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OBJECTIVE: To determine the association between food insecurity and pediatric nonalcoholic fatty liver disease (NAFLD). METHODS: Cross-sectional study of patients < 21 years of age with histologically confirmed NAFLD. The Household Food Security Survey Module was administered to determine food insecurity status. Skin lipidomics were performed to explore pathophysiologic mechanisms. RESULTS: Seventy-three patients with histologically confirmed NAFLD completed the Household Food Security Survey Module. Of these, the majority were male (81%) and non-Hispanic (53%), with a mean age at biopsy of 13 ± 3 years. Food insecurity was seen in 42% (n = 31). Comparison of features between food insecure and food secure subgroups revealed no differences in sex, ethnicity, BMI z-score, aminotransferases, or histologic severity. However, children experiencing food insecurity presented on average 2 years before their food secure counterparts (12.3 ± 3.0 vs 14.4 ± 3.6 years, P = .015). A subset of 31 patients provided skin samples. Skin lipidomics revealed that food insecurity was associated with down-regulated features from the lipoamino acid class of lipids, previously linked to inflammation and adipocyte differentiation. CONCLUSIONS: Food insecurity is highly prevalent in children with NAFLD and is associated with earlier presentation. Lipidomic analyses suggest a possible pathophysiologic link that warrants further exploration.

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OBJECTIVE: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: This was a retrospective study of patients aged <20 years followed from 2009 to 2018. Muscle mass was estimated in all patients by measuring magnetic resonance imaging-based total psoas muscle surface area (tPMSA) and correcting for height (tPMSA index = tPMSA/height2). Two cohorts were studied, one with histological confirmation of NAFLD (n = 100) and the other with magnetic resonance imaging (MRI) evidence of hepatic steatosis (n = 236). Histology was scored using Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) criteria. MRI-measured proton density fat fraction (PDFF) and liver stiffness were collected. Demographic, clinical, and socioeconomic status (using a validated Community Deprivation Index [CDI]) were assessed as covariates. Univariate regression analyses, followed by multivariable regression analyses, were used to determine the relationships between tPMSA index and NAS, MRI-PDFF, and liver stiffness, adjusting for clinical, demographic, and CDI variables. RESULTS: In the multivariable regression analyses, higher steatosis score was associated with a lower tPMSA index (OR, 0.73; 95% CI, 0.56-0.96) and younger age (OR, 0.84; 95% CI, 0.73-0.97). Liver PDFF was also significantly associated with the tPMSA index (P = .029), sex (P = .019), and CDI (P = .005). In contrast, liver stiffness was not associated with tPMSA in multivariable analyses. CONCLUSIONS: tPMSA index was independently associated with both imaging and histological features of hepatic steatosis severity in children. Future studies should directly explore the presence and directionality of causative links between muscle mass and steatosis, as well as whether interventions that enhance muscle mass can reduce disease severity in children with NAFLD.

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OBJECTIVES: To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity. STUDY DESIGN: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (<90 mL/min/1.73 m2), normal (90-136 mL/min/1.73 m2), or high (>136 mL/min/1.73 m2). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders. RESULTS: The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12-16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49-5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications. CONCLUSIONS: In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.

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OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management.

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OBJECTIVE: To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). STUDY DESIGN: A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5-20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose ), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. RESULTS: In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m(2) (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved ß-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). CONCLUSIONS: RYGB reduced body mass index and improved both insulin sensitivity and ß-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00360373.

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OBJECTIVES: To assess links between comorbid health status, severe excess weight, and weight-related quality of life (WRQOL) in adolescents with severe obesity and undergoing weight-loss surgery (WLS) to inform clinical care. STUDY DESIGN: Baseline (preoperative) data from Teen Longitudinal Assessment of Bariatric Surgery, a prospective multicenter observational study of 242 adolescents with severe obesity (MedianBMI = 50.5 kg/m(2); Meanage = 17.1; 75.6% female; 71.9% white) undergoing WLS, were used to examine the impact of demographics, body mass index (BMI), presence/absence of 16 comorbid conditions, and a cumulative comorbidity load (CLoad) index on WRQOL scores (Impact of Weight on Quality of Life-Kids). RESULTS: WRQOL was significantly lower than reference samples of healthy weight, overweight, and obese samples. Of 16 comorbid conditions, the most prevalent were dyslipidemia (74.4%), chronic pain (58.3%), and obstructive sleep apnea (56.6%). Male subjects had a greater CLoad (P = .01) and BMI (P = .01), yet less impairment in total WRQOL (P < .01) than females. CLoad was a significant predictor of male WRQOL. For females, psychosocial (vs physical) comorbidities, BMI, and white race were significant predictors of WRQOL impairment. Less prevalent conditions (eg, stress urinary incontinence) also emerged as contributors to lower WRQOL. CONCLUSIONS: WRQOL impairment is substantial for adolescents with severe obesity undergoing WLS, with predictors varying by sex. These patient-data highlight targets for education, support, and adjunctive care referrals before WLS. Furthermore, they provide a comprehensive empirical base for understanding heterogeneity in adolescent WRQOL outcomes after WLS, as weight and comorbidity profiles change over time.

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Management of pediatric chronic liver disease is limited by lack of validated noninvasive biomarkers of histologic severity. We demonstrate that magnetic resonance elastography is feasible and accurate in detecting significant hepatic fibrosis in a case series of 35 children with chronic liver disease, including severely obese children.

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OBJECTIVE: Surgical treatment of extreme obesity may be appropriate for some adolescents. We hypothesized that surgical weight loss outcomes may differ by preoperative level of extreme obesity (body mass index [BMI] > or=99th percentile). STUDY DESIGN: A longitudinal assessment of clinical characteristics from 61 adolescents who underwent laparoscopic Roux-en-Y gastric bypass at a single pediatric center from 2002 until 2007 was performed. Patients were categorized into 1 of 3 preoperative BMI groups: group 1, BMI = 40.0 to 54.9 (n = 23); group 2, BMI = 55.0 to 64.9 (n = 21); group 3, BMI = 65.0 to 95.0 (n = 17). Changes in BMI and cardiovascular risk factors between baseline and year 1 were evaluated using repeated-measures mixed linear modeling. RESULTS: BMI in the overall cohort at baseline (60.2 +/- 11 kg/m(2)) decreased by 37.4% at 1 year after surgery (P < .001). Percent BMI change varied little by preoperative BMI groups (-37.2%, -36.8%, and -37.7% for groups 1, 2, and 3 respectively; P = .8762). The rate of change in absolute BMI units significantly varied by preoperative BMI class (group x time interaction, P < .0001), with 1-year nadir BMI values for groups 1, 2, and 3 falling to 31 +/- 4 kg/m(2), 38 +/- 5 kg/m(2), and 47 +/- 9 kg/m(2), respectively. One year after surgery, only 17% of patients achieved a nonobese BMI (<30 kg/m(2)). Significant improvements in systolic and diastolic blood pressure (P < .0001), fasting insulin (P < .0001), total cholesterol (P = .0007), and triglyceride levels (P < .0001) were seen after surgery irrespective of baseline BMI class. Mean albumin levels remained normal despite significant caloric restriction and weight loss. CONCLUSIONS: Laparoscopic gastric bypass resulted in improvement or reversal of cardiovascular risk factors and resulted in a decrease in BMI of approximately 37% in all patients, regardless of starting BMI, 1 year after surgery. The timing of surgery for adolescent extreme obesity is an important consideration, because "late" referral for bariatric surgery at the highest of BMI values may preclude reversal of obesity.

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