Loneliness, Discrimination, Stress and Type 2 Diabetes Risk in Young Adults.

INTRODUCTION: The aim of this study was to determine the associations between type 2 diabetes (T2D) or prediabetes and loneliness and related social experiences in young adults, a population at increasingly high risk of T2D. METHODS: This was a cross-sectional analysis using data from adults ages 18-35 enrolled in the All of Us Research Program. Exposures included loneliness, social support, discrimination, neighborhood social cohesion, and stress, measured by standardized surveys. The main outcome was T2D or prediabetes by self-report or linked health record. Logistic regression determined odds of T2D/prediabetes for each survey measure, adjusting for age, sex, race or ethnicity, income, and family history. Latent class analysis (LCA) evaluated clustering of social experiences. Data was collected from 2018-2022 and analyzed May 2023-June 2024. RESULTS: The cohort included 14,217 young adults (28.2 ± 4.4 years; 70.3% (n=9,792) women; 64.1% (n=9,111) White, 10.6% (n=1,506) Hispanic, 5.7% (n=806) Black, 9.1% (n=1,299) multiracial). Overall, 5.5% (n=777) had either prediabetes or T2D. The two highest loneliness quartiles were associated with increased odds of prediabetes/T2D (Q3: OR 1.42 [95% CI 1.15-1.76]; Q4: 1.75 [95% CI 1.43-2.16]). Greater stress and discrimination and lower social support and neighborhood social cohesion were also associated with increased odds of prediabetes/T2D. LCA revealed three distinct phenotypes, with elevated odds of prediabetes/T2D in the two with the most adverse social profiles (OR 2.32 [95% CI 1.89-2.84] and OR 1.28 [95% CI 1.04-1.58]). CONCLUSIONS: Loneliness and related experiences are strongly associated with T2D and prediabetes in young adults. Whether these factors could be leveraged to reduce T2D risk should be investigated.

Diagnostic Accuracy of Transient Elastography in Hepatosteatosis in Youth With Obesity.

Context: Steatotic liver disease is common but overlooked in childhood obesity; diagnostic methods are invasive or expensive. Objective: We sought to determine the diagnostic accuracy of vibration-controlled transient elastography (VCTE) compared with magnetic resonance imaging (MRI) in adolescents with obesity and high risk for hepatosteatosis. Methods: Baseline data in 3 clinical trials enrolling adolescents with obesity were included (NCT03919929, NCT03717935, NCT04342390). Liver fat was assessed using MRI fat fraction and VCTE-based controlled attenuation parameter (CAP). Hepatosteatosis was defined as MRI fat fraction ≥5.0%. The area under the receiver-operating characteristic curves (AUROCs) for CAP against MRI was calculated, and optimal CAP using the Youden index for hepatosteatosis diagnosis was determined. Results: Data from 82 adolescents (age 15.6 ± 1.4 years, body mass index 36.5 ± 5.9 kg/m2, 81% female) were included. Fifty youth had hepatosteatosis by MRI (fat fraction 9.3% ; 95% CI 6.7, 14.0), and 32 participants did not have hepatosteatosis (fat fraction 3.1%; 95% CI 2.2, 3.9; P < .001). The hepatosteatosis group had higher mean CAP compared with no hepatosteatosis (293 dB/m; 95% CI 267, 325 vs 267 dB/m; 95% CI 248, 282; P = .0120). A CAP of 281 dB/m had the highest sensitivity (60%) and specificity (74%) with AUROC of 0.649 (95% CI 0.51-0.79; P = .04) in the entire cohort. In a subset of participants with polycystic ovary syndrome (PCOS), a CAP of 306 dB/m had the highest sensitivity (78%) and specificity (52%) and AUROC of 0.678 (95% CI 0.45-0.90; P = .108). Conclusion: CAP of 281 dB/m has modest diagnostic performance for hepatosteatosis compared with MRI in youth with significant obesity. A higher CAP in youth with PCOS suggests that comorbidities might affect optimal CAP in hepatosteatosis diagnosis.

Primary care perspectives on prescribing anti-obesity medication for adolescents.

BACKGROUND: Recent pediatric guidelines recommend clinicians offer anti-obesity medication (AOM) as an adjunct to intensive lifestyle intervention. OBJECTIVE: To investigate pediatricians' perspectives about prescribing AOM, including barriers and facilitators. METHODS: An investigator-developed survey was emailed to primary care pediatric physicians (n = 187) and advanced practice providers (n = 190) within an academic-affiliated network. The survey evaluated how willing clinicians were to prescribe AOM and their agreement with 25 statements about barriers and facilitators. Three vignettes explored AOM decision-making. Multinomial logistic regression was used to determine relative risk ratios for willingness to prescribe by agreement with each statement. RESULTS: Among 74 respondents (20% response rate), 24% were willing, 42% uncertain and 34% unwilling to prescribe. Most (64%) agreed that AOM should be managed only by specialists. Willingness to prescribe was associated with clinician motivation and belief in guideline practicality and applicability. Unwillingness was associated with beliefs that patients would not continue AOM long enough for benefit and that there was insufficient time or resources to implement. In vignettes, 52% were willing to prescribe AOM for a patient with severe obesity and metabolic complications, versus 11% for a patient with obesity and possible disordered eating. CONCLUSIONS: Willingness to prescribe AOM was low and was associated with perceived practicality and appropriateness for patients.

Prediabetes Prevalence by Adverse Social Determinants of Health in Adolescents.

Importance: Several clinical practice guidelines advise race- and ethnicity-based screening for youth-onset type 2 diabetes (T2D) due to a higher prevalence among American Indian and Alaska Native, Asian, Black, and Hispanic youths compared with White youths. However, rather than a biological risk, this disparity likely reflects the inequitable distribution of adverse social determinants of health (SDOH), a product of interpersonal and structural racism. Objective: To evaluate prediabetes prevalence by presence or absence of adverse SDOH in adolescents eligible for T2D screening based on weight status. Design, Setting, and Participants: This cross-sectional study and analysis used data from the 2011 to 2018 cycles of the National Health and Nutrition Examination Survey. Data were analyzed from June 1, 2023, to April 5, 2024. Participants included youths aged 12 to 18 years with body mass index (BMI) at or above the 85th percentile without known diabetes. Main Outcomes and Measures: The main outcome consisted of an elevated hemoglobin A1c (HbA1c) level greater than or equal to 5.7% (prediabetes or undiagnosed presumed T2D). Independent variables included race, ethnicity, and adverse SDOH (food insecurity, nonprivate health insurance, and household income <130% of federal poverty level). Survey-weighted logistic regression was used to adjust for confounders of age, sex, and BMI z score and to determine adjusted marginal prediabetes prevalence by race, ethnicity, and adverse SDOH. Results: The sample included 1563 individuals representing 10 178 400 US youths aged 12 to 18 years (mean age, 15.5 [95% CI, 15.3-15.6] years; 50.5% [95% CI, 47.1%-53.9%] female; Asian, 3.0% [95% CI, 2.2%-3.9%]; Black, 14.9% [95% CI, 11.6%-19.1%]; Mexican American, 18.8% [95% CI, 15.4%-22.9%]; Other Hispanic, 8.1% [95% CI, 6.5%-10.1%]; White, 49.1% [95% CI, 43.2%-55.0%]; and >1 or other race, 6.1% [95% CI, 4.6%-8.0%]). Food insecurity (4.1% [95% CI, 0.7%-7.5%]), public insurance (5.3% [95% CI, 1.6%-9.1%]), and low income (5.7% [95% CI, 3.0%-8.3%]) were each independently associated with higher prediabetes prevalence after adjustment for race, ethnicity, and BMI z score. While Asian, Black, and Hispanic youths had higher prediabetes prevalence overall, increasing number of adverse SDOH was associated with higher prevalence among White youths (8.3% [95% CI, 4.9%-11.8%] for 3 vs 0.6% [95% CI, -0.7% to 2.0%] for 0 adverse SDOH). Conclusions and Relevance: Adverse SDOH were associated with higher prediabetes prevalence, across and within racial and ethnic categories. Consideration of adverse SDOH may offer a more actionable alternative to race- and ethnicity-based screening to evaluate T2D risk in youth.

Semaglutide for management of obesity in adolescents: efficacy, safety, and considerations for clinical practice.

PURPOSE OF REVIEW: The purpose of this review is to describe the existing limited data related to the use of semaglutide in adolescents with obesity, supplementing with findings from adult studies of semaglutide use. RECENT FINDINGS: Semaglutide, as a once weekly subcutaneous injection for weight management, effectively reduces body mass index (BMI) while improving hyperglycemia, elevated alanine aminotransferase levels, hyperlipidemia, and quality of life in youth with obesity. As of this review, only one large randomized clinical trial of semaglutide in youth has been completed, with a follow-up duration of 68 weeks. Thus, long-term data on the safety in adolescents is limited, particularly regarding the risks of cholelithiasis, pancreatitis, suicidal ideation, and disordered eating. Due to the cost of semaglutide, particularly in the United States, limited cost effectiveness analyses have demonstrated unfavorable incremental cost-effectiveness ratios for semaglutide relative to phentermine-topiramate as an alternative antiobesity medication in adolescents. SUMMARY: Semaglutide represents an important advance in the pediatric obesity management, with clear short-term reductions in BMI and improvement in metabolic parameters. However, its long-term safety and efficacy for youth with obesity remain to be demonstrated. Additional research is needed to assess trends in utilization and adherence to minimize the risk of worsening socioeconomic disparities in pediatric obesity.

Utilizing the Glucose and Insulin Response Shape of an Oral Glucose Tolerance Test to Predict Dysglycemia in Children with Overweight and Obesity, Ages 8-18 Years.

Common dysglycemia measurements including fasting plasma glucose (FPG), oral glucose tolerance test (OGTT)-derived 2 h plasma glucose, and hemoglobin A1c (HbA1c) have limitations for children. Dynamic OGTT glucose and insulin responses may better reflect underlying physiology. This analysis assessed glucose and insulin curve shapes utilizing classifications-biphasic, monophasic, or monotonically increasing-and functional principal components (FPCs) to predict future dysglycemia. The prospective cohort included 671 participants with no previous diabetes diagnosis (BMI percentile ≥ 85th, 8-18 years old); 193 returned for follow-up (median 14.5 months). Blood was collected every 30 min during the 2 h OGTT. Functional data analysis was performed on curves summarizing glucose and insulin responses. FPCs described variation in curve height (FPC1), time of peak (FPC2), and oscillation (FPC3). At baseline, both glucose and insulin FPC1 were significantly correlated with BMI percentile (Spearman correlation r = 0.22 and 0.48), triglycerides (r = 0.30 and 0.39), and HbA1c (r = 0.25 and 0.17). In longitudinal logistic regression analyses, glucose and insulin FPCs predicted future dysglycemia (AUC = 0.80) better than shape classifications (AUC = 0.69), HbA1c (AUC = 0.72), or FPG (AUC = 0.50). Further research should evaluate the utility of FPCs to predict metabolic diseases.

Child Opportunity Index and clinical characteristics at diabetes diagnosis in youth: type 1 diabetes versus type 2 diabetes.

INTRODUCTION: Among youth with type 1 diabetes (T1D), longitudinal poor glycemic control is associated with adverse socioeconomic conditions at the neighborhood level. Child Opportunity Index (COI), which encompasses measures of education, health, environment, social, and economic factors, is associated with obesity in youth but has not been evaluated in youth with new-onset T1D or type 2 diabetes (T2D). We hypothesized that lower COI would be associated with adverse clinical outcomes at diabetes diagnosis, and due to differing risk factors and pathophysiology, that youth with new-onset T2D would have lower COI than youth with T1D. RESEARCH DESIGN AND METHODS: Retrospective cohort of youth with new-onset diabetes admitted to a large academic pediatric hospital. COI was compared by diabetes type using t-tests and Χ2 tests. Multivariable linear and logistic regression analyses were used to evaluate associations between COI and clinical characteristics, stratified by diabetes type and adjusted for age and sex. RESULTS: The cohort (n=484) differed in race and age by diabetes type (T1D: n=389; 10.0% black, 81.2% white; age 9.6±0.2 years; T2D: n=95; 44.2% black, 48.4% white; age 14.8±0.3 years). Youth with T2D had lower COI (p<0.001). Low COI was associated with diabetic ketoacidosis in T1D and T2D. Black youth with low COI had the highest hemoglobin A1c among youth with T2D and the highest obesity prevalence among youth with T1D. CONCLUSIONS: COI is associated with differing characteristics at diagnosis in youth-onset T1D and T2D but is worse among youth with T2D overall. These findings underscore the need to address socioeconomic adversity when designing interventions to reduce T2D risk and to improve outcomes at diabetes diagnosis in youth.

Relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes using continuous glucose monitoring systems.

AIMS: To evaluate relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring (CGM) glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes (T1D) who use CGM. METHODS: A cross-sectional survey and data collections were completed with 196 T1D adults who used CGM (59% also used automated insulin delivery devices (AIDs)). We assessed hypoglycemia awareness (Gold instrument), hypoglycemia beliefs (Attitudes to Awareness of Hypoglycemia instrument), CGM glycemic profiles, demographics, and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Analysis included simple and multiple linear regression analyses. RESULTS: Lower hypoglycemia awareness, weaker "hypoglycemia concerns minimized" beliefs, stronger "hyperglycemia avoidance prioritized" beliefs were independently associated with higher anxiety symptoms (P < 0.05), with similar trends in both subgroups using and not using AIDs. Lower hypoglycemia awareness were independently associated with greater depression symptoms (P < 0.05). In participants not using AIDs, more time in hypoglycemia was related to less anxiety and depression symptoms (P < 0.05). Being female and younger were independently associated with higher anxiety symptoms, while being younger was also independently associated with greater depression symptoms (P < 0.05). CONCLUSION: Our findings revealed relationships of impaired hypoglycemia awareness, hypoglycemia beliefs, CGM-detected hypoglycemia with anxiety and depression symptoms in T1D adults who use CGMs.

Emerging Adults With Type 2 Diabetes: Understanding Illness Experience and Transition to Adult Care.

PURPOSE: Youth-onset type 2 diabetes (T2D) is increasingly common and is often diagnosed shortly before transition from pediatric to adult care. Little is known about the experience of emerging adults (EAs) with T2D and the readiness, barriers, and facilitators to transition. This study sought to describe the illness experience of EAs with T2D and perceptions about transition, and explore themes by "transition readiness," measured by the Transition Readiness Assessment Questionnaire (TRAQ). METHODS: In this mixed-methods study, we conducted semi-structured interviews with EAs with T2D using a guide grounded in the health belief model, administered the TRAQ, and collected disease metrics from the electronic medical record. We developed a coding scheme using a directed content-analysis approach and triangulated qualitative and quantitative data to compare themes stratified by mean TRAQ score. RESULTS: Participants described modifying factors like adjusting to life with a chronic illness and coping with mental health issues as critical elements of the illness experience that influence transition. Individual beliefs emerged including the perceived risk of disease complications being informed by experience of family members, self-efficacy in diabetes care hinging on the ability to be highly organized, and transition as a daunting obstacle with numerous emotional and logistical barriers. Participants emphasized the need for support from caregivers and providers throughout transition. Themes did not vary significantly by TRAQ score. DISCUSSION: Experiences of EAs with T2D suggest more assistance is needed in the transition period to address factors such as mental health, organizational skills, and identifying support people to facilitate care.

Projected impact of anti-obesity pharmacotherapy use on racial and ethnic disparities in adolescent obesity.

BACKGROUND: Paediatric obesity disproportionately impacts individuals from minoritized racial and ethnic backgrounds. Recent guidelines support use of anti-obesity pharmacotherapy for adolescents with obesity, but the potential impact on disparities in obesity prevalence has not been evaluated. OBJECTIVES: To model changes in obesity prevalence with increasing utilization of anti-obesity pharmacotherapy among adolescents. METHODS: Data representative of American adolescents ages 12-17 years were obtained from the National Health and Nutrition Examination Survey, cycles 2011 through pre-pandemic 2020. A body mass index (BMI) reduction of 16.7% was applied to each participant based on clinical trial results of weekly subcutaneous semaglutide 2.4 mg among adolescents. Utilization disparities were based on utilization of the same medication class among adults. Obesity prevalence was calculated assuming utilization of 10%-100%, stratified by race and ethnicity. RESULTS: Among 4442 adolescents representing 26 247 384 American adolescents, projected overall obesity prevalence decreased from 22.2% to 8.4% with 100% utilization. However, disparities increased relative to Non-Hispanic White youth, with prevalence among Non-Hispanic Black and Mexican American youth ranging from 40%-60% higher to 90%-120% higher, respectively. CONCLUSIONS: Increasing utilization of anti-obesity pharmacotherapy may widen relative disparities in obesity, particularly if utilization is unequal. Advocacy for equitable access is needed to minimize worsening of obesity-related disparities.

Re-analysis and meta-analysis of summary statistics from gene-environment interaction studies.

MOTIVATION: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics. RESULTS: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction covariate adjustments. METAGEM (META-analysis of GEM summary statistics) extends current fixed-effects meta-analysis models to incorporate multiple exposures from multiple studies. We demonstrate the value and efficiency of these tools by exploring alternative methods of accounting for ancestry-related population stratification in genome-wide interaction study in the UK Biobank as well as by conducting a multi-exposure genome-wide interaction study meta-analysis in cohorts from the diabetes-focused ProDiGY consortium. These programs help to maximize the value of summary statistics from diverse and complex gene-environment interaction studies. AVAILABILITY AND IMPLEMENTATION: REGEM and METAGEM are open-source projects freely available at https://github.com/large-scale-gxe-methods/REGEM and https://github.com/large-scale-gxe-methods/METAGEM.

Barriers and Facilitators to Uptake of Continuous Glucose Monitoring for Management of Type 2 Diabetes Mellitus in Youth.

PURPOSE: The purpose of this study was to identify factors impacting the acceptability of continuous glucose monitoring (CGM) in adolescents and young adults (AYAs) with type 2 diabetes mellitus (T2DM). METHODS: In this single-center study, semistructured interviews were conducted with AYAs with T2DM and their parents to determine attitudes about CGM, including barriers and facilitators. Interviews were audio-recorded, transcribed, and evaluated using thematic analysis. RESULTS: Twenty AYAs and 10 parents participated (n = 30 total). AYAs were mean age 16.5 years (SD 2.2, range = 13.7-20.1) and had median diabetes duration of 1.3 years. Most were female (65%) and from minoritized background (40% non-Hispanic Black, 10% Hispanic, 5% Asian). Seven (35%) used CGM. The primary facilitator elicited was convenience over glucose meter use. Important barriers included the impact of physically wearing the device and drawing unwanted attention, desire for AYA privacy, and inadequate education about the device. CONCLUSIONS: In this diverse sample of AYAs with T2DM and their parents, CGM was generally regarded as convenient, although concerns about worsening stigma and conflict with parents were prevalent. These findings can guide the development of patient-centered approaches to CGM for AYAs with T2DM, a critical step toward reducing inequities in diabetes technology uptake.

Pediatric Obesity: Complications and Current Day Management.

Obesity affects approximately 1 in 5 youth globally and increases the risk of complications during adolescence and young adulthood, including type 2 diabetes, dyslipidemia, hypertension, non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovary syndrome. Children and adolescents with obesity frequently experience weight stigma and have an impaired quality of life, which may exacerbate weight gain. Pediatric obesity is typically defined using sex-, age-, and population-specific body mass index percentiles. Once identified, pediatric obesity should always be managed with lifestyle modification. However, adolescents with obesity may also benefit from anti-obesity medications (AOM), several of which have been approved for use in adolescents by the US Food and Drug Administration, including liraglutide, phentermine/topiramate, and semaglutide. For children with specific, rare monogenic obesity disorders, setmelanotide is available and may lead to significant weight loss. Metabolic and bariatric surgery may be used for the management of severe obesity in youth; though highly effective, it is limited to specialized centers and has had relatively low pediatric uptake. In this narrative review using pediatric-focused data from original research, reviews, clinical practice guidelines, governmental agencies, and pharmaceutical companies, we review obesity-related metabolic complications in youth and management strategies, including AOM and bariatric surgery.

Perception and Awareness of Diabetes Risk and Reported Risk-Reducing Behaviors in Adolescents.

Importance: Lifestyle change is central to diabetes risk reduction in youth with overweight or obesity. Feeling susceptible to a health threat can be motivational in adults. Objective: To evaluate associations between diabetes risk perception and/or awareness and health behaviors in youth. Design, Setting, and Participants: This cross-sectional study analyzed data from the US National Health and Nutrition Examination Survey 2011 to 2018. Participants included youths aged 12 to 17 years with body mass index (BMI) in the 85th percentile or higher without known diabetes. Analyses were conducted from February 2022 to February 2023. Main Outcomes and Measures: Outcomes included physical activity, screen time, and attempted weight loss. Confounders included age, sex, race and ethnicity, and objective diabetes risk (BMI, hemoglobin A1c [HbA1c]). Exposures: Independent variables included diabetes risk perception (feeling at risk) and awareness (told by clinician), as well as potential barriers (eg, food insecurity, household size, insurance). Results: The sample included 1341 individuals representing 8 716 794 US youths aged 12 to 17 years with BMI in the 85th percentile or higher for age and sex. The mean age was 15.0 years (95% CI, 14.9-15.2 years) and mean BMI z score was 1.76 (95% CI 1.73-1.79). Elevated HbA1c was present in 8.6% (HbA1c 5.7%-6.4%: 8.3% [95% CI, 6.5%-10.5%]; HbA1c ≥6.5%: 0.3% [95% CI, 0.1%-0.7%]). Nearly one-third of youth with elevated HbA1c reported risk perception (30.1% [95% CI, 23.1%-38.1%), while one-quarter (26.5% [95% CI, 20.0%-34.2%]) had risk awareness. Risk perception was associated with increased TV watching (ß = 0.3 hours per day [95% CI, 0.2-0.5 hours per day]) and approximately 1 less day per week with at least 60 minutes of physical activity (ß = -1.2 [95% CI, -2.0 to -0.4) but not with nutrition or weight loss attempts. Awareness was not associated with health behaviors. Potential barriers had mixed associations: larger households (≥5 members vs 1-2) reported lower consumption of non-home-prepared meals (OR 0.4 [95% CI, 0.2-0.7]) and lower screen time (ß = -1.1 hours per day [95% CI, -2.0 to -0.3 hours per day), while public insurance (vs private) was associated with approximately 20 fewer minutes per day of physical activity (ß = -20.7 minutes per day [95% CI, 35.5 to -5.8 minutes per day]). Conclusions and Relevance: In this cross-sectional study including a US-representative sample of adolescents with overweight or obesity, diabetes risk perception and awareness were not associated with greater engagement in risk-reducing behaviors in youth. These findings suggest the need to address barriers to engagement in lifestyle change, including economic disadvantage.

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy.

INTRODUCTION: Ultra-rare mendelian osteolytic disorders caused by different length in-frame activating duplications within exon 1 of TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK) comprise familial expansile osteolysis (FEO), expansile skeletal hyperphosphatasia (ESH), early-onset familial Paget's disease of bone (PDB2), juvenile Paget's disease 2 (JPD2), and panostotic expansile bone disease (PEBD). FEO typically presents with childhood-onset deafness followed by resorption of permanent dentition, and then appendicular bone pain, fractures, and deformities from progressive focal expansile osteolytic lesions emerging from a background of generalized high bone turnover. An 18-bp duplication in TNFRSF11A has been reported in all kindreds with FEO, whereas a 12-bp duplication was found in the young man with PEBD complicated by a massive jaw tumor. We report the clinical course and successful treatment with bisphosphonates of a girl with the 12-bp duplication yet a skeletal phenotype seemingly milder than PEBD. CASE PRESENTATION AND DISCUSSION: This 10-year-old girl presented for dental and orthodontic treatment and was found to have progressive external tooth root resorption. Speech delay was identified at age 18 months, and audiological evaluation showed both conductive and sensorineural hearing loss subsequently treated with a cochlear implant at age 3 years. Biochemical studies indicated increased bone turnover with elevated urinary N-telopeptide levels and serum alkaline phosphatase in the upper normal range. Low lumbar spine bone mineral density (BMD) was revealed by dual-energy X-ray absorptiometry, but whole-body Technetium-99 m bone scintigraphy was normal. Genetic testing identified the identical de novo 12-bp duplication within exon 1 of TNFRSF11A harbored by the young man with PEBD and massive jaw tumor. Bisphosphonate treatment, initiated with one dose of intravenous zoledronic acid that caused prolonged hypocalcemia, then comprised weekly oral alendronate that decreased bone turnover markers and normalized her BMD. CONCLUSION: Constitutive activation of RANK signaling should be considered a possible cause in any young person with rapid bone turnover, particularly in the context of early-onset deafness and/or root resorption of permanent teeth. Early diagnosis and anti-resorptive treatment, given judiciously to avoid sudden and prolonged hypocalcemia, may prevent further skeletal disease.

Promoting Sleep Duration in the Pediatric Setting Using a Mobile Health Platform: A Randomized Optimization Trial.

Objective: Determine the optimal combination of digital health intervention component settings that increase average sleep duration by ≥30 minutes per weeknight. Methods: Optimization trial using a 25 factorial design. The trial included 2 week run-in, 7 week intervention, and 2 week follow-up periods. Typically developing children aged 9-12y, with weeknight sleep duration <8.5 hours were enrolled (N=97). All received sleep monitoring and performance feedback. The five candidate intervention components (with their settings to which participants were randomized) were: 1) sleep goal (guideline-based or personalized); 2) screen time reduction messaging (inactive or active); 3) daily routine establishing messaging (inactive or active); 4) child-directed loss-framed financial incentive (inactive or active); and 5) caregiver-directed loss-framed financial incentive (inactive or active). The primary outcome was weeknight sleep duration (hours per night). The optimization criterion was: ≥30 minutes average increase in sleep duration on weeknights. Results: Average baseline sleep duration was 7.7 hours per night. The highest ranked combination included the core intervention plus the following intervention components: sleep goal (either setting was effective), caregiver-directed loss-framed incentive, messaging to reduce screen time, and messaging to establish daily routines. This combination increased weeknight sleep duration by an average of 39.6 (95% CI: 36.0, 43.1) minutes during the intervention period and by 33.2 (95% CI: 28.9, 37.4) minutes during the follow-up period. Conclusions: Optimal combinations of digital health intervention component settings were identified that effectively increased weeknight sleep duration. This could be a valuable remote patient monitoring approach to treat insufficient sleep in the pediatric setting.

Prospective Test Performance of Nonfasting Biomarkers to Identify Dysglycemia in Children and Adolescents.

INTRODUCTION: Test performance screening measures for dysglycemia have not been evaluated prospectively in youth. This study evaluated the prospective test performance of random glucose (RG), 1-h nonfasting glucose challenge test (1-h GCT), hemoglobin A1c (HbA1c), fructosamine (FA), and 1,5-anhydroglucitol (1,5-AG) for identifying dysglycemia. METHODS: Youth ages 8-17 years with overweight or obesity (body mass index, BMI, ≥85th percentile) without known diabetes completed nonfasting tests at baseline (n = 176) and returned an average of 1.1 years later for two formal fasting 2-h oral glucose tolerance tests. Outcomes included glucose-defined dysglycemia (fasting plasma glucose ≥100 mg/dL or 2-h plasma glucose ≥140 mg/dL) or elevated HbA1c (≥5.7%). Longitudinal test performance was evaluated using receiver-operating characteristic (ROC) curves and calculation of area under the curve (AUC). RESULTS: Glucose-defined dysglycemia, elevated HbA1c, and either dysglycemia or elevated HbA1c were present in 15 (8.5%), 11 (6.3%), and 23 (13.1%) participants at baseline, and 16 (9.1%), 18 (10.3%), and 28 (15.9%) participants at follow-up. For prediction of glucose-defined dysglycemia at follow-up, RG, 1-h GCT, and HbA1c had similar performance (0.68 (95% CI: 0.55-0.80), 0.76 (95% CI: 0.64-0.89), and 0.70 (95% CI: 0.56-0.84)), while FA and 1,5-AG performed poorly. For prediction of HbA1c at follow-up, baseline HbA1c had strong performance (AUC 0.93 [95% CI: 0.88-0.98]), RG had moderate performance (AUC 0.67 [95% CI: 0.54-0.79]), while 1-h GCT, FA, and 1,5-AG performed poorly. CONCLUSION: HbA1c and nonfasting glucose tests had reasonable longitudinal discrimination identifying adolescents at risk for dysglycemia, but performance depended on outcome definition.

Race- and Neighborhood-Related Disparities Spanning the COVID-19 Pandemic: Trajectories of Combined Glycemic Control and BMI in Youth With Diabetes.

OBJECTIVE: To use combined glycemic (HbA1c) and BMI z-score (BMIZ) trajectories spanning the coronavirus disease 2019 (COVID-19) pandemic to identify high-risk subgroups of adolescents with diabetes. RESEARCH DESIGN AND METHODS: Retrospective cohort of adolescents 10-19 years old with type 1 and type 2 diabetes with one or more visits at a large pediatric hospital from January 2018 through February 2020 (prepandemic) and April 2020 through August 2021 (pandemic). Group-based trajectory models were used to identify latent classes of combined BMIZ and HbA1c trajectories. Multinomial logistic regression was used to evaluate predictors of class membership, including Area Deprivation Index (ADI) (socioeconomic status proxy). RESULTS: The cohort included 1,322 youth with type 1 diabetes (93% White and 7% Black) and 59 with type 2 diabetes (53% Black and 47% White). For type 1 diabetes, six trajectory classes emerged. Black youth were more likely to be in the class with worsening glycemic control and concurrent BMIZ decrease at pandemic onset (relative risk ratio [RRR] vs. White: 3.0 [95% CI 1.3-6.8]) or in the class with progressively worsening glycemic control and obesity (RRR 3.0 [95% CI 1.3-6.8]), while those from the most deprived neighborhoods (RRR ADI tertile 3 vs. 1: 1.9 [95% CI 1.2-2.9]) were more likely to be in the class with stable obesity and glycemic control. For type 2 diabetes, three distinct trajectories emerged, two of which experienced worsening glycemic control with concurrent BMIZ decline at pandemic onset. CONCLUSIONS: Race and neighborhood deprivation were independently associated with distinct glycemic and BMIZ trajectory classes in youth with diabetes, highlighting persistent and widening disparities associated with the COVID-19 pandemic.