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Objectives: Hybrid closed-loop (HCL) systems improve glycemic control in type 1 diabetes mellitus (T1D), but their effectiveness in young, poorly controlled populations is not established and requires study., Methods: A pre-post study was performed using electronic health records of patients 3-24 years with baseline HbA 1c ≥9 % prescribed HCL within the New York City Health+Hospitals System assessing HbA 1c levels and hospitalizations before and after HCL initiation and factors associated with achieving HbA 1c <9 % after HCL initiation., Results: Of 47 children and adolescents who met inclusion criteria, 4.68 % female, 95.72 % non-White, and 82.22 % covered by public insurance, with a baseline average HbA 1c  10.6 % (2.28 IQR). The most prevalent pump type was Omnipod 5 (70.21 %). The HbA 1c was significantly lower in the postperiod than baseline (HbA 1c before=median 10.6 (IQR2.28), HbA 1c after=median 9.33 (IQR 2.97), difference 1.00 (IQR 1.64), p<0.05) with a decrease in median diabetes-related hospitalizations (preperiod 1.00 (IQR 1.00), postperiod 0.00 (IQR 1.00), difference -1.00, IQR 2, p<0.05). Lower baseline HbA 1c levels made reaching HbA 1c <9 % more likely. Multivariable analysis showed that the odds of having HbA 1c of <9 % was 2.1 times less likely for every one point increase in baseline HbA 1c and 12.5 times less likely for those with a pump at (p<0.05)., Conclusions: HCL therapy improved glycemic control and decreased diabetes-related hospitalizations in youth with poorly controlled T1DM. Higher baseline HbA 1c levels predicted less success with HCL therapy so those who stand to benefit most benefit least., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Obesity is prevalent among children and adults. Yet, understanding the relationship between parent and child weight trajectories is limited., Objective: (1) Examine the association between parent/child undesirable body mass index (BMI) category change. (2) Assess whether parental BMI category predicts child modified BMI z-score (mBMIz) annual change., Methods: We conducted a cross-sectional study of weight trajectories of 3821 parent-child dyads between March 2020 and December 2021 within the NYC Health + Hospitals system. Undesirability of child and parental BMI category change and the magnitude of mBMIz change by parental BMI are analysed., Results: Of 3821 children (mean [SD] baseline age, 9.84 [3.51]), 1889 were female. Of the 3220 parents (mean [SD] baseline age, 39.9 [8.51]), 2988 were female. Most children (53.52%) and parents (81.94%) presented with overweight and obesity. Undesirable BMI change in children was associated with concordant change in parents (adjusted OR: 1.7, 95% CI [1.45, 2.01], adjusted p < 0.001). Children of parents with obesity (adjusted coef: 0.076, 95% CI [0.004, 0.147], p < 0.038) and severe obesity (adjusted coef: 0.1317, 95% CI [0.024, 0.239], adjusted p < 0.016) demonstrated greater change in mBMIz than those of parents with normal weight or underweight., Conclusion: Parents and children have concordant weight trajectories, and public health interventions targeting both populations are essential., (© 2024 World Obesity Federation.)

Childhood obesity is highly prevalent among certain populations of New York. This cross-sectional pilot study examined the associations between parental attitudes about outdoor activities and body mass index (BMI). A questionnaire was distributed among parents of 1 to 13 aged children at ambulatory pediatric clinics. Of 104 children included in the study 57 were of normal weight and 47 were overweight or obese. Most parents of children with BMI <85% reported frequent playground utilization, considered longer hours to spend outside on weekdays, reported a larger total temperature range for outdoor playground utilization and a lower tolerable minimum temperature compared to parents of children with BMI ≥85%, p < .05. Only having a parent born outside of the United States remained a significant predictor of overweight and obesity in the final model. Parents of children with BMI < 85% are more willing to spend time outdoors, regardless of weather. Immigrant parents are protective against overweight., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The authors have no conflicts of interest to declare. They did not get any support for the present manuscript, grants or contracts from any entity, royalties or licenses, consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, payment for expert testimony, and support for attending meetings and/or travel. There are no patents planned, issued, or pending. They did not participate on a Data Safety Monitoring Board or Advisory Board. They do not have leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, stock or stock options, receipt of equipment, materials, drugs, medical writing, gifts or other services, other financial, or nonfinancial interests.

Following reports of increased new-onset diabetes and worse severity of DKA for children with diabetes following SARS-CoV-2 infection, we studied hospitalization rates for children with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in our center during the citywide shutdown. Methods . We conducted a retrospective chart review of children admitted to our two hospitals from January 1, 2018, to December 31, 2020. We included ICD-10 codes for diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar syndrome (HHS), and hyperglycemia only. Results . We included 132 patients with 214 hospitalizations: 157 T1DM, 41 T2DM, and 16 others (14 steroid induced, 2 MODY). Overall admissions rates for patients with all types of diabetes were 3.08% in 2018 to 3.54% in 2019 ( p = 0.0120) and 4.73% in 2020 ( p = 0.0772). Although there was no increase of T1DM admissions across all 3 years, T2DM admission rates increased from 0.29% to 1.47% ( p = 0.0056). Newly diagnosed T1DM rates increased from 0.34% in 2018 to 1.28% ( p = 0.002) in 2020, and new-onset T2DM rates also increased from 0.14% in 2018 to 0.9% in 2020 ( p = 0.0012). Rates of new-onset diabetes presenting with DKA increased from 0.24% in 2018 to 0.96% in 2020 ( p = 0.0014). HHS increased from 0.1% in 2018 to 0.45% in 2020 ( p = 0.044). The severity of DKA in newly diagnosed was unaffected ( p = 0.1582). Only 3 patients tested positive for SARS-CoV-2 infection by PCR. Conclusion . Our urban medical center is located in Central Brooklyn and serves a majority who are Black. This is the first study investigating pediatric diabetes cases admitted to Brooklyn during the first wave of the pandemic. Despite the overall pediatric admissions declining in 2020 due to the citywide shutdown, overall hospitalization rates in children with T2DM and in new-onset T1DM and T2DM increased, which is not directly associated with active SARS-CoV-2 infection. More studies are needed to elucidate the reason for this observed increase in hospitalization rates., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Assia Miller et al.)

Objectives: Determine whether the negative impact of the COVID-19 pandemic on weight gain trajectories among children attending well-child visits in New York City persisted after the public health restrictions were reduced., Study Design: Multicenter retrospective chart review study of 7150 children aged 3-19 years seen for well-child care between 1 January 2018 and 4 December 2021 in the NYC Health and Hospitals system. Primary outcome was the difference in annual change of modified body mass index z-score (mBMIz) between the pre-pandemic and early- and late-pandemic periods. The mBMIz allows for tracking of a greater range of BMI values than the traditional BMI z-score. The secondary outcome was odds of overweight, obesity, or severe obesity. Multivariable analyses were conducted with each outcome as the dependent variable, and year, age category, sex, race/ethnicity, insurance status, NYC borough, and baseline weight category as independent variables., Results: The difference in annual mBMIz change for pre-pandemic to early-pandemic = 0.18 (95% confidence interval [CI]: 0.15, 0.20) and for pre-pandemic to late-pandemic = 0.04 (95% CI: 0.01, 0.06). There was a statistically significant interaction between period and baseline weight category. Those with severe obesity at baseline had the greatest mBMIz increase during both pandemic periods and those with underweight at baseline had the lowest mBMIz increase during both pandemic periods., Conclusion: In NYC, the worsening mBMIz trajectories for children associated with COVID-19 restrictions did not reverse by 2021. Decisions about continuing restrictions, such as school closures, should carefully weigh the negative health impact of these policies., (© 2022 World Obesity Federation.)

Context: Disorders of sex development (DSD) are clinical conditions where there is a discrepancy between the chromosomal sex and the phenotypic (gonadal or genital) sex of an individual. Such conditions can be stressful for patients and their families and have historically been difficult to diagnose, especially at the genetic level. In particular, for cases of 46,XY gonadal dysgenesis, once variants in SRY and NR5A1 have been ruled out, there are few other single gene tests available., Objective: We used exome sequencing followed by analysis with a list of all known human DSD-associated genes to investigate the underlying genetic etiology of 46,XY DSD patients who had not previously received a genetic diagnosis., Design: Samples were either submitted to the research laboratory or submitted as clinical samples to the UCLA Clinical Genomic Center. Sequencing data were filtered using a list of genes known to be involved in DSD., Results: We were able to identify a likely genetic diagnosis in more than a third of cases, including 22.5% with a pathogenic finding, an additional 12.5% with likely pathogenic findings, and 15% with variants of unknown clinical significance., Conclusions: Early identification of the genetic cause of a DSD will in many cases streamline and direct the clinical management of the patient, with more focused endocrine and imaging studies and better-informed surgical decisions. Exome sequencing proved an efficient method toward such a goal in 46,XY DSD patients.

Background: Receptor activator of nuclear factor-κB ligand (RANKL) inhibitors are being considered for use in children with osteogenesis imperfecta (OI). We sought to assess efficacy of two doses of a RANKL inhibitor, osteoprotegerin-immunoglobulin Fc segment complex (OPG-Fc), in a growing animal model of OI, the col1α2-deficient mouse (oim/oim) and its wild-type controls (+/+)., Methods: Treated mice showed runting and radiographic evidence of osteopetrosis with either high- (20 mg/kg twice weekly) or low-dose (1 mg/kg/week) OPG-Fc. Because of this adverse event, OPG-Fc treatment was halted, and the mice were killed or monitored for recovery with monthly radiographs and assessment of serum osteoclast activity (tartrate-resistant acid phosphatase 5b, TRACP-5b) until 25 wk of age., Results: Twelve weeks of OPG-Fc treatment resulted in radiographic and histologic osteopetrosis with no evidence of bone modeling and negative tartrate-resistant acid phosphatase staining, root dentin abnormalities, and TRACP-5b activity suppression. Signs of recovery appeared 4-8 wk post-treatment., Conclusion: Both high- and low-dose OPG-Fc treatment resulted in osteopetrotic changes in infant mice, an outcome that was not seen in studies with the RANKL inhibitor RANK-immunoglobulin Fc segment complex (RANK-Fc) or in studies with older animals. Further investigations of RANKL inhibitors are necessary before their consideration for use in children.

Recently, a new class of agents targeting the receptor activator of nuclear factor-kappaB ligand (RANKL) pathway has been developed for the treatment of osteoporosis and other bone diseases. In the current study, inhibition of the RANKL pathway was evaluated to assess effects on "bone quality" and fracture incidence in an animal model of osteogenesis imperfect (OI), the oim/oim mouse. Juvenile oim/oim ( approximately 6 weeks old) and wildtype (+/+) mice were treated with either a RANKL inhibitor (RANK-Fc) or saline. After treatment, bone density increased significantly in the femurs of both genotypes. Femoral length decreased with RANK-Fc in +/+ mice. Geometric measurements at mid-diaphysis in the oim/oim groups showed increases in the ML periosteal and endosteal diameters and AP cortical thickness in the treated groups. Within +/+ groups, ML cortical thickness and ML femoral periosteal diameter were significantly increased with RANK-Fc. Biomechanical testing revealed increased stiffness in oim/oim and +/+ mice. Total strain was increased with treatment in the +/+ mice. Histologically, RANKL inhibition resulted in retained growth plate cartilage in both genotypes. The average number of fractures sustained by RANK-Fc-treated oim/oim mice was not significantly decreased compared to saline treated oim/oim mice. This preclinical study demonstrated that RANKL inhibition at the current dose improved density and some geometric and biomechanical properties of oim/oim bone, but it did not decrease fracture incidence. Further studies that address commencement of therapy at earlier time points are needed to determine whether this mode of therapy will be clinically useful in OI.

We report an 8 year-old girl with well-controlled perinatally acquired HIV infection who developed autoimmune type 1 diabetes mellitus (DM1A) confirmed by the presence of diabetes-related auto-antibodies. Although non-autoimmune insulin dependent diabetes mellitus (DM1B) and more frequently type 2 DM has been reported in patients affected with HIV, this is the first report of DM1A diagnosed in an HIV positive patient.

The role of target interactions in the development and functional maturation of peripheral neurons was investigated using an immortalized sympathetic precursor cell line. bMAH cells underwent neuronal differentiation in response to neurotrophic factors, but maintained an immature neuronal phenotype characterized by small cell bodies and continued cell division. Co-culture with cardiac myocytes, a target of sympathetic innervation, promoted the appearance of large-diameter postmitotic bMAH neurons. Analysis of bMAH maturation in the presence and absence of co-cultured myocytes indicated that myocyte-derived factors promoted the survival of maturing bMAH neurons prior to their acquisition of nerve growth factor dependence. Myocyte interactions also promoted the functional maturation of bMAH neurons, leading to an increase in the localization of synaptic vesicle proteins into neuritic varicosities and the acquisition of sympathetic-like intrinsic electrical properties. Like primary sympathetic neurons, mature bMAH neurons formed functional connections to cardiac myocytes as measured by evoked postsynaptic responses in connected myocytes. The effects of myocyte co-culture on developing bMAH neurons could be mimicked by myocyte conditioned medium, indicating that cardiac myocytes produce soluble factors that promote the appearance of mature neurons. These experiments indicate that targets of innervation play a role in directing the development and final maturation of peripheral neurons., (Copyright 2001 S. Karger AG, Basel)