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Type 2 diabetes (T2D) prevalence in the 10- to 19-year-old population has doubled over the past two decades in the United States.[1] It is present in nearly 2 persons per 1000 among Black and American Indian youth, in about 1 per 1000 among Hispanic youth, but in 0.2 per 1000 among non-Hispanic white youth, the incidence of T2D has similarly doubled among adolescents in the United States over this period, from 9 to 18 cases per 100 000 per year, with incidence again particularly high in Black and American Indian youth.[2] The incidence of type 1 diabetes (T1D) in the United States also increased, from 20 to 22 per 100 000 persons age <20 during the same period,[2] and its prevalence increased from 1.5 to 2.2 per 1000,[1] with a different racial and ethnic composition, more common in non-Hispanic white, then Black, then Hispanic, then Asian and then American Indian. Trends in incidence of youth-onset type 1 and type 2 diabetes in the USA, 2002-18: results from the population-based SEARCH for Diabetes in Youth study. Trends in prevalence of type 1 and type 2 diabetes in children and adolescents in the US, 2001-2017. [Extracted from the article]

Duncan et al. reviewed the response to growth hormone stimulation testing after priming in peripubertal children. The concern is that there is little research documenting the response to growth hormone treatment in patients with sex hormone primed growth hormone stimulation testing and those unprimed. The controversy about priming or not can be summarized as follows: if one wants to know if the production of growth hormone during puberty will be adequate in terms of peak growth hormone responses then stimulation with priming should be done. [ABSTRACT FROM AUTHOR]

Multivariable logistic regression was used to assess associations between previous SARS- CoV-2 infection and islet autoimmunity In Colorado, out of 4717 children, 32.3% (1524) had prior SARS-CoV-2 infection (median age, 8.6 years; 50.3% female). The prevalence of multiple or single high-affinity islet autoantibodies did not significantly differ between children with or without previous SARS-CoV-2 infection in Colorado (1.18% vs. 0.91%, I p i = .43) or Bavaria (0.42% vs. 0.41%, I p i = .88). Among 1524 children in Colorado, multiple islet autoantibodies for T1DM were detected in 21(0.45%) children and 26 (0.55%) children had a single islet autoantibody. [Extracted from the article]

Cerebral edema (CE) is a potentially devastating complication of diabetic ketoacidosis (DKA) that almost exclusively occurs in children. Since its first description in 1936, numerous risk factors have been identified; however, there continues to be uncertainty concerning the mechanisms that lead to its development. Currently, the most widely accepted hypothesis posits that CE occurs as a result of ischemia–reperfusion injury, with inflammation and impaired cerebrovascular autoregulation contributing to its pathogenesis. The role of specific aspects of DKA treatment in the development of CE continues to be controversial. This review critically examines the literature on the pathophysiology of CE and attempts to categorize the findings by types of brain injury that contribute to its development: cytotoxic, vasogenic, and osmotic. Utilizing this scheme, we propose a multifactorial pathway for the development of CE in patients with DKA. [ABSTRACT FROM AUTHOR]

Greig F, Rapaport R, Klein G, Akler G, Annunziato R, Miloh T, Arnon R, Florman S, Kerkar N. Characteristics of diabetes after pediatric liver transplant. Abstract: Studies of DALT in pediatric recipients describe incidence and risk factors, but diagnostic criteria varied. This study reports characteristics and course of pediatric DALT by established diabetes criteria. Retrospective chart review of pediatric LT recipients evaluated for hyperglycemia (1/1/1997-12/30/2009) and matched, non-diabetic controls. DALT: random blood glucose >11.1 m m, ≥2 times, with insulin treatment. DALT diagnosed in 8.0% (24/300) included 7/24 (29.2%) with severe hyperglycemia (>27.7 m m), ketoacidosis in 2/24 (8.3%). At diagnosis, age was ≥11 yr old in 22/24 (91.7%); body mass was lean (BMIz −0.2 ± 1.5). Mean blood glucose was 24.6 m m with negative diabetes autoantibodies (19/19) and elevated C-peptide (2.3 n m). DALT onset median 5.0 months included 29.1% >12 months. Insulin duration median 4.6 months included 41.7% >6 months. DALT resolved in 83.3% over 4.9 (0.9-9.1) yr. DALT differed from controls by increased preceding rejections, prednisolone dose, tacrolimus level, and triple immunosuppression (all p < 0.01). In conclusion, pediatric DALT occurred in non-obese adolescents with insulin resistance, distinct from diabetes types 1 or 2. DALT was associated with preceding rejection and increased immunosuppression. Blood glucose monitoring, especially during increased immunosuppression following LT, could allow early diagnosis and reduce morbidity. [ABSTRACT FROM AUTHOR]

This article explores the basic development and pathophysiology of the thyroid gland. New factors in the normal development of the thyroid in the neonate are mentioned. The incidence of congenital hypothyroidism continues to increase. We describe congenital hypothyroidism, its possible etiologies, treatment and outcomes. We explore hypothyroxinanemia in pre-term neonates and the risk/benefit of prophylactic thyroid hormone replacement. We discuss the late rise of thyrotropin (TSH) in ill infants and those with very low birth weight. Ill infants or those born premature should have their thyroid function tests routinely monitored. On the occasion of borderline thyroid function test results, TRH testing can be useful in identifying those infants with either persistent or transient hypothyroidism. TRH testing is also helpful in identifying those patients with secondary hypothyroidism. With the early identification and prompt and proper treatment, neonates with congenital hypothyroidism, transient or persistent, should have positive long-term outcomes. [ABSTRACT FROM AUTHOR]

Ojective: To examine whether age at diagnosis and gender affect early metabolic control in children with type 1 diabetes. Design and methods: Data on age at diagnosis, gender, pubertal status, and metabolic control were gathered by a retrospective chart review of children diagnosed between 1992 and 2005. Mean hemoglobin A1c (HbA1c) values were compared at five time points: at diagnosis and at 6, 12, 24, and 36 months after diagnosis. Results: At diagnosis, girls aged 6–12 years presented with significantly higher HbA1c levels than girls diagnosed at older or younger ages. Their HbA1c at diagnosis was also significantly higher than that in boys of the same age. There was no gender difference among children diagnosed at ages 0–5 or 13+ yr. At 6 months after diagnosis, only age at diagnosis was associated with metabolic control, with children diagnosed when older presenting with lower HbA1c levels. At 12, 24, and 36 months after diagnosis, there were no significant effects of age at diagnosis or gender on glycemic status. Conclusion: At initial diagnosis, girls in the 6–12 age group presented with higher HbA1c levels compared with boys and girls of other age groups. Although endocrine changes associated with puberty may partly explain the findings, more investigation to elucidate mechanisms accounting for the interaction of age and gender with glycemic status is needed. [ABSTRACT FROM AUTHOR]

Unlabelled: Although most children born small for gestational age catch up in growth by age 2 y, up to 14% remain more than 2 standard deviations below the mean for height. Recombinant growth hormone is approved by the US Food and Drug Administration and by the European Agency for Evaluation of Medicinal Products for the treatment of children born small for gestational age who fail to manifest catch-up growth by 2 y or 4 y, respectively.Conclusion: We conclude from clinical studies that growth hormone therapy can induce catch-up growth in these children. [ABSTRACT FROM AUTHOR]

The germ theory of disease was first described after the 16th century and further propagated by pioneers such as Lister, Koch, Pasteur, and Metchnikoff. One mouse study showed a marked reduction in T1D in offspring whose mothers (with non-obese diabetes) exclusively consumed a gluten-free diet during pregnancy compared with those mothers who had gluten intake.[4] Diabetic ketoacidosis (DKA) is a dreaded and common acute complication of T1D in children. [Extracted from the article]

The author comments on the article "Are Short Boys with Constitutional Delay of Growth and Puberty Candidates for rGH Therapy according to the FDA Recommendations?," by Krajewska-Siuda and colleagues. He cites flaws in the paper, but concludes that the study confirms the limitations of existing methods of height prediction while highlighting the growing debate of growth hormone (GH) treatment for idiopathic short stature (ISS).

The T1D Exchange Quality Improvement Collaborative (T1DX-QI) is a network of over 55 diabetes centers that aims to improve diabetes care and outcomes for individuals with type 1 diabetes (T1D). The network focuses on refining best practices, emphasizing quality of care, and using real-world data to drive improvements. The November 2023 conference highlighted various topics, including psychosocial aspects of care and improving technology advancement and access. The abstracts presented at the conference covered a range of subjects, such as screening for eating disorders and anxiety, implementing social determinants of health screening, identifying barriers to technology use, and exploring remote patient monitoring. The T1DX-QI Collaborative continues to work towards improving overall health outcomes, reducing complications, and closing health equity gaps for people living with T1D. [Extracted from the article]

No abstract available [ABSTRACT FROM AUTHOR]

Keywords: liraglutide; mindfulness and T2D; pediatric diabetes; pediatric type 2 diabetes mellitus; T2D; uric acid and T2D Higher baseline SUA increased the risk of incident hypertension (hazard ratio [HR] 1.19; 95% CI, 1.03-1.38, per 1 mg/dL increase in SUA) and elevated UAE (HR 1.24; 95% CI, 1.03-1.48) in adjusted models. SUA could be a potential marker to be used for screening in identifying youth with T2D at risk for hypertension and renal disease. Liraglutide, mindfulness and T2D, pediatric diabetes, pediatric type 2 diabetes mellitus, T2D, uric acid and T2D. [Extracted from the article]

Two male patients, who presented at 13.5 and 13.9 years of age with growth failure and short stature, were ultimately diagnosed with isolated growth hormone deficiency (GHD). Patient 1 was first evaluated when his height declined from −0.67 SD to −1.3 SD. He had a peak growth hormone (GH) concentration to GH stimulation test (GHST) of 16.9 ng/mL (16.9 μg/L) and remained untreated. As puberty advanced, his height decreased further to −1.65 SD. A second GHST while his serum testosterone was 79 ng/dL (2.74 nmol/L) had a peak GH of 5.4 ng/mL (5.4 μg/L), consistent with GHD. He was treated with GH for 4.8 years and reached adult height of 180.5 cm (0.57 SD), gaining 2.22 SDS. Patient 2, height −2.63 SD, had an unstimulated peak GH concentration of 19 ng/mL (19 μg/L). As puberty advanced, his height decreased further to −2.96 SD. Repeat peak GH concentration was 9.2 ng/mL (9.2 μg/L) when serum testosterone was 83.9 ng/dL (2.91 nmol/L). GH treatment resulted in rapid increase of height velocity from 1.8 cm/year to 11.3 cm/year in 6 months, consistent with GHD. Both patients demonstrate that GHD may develop over time and cannot be excluded by a single GHST. Longitudinal monitoring of children with poor growth as puberty progresses is essential to uncover GHD. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Idiopathic Short Stature," by M. M. Lee in the June 15, 2006 issue.

CD antibodies were first discovered between T1DM diagnosis and 5 years after diagnosis in only two-thirds of the patients leaving one-third to be diagnosed more than 5 years after DM diagnosis. Keywords: celiac disease; pediatrics; type 1 diabetes EN celiac disease pediatrics type 1 diabetes 525 526 2 05/04/21 20210601 NES 210601 Type 1 diabetes mellitus (T1DM) is known to be associated with celiac disease (CD) as well as other autoimmune conditions. [Extracted from the article]

Equity in Diabetes Care & Transformation: Implementation & Spread of social determinants of health screening in diabetes clinic. Towards risk-based Management of Type 1 diabetes (T1D): developing a population health dashboard based on performing diabetes self-management habits. Health equity, quality improvement, type 1 diabetes, learning health systems Keywords: health equity; learning health systems; quality improvement; type 1 diabetes EN health equity learning health systems quality improvement type 1 diabetes 780 782 3 12/01/22 20221101 NES 221101 INTRODUCTION The T1D Exchange Quality Improvement Collaborative (T1DX-QI) continues to be a leader in driving innovation advancements in type 1 diabetes (T1D) care.[1] With over 50 diabetes centers in its consortium across the United States, including 32 pediatric and 18 adult centers, T1DX-QI has been able to capture T1D electronic medical record data on over 55 000 people with T1D. [Extracted from the article]

A 12-yr-old boy initially presented with chronic urticaria. Autoimmune thyroid disease was then diagnosed during routine evaluation. He developed type 1 diabetes shortly after thyroid hormone replacement was initiated. This case emphasizes the importance of routine screening for other autoimmune disorders in patients in whom one disorder is already present. [ABSTRACT FROM AUTHOR]

Keywords: learning health systems; quality improvement; real world evidence; type 1 diabetes EN learning health systems quality improvement real world evidence type 1 diabetes 83 87 5 01/10/22 20220101 NES 220101 INTRODUCTION Since the discovery of insulin 100 years ago, there have been continual advances in medications and technologies for the management of type 1 diabetes (T1D). The sharing of data in the T1DX-QI database informs QI-based population health interventions to improve outcomes. QI, quality improvement; T1D, type 1 diabetes; T1DX-QI, T1D Exchange Quality Improvement Collaborative gl In this commentary, we describe the goals of the T1DX-QI and highlight QI and population health conference abstracts recently presented at the 2021 T1DX-QI conference. [Extracted from the article]

2020; 27 (6): 256 - 259. doi: 10.12788/jcom.0031 19 Alonso, GT, Rioles, N & Ebekozien, O. A population health data platform to improve outcomes in the T1D exchange quality improvement collaborative (T1DX-QI). GLO:55QH/01jan22:jdb13235-fig-0001.jpg PHOTO (COLOR): 1 Key driver diagram describing T1D exchange health equity program gl T1DX-QI APPROACHES TO ADDRESSING HEALTH INEQUITIES IN THE UNITED STATES Identify inequities with real-world EMR data The T1DX-QI uses its unique EMR database with de-identified data on over 35 000 people with T1D to perform population health analysis. Keywords: disparities; health equity; quality improvement; real-world evidence; solution; type 1 diabetes EN disparities health equity quality improvement real-world evidence solution type 1 diabetes 79 82 4 01/10/22 20220101 NES 220101 GLO:55QH/01jan22:jdb13235-toc-0001.jpg PHOTO (COLOR): . gl INTRODUCTION Approximately 1.6 million people in the United States have type 1 diabetes (T1D).1 The incidence of T1D is increasing in the United States across all populations, most significantly among Hispanic and non-Hispanic Black (NHB) patients.2,3 Unfortunately, widespread inequities exist in health outcomes among patients with T1D in the United States.4-7 In 2016, the T1D Exchange Quality Improvement Collaborative (T1DX-QI) was established.8 T1DX-QI is a learning health network9 with over 40 centers across the United States. [Extracted from the article]

Purpose: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche. Methods: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at <8 years old, measurable pubertal luteinizing hormone and/or estradiol concentrations, and bone age advancement. Indications to treat were advanced bone age and psychosocial concerns. Descriptive summaries were reported as frequency and proportion for categorical variables and mean and standard deviation for continuous measures. Linear regression models were developed to evaluate the associations of clinical factors with the time interval to menarche. Results: Mean age was 9.4±1.6 years at treatment onset, and treatment duration was 2.2±1.4 years. Menarche occurred at 12.6±1.1 years, which was 1.04±0.5 years after treatment discontinuation. This was negatively associated with Tanner stage of breast development and bone age at treatment onset and change in bone age during treatment. No association was seen between time interval to menarche and treatment duration, medication, or body mass index. Conclusion: We found the average time interval to menarche after GnRHa treatment in our population of female patients with CPP to be 1.04±0.5 years; this is in agreement with other reports. Tanner stage of breast development, bone age at treatment onset, and change in bone age were negatively associated with time interval to menarche. These data provide clinical correlates that assist providers during anticipatory guidance of patients with CPP after GnRHa treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: Studies are lacking regarding the timing of peak growth hormone (PGH) response. We aim to elucidate the timing of PGH response to arginine and levodopa (A-LD) and evaluate the influence of body mass index (BMI) and other metabolic parameters on PGH. Methods: During growth hormone (GH) stimulation testing (ST) with A-LD, serum GH was measured at baseline and every 30 min up to 180 min. The PGH cut-off was defined as <10 ng/mL. IGF-1, IGF BP3, BMI, and metabolic parameters were obtained in a fasting state at baseline. Results: In the 315 tested children, stimulated PGH levels occurred at or before 120 min in 97.8% and at 180 min in 2.2%. GH area under the curve (AUC) positively correlated with PGH in all patients and with IGF-1 in pubertal males and females. BMI negatively correlated with PGH in all subjects. GH AUC negatively correlated with HOMA-IR and total cholesterol. Conclusion: We propose termination of the GH ST with A-LD at 120 min since omission of GH measurement at 180 min did not alter the diagnosis of GH deficiency based on a cut-off of < 10 ng/mL. BMI should be considered in the interpretation of GH ST with A-LD. The relationships between GH AUC and metabolic parameters need further study. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; diabetes ketoacidosis; new diagnosis; type 1 diabetes mellitus EN COVID-19 diabetes ketoacidosis new diagnosis type 1 diabetes mellitus 270 272 3 02/03/21 20210301 NES 210301 GLO:55QH/01mar21:jdb13141-toc-0001.jpg PHOTO (COLOR): . gl B Highlights b Our multicenter study reports a higher proportion of diabetic ketoacidosis presentation of over 60% in newly diagnosed patients with type 1 diabetes with or without confirmed coronavirus disease 2019 (COVID-19) at diagnosis. A total of 71% of the patients with newly diagnosed T1D with positive COVID-19 testing were Hispanic and non-Hispanic Blacks, while 60% of the patients with newly diagnosed T1D and negative COVID-19 testing were White. 2 Abbreviations: COVID-19, coronavirus disease 2019; DKA, diabetic ketoacidosis; HbA1c, glycosylated hemoglobin; IQR, interquartile range; NH, non-Hispanic; SD, standard deviation; T1D, type 1 diabetes. [Extracted from the article]

Background: Papillary thyroid cancer (PTC) is an uncommon pediatric disease with an excellent prognosis. In follow-up surveillance, neck ultrasound (US), basal and thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) levels, and diagnostic whole-body radioactive iodine scans (DxWBS) have been traditionally used in both adults and children for the detection of recurrence or metastases of PTC. Methods: Two pediatric patients with metastatic PTC were followed after standard ablative treatment with routine neck US and serum Tg levels, as well as periodic DxWBS. Results: Neck US identified recurrent and metastatic PTC which DxWBS failed to detect. Conclusion: Neck US was superior to DxWBS in the detection of recurrent PTC in these 2 pediatric patients. These findings are consistent with the 2015 American Thyroid Association (ATA) Guidelines that neck US is an ideal imaging modality in pediatric patients for the surveillance of PTC local recurrence or lymph node metastases. [ABSTRACT FROM AUTHOR]

The author argues against the term small for gestational age, describing newborns with lower-than-expected length, head circumference and/or weight.

Background Elevated levels of alanine aminotransferase ( ALT) are associated with obesity and are often a consequence of non-alcoholic fatty liver disease ( NAFLD). The aim of the present study was to assess the relationship between ALT and risk factors for adiposity-related co-morbidities in a diverse population of middle school children. Methods We measured height, weight, body fatness (bioelectrical impedance), waist circumference, insulin sensitivity, phase 1 insulin release (acute insulin response following intravenous glucose), beta-cell function (acute insulin response corrected for insulin sensitivity), ALT, lipid profiles, and circulating concentrations of interleukin-6 ( IL-6), C-reactive protein, adiponectin, and tumor necrosis factor-α ( TNF-α) in a multi-ethnic/racial population of 106 middle school students (aged 11-14 years, 45 female) of varying body mass indexes ( BMI). Results Alanine aminotransferase was significantly correlated with BMI, % body fat, fat mass, waist circumference, fasting insulin, insulin resistance, triglycerides, and was inversely correlated with high-density lipoprotein cholesterol in children, even though all values of ALT were 'normal' (range of 4.0-33.0 U/L). ALT was significantly higher in males than females even when corrected for body fatness. Significant correlations with lipids and insulin resistance persisted even when adjusted for age, gender, and body fatness. Conclusion Even within the normative range, ALT levels were significantly correlated with anthropomorphic and biochemical risk factors for adiposity-related co-morbidities in youth. Therefore, because ALT is correlated with dyslipidemia, insulin resistance, and central fat distribution, it might also serve as a marker of risk for adiposity-related co-morbidities beyond NAFLD. [ABSTRACT FROM AUTHOR]

Background/Aims: Growth hormone (GH) treatment regimens for children with non-GH-deficient, idiopathic short stature (ISS) have not been optimized. To compare the efficacy, efficiency, and safety of an individualized, target-driven GH regimen with standard weight-based dosing after 4 years of treatment. Methods: This is a 4-year, open-label, multicenter, randomized trial comparing individualized, formula-based dosing of Genotropin® versus a widely used ISS dose of Genotropin®. Subjects were prepubertal, had a bone age of 3-10 years for males and 3-9 years for females, were naive to GH treatment, and had a height standard deviation score (Ht SDS) of -3 to -2.25, a height velocity <25th percentile for their bone age, and peak stimulated GH >10 ng/ml. After the first 2 years, the individualized-dosing group was further randomized to either 0.18 or 0.24 mg/kg/week. Results: At 4 years, subjects in all treatment regimens achieved similar average height gains of +1.3 SDS; however, the individualized dosing regimen utilized less GH to achieve an equivalent height gain. Conclusion: Individualized, formula-based GH dosing, followed by a dose reduction after 2 years, provides a more cost-effective growth improvement in patients with ISS than currently employed weight-based regimens. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Controversy exists regarding the diagnosis and treatment of mild congenital hypothyroidism (MCH). We studied the value of 123I imaging in patients with MCH. Methods: Retrospective chart review of infants and children <4 years of age who underwent 123I imaging: group 1 = MCH [thyroid-stimulating hormone (TSH) <25 µIU/ml, normal free T4/T3], group 2 = severe congenital hypothyroidism (TSH ≥25 µIU/ml), and group 3 = MCH in infancy imaged after treatment withdrawal at age 3 years. Data collected included 4- and 24-hour 123I uptake, TSH, free T4/total T3 at imaging, age at imaging, and levothyroxine (L-T4) dose at 1 year of. Results: Thirty-six patients underwent 123I imaging. In group 1 (n = 20, median TSH: 8.49 µIU/ml), 85% had abnormal imaging consistent with dyshormonogenesis. Two patients were referred after 1 year of age. The median age at imaging for the remaining 18 patients was 54 days. Median L-T4 dose at 1 year of age for these 18 patients was 2.8 μg/kg, which is consistent with dyshormonogenesis. Ninety-one percent of group 2 (n = 11, median TSH: 428.03 µIU/ml) had abnormal imaging. The median age at imaging was 13 days. Four patients in group 3 had abnormal 123I imaging and restarted treatment. Conclusion:123I imaging is a valuable tool for evaluation, diagnosis, and treatment of MCH. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Context: Short stature homeobox-containing gene (SHOX) variants of unknown clinical significance occur frequently among children with short stature, yet their growth hormone (GH)/insulin-like growth factor-1 (IGF-1) status and response to GH have not been studied. Objective: To define GH and IGF-1 status in children with SHOX variants and assess their response to GH. Patients and Methods: This is a retrospective review of children with short stature. Children with SHOX variants were compared to those with no variants. Height standard deviation scores (SDS) and IGF-1 SDS at baseline and during GH treatment at 6, 12, and 24 months were analyzed. Growth velocity (GV), maximum GH dose, IGF-BP3, and changes in height SDS, IGF-1 SDS, and GV were compared. Results: Among 355 children, 83 (23%) had SHOX variants. Nineteen different SHOX variants were detected. There was no difference in age, height SDS, IGF-1 SDS, or IGF-BP3 between children with SHOX variants and those with normal SHOX. Height SDS, IGF-1 SDS, IGF-BP3, GV, and GH dose were not different between patients with SHOX variants and those without. Conclusions: The GH and IGF-1 characteristics of children with short stature were not different between children with SHOX+ variants and children with no variants. Although these findings suggest that SHOX variants are polymorphisms, studies prospectively comparing individual SHOX variants are needed. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Autism spectrum disorder (ASD) is now understood to have multiple genetic risk genes and one example is SHANK3. SHANK3 deletions and mutations disrupt synaptic function and result in Phelan-McDermid syndrome (PMS), which causes a monogenic form of ASD with a frequency of at least 0.5% of ASD cases. Recent evidence from preclinical studies with mouse and human neuronal models of SHANK3 deficiency suggest that insulin-like growth factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits. The objective of this study was to pilot IGF-1 treatment in children with PMS to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors. Methods Nine children with PMS aged 5 to 15 were enrolled in a placebo-controlled, double-blind, crossover design study, with 3 months of treatment with IGF-1 and 3 months of placebo in random order, separated by a 4-week wash-out period. Results Compared to the placebo phase, the IGF-1 phase was associated with significant improvement in both social impairment and restrictive behaviors, as measured by the Aberrant Behavior Checklist and the Repetitive Behavior Scale, respectively. IGF-1 was found to be well tolerated and there were no serious adverse events in any participants. Conclusions This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. Results also provide proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function. [ABSTRACT FROM AUTHOR]

Background The prevalence of obesity in U.S. has been rising at an alarming rate, particularly among Hispanic, African, and Asian minority groups. This trend is due in part to excessive calorie consumption and sedentary lifestyle. We sought to investigate whether parental origins influence eating behaviors in healthy urban middle school students. Methods A multiethnic/racial population of students (N = 182) enrolled in the ROAD (Reduce Obesity and Diabetes) Study, a school-based trial to assess clinical, behavioral, and biochemical risk factors for adiposity and its co-morbidities completed questionnaires regarding parental origins, length of US residency, and food behaviors and preferences. The primary behavioral questionnaire outcome variables were nutrition knowledge, attitude, intention and behavior, which were then related to anthropometric measures of waist circumference, BMI z-scores, and percent body fat. Two-way analysis of variance was used to evaluate the joint effects of number of parents born in the U.S. and ethnicity on food preference and knowledge score. The Tukey-Kramer method was used to compute pairwise comparisons to determine where differences lie. Analysis of covariance (ANCOVA) was used to analyze the joint effects of number of parents born in the US and student ethnicity, along with the interaction term, on each adiposity measure outcome. Pearson correlation coefficients were used to examine the relationships between maternal and paternal length of residency in the US with measures of adiposity, food preference and food knowledge. Results African Americans had significantly higher BMI, waist circumference and body fat percentage compared to other racial and ethnic groups. Neither ethnicity/race nor parental origins had an impact on nutrition behavior. Mothers' length of US residency positively correlated with students' nutrition knowledge, but not food attitude, intention or behavior. Conclusions Adiposity measures in children differ according to ethnicity and race. In contrast, food behaviors in this middle school sample were not influenced by parental origins. Longer maternal US residency benefited offspring in terms of nutrition knowledge only. We suggest that interventions to prevent obesity begin in early childhood. [ABSTRACT FROM AUTHOR]

Greig F, Hyman S, Wallach E, Hildebrandt T, Rapaport R. Which obese youth are at increased risk for type 2 diabetes? Latent class analysis and comparison with diabetic youth. Purpose: Most obese youth screened for diabetes have normal fasting glucose levels. Identification of youth with increased risk for type 2 diabetes (T2D) is needed within this large population to guide further management. Methods: Retrospective chart review was performed for obese youth, 8-20 yr old, who met American Diabetes Association criteria for screening (OB) or had T2D (D). Measures included body mass index z-score (BMIz) and homeostasis model assessment of insulin resistance (HOMA-IR) by fasting plasma glucose (FPG) and insulin. Statistics compared OB with D and further examined OB by latent class analysis (LCA). Results: Normal FPG was found in 91.5% of all obese youth (OBt n = 94) Comparison of OB with normal FPG (OBng; n = 86) and D (n = 44) was significant for family history of T2D (p = 0.008) without other associations. Evaluation of OBng by LCA showed three classes with increasing BMIz and HOMA-IR. Class 3 (32.5%; BMIz 2.66 ± 0.38; HOMA-IR 6.72 ± 2.29) differed from classes 1 and 2 (p < 0.05), and was associated with family history of T2D. Conclusion: Currently recommended screening of obese youth by FPG is normal in 91.5%, but lacks further information to detect increased risk for youth-onset T2D. Evaluation of obese youth by LCA identified one third (class 3) in whom the combination of higher levels of BMIz, HOMA-IR, and family history suggests the greatest risk for T2D and targets them for further evaluation and intensive preventative management. [ABSTRACT FROM AUTHOR]

We sought to determine whether poor metabolic control during the early stages of Type 1 diabetes mellitus predicts control during subsequent years. We hypothesized that poor control in the first year after diagnosis would predict poor control in the following year, and that poor control in the second year after diagnosis would predict poor metabolic control in subsequent years. We conducted a retrospective review of a cohort of urban children treated for diabetes at our institution who were diagnosed between 1992 and 2005. We calculated odds ratios to determine whether control in Year 1 or in Year 2 predicted control in Years 3-6. Cox regression analyses were used to determine whether poor early control predicted progression to subsequent poor control. Metabolic control in the first year after diagnosis was not a good predictor of future control. However, poor metabolic control in the second year after diagnosis was highly predictive of poor control in subsequent years and predicted faster progression to poor control. The findings suggest that poor metabolic control in Year 2 may be a predictor of subsequent poor metabolic control. Targeting prevention interventions to reduce non-adherence and to enhance metabolic control to families that show poor metabolic control in Year 2 may prove to be an optimum investment in terms of improved medical outcomes and enhanced quality of life. [ABSTRACT FROM AUTHOR]

Context Low concentrations of serum LH and/or oestradiol (E2) in girls with early physical signs of precocious puberty pose a diagnostic challenge. Objective To assess the diagnostic value of the leuprolide stimulation test in female precocious puberty. Design Retrospective Chart Review. Setting Outpatient clinic. Patients and intervention Thirty-nine girls, 6·9 (1·4) years, with premature stage II–III breast development, with or without pubarche, underwent stimulation testing with subcutaneous leuprolide (20 μg/kg) with the following hormonal measurements in serum: FSH, LH, oestradiol at baseline; FSH and LH at 1 and 2 h; oestradiol at 24 h. Twelve girls with isolated pubarche were also tested with leuprolide. Main outcome measure A pubertal hormonal pattern was defined as at least one of the following: a baseline serum level of LH ≥ 0·3 U/l, a baseline oestradiol ≥ 37 pmol/l (10 ng/l), a stimulated (peak) LH ≥ 5·0 U/l, a stimulated oestradiol ≥ 184 pmol/l (50 ng/l) to leuprolide. The hormonal response was related to the clinical course during a period of observation of at least 6 months. Results Following leuprolide stimulation, the hormonal response was concordant with pubertal progression ( n = 23) or lack thereof ( n = 16) in all children. At baseline, pubertal serum concentrations of LH and/or oestradiol were associated with pubertal progression in all, while serum prepubertal LH and/or oestradiol concentrations were associated with pubertal progression in approximately 50% of the patients. Conclusions In girls with early clinical signs of precocious puberty and low serum concentrations of LH and oestradiol in random samples, the LH and oestradiol responses to leuprolide stimulation accurately predict pubertal progression. [ABSTRACT FROM AUTHOR]

Objective. Exposure to emotionally traumatic events is common among children who are treated in pediatric medical care settings, and it is important to recognize the emotional reactions that children might develop as a response to the trauma. Practitioners sometimes rely on parental reports of the child's emotional reactions, but these reports may be biased by the parent's own posttraumatic symptoms. Understanding the differences between parent and child reports of the child's emotional symptoms is essential to guide proper diagnosis and care. This study evaluated discrepancies in parental versus child reports of the child's emotional trauma symptoms in pediatric medical care settings. Methods. We enrolled children and adolescents (age: 8-19) who had not previously received a diagnosis of a psychiatric disorder and were treated in pediatric specialty care clinics at Mount Sinai Medical Center in New York. We used the UCLA posttraumatic stress reaction index, child, adolescent, and parent versions, to evaluate child and parent reports of symptoms of posttraumatic stress disorder (PTSD) in the child. The Impact of Event Scale was used to evaluate the parents' own posttraumatic symptoms. We conducted a "best estimate" psychiatric diagnostic procedure to determine whether the child met diagnostic criteria for PTSD and evaluated the association between the diagnostic status (as determined by the "best estimate" procedure) and the results of the questionnaires. Results. A total of 115 patients and parents consented to the study, and 76 completed the evaluation. Sixty-four percent of the parents identified the child's traumatic experience as their own most traumatic experience, too. The child's self-report of PTSD symptoms was significantly correlated with the diagnosis of PTSD in the child. In contrast, parents' reports of their child's PTSD symptoms were not significantly associated with the child's diagnosis. Parents' own posttraumatic symptoms were associated... [ABSTRACT FROM AUTHOR]

Little is known about the fate of autoreactive CD4 T cells in blood. Using a mouse model for spontaneous autoimmune diabetes we demonstrated that the status of the autoimmune process in pancreas could be pictured through the frequency and phenotype of autoreactive CD4 T cells in the blood. Early during the prediabetic stage, the frequency of these cells in blood decreased as a consequence of their recruitment in the pancreas. This was followed by an imbalance between CD4+CD25+ and CD4+CD69+ T cells in the pancreas that was mirrored in the phenotype of autoreactive T cells in the blood. Waves of activated CD4+CD69+ T cells in blood preceded the disease onset suggesting that the autoimmune attack on pancreas is a discontinuous “hit-and-run” rather than a continuous process. Tracking autoreactive CD4 T cells in blood may help in identifying prediabetic humans and monitoring the disease progression during therapeutic interventions. [Copyright &y& Elsevier]

Background: Hyperthyroidism has been associated with liver function abnormalities; however, cholestasis as the presenting feature of adolescent Graves' disease has not been previously reported. Patient Summary: The patient was a 17-year-old girl who presented with severe cholestasis and was found to have Graves' disease. She also had a positive hepatitis A immunoglobulin M antibody but her clinical course, the liver histopathology, and her mildly elevated transaminases indicated that the acute hepatitis A infection was not dominant at the time of presentation with severe cholestasis. Other causes of cholestasis, including congestive heart failure, autoimmune hepatitis, and viral infection, were excluded. Treatment with methimazole resolved the hyperthyroidism, and the cholestasis improved, as well. Conclusion: Severe cholestasis is a rare presenting feature of Graves' disease. With careful monitoring, methimazole can be used to treat the hyperthyroidism in the setting of cholestasis. [ABSTRACT FROM AUTHOR]

Background: Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero. Case presentation: A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal < 35). Cortisol response to cosyntropin on the 3rd day of life (DOL) was 10 mcg/ml; the subnormal cortisol response may have resulted from prematurity and the predelivery treatment with betamethasone. The elevation of several adrenal corticosteroids was not consistent with any specific enzymatic defect. Hydrocortisone and fludrocortisone were initiated at another hospital for suspected mild glucocorticoid and mineralocorticoid deficiencies. Genetic screening for adrenal and gonadal developmental defects performed when transferred to our care were normal. All medications were gradually discontinued over 5–8 months. Adrenal and testicular responses to cosyntropin and human chorionic gonadotropin (hCG) were normal at 8 months. Conclusions: We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies. [ABSTRACT FROM AUTHOR]

Introduction: Deterioration in glycemic control often occurs during adolescence in children with type 1 diabetes (T1D). Shared appointments have been shown to improve quality of life scores and treatment adherence in children with chronic illnesses. Objective: To examine the impact of combined individual visits and shared education appointments in adolescents with T1D on diabetes control, self-management, and diabetes related distress. Methods: Adolescents ages 11-19y with T1D for over 1y and poor control/adherence defined by HbA1C > 9%, 2 or more DKA episodes in the past year or 2 missed appointments were enrolled in a 6 month DKA prevention program consisting of monthly individual visits followed by an hour long shared education visit. HbA1C levels were obtained every 3 mo. Participants completed a diabetes distress score (DDS) and diabetes self-management questionnaire (DMSQ) prior to participation and at the 6th visit. Participants were followed for an additional 6 months after completion of the program. Those who attended 2 or more session were included in the analysis. Results: Ten adolescents (8 female, average age 13.9 y, diabetes duration from 1-11 y, average A1C 10.6% SD 2.0) were enrolled. None of the 10 participants had DKA during the program. There was no statistically significant change in A1C. No changes were noted in the DDS; however there was improvement in dietary control on DMSQ from 4.0 to 5.7 (p value 0.058). Six attended 5 or more of the sessions. Those 6 participants had a decrease in average A1C by 0.3% over 6 mo with no DKA episodes within 6 mo of completion. The 4 participants who attended 2-4 sessions had an increase in average A1C of 0.85% over the same period and 3 had DKA episodes within 6 mo after completion. Conclusions: Shared education visits may be a valuable approach to the care of adolescents with diabetes. No episodes of DKA and no significant changes in glycemic control were noted in 6 mo; however larger long-term studies are needed to explore whether continued shared visits can improve glycemic control. Disclosure: M. Wilkes: None. T. Murphy: None. A. Aluf: None. D. Sperber: None. A. Sherry: None. S. Sethuram: None. L. Choleva: None. R. Rapaport: None. [ABSTRACT FROM AUTHOR]

The article focuses on a study concerning the reproducibility of homeostatic model assessment of insulin resistance (HOMA-IR) measurements during evaluation of pediatric obese patients. The study examined the reproducibility of HOMA-IR made on two occasions in obese youth at risk for type 2 diabetes (T2D). It notes that the subjects were grouped by specified HOMA-IR levels. Results indicated that HOMA-IR for obese youth have the tendency to vary more as compared to those of obese adults.

The authors present case studies describing defects in the differentiation of male external genitalia in genetically male family members and amenorrhea in a genetically female family member. DNA-sequencing analysis revealed homozygous mutations of the luteinizing hormone (LH)-receptor gene in each kindred that impaired the function of the LH receptor and prevented it from transmitting the hormonal signal in the testes and ovaries of the affected patients.