Gonadotropin-releasing hormone analogs treatment in girls with central precocious puberty and early fast puberty.

BACKGROUND: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for children with central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with CPP and early fast puberty (EFP). METHODS: This retrospective observational study included anthropometric, clinical and laboratory data retrieved from medical files of girls with CPP or EFP, treated with GnRHa and followed at a tertiary endocrine clinic during 2007-2021. RESULTS: For both CPP (n = 144) and EFP (n = 231) groups, mean height-SDS at GnRHa initiation and termination and at the last follow-up visit was greater than mid-parental height-SDS (P < 0.001). Only among girls with EFP, mean BMI-SDS was higher at treatment termination than initiation (P = 0.025). Median ages at menarche of the CPP and EFP groups were 11.8 and 12.0 years. Menstrual irregularities were reported in 20.3% of girls with CPP and in 18.7% of those with EFP. Adverse effects to treatment were reported in 3.5% and 3.9% of girls with CPP and EFP, respectively. CONCLUSIONS: In this large cohort, GnRHa treatment in girls with EFP was effective without significant adverse effects as in those with CPP. A randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty. IMPACT STATEMENT: Gonadotropin-releasing hormone analog (GnRHa) is the standard treatment for central precocious puberty (CPP). We assessed efficacy and safety of GnRHa treatment in girls with early fast puberty (EFP), characterized by pubertal signs between ages 8-9 years with fast pubertal signs advancement and accelerated growth and bone maturation and in girls with CPP. We found in this large cohort that GnRHa treatment in girls with EFP was effective and safe as in those with CPP. A prospective randomized controlled trial is required to examine the psychological impact of GnRHa treatment of variant early puberty.

Disordered eating behaviours in adolescents with type 1 diabetes can be influenced by their weight at diagnosis and rapid weight gain subsequently.

AIMS: To assess the prevalence and disease-related risk factors for disordered eating behaviours among adolescents with type 1 diabetes and also to search for risk factors at disease diagnosis that can predict the development of disordered eating behaviours. METHODS: A retrospective observational study of 291 adolescents aged 15-19 years with type 1 diabetes who completed the Diabetes Eating Problem Survey-Revised (DEPS-R) as is routine in our diabetes clinic. The prevalence of disordered eating behaviours and risk factors for their development was assessed. RESULTS: In 84 (28.9%) adolescents, disordered eating behaviours were found. Disordered eating behaviours were positively associated with female sex (ß = 3.01 [SE = 0.97], p = 0.002), higher BMI-Z score (ß = 2.08 [SE = 0.49], p < 0.001), higher HbA1c (ß = 0.19 [SE = 0.03], p < 0.001) and treatment with multiple daily injections of insulin (ß = 2.19 [SE = 1.02], p = 0.032). At type 1 diabetes diagnosis, higher BMI-Z score (ß = 1.54 [SE = 0.63], p = 0.016) for those diagnosed before age 13 years and increased weight gain at 3 months post-diagnosis (ß = 0.88 [SE = 0.25], p = 0.001) in females diagnosed at age 13 years or older were found to be risk factors for disordered eating behaviours. CONCLUSIONS: Disordered eating behaviours are common among adolescents with type 1 diabetes and are associated with various parameters, including BMI at diagnosis and the rate of weight gain at 3 months post-diagnosis in females. Our findings highlight the need for early preventive efforts for disordered eating behaviours and interventions to avoid late diabetes complications.

Optic pathway glioma and endocrine disorders in patients with and without NF1.

BACKGROUND: Optic pathway gliomas (OPGs) are classified by anatomic location and the association with neurofibromatosis type 1 (NF1). Children with OPGs face sequelae related to tumor location and treatment modalities. We assessed the prevalence of endocrine dysfunction in children with OPGs and compared outcomes between those with and without NF1. METHODS: We performed a retrospective medical record review of medical history, and clinical and laboratory data, of children diagnosed with OPGs (n = 59, 61% with NF1) during 1990-2020, followed at a tertiary endocrine clinic. Growth and puberty parameters and occurrence of endocrine dysfunction were evaluated. RESULTS: Isolated optic nerve involvement was higher among patients with than without NF1. Patients without NF1 were younger at OPG diagnosis and more often treated with debulking surgery or chemotherapy. At the last endocrine evaluation, patients without NF1 had comparable height SDS, higher BMI SDS, and a higher rate of endocrine complications (78.3% vs. 41.7%, p = 0.006). Younger age at diagnosis, older age at last evaluation, and certain OPG locations were associated with increased endocrine disorder incidence. CONCLUSIONS: Endocrine dysfunction was more common in patients without NF1; this may be related to younger age at presentation, tumor locations, a greater progressive rate, and more aggressive treatments. IMPACT: The literature is sparse regarding sporadic OPGs, and the mean duration of follow-up is shorter than at our study. Our data show a higher rate of endocrine dysfunction in patients with OPGs than previously described. We also found a higher prevalence of endocrine dysfunctions among patients without compared to those with NF-1. A better understanding of the true prevalence of endocrine disabilities that may evolve along time can help in guiding physicians in the surveillance needed in patients with OPG.

Changes in body mass index in children and adolescents in Israel during the COVID-19 pandemic.

BACKGROUND: The current coronavirus disease 2019 (COVID-19) pandemic has health, social, and economic implications. Our primary objective was to evaluate changes in body mass index (BMI) from the pre-pandemic to COVID-19 pandemic period among a large pediatric population in Israel. METHODS: This retrospective cohort study is based on data from Clalit Health Services, the largest health maintenance organization in Israel. The data accessed included sociodemographic, anthropometric, and clinical parameters of persons aged 2-20 years with at least one BMI measurement during 2017-2019 (pre-pandemic period) and one between April 1, 2020 and December 31, 2020 (pandemic period). RESULTS: The cohort comprised 36,837 individuals (50.8% females); median age 11.2 years, 83.6% were Jewish and 10.3% of Arab ethnicity. BMI-SDS increased in both sexes (p < 0.001), in both ethnicities (p < 0.001), in all socioeconomic position clusters (p < 0.001), in children aged 2-18 years (P < 0.001), and in children with underweight or normal-weight in the pre-pandemic period (p < 0.001). For 21,610 individuals (35.6%), BMI-SDS increased ≥0.25 SD. The increase in BMI-SDS was greater in children aged 2-6 compared to 6.1-18 years; BMI-SDS decreased among those aged 18.1-20 years (P < 0.001). The increase in BMI-SDS was greater among those with underweight than normal weight; BMI-SDS decreased among those with overweight and obesity (P < 0.001). During the pandemic, overweight or obesity presented in 11.2% of those with normal weight in the pre-pandemic period; and obesity presented in 21.4% of those with overweight in the pre-pandemic period. CONCLUSIONS: The COVID-19 pandemic correlated with overall weight gain among children and adolescents, with the most substantial weight gain in children aged 2-6 years. Notably, the most significant increase in BMI-SDS was observed in children with underweight; BMI-SDS decreased in children with overweight and obesity. Policies should be established during the pandemic that focus on increasing physical activity, reducing sedentary time, and promoting healthy diets.

Diabetes ketoacidosis recovery in youth with newly diagnosed and established type 1 diabetes.

BACKGROUND: The objective of this study was to describe the differences in metabolic parameters and in time to recovery from diabetes ketoacidosis (DKA), between children and adolescents with newly diagnosed diabetes compared with established type 1 diabetes (T1DM). METHODS: This was a single-center, retrospective study. The cohort consists of 356 children and adolescents with T1DM who had DKA during 2008-2018. Data were obtained from the patients' medical files. Recovery of DKA was defined as the resolution of acidosis (pH >7.3 and bicarbonate >15 meq/L). RESULTS: The mean time to recovery from DKA was significantly longer in patients with newly diagnosed diabetes than in those with established diabetes (13± versus 8.5± h) (p < 0.001). This difference was maintained in an analysis according to DKA severity: mild, moderate, and severe. pH at presentation did not differ between the groups, but bicarbonate at presentation was significantly lower in patients with newly diagnosed diabetes than in those with established diabetes, 9.9± versus 12± mmol/L (p < 0.001). Potassium and phosphorus levels were lower, and sodium and chloride levels were higher in patients with newly diagnosed diabetes than in those with established diabetes (p < 0.001). CONCLUSIONS: DKA is associated with a shorter recovery time in patients with established diabetes compared to newly diagnosed diabetes. This may have implications on the treatment of people with established diabetes. IMPACT: DKA is associated with a shorter recovery time in patients with established diabetes compared with newly diagnosed diabetes. Shorter recovery time in a patient with established diabetes compared with newly diagnosed diabetes was observed in any DKA severity. The time to recovery from DKA did not differ significantly between patients treated with an insulin pump and those treated with multiple daily injections. Triggers for DKA among patients with established diabetes were poor compliance with treatment, infection, pump dysfunction, and dehydration.

Serum IGF1 and linear growth in children with congenital leptin deficiency before and after leptin substitution.

BACKGROUND: Evidence from in vitro and rodent studies suggests that leptin, a key signal of long-term energy reserves, promotes IGF1 synthesis and linear growth. This effect of leptin has not been fully investigated in humans. The aim of our study was to investigate the effect of leptin substitution on growth factors and linear growth in children with congenital leptin deficiency (CLD). METHODS: In this cohort study we included eight pediatric patients (six males), age 0.9-14.8 years, who were diagnosed with CLD and received leptin substitution at our University Medical Center. We calculated standard deviation scores (SDS) for serum levels of IGF1 and IGFBP3, IGF1/IGFBP3 molar ratio, and height at baseline (T0) and 12 months (T12) after the initiation of substitution with metreleptin. RESULTS: All patients had severe obesity (BMI-SDS mean ± SD: 4.14 ± 1.51) at T0 and significant BMI-SDS reduction to 2.47 ± 1.05 at T12. At T0, all patients were taller than the mid-parental median, yet had low IGF1 and IGF1/IGFBP3 molar ratios (IGF1-SDS[Formula: see text]T0: -1.58 ± 0.92, IGF1/IGFBP3 molar ratio-SDS[Formula: see text]T0: -1.58 ± 0.88). At T12, IGF1-SDS increased significantly (∆T0-12: 1.63 ± 1.40, p = 0.01), and IGFBP3-SDS and IGF1/IGFBP3 molar ratio-SDS showed a trend toward an increase. In the three children within the childhood growth period (post-infancy, pre-puberty) height-SDS increased (∆height-SDST0-12: 0.57 ± 0.06, p = 0.003) despite substantial weight loss. CONCLUSIONS: These results in CLD patients are contrary to observations in children with idiopathic obesity who typically have above-mean IGF1 levels that decrease with weight loss, and therefore suggest that leptin increases IGF1 levels and promotes linear growth.

Clinical and Esophagogastroduodenoscopy Findings in Pediatric Patients With Severe Obesity Evaluated Before Bariatric Surgery.

OBJECTIVES: Severe obesity in the pediatric population has lifelong consequences. Bariatric surgery has been suggested for selected adolescents with severe obesity after careful evaluation. The indications for preoperative esophagogastroduodenoscopy (EGD) in this age group are not clear, despite its established usefulness in adults. We aimed to assess the usefulness of EGD before bariatric surgery in pediatric patients with severe obesity and metabolic comorbidities. METHODS: We conducted a retrospective chart review in a single tertiary pediatric medical center of adolescents treated during 2011 to 2018. Data collected from electronic medical records included patient demographics, endoscopic findings, and laboratory parameters. RESULTS: A total of 80 patients (40 boys) underwent evaluation. Macroscopic abnormalities were detected in 54% of the endoscopies, including gastritis, esophagitis, and duodenitis in 46%, 16%, and 13%, respectively. Forty-nine percentage of the biopsies showed histological abnormalities; in 35 (44%) patients, Helicobacter pylori was detected. Thirty-three patients (41%) received medical treatment and 2 (2.5%) required a second EGD. Metabolic comorbidities included hypertriglyceridemia (38% of the patients), low high-density lipoprotein (23%), and prediabetic (16%) or diabetic levels of HbA1C (4%). Fifty-five percentage of the cohort had elevated alanine aminotransferase (ALT), suggestive of nonalcoholic fatty liver disease (NAFLD). CONCLUSIONS: Endoscopies performed before bariatric surgeries suggest a higher prevalence of clinically significant findings, many of which required treatment. These findings support incorporating an EGD into the preoperative evaluation of this patient population.

Birth during the moderate weather seasons is associated with early onset of type 1 diabetes in the Mediterranean area.

AIM: To assess the association of seasonal and perinatal parameters with early age of type 1 diabetes (T1D) onset. METHODS: A cross-sectional review of all medical records of T1D patients born between the years 1990 and 2005, and diagnosed before/by the age of 10 years, from 13 university-affiliated paediatric medical centres in Israel, was performed. Data included: gender, ethnicity, seasons of birth and disease onset, birth gestational age and weight, and autoimmune diseases of the probands and their first-degree family members. Statistical analysis included the Chi-square test or Mann-Whitney test, as appropriate and multivariate regression analysis. RESULTS: Enrolled were 1571 T1D patients at a median age of T1D onset 6.9 years (IQR 4.4,8.4); 336 of them presented before 4 years of age. The median age of this group was 2.5 years (IQR 1.7,3.2), and of the 1235 patients who presented after 4 years of age, median presentation age was 7.5 years (IQR 6.1,8.8). Multivariate regression analysis demonstrated that a more recent birth year; OR = 1.06, 95% CI 1.02-1.1, P = 0.003, and birth during the moderate weather months (September, October, March, and April) were significantly associated with younger age at T1D onset; OR = 1.68, 95% CI 1.17-2.4, P = 0.005. CONCLUSIONS: Our novel finding demonstrates the association between younger than 4 years old age at presentation and birth during moderate weather months. The results also support previous reports, that there is a slight increase in the annual incidence of T1D in the youngest age groups.

Type 1 diabetes mellitus management in young children: implementation of current technologies.

The use of advanced technologies for diabetes management is on the rise among pediatric patients with type 1 diabetes (T1D). Continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring, predictive low glucose suspend, hybrid closed-loop insulin delivery systems-all enable better diabetes management and glycemic control. However, when used by children, and especially very young children, specific aspects must be taken into consideration, including technical parameters, ease of use, parental stress, and satisfaction. The unique characteristics of T1D in children aged <6 years are reviewed and studies of the pros and cons of different technologies in this specific age group are presented. Addressing such issues when implementing advanced technologies among very young children with T1D will enable better diabetes management and will hopefully ease a tremendous burden of both children and families.

Oxidative stress in obese children and adolescents with and without type 2 diabetes mellitus is not associated with obstructive sleep apnea.

PURPOSE: Obesity, obstructive sleep apnea (OSA), and type 2 diabetes mellitus (T2DM) are associated with chronic low-grade inflammation and oxidative stress. In adults, increased lipid peroxidation, a marker of oxidative stress, was found in both metabolic syndrome and OSA. Studies on oxidative stress in children with T2DM and OSA are scarce. METHODS: Plasma oxidized low-density lipoprotein (Ox-LDL) levels were evaluated in obese children and adolescents with/without T2DM, and the contribution of OSA to oxidative stress was investigated. RESULTS: Ten patients with T2DM, 8 with impaired glucose tolerance (IGT), and 20 body mass index-standard deviation score (BMI-SDS)-matched non-diabetic children (controls) were studied. They all underwent overnight polysomnography. Fasting plasma concentrations of Ox-LDL were measured and compared to the glycemic status and to the presence of OSA. Fourteen patients (36%) were diagnosed with OSA and 21 (55%) with hypertension. There were no significant group differences in plasma Ox-LDL levels or between patients with/without OSA. Plasma Ox-LDL levels were significantly higher among patients with hypertension compared to controls (P = 0.01), while they correlated with homeostasis model assessment (P = 0.02), BMI-SDS (P = 0.049), and systolic blood pressure (P = 0.002). CONCLUSIONS: The findings of this pilot study suggest that increased lipid peroxidation is associated with insulin resistance and hypertension in obese children and adolescents, while OSA has most likely minor influence.

A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (Glassia®) in the Treatment of Recent-Onset Type 1 Diabetes.

Our aim was to assess the efficacy, safety, and tolerability of alpha-1 antitrypsin (AAT) as a therapeutic modality for ß-cell preservation in patients with recent-onset type 1 diabetes. Seventy type 1 diabetes patients (37 males; mean age 13.1 ± 4.1years) were randomized to treatment with 22 infusions of AAT (Glassia®) (60 or 120 mg/kg) or placebo. The primary outcome was the area under the curve (AUC) of C-peptide from a 2-h mixed-meal tolerance test after 52 weeks. At week 52, C-peptide was 0.9, 0.45, and 0.48 pmol/mL in the AAT-120, AAT-60, and placebo groups (p = 0.170 and p = 0.866 vs. placebo, respectively). The declines in C-peptide glycated hemoglobin (HbA1c) and the total insulin dose (U/kg) were similar across groups. Within the predefined 12-18-years subgroup, the C-peptide AUC decreased significantly in the placebo and AAT-60 groups (-0.34 and -0.54 pmol/mL, respectively, p < 0.01), with a borderline decrease in the AAT-120 group (-0.29 pmol/mL, p = 0.047). The mean HbA1c level was significantly lower in the AAT-120 group compared to the placebo (6.7% ± 0.9% vs. 8.2 ± 1.4%, p = 0.05), and a higher percentage of patients attained HbA1c ≤ 7% (75% vs. 25%, p = 0.05). AAT was tolerated well, with a similar safety profile between groups. The AAT intervention showed promise in the subgroup of adolescents with recent-onset type 1 diabetes. Further studies are warranted to determine the impact and proposed mechanism of action of AAT in ß-cell preservation.

Prevalence of early and late prematurity is similar among pediatric type 1 diabetes patients and the general population.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) has increased in recent decades, as has the incidence of preterm births (<37 weeks). We aimed to evaluate and compare the prevalence of prematurity and early prematurity (<34 weeks) and birth season variability among T1DM and non-T1DM children. METHODS: A nationwide cross-sectional study was conducted, with linkage of data from 13 paediatric diabetes centers and Israeli National Registries, including T1DM patients and general non-T1DM population, born during 2000 to 2013. Gathered data included ethnicity, gender, birth week, weight, and season. The prevalence of prematurity and birth season were compared with the general population birth registry using Pearson Chi-square test. RESULTS: The study population included 1452 T1DM patients, 52.7% males, and 2 138 668 subjects in the general non-T1DM population, 51.2% males. The prevalence of late and early prematurity was similar between groups (6.1% and 2.2% in the T1DM group vs 5.6% and 2.0% in the general non-T1DM group, P = 0.25 and P = 0.38, respectively). OR for prematurity among T1DM patients was 1.15 (0.95-1.39), P = 0.16. No difference in birth season was demonstrated between preterm and term, in T1DM and general non-T1DM populations. Ethiopian descent was more prevalent among T1DM patients compared with the non-T1DM population, in both term and preterm born. CONCLUSIONS: This is the largest population-based study, and the first in the Middle East geographical area, indicating that prematurity, including early prematurity, is not associated with T1DM during childhood. The study was registered at https://clinicaltrials.gov/: NCT02929953.

Which predictors differentiate between obese children and adolescents with cardiometabolic complications and those with metabolically healthy obesity?

BACKGROUND/AIMS: Childhood obesity and associated metabolic comorbidities is a major global health concern. Metabolically healthy obesity (MHO) may represent a subgroup of individuals in which excessive body fat accumulation does not lead to adverse metabolic effects. We aimed to determine the prevalence of MHO among obese Israeli children and adolescents and to find predictors for metabolically unhealthy obesity (MUO). METHODS: In a retrospective study, demographic, anthropometric, lifestyle, and cardiometabolic data were retrieved from medical records of patients with a body mass index (BMI) >95th percentile aged 6 to 17.6 years, attending a tertiary pediatric obesity clinic between 2008 and 2015, with at least 1 year of follow-up. Participants were dichotomized as either MHO or MUO based on cardiometabolic risk factor clustering (blood pressure, serum lipids, and glucose). Multivariable logistic regression was used to determine predictors of MUO. RESULTS: Of the 230 children (median age 9.9 years) fulfilling study criteria, 48 (20.9%) were classified as MHO. Occurrence of MUO was associated with male gender, Arabic ethnicity, higher BMI-SD score, higher tri-ponderal mass index (TMI), and higher insulin resistance (IR) (presence of acanthosis nigricans and a higher level of homeostasis model assessment-IR [HOMA-IR]). Male gender (odds ratio [OR] 2.27, P = .033), presence of acanthosis nigricans at baseline (OR 2.35, P = .035), and a greater increase in BMI-SDS during follow-up (OR 2.82, P = .05) were the best predictors of MUO. CONCLUSIONS: The MHO phenotype was present in only 20.9% of obese Israeli children. MUO was significantly associated with male gender, with presence of acanthosis nigricans, and with a greater increase in BMI-SDS during follow-up.

Ketoacidosis at onset of type 1 diabetes is a predictor of long-term glycemic control.

BACKGROUND: Few studies have evaluated the impact of diabetic ketoacidosis (DKA) at diabetes onset on long-term glycemic control in patients with type 1 diabetes (T1D). OBJECTIVE: We aimed to determine any differences in long-term glycemic control between children/adolescents with T1D presenting with DKA at diabetes onset and those without. METHODS: This retrospective study comprised 335 patients diagnosed with T1D from September 2007 to December 2012, among which 132 (39.4%) presented with DKA. Variables compared between patients with DKA at onset and those without: yearly hemoglobin A1c (HbA1c) levels, daily insulin dose, yearly rates of severe hypoglycemia and DKA, percent of patients achieving target HbA1c levels. RESULTS: After the first year of diabetes, the mean daily insulin dose and HbA1c level were significantly higher in the group with DKA at onset (0.74 ± 0.26 vs 0.69 ± 0.27 units/kg/d, P = .049, and 7.85 ± 1.13% vs 7.49 ± 0.94%, P = .01, respectively), despite similarity of therapy (multiple daily injections or continuous subcutaneous insulin infusion), with a similar but not statistically significant trend subsequently. Mean HbA1c since onset was significantly higher in the DKA group (8.08 ± 0.95% vs 7.86 ± 0.95%, P = .025). A significantly higher percentage of patients in the group without DKA at onset achieved a mean level of HbA1c since onset within glycemic targets (32% vs 20.5%, P = .02). In the DKA group, the frequency of subsequent DKA episodes per diabetes years was significantly higher (P = .042). CONCLUSIONS: DKA at diagnosis was associated with less favorable long-term glycemic control as assessed by HbA1c and the rate of DKA episodes. T1D patients presenting with DKA may therefore need stricter treatment and tight follow-up.

Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry.

OBJECTIVE: To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D). METHODS: An international cross-sectional study including 23 026 T1D children (2-18 years, duration of diabetes ≥1 year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS < -2SD), OW (+1SD < BMI-SDS ≤ +2SD), and obese (OB) (BMI-SDS > +2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes. RESULTS: The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean ± SEM: 0.54 ± 0.05 vs 0.40 ± 0.05, P < 0.0001). In males, BMI-SDS significantly decreased by age (P < 0.0001) in the first three age categories 0.61 ± 0.06 (2 to <10 years), 0.47 ± 0.06 (10 to <13 years), 0.34 ± 0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P < 0.0001): 0.54 ± 0.04 (2 to <10 years), 0.39 ± 0.04 (10 to <13 years), 0.55 ± 0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2 years: 0.38 ± 0.05, 2 to <5 years: 0.44 ± 0.05, and ≥5 years: 0.50 ± 0.05, P < 0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20% ± 0.10% vs 8.06% ± 0.10%, P < 0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups. CONCLUSIONS: The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D.

Targets and teamwork: Understanding differences in pediatric diabetes centers treatment outcomes.

OBJECTIVE: The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes. RESEARCH DESIGN AND METHODS: Children, under the age of 11 with type 1 diabetes and their parents treated at the study centers participated. Clinical, medical, and demographic data were obtained, along with blood sample for centralized assay. Parents and all members of the diabetes care team completed questionnaires on treatment targets for hemoglobin A1c (HbA1c) and recommended frequency of blood glucose monitoring. RESULTS: Totally 1113 (53% male) children (mean age 8.0 ± 2.1 years) from 18 centers in 17 countries, along with parents and 113 health-care professionals, participated. There were substantial differences in mean HbA1c between centers ranging from 7.3 ± 0.8% (53 mmol/mol ± 8.7) to 8.9 ± 1.1% (74 mmol/mol ± 12.0). Centers with lower mean HbA1c had (1) parents who reported lower targets for their children, (2) health-care professionals that reported lower targets and more frequent testing, and (3) teams with less disagreement about recommended targets. Multiple regression analysis indicated that teams reporting higher HbA1c targets and more target disagreement had parents reporting higher treatment targets. This seemed to partially account for center differences in Hb1Ac. CONCLUSIONS: The diabetes care teams' cohesiveness and perspectives on treatment targets, expectations, and recommendations have an influence on parental targets, contributing to the differences in pediatric diabetes center outcomes.

Real-Life Glycemic Control in Children with Type 2 Diabetes: A Population-Based Study.

OBJECTIVES: To characterize children and adolescents with type 2 diabetes mellitus (T2DM) insured by a large health maintenance organization, and to identify variables associated with treatment quality and disease outcome. STUDY DESIGN: Children and adolescents diagnosed with T2DM over a 9-year period were identified from the database of Clalit Health Services, a large health maintenance organization in Israel (1 213 362 members aged 0-18 years). Demographic, anthropometric, clinical, and laboratory data were analyzed. RESULTS: A total of 96 patients (47 males) met our inclusion criteria. The mean age at diagnosis of T2DM was 14.25 ± 2.51 years. At the time of diagnosis, the median hemoglobin A1c (HbA1c) level was 7.8%, and additional components of the metabolic syndrome were present in 14.9%-67.4% of the patients. At the end of the follow-up period (3.11 ± 1.75 years), >50% of the patients were being treated with insulin; the median HbA1c value was 7.97%, and 44.6% of the patients achieved the target HbA1c of <7.0%. On multivariate linear regression analysis, the variables found to predict worse glycemic control (ie, higher HbA1c) were a higher HbA1c at diagnosis, a higher body mass index SD score at diagnosis, fewer annual HbA1c tests, and Arabic ethnicity [F(4,81) = 7.139; P < .001; R2 = 0.271]. CONCLUSION: This population-based study of pediatric patients with T2DM demonstrates that reasonable glycemic control can be achieved in both community and outpatient hospital settings. Nevertheless, there is room for improvement in intervention programs to optimize outcomes and decrease the risk of complications.

Do children, adolescents, and young adults with type 1 diabetes have increased prevalence of sleep disorders?

BACKGROUND: Sleep has been shown to impact glucose regulation, and may be altered in persons with type 1 diabetes (T1D). OBJECTIVE: To assess sleep characteristics in T1D patients and the possible association between sleep disturbances and diabetes-related variables. SUBJECTS AND METHODS: In a cross-sectional study in 154 young patients with T1D and 154 age-range-matched nondiabetic controls subjective sleep characteristics were assessed using validated questionnaires: Sleep Disturbance Scale for Children (SDSC), Adolescent Sleep-Wake Scale (ASWS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS). Clinical and disease-related variables were obtained from medical charts. RESULTS: Sleep disorders were frequent in all age groups, with no significant difference in prevalence or total scores of the SDSC, ASWS, PSQI, or ESS between the patients and the controls. In T1D children, SDSC score was significantly higher in those using continuous glucose monitoring (CGM) vs glucose meters (P = .042). The score of disorders related to "initiating and maintaining sleep" was significantly higher in those treated with pumps vs patients treated with injections (P = .014), in those using CGM vs glucose meters (P = .02), and in those with nocturnal hypoglycemia vs those without (P = .023). The percentage of children with excessive daytime sleepiness was significantly lower in patients vs controls (P = .035). No significant differences were found in the other two age groups. CONCLUSIONS/INTERPRETATION: The prevalence of sleep disorders among most of the young T1D patients was no higher than in the nondiabetic population. Studies using objective sleep measures are warranted to further assess sleep quality in T1D patients.

Basal 17-hydroxyprogesterone cannot accurately predict nonclassical congenital adrenal hyperplasia in children and adolescents.

AIM: This study explored whether using the suggested diagnostic serum basal level of 17-hydroxyprogesterone (6.0 nmol/L) would lead to underdiagnosis of nonclassical congenital adrenal hyperplasia. METHODS: We retrospectively studied 123 patients with nonclassical congenital adrenal hyperplasia, defined as an adrenocorticotropic hormone-stimulated 17-hydroxyprogesterone level of more than 45 nmol/L. Of these 13 had basal 17-hydroxyprogesterone levels of less than 6.0 nmol/L and 110 exceeded that level. The 42 controls had idiopathic premature pubarche. Clinical and laboratory data were reviewed and compared. RESULTS: There were no differences between patients with 17-hydroxyprogesterone levels of <6.0 nmol/L or ≥6.0 nmol/L based on age at presentation, gender, anthropometric measurements, bone age advancement, age at glucocorticoid initiation and hydrocortisone dosage. Patients with basal 17-hydroxyprogesterone <6.0 nmol/L had significantly lower stimulated 17-hydroxyprogesterone levels (p = 0.02) and higher stimulated serum cortisol levels (p < 0.008). Children with nonclassical congenital adrenal hyperplasia and premature pubarche were clinically indistinguishable from controls with idiopathic premature pubarche. Androgen levels were significantly higher in the nonclassical congenital adrenal hyperplasia group. CONCLUSION: A basal 17-hydroxyprogesterone threshold of 6.0 nmol/L was not a sensitive predictive marker for diagnosing nonclassical congenital adrenal hyperplasia. Children whose clinical presentation suggests nonclassical congenital adrenal hyperplasia should undergo diagnostic adrenocorticotropic hormone stimulation testing.

Effect of Nutritional Supplementation on Growth in Short and Lean Prepubertal Children after 1 Year of Intervention.

OBJECTIVE: To determine the 1-year effectiveness and safety of nutritional supplementation with the study formula on linear growth and weight gain in short and lean prepubertal children and to validate the previously reported findings in those initially treated with placebo. STUDY DESIGN: Two-phase 1-year intervention (double-blind placebo-controlled [0-6 months] and open-labeled extension [6-12 months]) in which all participants were offered to continue the study using the study formula. Anthropometric measures and 3-day food diary were assessed at baseline and after 6 and 12 months of intervention. RESULTS: A total of 129 out of 150 children (86%) completed the open-labeled extension-phase. In "good" consumers of the formula (intake ≥50% of recommended dose) throughout the entire year height-SDS continued to improve in the extension phase, with a total gain of 0.19 ± 0.14 SD. In "good" consumers of the formula initially randomized to the placebo-group, the gain in height-SDS significantly improved (from 0.04 ± 0.13 to 0.12 ± 0.11; P = .001), replicating the results of the "good" consumers of the formula during the blinded-phase (0.12 ± 0.12). "Poor" consumers (intake <50% of recommended dose) did not improve their height-SDS. No significant changes in body mass index SDS were observed with the consumption of the formula. A dose-response was found between the amount of formula consumed/kg and the increment in height-SDS and weight-SDS (r = 0.36; P < .001 and r = 0.18; P = .041, respectively). No serious adverse events were reported. CONCLUSIONS: One year of a nutritional supplement was effective in promoting the linear growth of short and lean prepubertal children, with no change in body mass index status. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01158352.