories of overweight (BMI 25.0-29.9) and obese class II/III (BMI≥35) were associated with increased neonatal inflammation scores (β=0.12, 95% CI: 0.02, 0.21; p=0.02, and β=0.13, CI: −0.002, 0.26; p=0.05, respectively) but no increase was observed in the obese class I group (BMI 30-34.9). Mothers with class I and class II/III obesity had newborns with increased IgM levels (β=0.11, CI: 0.04, 0.17; p=0.001 and β=0.12, CI: 0.05, 0.19); p