Search

ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges.

Objectives Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into β cells. To explore relationships between BCAAs and tryptophan metabolism, adiposity, and glucose tolerance, we compared urine metabolites in overweight/obese youth with type 2 diabetes (T2D) with those in nondiabetic overweight/obese and lean youth. Methods Metabolites were measured in 24-hour and first-morning urine samples of 56 nondiabetic adolescents with overweight/obesity, 42 adolescents with T2D, and 43 lean controls, aged 12 to 21 years. Group differences were assessed by Kruskal Wallis or ANOVA. Results Groups were comparable for age, pubertal status, and ethnicity. Youth with T2D were predominantly female and had highest percent body fat. BCAAs, branched-chain ketoacids (BCKAs), tryptophan, and kynurenine were higher in urine of subjects with T2D. There were no differences between lean controls and nondiabetic youth with overweight/obesity. T2D was associated with diversion of tryptophan from the serotonin to the kynurenine pathway, with higher urinary kynurenine/serotonin ratio and lower serotonin/tryptophan and 5-HIAA/kynurenine ratios. Urinary BCAAs, BCKAs, tryptophan, and ratios reflecting diversion to the kynurenine pathway correlated positively with metrics of body fat and hemoglobin A1c. Increases in these metabolites in the obese T2D group were more pronounced and statistically significant only in adolescent girls. Conclusion Increases in urinary BCAAs and BCKAs in adolescent females with T2D are accompanied by diversion of tryptophan metabolism from the serotonin to the kynurenine pathway. These adaptations associate with higher risks of T2D in obese adolescent females than adolescent males. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) (5,047 participants, mean follow-up 5.0 years), differences in glycemic control were demonstrated over time among four randomized therapies added to metformin. Weight gain and hypoglycemia are also important outcomes for people with type 2 diabetes. We compared the effects of the four randomized GRADE medications on a composite outcome incorporating glycemic deterioration, weight gain, and hypoglycemia. RESEARCH DESIGN AND METHODS: The composite outcome was time to first occurrence of any of the following: HbA1c >7.5%, confirmed; ≥5% weight gain; or severe or recurrent nonsevere hypoglycemia. Secondary analyses included examination of individual components of the composite outcome, subgroup effects and potential mediators, and treatment satisfaction. Cumulative incidence was estimated with the Kaplan-Meier estimator. Cox proportional hazards models were used to assess pairwise group differences in risk of an outcome. RESULTS: Risk of reaching the composite outcome (events per 100 participants per treatment year [PTYs]) was lowest with liraglutide (19 per 100 PTYs) followed by sitagliptin (26 per 100 PTYs), glargine (29 per 100 PTYs), and glimepiride (40 per 100 PTYs); all pairwise comparisons were statistically significant. The order was the same for risk of weight gain and hypoglycemia, but risk of glycemic deterioration was lowest with glargine, followed by liraglutide, glimepiride, and sitagliptin. No significant heterogeneity in risk of composite outcome was detected across prespecified covariates. Participants who reached the composite outcome had modestly but significantly lower treatment satisfaction. CONCLUSIONS: Among participants treated with common second-line drug classes for type 2 diabetes, the liraglutide group had the lowest and glimepiride the highest risk of reaching a composite outcome encompassing glycemic deterioration, weight gain, and hypoglycemia. These findings may inform decision-making regarding type 2 diabetes therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND. In women with obesity, excess gestational weight gain ([greater than or equal to] 270 g/week) occurs in 2 out of 3 pregnancies and contributes to metabolic impairments in both mother and baby. To improve obstetrical care, objectively assessed information on energy balance is urgently needed. The objective of this study was to characterize determinants of gestational weight gain in women with obesity. METHODS. This was a prospective, observational study of pregnant women with obesity. The primary outcome was energy intake calculated by the energy intake-balance method. Energy expenditure was measured by doubly labeled water and whole-room indirect calorimetry and body composition as a 3-compartment model by air displacement plethysmography and isotope dilution in early (13-16 weeks) and late (35-37 weeks) pregnancy. RESULTS. In pregnant women with obesity (n = 54), recommended weight gain (n = 8, 15%) during the second and third trimesters was achieved when energy intake was 125 [+ or -] 52 kcal/d less than energy expenditure. In contrast, women with excess weight gain (67%) consumed 186 [+ or -] 29 kcal/d more than they expended (P < 0.001). Energy balance affected maternal adiposity (recommended: -2.5 [+ or -] 0.8 kg fat mass; excess: +2.2 [+ or -] 0.5; inadequate: -4.5 [+ or -] 0.5; P < 0.001) but not fetal growth. Weight gain was not related to demographics, activity, metabolic biomarkers, or diet quality. We estimated that energy intake requirements for recommended weight gain during the second and third trimesters were not increased as compared with energy requirements early in pregnancy (34 [+ or -] 53 kcal/d, P = 0.83). CONCLUSION. We here provide what we believe are the first evidence-based recommendations for energy intake in pregnant women with obesity. Contrary to current recommendations, energy intake should not exceed energy expenditure. TRIAL REGISTRATION. ClinicalTrials.gov, NCT01954342. FUNDING. This study was funded by the National Institutes of Health (R01DK099175) and the Clinical Research Cores at Pennington Biomedical Research Center (U54GM104940 and P30DK072476)., Introduction According to the 2009 Institute of Medicine guidelines, women entering pregnancy with obesity should limit total weight gain to 5-9 kg (1). Despite these recommendations, excess gestational weight gain [...]

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end‐stage liver disease. NAFLD diagnosis and follow‐up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments. Purpose/Hypothesis: The goal of this pilot study was to harmonize commercially available 3 T magnetic resonance imaging (MRI) measurements of liver fat and stiffness in human participants across academic sites and MRI vendors. Study Type: Cohort. Subjects: Four community‐dwelling adults with obesity. Field strength/Sequence: 1.5 and 3 T, multiecho 3D imaging, PRESS, and GRE. Assessment: Harmonized proton density fat fraction (PDFF) and magnetic resonance spectroscopy (MRS) protocols were used to quantify the FF of synthetic phantoms and human participants with obesity using standard acquisition parameters at four sites that had four different 3 T MRI instruments. In addition, a harmonized magnetic resonance elastography (MRE) protocol was used to quantify liver stiffness among participants at two different sites at 1.5 and 3 T field strengths. Data were sent to a single data coordinating site for postprocessing. Statistical Tests: Linear regression in MATLAB, ICC analyses using SAS 9.4, one‐sided 95% confidence intervals for the ICC. Results: PDFF and MRS FF measurements were highly repeatable among sites in both humans and phantoms. MRE measurements of liver stiffness in three individuals at two sites using one 1.5 T and one 3 T instrument showed repeatability that was high although lower than that of MRS and PDFF. Conclusions: We demonstrated harmonization of PDFF, MRS, and MRE‐based quantification of liver fat and stiffness through synthetic phantoms, traveling participants, and standardization of postprocessing analysis. Multisite MRI harmonization could contribute to multisite clinical trials assessing the efficacy of interventions and therapy for NAFLD. Level of Evidence: 2 Technical Efficacy Stage: 2 [ABSTRACT FROM AUTHOR]

Context: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear. Objective: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation. Methods: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean ± SD body mass index: 31.5 ± 4.7 kg/m²) were randomized to a control group or exercise groups that reflected exercise recommendations for health (8 kcal/kg/week [KKW]) or weight loss and weight maintenance (20 KKW). Waist circumference was measured, and dual-energy X-ray absorptiometry assessed central adiposity. Predicted weight change was estimated and weight compensation (weight change – predicted weight change) was calculated. Results: Between-group change in waist circumference (control: .0 cm [95% CI, −1.0 to 1.0], 8 KKW: −.7 cm [95% CI, −1.7 to .4], 20 KKW: −1.3 cm [95% CI, −2.4 to −.2]) and visceral adipose tissue (VAT; control: −.02 kg [95% CI, −.07 to .04], 8 KKW: −.01 kg [95% CI, −.07 to .04], 20 KKW: −.04 kg [95% CI, −.10 to .02]) was similar (P ≥ .23). Most exercisers (82.6%) compensated (weight loss less than expected). Exercisers who compensated exhibited a 2.5-cm (95% CI, .8 to 4.2) and .23-kg (95% CI, .14 to .31) increase in waist circumference and VAT, respectively, vs those who did not (P < .01). Desire to eat predicted VAT change during exercise (β = .21; P = .03). Conclusion: In the presence of significant weight compensation, exercise at doses recommended for health and weight loss and weight maintenance leads to negligible changes in central adiposity. [ABSTRACT FROM AUTHOR]

BackgroundLess than one-third of women gain an appropriate amount of weight during pregnancy, which can influence the long-term health of both the mother and the child. Economically disadvantaged women are the most vulnerable to maternal obesity, excessive weight gain during pregnancy, and poor birth outcomes. Effective and scalable health care strategies to promote healthy weight gain during pregnancy specifically tailored for these women are lacking. ObjectiveThis paper presents the design and protocol of a biphasic, community-based eHealth trial, SmartMoms in WIC, to increase the adherence to healthy gestational weight gain (GWG) recommendations in low-income mothers receiving women, infant, and children (WIC) benefits. MethodsPhase 1 of the trial included using feedback from WIC mothers and staff and participants from 2 community peer advisory groups to adapt an existing eHealth gestational weight management intervention to meet the needs of women receiving WIC benefits. The health curriculum, the format of delivery, and incentive strategies were adapted to be culturally relevant and at an appropriate level of health literacy. Phase 2 included a pragmatic randomized controlled trial across the 9 health care regions in Louisiana with the goal of enrolling 432 women. The SmartMoms in WIC intervention is an intensive 24-week behavioral intervention, which includes nutrition education and exercise strategies, and provides the technology to assist with weight management, delivered through a professionally produced website application. ResultsPhase 1 of this trial was completed in July 2019, and recruitment for phase 2 began immediately thereafter. All data are anticipated to be collected by Spring 2023. ConclusionsThe SmartMoms in WIC curriculum was methodically developed using feedback from community-based peer advisory groups to create a culturally relevant, mobile behavioral intervention for mothers receiving WIC benefits. The randomized clinical trial is underway to test the effectiveness of a sustainable eHealth program on the incidence rates of appropriate GWG. SmartMoms in WIC may be able to offer an innovative, cost-effective, and scalable solution for GWG management in women served by WIC. Trial RegistrationClinicalTrials.gov NCT04028843; https://clinicaltrials.gov/ct2/show/NCT04028843 International Registered Report Identifier (IRRID)DERR1-10.2196/18211

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self‐reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI < −0.15%), moderate (HGI −0.15% to +0.15%) and high (HGI > +0.15%) HGI subgroups. Results: The prevalence of prediabetes was 42.4% based on FPG, 27.2% based on HbA1c and 17.2% based on 2hOGTT. FPG and HbA1c thus overdiagnosed prediabetes by 25.2% and 10.0%, respectively, compared to the OGTT gold standard. Prevalence was (1) similar in low, moderate and high HGI participants based on 2hOGTT, (2) highest in low HGI participants based on FPG, and (3) highest in high HGI participants based on HbA1c. Among participants with mismatched FPG and HbA1c, OGTT was normal in (1) 79.5% of participants with normal FPG but prediabetic HbA1c (mean HGI = +0.53%), and (2) 75.2% of participants with normal HbA1c but prediabetic FPG (mean HGI = −0.30%). Conclusions: FPG overdiagnosed prediabetes in people with low HGI. HbA1c overdiagnosed prediabetes in people with high HGI. Clinical use of HGI could improve prediabetes diagnosis and help health care providers avoid inappropriate or delayed treatment of people with extremes of HGI. [ABSTRACT FROM AUTHOR]

Objective: To conduct a preliminary assessment of the relationships between cardiorespiratory fitness, adiposity, and cardiometabolic health using gold standard measures in diverse youth ranging from overweight to severe obesity. Methods: Twenty of 30 participants (mean [SD]; age 13.2 [1.8] y, 55% female, 45% African American) met the criteria for VO2peak during a graded cycle ergometer test to volitional fatigue. The body composition was measured by dual-energy X-ray absorptiometry (percentage of body fat, fat mass index, and fat-free mass) and magnetic resonance imaging (abdominal visceral and subcutaneous [SAT] adipose tissue). The VO2peak was expressed relative to fat-free mass. Fasting lipid levels, glycemic biomarkers, and vital signs were examined individually and used in a composite cardiometabolic risk score. Accelerometer-measured physical activity and sedentary time were included as covariates. Results: VO2peak was negatively associated with abdominal SAT (r = −.49, P <.05), but not visceral adipose tissue or markers of cardiometabolic health. The association between SAT and VO2peak was partly explained by habitual sedentary time. Conclusions: We demonstrated a significant negative association between cardiorespiratory fitness and SAT in a diverse group of high-risk youth. The inclusion of rigorous, laboratory-based measures and youth with severe obesity extends the previous work in pediatric populations. [ABSTRACT FROM AUTHOR]

BackgroundTwo-thirds of pregnant women exceed gestational weight gain (GWG) recommendations. Because excess GWG is associated with adverse outcomes for mother and child, development of scalable and cost-effective approaches to deliver intensive lifestyle programs during pregnancy is urgent. ObjectiveThe aim of this study was to decrease the proportion of women who exceed the Institute of Medicine (IOM) 2009 GWG guidelines. MethodsIn a parallel-arm randomized controlled trial, 54 pregnant women (age 18-40 years) who were overweight (n=25) or obese (n=29) were enrolled to test whether an intensive lifestyle intervention (called SmartMoms) decreased the proportion of women with excess GWG, defined as exceeding the 2009 IOM guidelines, compared to no intervention (usual care group). The SmartMoms intervention was delivered through mobile phone (remote group) or in a traditional in-person, clinic-based setting (in-person group), and included a personalized dietary intake prescription, self-monitoring weight against a personalized weight graph, activity tracking with a pedometer, receipt of health information, and continuous personalized feedback from counselors. ResultsA significantly smaller proportion of women exceeded the IOM 2009 GWG guidelines in the SmartMoms intervention groups (in-person: 56%, 10/18; remote: 58%, 11/19) compared to usual care (85%, 11/13; P=.02). The remote intervention was a lower cost to participants (mean US $97, SD $6 vs mean US $347, SD $40 per participant; P