Childhood Obesity and Cardiovascular Disease Risk.

PURPOSE OF REVIEW: The global epidemic of youth-onset obesity is tightly linked to the rising burden of cardiometabolic disease across the lifespan. While the link between childhood obesity and cardiovascular disease is established, this contemporary review summarizes recent and novel advances in this field that elucidate the mechanisms and impact of this public health issue. RECENT FINDINGS: The review highlights the emerging data supporting the relationship between childhood adverse events, social determinants of health, and systemic and institutional systems as etiological factors. We also provide updates on new screening and treatment approaches including updated nutrition and dietary guidelines and benchmarks for pediatric obesity screening, novel pharmacological agents for pediatric obesity and type 2 diabetes such as glucagon-like 1 peptide receptor agonists, and we discuss the long-term safety and efficacy data on surgical management of pediatric obesity. The global burden of pediatric obesity continues to rise and is associated with accelerated and early vascular aging especially in youth with obesity and type 2 diabetes. Socio-ecological determinants of risk mediate and moderate the relationship of childhood obesity with cardiometabolic disease. Recognizing the importance of neighborhood level influences as etiological factors in the development of cardiovascular disease is critical for designing effective policies and interventions. Novel surgical and pharmacological interventions are effective pediatric weight-loss interventions, but future research is needed to assess whether these agents, within a socio-ecological framework, will be associated with abatement of the pediatric obesity epidemic and related increased cardiovascular disease risk.

Cardiometabolic risk in young adults with Down syndrome.

Studies regarding cardiometabolic risk (CMR) for individuals with Down syndrome (DS) conflict. Our previous research in youth with DS, aged 10-20 years, found increased prevalence of dyslipidemia and prediabetes compared to matched peers without DS. Herein, we compare CMR in young adults with DS, aged 18-35 years, to a similar population-based sample from the 2001-2018 National Health and Nutrition Examination Survey (NHANES). The group with DS had higher NonHDL-C (mean DS 131.9 mg/dL; NHANES 126.1 p < 0.001), lower HDL-C (DS 47.5 mg/dL; NHANES 52.2 p < 0.001), higher LDL-C (DS 109.3 mg/dL; NHANES 105.4 p < 0.001), higher triglycerides (DS 102.9 mg/dL; NHANES 86.9 p < 0.001), but lower fasting glucose (DS 85.8 mg/dL; NHANES 95.2 p < 0.0001), lower HOMA-IR (DS 2.17; NHANES 2.24 p = 0.0006), lower systolic (DS 109.7 mmHg; NHANES 114.6 p < 0.0001) and lower diastolic (DS 60.9 mmHg; NHANES 67.8 p < 0.0001) blood pressures. There was relationship of higher HDL-C, triglycerides, glucose, systolic, and diastolic blood pressure with increasing BMI in the NHANES cohort which was dampened in the group with DS. These results indicate that more information is needed to guide clinicians in screening for CMR in individuals with DS.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Altered adipokines in obese adolescents: a cross-sectional and longitudinal analysis across the spectrum of glycemia.

Obesity and type 2 diabetes are rapidly increasing in the adolescent population. We sought to determine whether adipokines, specifically leptin, C1q/TNF-related proteins 1 (CTRP1) and CTRP9, and the hepatokine fibroblast growth factor 21 (FGF21), are associated with obesity and hyperglycemia in a cohort of lean and obese adolescents, across the spectrum of glycemia. In an observational, longitudinal study of lean and obese adolescents, we measured fasting laboratory tests, oral glucose tolerance tests, and adipokines including leptin, CTRP1, CTRP9, and FGF21. Participants completed baseline and 2-year follow-up study visits and were categorized as lean (LC, lean control; n = 30), obese normoglycemic (ONG; n = 61), and obese hyperglycemic (OHG; n = 31) adolescents at baseline and lean (n = 8), ONG (n = 18), and OHG (n = 4) at follow-up. Groups were compared using ANOVA and regression analysis, and linear mixed effects modeling was used to test for differences in adipokine levels across baseline and follow-up visits. Results showed that at baseline, leptin was higher in all obese groups (P < 0.001) compared with LC. FGF21 was higher in OHG participants compared with LC (P < 0.001) and ONG (P < 0.001) and positively associated with fasting glucose (P < 0.001), fasting insulin (P < 0.001), Homeostasis Model Assessment-Insulin Resistance Index (HOMA-IR; P < 0.001), and hemoglobin A1c (HbA1c; P = 0.01). CTRP1 was higher in OHG compared with ONG (P = 0.03). CTRP9 was not associated with obesity or hyperglycemia in this pediatric cohort. At 2 years, leptin decreased in ONG (P = 0.003) and FGF21 increased in OHG (P = 0.02), relative to lean controls. Altered adipokine levels are associated with the inflammatory milieu in obese youth with and without hyperglycemia. In adolescence, the novel adipokine CTRP1 was elevated with hyperglycemia, whereas CTRP9 was unchanged in this cohort.NEW & NOTEWORTHY Leptin is higher in obese adolescents and FGF21 is higher in obese hyperglycemic adolescents. The novel adipokine CTRP1 is higher in obese hyperglycemic adolescents, whereas CTRP9 was unchanged in this adolescent cohort.

Diabetes and cardiometabolic risk in South Asian youth: A review.

South Asians are at increased risk for developing type 2 diabetes and cardiovascular disease at lower body mass index compared to other ancestral groups. Many factors contribute to this increased risk, including genetics, maternal-fetal factors, diet, fitness, body composition, and unique pathophysiology. Increased cardiometabolic risk is also seen at younger ages in South Asian individuals as compared to their White counterparts. This risk persists in migrant communities outside of South Asia. With the growing prevalence of obesity, diabetes, and cardiovascular disease in the South Asian population, it is imperative that we had better understand the mechanisms underlying this increased risk and implement strategies to address this growing public health problem during childhood and adolescence.

Metformin improves blood glucose by increasing incretins independent of changes in gluconeogenesis in youth with type 2 diabetes.

AIMS/HYPOTHESIS: Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT). METHODS: This is a case-control observational study in youth with type 2 diabetes who were not on metformin (n = 18) compared with youth with NGT (n = 10) who were evaluated with a 2 day protocol. A 75 g OGTT was administered to measure intact glucagon-like 1 peptide (iGLP-1), gastric inhibitory polypeptide (GIP) and peptide YY (PYY). Insulinogenic index (IGI) and whole-body insulin sensitivity were calculated using glucose and insulin levels from the OGTT. Basal rates of gluconeogenesis (2H2O), glucose production ([6,6-2H2]glucose) and whole-body lipolysis ([2H5]glycerol) were measured after an overnight fast on study day 2. Youth with type 2 diabetes (n = 9) were subsequently evaluated with an identical 2 day protocol after 3 months on the metformin study. RESULTS: Compared with individuals with NGT, those with type 2 diabetes had higher fasting (7.8 ± 2.5 vs 5.1 ± 0.3 mmol/l, mean ± SD p = 0.002) and 2 h glucose concentrations (13.8 ± 4.5 vs 5.9 ± 0.9 mmol/l, p = 0.001), higher rates of absolute gluconeogenesis (10.0 ± 1.7 vs 7.2 ± 1.1 µmol [kg fat-free mass (FFM)]-1 min-1, p < 0.001) and whole-body lipolysis (5.2 ± 0.9 vs 4.0 ± 1.4 µmol kgFFM-1 min-1, p < 0.01), but lower fasting iGLP-1 concentrations (0.5 ± 0.5 vs 1.3 ± 0.7 pmol/l, p < 0.01). Metformin decreased 2 h glucose (pre metformin 11.4 ± 2.8 vs post metformin 9.9 ± 1.9 mmol/l, p = 0.04) and was associated with ~20-50% increase in IGI (median [25th-75th percentile] pre 1.39 [0.89-1.47] vs post 1.43 [0.88-2.70], p = 0.04), fasting iGLP-1 (pre 0.3 ± 0.2 vs post 1.0 ± 0.7 pmol/l, p = 0.02), 2 h iGLP (pre 0.4 ± 0.2 vs post 1.2 ± 0.9 pmol/l, p = 0.06), fasting PYY (pre 6.3 ± 2.2 vs post 10.5 ± 4.3 pmol/l, p < 0.01) and 2 h PYY (pre 6.6 ± 2.9 vs post 9.0 ± 4.0 pmol/l, p < 0.01). There was no change in BMI, insulin sensitivity or GIP concentrations pre vs post metformin. There were no differences pre vs post metformin in rates of glucose production (15.0 ± 3.9 vs 14.9 ± 2.2 µmol kgFFM-1 min-1, p = 0.84), absolute gluconeogenesis (9.9 ± 1.8 vs 9.7 ± 1.7 µmol kgFFM-1 min-1, p = 0.76) or whole-body lipolysis (5.0 ± 0.7 vs 5.3 ± 1.3 µmol kgFFM-1 min-1, p = 0.20). Post metformin iGLP-1 and PYY concentrations in youth with type 2 diabetes were comparable to levels in youth with NGT. CONCLUSIONS/INTERPRETATION: Overall, the improved postprandial blood glucose levels and increase in incretins observed in the absence of changes in insulin sensitivity and gluconeogenesis, support an enteroinsular mechanistic pathway in youth with type 2 diabetes treated with short-term metformin.

Cross-Sectional Study of Arterial Stiffness in Adolescents with Down Syndrome.

OBJECTIVES: To test whether youth with Down syndrome have aortic stiffness indices, as measured by pulse wave velocity (PWV), that differ from youth without Down syndrome and to compare reference-based age-adjusted (age-PWV-Z) and height-adjusted (Ht-PWV-Z) in youth with and without Down syndrome. STUDY DESIGN: Cross-sectional study of PWV in 129 adolescents with Down syndrome and 97 youth of comparable age, sex, race/ethnicity, and body mass index (BMI). PWV, age-PWV-Z, and Ht-PWV-Z were compared. Regression models were developed to test for associations with PWV. RESULTS: Youth with Down syndrome and controls were comparable in BMI-Z (1.4 [-1.5 to 2.8] vs 1.2 [-2.0 to 2.8], P = .57) but not Ht-Z (-2.3 [-4.7 to 0.8] vs 0.4 [-2.0 to 2.6], P < .0001). PWV (m/s, 5.0 [3.1-7.9] vs 5.0 [3.6-8.0], P = .5) and mean arterial pressure (MAP, mm Hg) (78 [61-102] vs 74 [64-97], P = .09) were not different between groups. In adjusted analyses confined to Down syndrome, PWV was associated only with BMI, but not age, black race, or MAP (R2 = 0.11). In contrast, BMI, age, black race, and MAP were all positively associated with and better explained PWV in controls (R2 = 0.50). PWV was not associated with height in youth with or without Down syndrome. Although age-PWV-Z was not different in Down syndrome (-0.36 [-2.93 to 3.49]) vs -0.15 [-2.32 to 3.22]), Ht-PWV-Z was greater in Down syndrome (0.32 [-2.28 to 4.07] vs -0.08 [-2.64 to 2.64], P = .002), and Ht-PWV-Z was greater than age-PWV-Z in Down syndrome (P < .0001). CONCLUSIONS: The lack of relationship of PWV, an independent predictor of adult cardiovascular events, with its traditional determinants including MAP suggests Down syndrome-specific phenomena may alter such relationships in this population. In youth with Down syndrome, Ht-adjusted PWV may overestimate aortic stiffness. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01821300.

Prevalence of unsuspected abnormal echocardiograms in adolescents with down syndrome.

The purpose of this article is to describe the prevalence of cardiac disease previously undiagnosed in healthy asymptomatic children and adolescents with Down syndrome (DS). Subjects with DS ages 10-20 years were recruited from two sites, the Children's Hospital of Philadelphia (Philadelphia, PA) and Children's National Health System (Washington, DC) for a cross-sectional study of body composition and cardiometabolic risk. Echocardiographic and clinical data were collected from patients enrolled in the parent study of cardiometabolic risk. Nine (6%) new cardiac diagnoses were identified out of 149 eligible patients. All new findings resulted in outpatient referrals to pediatric cardiology. Current guidelines recommend screening all newborns with DS for congenital heart disease. Older patients with DS may benefit from rescreening.

Relationships of Body Composition to Cardiac Structure and Function in Adolescents With Down Syndrome are Different than in Adolescents Without Down Syndrome.

Median survival in Down syndrome (DS) is 60 years, but cardiovascular disease risk and its markers such as left ventricular mass (LVM) have received limited attention. In youth, LVM is typically scaled to height2.7 as a surrogate for lean body mass (LBM), the strongest predictor of LVM, but whether this algorithm applies to DS, a condition which features short stature, is unknown. To examine the relationships of LVM and function with height, LBM, and moderate-to-vigorous physical activity(MVPA) in DS, DS youth aged 10-20 years, and age-, sex-, BMI-, race-matched nonDS controls underwent echocardiography for LVM, ejection fraction (EF), and left ventricular diastolic function (measured as E/E'); dual-energy X-ray absorptiometry (DXA)-measured LBM; accelerometry for MVPA. (DS vs. nonDS median [min-max]): DS had lower height (cm) (144.5 [116.7-170.3] vs. 163.3 [134.8-186.7]; p < 0.0001); LBM (kg) (33.48 [14.5-62.3] vs 41.8 [18.07-72.46], p < 0.0001); and LVM (g) (68.3 [32.1-135] vs 94.0 [43.9-164.6], p < 0.0001); similar EF (%) (65 [54-77] vs 64 [53-77], p = 0.59); and higher E/E' (8.41 [5.54-21.4] vs 5.81 [3.44-9.56], p < 0.0001). In height2.7-adjusted models, LVM was lower in DS (ß = - 7.7, p = 0.02). With adjustment for LBM, LVM was even lower in DS (ß = - 15.1, p < 0.0001), a finding not explained by MVPA. E/E' remained higher in DS after adjustment for age, height, HR, SBP, and BMI (ß = 2.6, p < 0.0001). DS was associated with stiffer left ventricles and lower LVM, the latter magnified with LBM adjustment. Scaling to height2.7, the traditional approach for assessing LVM in youth, may underestimate LVM differences in DS. Whether lower LVM and diastolic function are intrinsic to DS, pathologic, or protective remains unknown.Clinical Trial Registration: NCT01821300.

Cognitive Performance as Predictor and Outcome of Adolescent Bariatric Surgery: A Nonrandomized Pilot Study.

Objectives: Evidence in adults suggests that improvements in cognitive performance may follow weight loss resulting from bariatric surgery, and baseline cognitive performance may be associated with weight loss following surgery. This has not been evaluated in adolescents. Method: Participants were 38 adolescents of age 14-21 years composed of three groups: (1) 12 adolescents with severe obesity who received vertical sleeve gastrectomy during the study (VSG); (2) 14 adolescents with severe obesity who were wait-listed for VSG (WL); and (3) 12 healthy weight controls (HC). Participants completed testing of visual memory, verbal memory, and executive functioning at baseline (T1), which occurred presurgery for the VSG group, and approximately 4 months after baseline (T2). Body mass index (BMI) was assessed at T1, T2, and additionally at 6 months following VSG for the adolescents who received surgery. Results: Although there was evidence of greater improvement for the VSG as compared with WL and HC groups in visual and verbal memory, group differences did not reach significance and effect sizes were small (η2 < 0.01). There was a significant positive association between indices of baseline executive functioning and excess BMI loss at 6 months postsurgery. Conclusions: This small pilot study showed no significant differences by group in cognitive performance post-VSG. There was a significant association of baseline cognitive performance with weight loss outcomes. Given the very preliminary nature of these results in a small sample, future research should examine these relationships in a larger sample and evaluate mechanisms of these associations (e.g., insulin resistance, sleep, physical activity).

Caregiver-Reported Quality of Life in Youth with Down Syndrome.

OBJECTIVES: To describe caregiver-reported quality of life (QOL) in youth with Down syndrome (DS) and to examine the role of obesity on QOL. STUDY DESIGN: Caregivers of youth with and without DS aged 10 through 20 years completed questionnaires examining QOL (Pediatric Quality of Life Questionnaire) and weight-related QOL (Impact of Weight on Quality of Life - Kids). Age- and sex-specific z scores were generated for body mass index. Obesity was defined as a body mass index ≥95th percentile for age and sex. RESULTS: Caregiver-reported Total QOL, Physical Health, and Psychosocial Health summary scores were all lower in the DS group compared with the non-DS controls (P < .001). Social and School Functioning were also lower (P < .001), but Emotional Functioning did not differ between DS and non-DS groups (P = .31). Physical Functioning (P = .003) and Total scores (P = .03) differed between youth without DS with and without obesity, but no differences were reported between youth with DS with and without obesity. On the Impact of Weight on Quality of Life - Kids, caregivers of youth with DS reported greater Body Esteem (P = .020) and Social Life scores (P = .03) than caregivers of non-DS youth. Caregivers of youth with obesity, regardless of DS status, reported significantly lower weight-specific QOL scores than caregivers of youth without obesity. CONCLUSION: Caregivers reported lower QOL in youth with DS compared with youth without DS with the exception of emotional functioning. Obesity influences most domains of weight-related QOL in youth with and without DS; therefore, providers should address weight concerns in youth with obesity even in the presence of DS. CLINICAL TRIAL REGISTRATION: NCT01821300.

Body composition estimation using skinfolds in children with and without health conditions affecting growth and body composition.

BACKGROUND: Body composition prediction equations using skinfolds are useful alternatives to advanced techniques, but their utility across diverse paediatric populations is unknown. AIM: To evaluate published and new prediction equations across diverse samples of children with health conditions affecting growth and body composition. SUBJECTS AND METHODS: Anthropometric and dual-energy X-ray absorptiometry (DXA) body composition measures were obtained in children with Down syndrome (n = 59), Crohn disease (n = 128), steroid-sensitive nephrotic syndrome (n = 67) and a healthy reference group (n = 835). Published body composition equations were evaluated. New equations were developed for ages 3-21 years using the healthy reference sample and validated in other groups and national survey data. RESULTS: Fat mass (FM), fat-free mass (FFM) and percentage body fat (%BF) from published equations were highly correlated with DXA-derived measures (r = 0.71-0.98), but with poor agreement (mean difference = 2.4 kg, -1.9 kg and 6.3% for FM, FFM and %BF). New equations produced similar correlations (r = 0.85-1.0) with improved agreement for the reference group (0.2 kg, 0.4 kg and 0.0% for FM, FFM and %BF, respectively) and in sub-groups. CONCLUSIONS: New body composition prediction equations show excellent agreement with DXA and improve body composition estimation in healthy children and those with selected conditions affecting growth.

Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.

OBJECTIVE: Elevated rates of gluconeogenesis are an early pathogenic feature of youth-onset type 2 diabetes (Y-T2D), but targeted first-line therapies are suboptimal, especially in African American (AA) youth. We evaluated glucose-lowering mechanisms of metformin and liraglutide by measuring rates of gluconeogenesis and ß-cell function after therapy in AA Y-T2D. METHODS: In this parallel randomized clinical trial, 22 youth with Y-T2D-age 15.3 ± 2.1 years (mean ± SD), 68% female, body mass index (BMI) 40.1 ± 7.9 kg/m2, duration of diagnosis 1.8 ± 1.3 years-were randomized to metformin alone (Met) or metformin + liraglutide (Lira) (Met + Lira) and evaluated before and after 12 weeks. Stable isotope tracers were used to measure gluconeogenesis [2H2O] and glucose production [6,6-2H2]glucose after an overnight fast and during a continuous meal. ß-cell function (sigma) and whole-body insulin sensitivity (mSI) were assessed during a frequently sampled 2-hour oral glucose tolerance test. RESULTS: At baseline, gluconeogenesis, glucose production, and fasting and 2-hour glucose were comparable in both groups, though Met + Lira had higher hemoglobin A1C. Met + Lira had a greater decrease from baseline in fasting glucose (-2.0 ± 1.3 vs -0.6 ± 0.9 mmol/L, P = .008) and a greater increase in sigma (0.72 ± 0.68 vs -0.05 ± 0.71, P = .03). The change in fractional gluconeogenesis was similar between groups (Met + Lira: -0.36 ± 9.4 vs Met: 0.04 ± 12.3%, P = .9), and there were no changes in prandial gluconeogenesis or mSI. Increased glucose clearance in both groups was related to sigma (r = 0.63, P = .003) but not gluconeogenesis or mSI. CONCLUSION: Among Y-T2D, metformin with or without liraglutide improved glycemia but did not suppress high rates of gluconeogenesis. Novel therapies that will enhance ß-cell function and target the elevated rates of gluconeogenesis in Y-T2D are needed.

Approach to the Patient: Youth-Onset Type 2 Diabetes.

Youth-onset type 2 diabetes is a growing epidemic with a rising incidence worldwide. Although the pathogenesis and diagnosis of youth-onset type 2 diabetes are similar to adult-onset type 2 diabetes, youth-onset type 2 diabetes is unique, with greater insulin resistance, insulin hypersecretion, and faster progression of pancreatic beta cell function decline. Individuals with youth-onset type 2 diabetes also develop complications at higher rates within short periods of time compared to adults with type 2 diabetes or youth with type 1 diabetes. The highest prevalence and incidence of youth-onset type 2 diabetes in the United States is among youth from minoritized racial and ethnic groups. Risk factors include obesity, family history of type 2 diabetes, comorbid conditions and use of medications associated with insulin resistance and rapid weight gain, socioeconomic and environmental stressors, and birth history of small-for-gestational-age or pregnancy associated with gestational or pregestational diabetes. Patients with youth-onset type 2 diabetes should be treated using a multidisciplinary model with frequent clinic visits and emphasis on addressing of social and psychological barriers to care and glycemic control, as well as close monitoring for comorbidities and complications. Intensive health behavior therapy is an important component of treatment, in addition to medical management, both of which should be initiated at the diagnosis of type 2 diabetes. There are limited but growing pharmacologic treatment options, including metformin, insulin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors. Although long-term outcomes are not fully known, metabolic/bariatric surgery in youth with type 2 diabetes has led to improved cardiometabolic outcomes.

Diet Quality and Cardiometabolic Risk Factors in Adolescents with Down Syndrome.

BACKGROUND: Youth with Down syndrome (DS) have a high prevalence of obesity and dyslipidemia. Diet quality may influence cardiometabolic risk (CMR) in youth. OBJECTIVE: The aim of this secondary analysis was to investigate the relationship between diet quality (Healthy Eating Index [HEI-2015]) with CMR factors in youth with DS compared with age, sex, race, ethnicity, and body mass index percentile matched, typically developing controls. DESIGN: Adolescents (aged 10 to 20 years) with DS and controls of comparable age, sex, race, ethnicity, and body mass index percentile were recruited from 2012 to 2017 for a cross-sectional study from two large children's hospitals (Children's Hospital of Philadelphia and the Children's National Health System in Washington, DC). PARTICIPANTS AND SETTING: CMRs in 143 adolescents with DS were compared with 100 controls. Exclusion criteria consisted of major organ-system illnesses. MAIN OUTCOME MEASURES: The average of three 24-hour dietary recalls was used to calculate the HEI-2015. Anthropometrics, blood pressure, and fasting labs were collected. STATISTICAL ANALYSES PERFORMED: Group differences were tested using Wilcoxon rank-sum tests. Relationships of CMR factors with HEI-2015 score within DS and controls were tested using linear regression models adjusted for sex, age, race, and body mass index z score. RESULTS: Compared with controls (n = 100, median age = 14.8 years [interquartile range = 12.2 to 17.3 years]; 41% male; 24% African American; 65% with body mass index ≥85th percentile), adolescents with DS (n = 143, median age = 14.7 years [interquartile range = 11.4 to 17.4 years]; 44% male; 18% African American; 62% with body mass index ≥85th percentile) had higher scores (more aligned with dietary recommendations) for total HEI-2015 (DS: 52.7 [interquartile range = 46.8 to 58.6] vs controls: 45.1 [interquartile range = 39.5 to 55.0]; P < 0.0001). Youth with DS also had higher HEI-2015 component scores for fruits, greens/beans, dairy, refined grains, and saturated fats, but lower whole grains and sodium scores. Within the group with DS, total HEI-2015 was not significantly associated with CMR measures. Whereas HEI-2015 in the DS group was negatively associated with fasting glucose levels, the difference did not meet the set level of statistical significance (-0.14, 95% CI -0.29 to 0.00; P = 0.053). CONCLUSIONS: Adolescents in both the control and DS groups reported low-quality diets, although the DS group had HEI-2015 scores more closely aligned with recommendations. In the DS group, diet quality was not significantly associated with CMR factors. Although further research is needed, these results suggest that dyslipidemia in youth with DS may not be related to dietary intake.

Endocrine Health and Health Care Disparities in the Pediatric and Sexual and Gender Minority Populations: An Endocrine Society Scientific Statement.

Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.

Short-term use of CGM in youth onset type 2 diabetes is associated with behavioral modifications.

Background: Continuous glucose monitoring (CGM) is beneficial to glycemic control in youth with type 1 diabetes (T1D) and adults with type 2 diabetes (T2D); however, studies in youth with T2D are limited. Objective: Determine if 10-day trial CGM use in youth with T2D improves glycemic control and behavioral modifications. Methods: Youth with T2D > 3 months, on insulin, with no prior CGM use were enrolled. Staff placed CGM and provided education. Participants received 5-day and 10-day follow-up phone calls to review CGM data, behavioral modifications, and adjust insulin doses as needed. We compared 5-day to 10-day TIR, and baseline to 3-6 month HbA1c via paired t-test. Results: Participants (n=41) had median age of 16.2 y, were 61% female, 81% NH Black, median diabetes duration of 0.8 y, and baseline HbA1c of 10.3%. A majority had household income<$50,000 (81%) and parental education level of HS or less (73%). Average 5-day TIR 49% was similar to 10-day TIR 51% (p=0.62). There was no change in HbA1c after 3-6 months (10.2% v 10.3%, p=0.89). Nineteen participants completed full 10-day CGM use; of those, 84% wanted a CGM long-term. Adolescents reported behavioral changes including increased blood sugar checks, increased insulin administration and overall improved diabetes management. Conclusion: Although 10-day CGM use did not impact short-term or long-term glycemic control in youth with T2D, most participants reported behavioral changes and wanted to continue using CGM. Future studies with longer use of CGM may clarify the potential impact of CGM in youth with T2D.

Physical Activity in Youth with Down Syndrome and Its Relationship with Adiposity.

PURPOSE: The aims of this study are to (1) compare physical activity (PA) and sedentary activity (SA) in youth with and without Down syndrome (DS and non-DS) and examine the relationships of PA and SA with their traditional risk factors (age, sex, race, and body mass index Z score [BMI-Z]) and (2) explore the relationship of PA with visceral fat (VFAT) in both groups. METHODS: SenseWear accelerometry data from at least 2 weekdays and 1 weekend day were collected from youth with DS (N = 77) and non-DS (N = 57) youth. VFAT was measured by dual x-ray absorptiometry. RESULTS: In age-, sex-, race-, and BMI-Z-adjusted models, those with DS engaged in more minutes of light PA (LPA) ( p < 0.0001) and less SA ( p = 0.003) and trended toward fewer minutes of moderate-to-vigorous PA (MVPA) ( p = 0.08) than non-DS youth. No race or sex differences in MVPA were detected in those with DS, unlike non-DS. After additional adjustment for pubertal status, the relationship between MVPA and VFAT approached significance ( p = 0.06), whereas the relationships of LPA and SA with VFAT were maintained ( p ≤ 0.0001 for both). CONCLUSION: Youth with DS engage in more LPA compared with non-DS, which, in typically developing populations, can confer a more favorable weight status. Increasing the opportunity for youth with DS to engage in LPA as part of their activities of daily living may offer a viable strategy for achieving healthy weight when barriers restrict pursuit of more vigorous PA.

Prediabetic obese adolescents have a more atherogenic lipoprotein profile compared with normoglycemic obese peers.

OBJECTIVE: To compare lipoprotein profiles of prediabetic to normoglycemic obese adolescents. STUDY DESIGN: Cross-sectional study of 95 obese, pubertal adolescents (12-17 years), who underwent oral glucose tolerance test, lipid panel, and lipoprotein subclass particle analysis (nuclear magnetic resonance spectroscopy). Univariate and linear regression analyses compared prediabetic and normoglycemic groups. RESULTS: Of 95 obese adolescents enrolled in the study, 22.1% (n = 21) had prediabetes. They were similar to normoglycemic adolescents (n = 74) in age, race, body mass index, standard lipids, total low-density lipoprotein particles (LDL-P), and total high-density lipoprotein particles (HDL-P). However, prediabetics had higher concentrations of small LDL-P (714.0 ± 288.0 vs 537.7 ± 266.5 nmol/L, P = .01) and smaller LDL-P size (20.73 ± 0.41 vs 21.18 ± 0.65 nm, P = .003), than normoglycemic youth. Prediabetics had higher small HDL-P (18.5 ± 3.8 vs 16.6 ± 3.9 umol/L, P = .046), lower large HDL-P (4.49 ± 2.0 vs 6.32 ± 2.6 umol/L, P = .004), and smaller HDL-P size (8.73 ± 0.31 vs 9.01 ± 0.39 nm, P = .003). After adjusting for demographics, Tanner stage, and body mass index using multiple linear regression, all differences remained significant except for small HDL-P. After additional adjustment for Homeostasis Model Assessment-Insulin Resistance Index, only LDL-P size difference remained significant. CONCLUSION: Obese prediabetic adolescents have a significantly more atherogenic lipoprotein profile compared with obese normoglycemic peers. Prediabetic adolescents may benefit from more aggressive interventions to decrease future cardiovascular risk.