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Background: Proteomics offers potential for detecting and monitoring anorexia nervosa (AN) and its variant, atypical AN (atyp-AN). However, research has been limited by small protein panels, a focus on adult AN, and lack of replication. Methods: In this study, we performed Olink multiplex profiling of 92 inflammation-related proteins in females with AN/atyp-AN (n = 64), all of whom were ≤90% of expected body weight, and age-matched healthy control individuals (n = 44). Results: Five proteins differed significantly between the primary AN/atyp-AN group and the healthy control group (lower levels: HGF, IL-18R1, TRANCE; higher levels: CCL23, LIF-R). The expression levels of 3 proteins (lower IL-18R1, TRANCE; higher LIF-R) were uniquely disrupted in participants with AN in our primary model. No unique expression levels emerged for atyp-AN. In the total sample, 12 proteins (ADA, CD5, CD6, CXCL1, FGF-21, HGF, IL-12B, IL18, IL-18R1, SIRT2, TNFSF14, TRANCE) were positively correlated with body mass index and 5 proteins (CCL11, FGF-19, IL8, LIF-R, OPG) were negatively correlated with body mass index in our primary models. Conclusions: Our results replicate the results of a previous study that demonstrated a dysregulated inflammatory status in AN and extend those results to atyp-AN. Of the 17 proteins correlated with body mass index, 11 were replicated from a previous study that used similar methods, highlighting the promise of inflammatory protein expression levels as biomarkers of AN disease monitoring. Our findings underscore the complexity of AN and atyp-AN by highlighting the inability of the identified proteins to differentiate between these 2 subtypes, thereby emphasizing the heterogeneous nature of these disorders.

Abstract Background Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment. Methods A sample of 71 participants ages 10–23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed. Results The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed. Conclusions These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms.

Abstract Background Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD. Methods We performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10–23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood. Results Total body BMD Z-scores were significantly lower in ARFID than in HC (− 1.41 ± 0.28 vs. − 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (β = -0.481, p = 0.032). Conclusion Our findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID.

Abstract Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN (n = 34) or AtypAN (n = 25), ages 10–22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.

ABSTRACT Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross‐sectional analysis of girls ages 10–16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food‐frequency questionnaire and BMD, microarchitecture, and strength estimates with dual‐energy X‐ray absorptiometry and high‐resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p =

Plain English summary Few measures are available for detecting avoidant/restrictive food intake disorder (ARFID) in clinics or research settings. This makes it difficult for individuals with the disorder to be identified and offered appropriate care. We developed the Pica, ARFID, and Rumination Disorder Interview ARFID Questionnaire (PARDI-AR-Q), a brief self-report measure of possible ARFID, and evaluated how well it worked in the current study. In our preliminary study of 71 adolescents and adults, most individuals with ARFID (90%) scored positive on this measure, whereas most healthy control participants (93%) scored negative. Our findings provide early support for the PARDI-AR-Q as a promising new measure for detecting possible ARFID when a full clinical interview is not possible.

ObjectiveStudies in estrogen deficiency states such as primary ovarian insufficiency and Turner syndrome suggest that estrogen status may be an important modulator of mood and emotions. In this study we compared depressive and anxiety symptoms between adolescent and young adult female oligo-amenorrheic athletes (AA) and eumenorrheic females (EM), and explored structural, and functional changes in related brain areas during reward processing, a behavioral construct that is altered in depression and anxiety.MethodsWe included (i) 24 AA participating in ≥4 hours/week of aerobic exercise or running ≥20 miles/week for ≥6 months in the preceding year, with lack of menstrual cycles for ≥3 months within at least 6 preceding months of oligo-amenorrhea, OR in premenarchal girls, absence of menses at >15 years), and (ii) 27 EM aged 14-25 years. Participants completed the Beck Depression Inventory-II (BDI-II), State and Trait Anxiety Inventory (STAI), and Mood and Anxiety Symptoms Questionnaire (MASQ). Structural MRI and brain activation during a functional MRI (fMRI) task that probes reward and punishment processing was examined in a subset of 10 AA and 23 EM.ResultsMedian (IQR) age and BMI of AA and EM groups were 20.6 (19.0-22.6) vs. 20.6 (19.2-23.7) years, p=0.6 and v 20.3 (18.8-21.5) vs. 21.9 (19.6-23.5) kg/m2, p=0.005, respectively. While groups did not differ for BDI-II scores, AA had higher anhedonic depression MASQ scores (p=0.04), and STAI (p=0.03) scores vs. EM. In the fMRI subset, AA had higher caudate volumes vs. EM [F(1, 29)=9.930, p=0.004]. Lower activation observed in the right caudate during reward anticipation in AA compared with EM (p=0.036) suggests blunted reward processing in the striatum in estrogen deficient states.ConclusionAthletes with amenorrhea had higher depressive and anxiety symptomatology compared to eumenorrheic young women. Exploratory analyses demonstrated increased caudate volumes and decreased caudate activation during reward processing in athletes with amenorrhea suggesting that estrogen may play a role in reward processing.

ObjectiveAnorexia nervosa (AN) is commonly associated with depression, anxiety, and deficits in socioemotional functioning. Basal levels of oxytocin, a neurohormone with antidepressant, anxiolytic, and prosocial properties, are low in women with AN. However, the relationship between oxytocin and psychopathology of AN/atypical AN has not been examined in individuals with primarily food restriction (AN/AtypAN-R) or those with restriction plus binge/purge behaviors (AN/AtypAN-BP) alone, which is important to further elucidate the neurobiology of different AN presentations. We investigated whether oxytocin levels are related to eating, affective, and socioemotional psychopathology in women with AN/AtypAN-R and separately AN/AtypAN-BP.MethodsIn a cross-sectional study of 53 women with low-weight AN or atypical AN based on DSM-5 (AN/AtypAN-R: n=21, AN/AtypAN-BP: n=32), we obtained fasting serum oxytocin levels and self-report measures of psychopathology, including the Eating Disorder Examination–Questionnaire (EDE-Q), Beck Depression Inventory-IA (BDI), State-Trait Anxiety Inventory (STAI), and Toronto Alexithymia Scale (TAS-20).ResultsIn individuals with AN/AtypAN-R, oxytocin levels were negatively associated with eating psychopathology (EDE-Q Global Score: r=-0.49, p=0.024), depressive and anxiety symptoms (BDI Total Score: r=-0.55, p=0.009; STAI Trait Score: r=-0.63, p=0.002), and socioemotional symptoms (TAS-20 Difficulty Identifying Feelings Score: r=-0.49, p=0.023). In contrast, in those with AN/AtypAN-BP oxytocin levels were negatively associated with depressive symptoms only (BDI Total Score: r=-0.52, p=0.049).ConclusionsThese findings support the notion that AN/AtypAN-R and AN/AtypAN-BP might have divergent underlying neurobiology. Understanding these differences is crucial to develop targeted treatments for a population with high levels of chronicity, for which no specific pharmacological treatments are currently available.Clinical trial registrationhttps://clinicaltrials.gov, identifier: NCT01121211.

Abstract Background Anorexia nervosa (AN) is associated with structural brain abnormalities. Studies have reported less cerebral tissue and more cerebrospinal fluid (CSF) in individuals with AN relative to healthy controls, although findings are variable and inconsistent due to variations in sample size, age, and disease state (e.g., active AN, weight-recovered AN). Further, it remains unclear if structural brain abnormalities observed in AN are a consequence of specific brain pathologies or malnutrition, as very few longitudinal neuroimaging studies in AN have been completed. Methods To overcome this issue, this comprehensive meta-analysis will combine region-of-interest (ROI) and voxel-based morphometry (VBM) approaches to understand how regional and global structural brain abnormalities differ among individuals with AN and healthy controls (HCs). Additionally, we aim to understand how clinical characteristics and physiological changes during the course of illness, including acute illness vs. weight recovery, may moderate these structural abnormalities. We will create an online database of studies that have investigated structural brain abnormalities in AN. Data will be reviewed independently by two members of our team using MEDLINE databases, Web of Science, PsycINFO, EMBASE, and CINAHL. We will conduct ROI and VBM meta-analysis using seed-based d mapping in AN and HCs. We will include all studies that include structural neuroimaging of individuals with AN (both acute and weight-recovered) and HCs between January 1997 and 2020. Discussion This systematic review will assess the effects of AN compared to HC on brain structure. Futhermore, it will explore the role of acute AN and weight-recovered AN on brain structure. Findings will help researchers and clinicians to better understand the course of illness in AN and the nature of recovery, in terms of weight, malnutrition, and the state of the brain. Systematic review registration PROSPERO CRD42020180921

Functional hypothalamic amenorrhea is a state of reversible hypogonadism common in adolescents and young women that can be triggered by energy deficit or emotional stress or a combination of these factors. Energy deficit may be a consequence of (i) reduced caloric intake, as seen in patients with eating disorders, such as anorexia nervosa, or (ii) excessive exercise, when caloric intake is insufficient to meet the needs of energy expenditure. In these conditions of energy deficit, suppression of the hypothalamic secretion of gonadotrophin-releasing hormone (with resulting hypoestrogenism) as well as other changes in hypothalamic-pituitary function may occur as an adaptive response to limited energy availability. Many of these adaptive changes, however, are deleterious to reproductive, skeletal, and neuropsychiatric health. Particularly, normoestrogenemia is critical for normal bone accrual during adolescence, and hypoestrogenemia during this time may lead to deficits in peak bone mass acquisition with longstanding effects on skeletal health. The adolescent years are also a time of neurological changes that impact cognitive function, and anxiety and depression present more frequently during this time. Normal estrogen status is essential for optimal cognitive function (particularly verbal memory and executive function) and may impact emotion and mood. Early recognition of women at high risk of developing hypothalamic amenorrhea and its timely management with a multidisciplinary team are crucial to prevent the severe and long-term effects of this condition.

Background: Areal bone mineral density (BMD) of the lumbar spine by DXA is greater in Black compared to White adolescents. Bone strength is determined not only by BMD but also its microenvironment, and marrow adipose tissue (MAT) has been shown to be an important determinant of skeletal integrity, independent of BMD. Racial differences in volumetric BMD (vBMD) and MAT in adolescents and young adults with obesity are unknown. Objective: To assess racial differences in lumbar vBMD and MAT in Black and White adolescents and young adults with obesity and to assess body composition determinants of bone parameters. We hypothesized that Blacks will have higher vBMD and lower MAT of the lumbar spine compared to Whites. Methods: The study group comprised 77 adolescents/young adults, 25 Black and 52 White, (mean age 18.2 ± 2.5 years, range 13 to 24 years) with moderate to severe obesity (mean body mass index (BMI) 46.2 ± 7.3 kg/m2, range 35.5 to 69.7 kg/m2). Groups were similar in age, BMI, and sex distribution (p > 0.84). Subjects underwent QCT of the lumbar spine (L1−L2) for assessment of vBMD with the use of a calibration phantom and 1H-MRS/MRI for quantification of lumbar MAT content (L1-L2) and abdominal fat and thigh muscle mass. Groups were compared by Student's t-test or Wilcoxon test. Correlation analysis was performed to assess associations between bone parameters and body composition. Results: Black adolescents/young adults with obesity had higher vBMD compared to Whites (p 0.1). Conclusion: There are racial differences in lumbar vBMD in adolescents and young adults with moderate to severe obesity, with Blacks having higher vBMD than Whites, while there were no differences in MAT content. The known inverse association between BMD and MAT was only observed in Whites but not in Blacks, suggesting possible racial differences in stem cell differentiation into the bone and fat lineages.

Purpose: Combined hormonal contraceptive therapy has been associated with negative bone mineral density outcomes that may be route-dependent [i.e., combined oral contraception (COC) vs. contraceptive vaginal ring (CVR)] and involve the hepatic growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. The objective of the pilot study was to assess the impact of route of contraceptive administration on IGF-I and procollagen type I N-terminal propeptide (PINP) responses to an IGF-I Generation Test. We hypothesized that the peak rise in IGF-I and PINP concentration and area under the curve (AUC) would be attenuated following COC, but not CVR, use.Methods: Healthy, premenopausal women not taking hormonal contraception were recruited. Women were enrolled in the control group (n = 8) or randomly assigned to COC (n = 8) or CVR (n = 8) for two contraceptive cycles. IGF-I Generation Tests were used as a probe to stimulate IGF-I release and were completed during the pre-intervention and intervention phases. Serum IGF-I and PINP were measured during both IGF-I Generation Tests. The study was registered at ClinicalTrials.gov (NCT02367833).Results: Compared to the pre-intervention phase, peak IGF-I concentration in response to the IGF-I Generation Test in the intervention phase was suppressed in the COC group (p < 0.001), but not the CVR or Control groups (p > 0.090). Additionally, compared to the pre-intervention phase, PINP AUC during the intervention phase was suppressed in both COC and CVR groups (p < 0.001), while no difference was observed in the control group (p = 0.980).Conclusion: These data suggest that changes in recombinant human GH-stimulated hepatic IGF-I synthesis in response to combined hormonal contraception (CHC) use are dependent on route of CHC administration, while the influence on PINP is route-independent. Future research is needed to expand these results with larger randomized control trials in all age ranges of women who utilize hormonal contraception.Clinical Trial Registration:www.ClinicalTrials.gov registration NCT02367833.

Objective: We sought to compare the short and long-term outcomes of MBS in adolescents vs. adults who have undergone a Roux-en-Y gastric bypass (RYGB) or Sleeve gastrectomy (SG).Design: Retrospective cohort study.Setting: Single tertiary care academic referral center.Participants: One hundred fifty adolescent (≤ 21-years) and adult (>21-years) subjects with severe obesity between 15 and 70 years of age who underwent RYGB or SG.Outcomes: Metabolic parameters, weight and height measures were obtained pre-and post-surgery (at 3 and 6 months, and then annually for 4 years).Results: Median pre-surgical body mass index (BMI) was higher in adolescents (n = 76) vs. adults (n = 74): 50 (45–57) vs. 44 (40–51) kg/m2 (p < 0.0001). However, obesity related complications were greater in adults vs. adolescents: 66 vs. 21% had hypertension, 68 vs. 28% had dyslipidemia, and 42 vs. 21% had type 2 diabetes mellitus (all p < 0.010). % BMI reduction and % weight loss (WL) were greater in adolescents vs. adults at all time points (p < 0.050). %WL was higher in adolescents who underwent SG at each time point (p < 0.050), and trended higher among adolescents who underwent RYGB (p = 0.060), compared to adults with the respective procedure. Follow-up data showed greater resolution of type 2 diabetes and hypertension in adolescents than adults (87.5 vs. 54.8%; p = 0.04, and 68.7 vs. 35.4%; p = 0.040).Conclusion: Adolescents compared to adults had greater reductions in BMI and weight, even at 4 years, and greater resolution of type 2 diabetes and hypertension. Earlier intervention in the treatment of severe obesity with MBS may lead to better outcomes.

Purpose: Proton radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials: Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results: A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions: In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB.

The Wnt-β-catenin pathway receptor, low-density lipoprotein receptor-related protein 5 (LRP5), is a known regulator of bone mineral density. It has been hypothesized that specific human polymorphisms in LRP5 impact bone density, in part, by altering the anabolic response of bone to mechanical loading. Although experiments in animal models support this hypothesis, there is limited evidence that LRP5 polymorphisms can alter the anabolic response of bone to mechanical loading in humans. Herein, we report a young male who harbors a rare LRP5 missense mutation (A745V) and who provides potential proof of principle for this mechanotransduction hypothesis for low bone density. The subject had no history of fractures until age 18, a year into a career in competitive distance running. As he continued to run over the following 2 years, his mileage threshold to fracture steadily and rapidly decreased until he was diagnosed with severe osteoporosis (lumbar spine BMD Z-score of −3.2). By contextualizing this case within the existing LRP5 and mechanical stress literature, we speculate that this represents the first documented case of an individual in whom a genetic mutation altered the anabolic response of bone to mechanical stress in a manner sufficient to contribute to osteoporosis.

Introduction: Resting energy expenditure (REE) is often evaluated in adults and adolescents with obesity to estimate caloric requirements when advising dietary changes. However, data are lacking regarding the accuracy of methods used to clinically assess REE in adolescents with severe obesity. Moreover, there are no data regarding the effects of sleeve gastrectomy (SG) on REE in adolescents. We evaluated the accuracy and error rate between estimated and measured REE in adolescents with severe obesity and changes in REE following (SG).Materials and Methods:Cross-sectional study (CSS): 64 adolescents and young adults, 14–22 years old, with moderate to severe obesity were enrolled. We measured REE (mREE) by indirect calorimetry and estimated REE (eREE) using Derumeaux (Deru), Mifflin-St Jeor (MS), Harris Benedict (HB), and World Health Organization (WHO) equations. DXA was used to determine body composition. Bland Altman analysis evaluated agreement between eREE and mREE. Longitudinal study: 12 subjects had repeat indirect calorimetry and DXA 1 year after SG. Longitudinal analysis was used to assess changes in REE and body composition.Results:CSS: Median BMI was 45.2 kg/m2 and median age was 18.0 (16.3–19.9) years. mREE correlated strongly with eREE . Bland Altman analysis demonstrated that only a few points were beyond the 1.96 SD limit of disagreement. However, there was considerable overestimation of mREE by most equations. Longitudinal Study: In the subset that underwent SG, after 12-months, absolute REE decreased from 1709 (1567.7–2234) to 1580.5 (1326–1862.5) Calories (p = 0.002); however, the ratio of REE/Total Body Weight (TBW) increased from 13.5 ± 2.3 at baseline to 15.5 ± 2.2 at 1 year (p = 0.043). When evaluating parameters affecting % total weight loss, we found that it correlated positively with REE/TBW at 12 months (R = 0.625; p = 0.03) and negatively with % fat mass at 12 months (R = −0.669; p = 0.024).Discussion: In adolescents with moderate-severe obesity, despite a correlation between mREE using indirect calorimetry and eREE using the Deru, MS, HB, and WHO equations, there is significant over-estimation of REE at the individual level, challenging their clinical utility. One year after SG, REE/TBW increased and strongly correlated with % total weight loss in adolescents.

BackgroundMidkine (MDK), one of the heparin-binding growth factors, is highly expressed in multiple organs during embryogenesis. Plasma concentrations have been reported to be elevated in patients with a variety of malignancies, in adults with obesity, and in children with short stature, diabetes, and obesity. However, the concentrations in healthy children and their relationships to age, nutrition, and linear growth have not been well studied.Subjects and methodsPlasma MDK was measured by immunoassay in 222 healthy, normal-weight children (age 0-18 yrs, 101 boys), 206 healthy adults (age 18-91 yrs, 60 males), 61 children with BMI ≥ 95th percentile (age 4-18 yrs, 20 boys), 20 girls and young women with anorexia nervosa (age 14-23 yrs), and 75 children with idiopathic short stature (age 3-18 yrs, 42 boys). Body fat was evaluated by dual-energy X-ray absorptiometry (DXA) in a subset of subjects. The associations of MDK with age, sex, adiposity, race/ethnicity and stature were evaluated.ResultsIn healthy children, plasma MDK concentrations declined with age (r = -0.54, P < 0.001) with values highest in infants. The decline occurred primarily during the first year of life. Plasma MDK did not significantly differ between males and females or between race/ethnic groups. MDK concentrations were not correlated with BMI SDS, fat mass (kg) or percent total body fat, and no difference in MDK was found between children with anorexia nervosa, healthy weight and obesity. For children with idiopathic short stature, MDK concentrations did not differ significantly from normal height subjects, or according to height SDS or IGF-1 SDS.ConclusionsIn healthy children, plasma MDK concentrations declined with age and were not significantly associated with sex, adiposity, or stature-for-age. These findings provide useful reference data for studies of plasma MDK in children with malignancies and other pathological conditions.

Introduction: Obesity is associated with early co-morbidities and higher mortality. Even though weight loss surgery (WLS) in adolescents with severe obesity reliably achieves safe and lasting improvement in BMI and superior resolution of comorbid diseases, its utilization among young patients in the clinical practice stands unclear.Objective: To show the prevalence of weight loss surgery utilization rates in adolescents and young adults among several healthcare institutions in the United States.Method: WLS in 14–25 years old between 2000 and 2017 was obtained from Washington University, Morehouse Medical, University of Texas, Wake Forest Baptist Medical Center, Beth Israel Deaconess Medical Center, Boston Children's Hospital, Boston Medical Center, and Partners Healthcare using the Shared Health Research Information Network (SHRINE) and Research Patient Data Registry (RPDR) web-based query tools. ICD-9 codes were used for bariatric surgery.Results: Among 2500635 individuals, 18008 (0.7%) had severe obesity. At Partners, 1879 patients had severe obesity, of which 404 (21.5%) underwent WLS, whereas at Washington University, 44 (2.5%) of 1788 the underwent WLS. 13 (2.3%) of the 575 at BIDMC, 43 (1.5%) of the 2969 at BMC, and 37 (0.4%) of 8908 at BCH underwent WLS (p < 0.0001 for all).Discussion: Even though WLS has shown to be the most effective treatment to create sustainable changes in metabolic derangements for moderate to severe obesity and its comorbidities, it has been underutilized. Further studies need to be conducted to ensure WLS is utilized for those patients who would achieve the most benefit.

Background: Obesity is prevalent among adolescents and is associated with serious health consequences. Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) are bariatric procedures that cause significant weight loss in adults and are increasingly being performed in adolescents with morbid obesity. Data comparing outcomes of RYGB versus SG in this age-group are scarce. This study aims to compare short-term (1-6 months) and longer-term (7-18 months) body mass index (BMI) and biochemical outcomes following RYGB and SG in adolescents/young adults.Methods: A retrospective study using data extracted from medical records of patients 16-21 years who underwent RYGB or SG between 2012-2014 at a tertiary care academic medical center. Results: Forty-six patients were included in this study: 24 underwent RYGB and 22 underwent SG. Groups did not differ for baseline age, sex, race or BMI. BMI reductions were significant at 1-6 months and 7-18 months within groups (p

[This corrects the article DOI: 10.1371/journal.pone.0156353.].

The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT.We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status.The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18-25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition.Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones.Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.

Irisin and FGF21 are novel hormones implicated in the "browning" of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14-21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.