Muscle-to-fat ratio in children and adolescents with type 1 diabetes in predicting glycaemic control and partial clinical remission.

BACKGROUND: Advances in treatment could mitigate the expected adverse changes in the body composition of children and adolescents with type 1 diabetes (T1D). OBJECTIVES: To examine the evolution of weight status and body composition and their association with glycaemic control and partial clinical remission in youth with T1D. METHODS: Ninety-nine participants with T1D (median age 9.5 years [interquartile range 7.3, 12.9], 59.6% boys) were longitudinally followed for 3 years since diagnosis. Data at seven pre-determined time points were extracted from medical files. Outcome measures included body mass index (BMI) z-scores, muscle-to-fat ratio (MFR) z-scores, haemoglobin A1c (HbA1c) levels, continuous glucose monitoring metrics, and insulin dose-adjusted HbA1c (IDAA1c) levels. RESULTS: The BMI z-scores increased significantly (p < 0.001) for both sexes, with no significant change in MFR z-scores over time. The girls had higher BMI z-scores (p < 0.001) and lower MFR z-scores than the boys (p = 0.016). The mean HbA1c levels decreased during the first month and at 3 months since diagnosis (p < 0.001), then plateaued and achieved a median overall HbA1c of 7.1% for the entire cohort. At 12 months, 37 participants (37.6%) were in partial clinical remission, as evidenced by IDAA1c ≤ 9. The odds of partial clinical remission at 2 years increased by 2.1-fold for each standard deviation increase in the MFR z-score (p < 0.001). Higher MFR z-scores were associated with better metabolic control. CONCLUSIONS: Integration of body composition assessments could mitigate adverse body changes in paediatric patients with T1D.

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.

Nondisclosure of Type 1 Diabetes in Adolescence: A Single-Center Experience.

Objective: The aim of this study was to assess the extent of nondisclosure of type 1 diabetes in adolescents and investigate its association with several psychosocial parameters and clinical outcomes. Research design and methods: This was a cross-sectional study based on data collected from 69 adolescents with type 1 diabetes who were 12-18 years of age and followed at our diabetes clinic. The degree of disclosure, demographics, diabetes management, and psychosocial issues were assessed via questionnaires. Clinical parameters were derived from medical records. Associations between nondisclosure status and clinical and psychosocial study variables were assessed. Results: Fifty-three participants (77%) reported some extent of nondisclosure. Nondisclosure was associated with low self-esteem, reduced friend support, and increased diabetes-related worries. Nondisclosure was also found to be associated with diminished self-care behaviors related to insulin administration and with elevated A1C. Conclusion: Our results demonstrate that nondisclosure of type 1 diabetes in adolescents may be more common than initially recognized and is likely associated with unfavorable psychological outcomes and reduced self-care and diabetes management. Our results emphasize the importance of social interactions and disclosure in adolescents and may serve as a potential stepping stone to address other social barriers hindering diabetes management.

Neurodevelopmental Outcomes Among Infants Born Preterm Fed With Mother's Own Milk: A Comparison of Singletons and Twins.

OBJECTIVE: To examine associations between early exposure to mother's own milk (MOM) and neurodevelopmental outcomes among preterm infants, and to compare these associations between singletons and twins. STUDY DESIGN: Retrospective cohort study that included low-risk infants born at <32 weeks gestational age. Nutrition was documented over a 3-day period at mean ages of 14 and 28 days of life; an average of the 3 days was calculated. The Griffiths Mental Development Scales (GMDS) were administered at 12 months corrected age. RESULTS: Preterm infants (n = 131) with median gestational age of 30.6 weeks were included; 56 (42.7%) were singletons. On days 14 and 28 of life, 80.9% and 77.1% were exposed to MOM, respectively. Exposure rate was comparable, but MOM intake (mL/kg/day) was higher among singletons than among twins (P < .05). At both time points, MOM-exposed infants scored higher on personal-social, hearing-language, and total GMDS assessments than nonexposed infants. These differences were significant for the entire cohort and for twins (P < .05). MOM intake correlated with total GMDS score for both singletons and twins. Any exposure to MOM was associated with additional 6-7 points on total GMDS score or 2-3 additional points for every 50 mL/kg/day of MOM. CONCLUSIONS: The study supports the positive association between early MOM exposure among low-risk preterm infants and neurodevelopmental outcomes at 12 months corrected age. The differential effects of MOM exposure on singletons vs twins need further exploration.

Sex differences in body composition in youth with type 1 diabetes and its predictive value in cardiovascular disease risk assessment.

BACKGROUND: Women with type 1 diabetes (T1D) are more susceptible than men to cardiovascular disease (CVD). Signs of increased risk may already appear among adolescent girls. OBJECTIVES: We explored the contribution of body composition to the development of CVD risk factors among youth with T1D. METHODS: One hundred and eighty nine subjects with T1D (mean age 15.3 ± 5.1 years, 55% boys) followed between January 2018-January 2022 were included in this observational study. Sociodemographic and clinical data were extracted from medical files. Body composition was measured by bioelectrical impedance analysis, and muscle-to-fat ratio (MFR) z-scores were calculated. Logistic regression model assessed the association between body composition (MFR z-scores) and evidence of CVD risk factors. RESULTS: Females were characterised by higher median BMI z-scores (0.47 vs. 0.04, p = 0.012), higher fat and truncal fat percentage levels (p ≤ 0.001) and lower median MFR z-scores (-0.64 vs. -0.25, p ≤ 0.001), higher median triglyceride (TG) levels (71 vs. 61 mg/dl, p = 0.05), longer disease duration to initiation of insulin pump therapy (p = 0.041), and more time spent in marked hypoglycemia (1 vs. 0.2%, p = 0.007) than males. Males' MFR z-scores were associated with several diabetes-related parameters (age at diagnosis, CGM metrics, HbA1c and insulin dose), while the females'' MFR z-scores were linked to the atherogenic dyslipidemia index (TG:HDL ratio). The odds for CVD risk factors were doubled for every 1 SD decrease in MFR z-score (OR = 0.50, CI [0.30-0.84], p = 0.009) and also increased with age (OR = 1.07, CI [1.004-1.148], p = 0.038). CONCLUSIONS: Body composition measurement has a predictive value in CVD risk assessment in youth with T1D, with unique characteristics and influences in each sex.

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.

Fear of hyperglycaemia in parents of children with type 1 diabetes mellitus - A multi-centre multinational study.

AIMS: Study aims: (1) developing and validating a novel questionnaire for measuring fear of hyperglycaemia among parents of children with type 1 diabetes (T1D) - the Hyperglycaemia Fear Survey - Parent version (FoHyper-P); (2) investigating correlations between parental fear of hyperglycaemia and objective measures of glycaemic control. METHODS: A multi-centre, multinational study of 152 parents of children with T1D was conducted in three large diabetes clinics from Israel, Poland, and Greece. Inclusion criteria were parents of children aged 6-16 years, at least 6 months from diagnosis, at least 3 months of CGM use and parental involvement in care. Parents filled the FoHyper-P and the Hypoglycaemia Fear Survey - Parent Version (HFS-P). Patient data were obtained via electronic medical records and informative questionnaires. Bonferroni correction was performed to counteract multiple comparisons. RESULTS: Significant strong-moderate correlations were found between FoHyper-P and HFS-P including total questionnaires scoring (r = 0.747, pBonf < 0.001), worries subscales (r = 0.735, pBonf <0.001), and behaviour subscales (r = 0.532, pBonf <0.001). Using linear regression models, we found a positive association between the worry subscale and HbA1C. Weak correlations (p < 0.05, not significant after Bonferroni correction) were found between time in range, time above range and parental fear of hyperglycaemia as well as between worry subscales and a higher HbA1C in the past year, percent of hyperglycaemia and lower TIR. CONCLUSIONS: The FoHyper-P is a novel, validated tool for assessing parental fear of hyperglycaemia. Integrating it into clinical practice addresses an underestimated aspect of parental diabetes management, enabling better care for children with T1D.

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.

Clinical characteristics, growth patterns, and long-term diabetes complications of 24 patients with neonatal diabetes mellitus: A single center experience.

OBJECTIVES: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes, diagnosed before age 6 months. We aimed to describe the clinical characteristics, molecular genetics, and long-term follow-up of NDM patients from a single pediatric endocrine center in Israel. METHODS: Retrospective study (1975-2020) of all patients diagnosed with diabetes before 6 months of age, who tested negative for pancreatic autoantibodies. Medical records were reviewed for demographic, familial and medical history, and clinical and biochemical features; a genetic analysis was performed. RESULTS: Of 24 patients, nine had transient neonatal diabetes (TNDM) and 15 permanent neonatal diabetes (PNDM), of whom five had rare syndromic causes. Genetic etiology was revealed in 87.5% of the NDM cohort, and the most common causes were ABCC8 mutations in TNDM and KCNJ11 and insulin gene mutations in PNDM. The switch from insulin to off-label sulfonylurea therapy was successful for 5/9 (56%) of the qualifying candidates. Severe hypoglycemia and diabetic ketoacidosis developed in 2 (8%) patients, and chronic diabetes complications in 5 (21%) patients with more than 10 years NDM. At last follow-up, weight and height of all but two syndromic PNDM patients were normal. The median height-SDS of the TNDM subgroup was significantly taller and the mean weight-SDS significantly heavier than those of the PNDM subgroup (-0.52 (-0.67, -0.09) vs. -0.9 (-1.42, -0.3) (p = 0.035) and 0.22 ± 0.69 vs. -0.89 ± 1.21 (p = 0.02), respectively). PNDM patients showed no incremental change in mean weight SDS over the time. CONCLUSION: The Israeli NDM cohort has clinical and genetic characteristics comparable with other populations. Patients with TNDM were taller and heavier than those diagnosed with PNDM, although both show rapid catch-up growth and reached normal growth parameters. Chronic diabetes complications developed in patients with long-standing NDM.

Alarming increase in ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the first wave of the COVID-19 pandemic in Israel.

OBJECTIVE: To evaluate the incidence and severity of ketoacidosis (DKA) at type 1 diabetes diagnosis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Israel. RESEARCH DESIGN AND METHODS: A population-based study the product of a national collaboration of Israeli pediatric diabetes centers investigated the presentation of childhood-onset type 1 diabetes. The frequencies of DKA and severe DKA observed during the COVID-19 period from March 15, 2020 (commencement of the first nationwide lockdown) until June 30, 2020 were compared with the same periods in 2019, 2018, and 2017 using multivariable logistic regression, adjusting for age, sex, and socioeconomic position. RESULTS: During the COVID-19 period, DKA incidence was 58.2%, significantly higher than in 2019 (adjusted OR [aOR] 2.18 [95% CI, 1.31-3.60], P = 0.003); 2018 (aOR 2.05 [95% CI, 1.26-3.34], P = 0.004); and 2017 (aOR, 1.79 [95% CI, 1.09-2.93], P = 0.022). The incidence of severe DKA was 19.9%, significantly higher than in 2018 (aOR, 2.49 [95% CI, 1.20-5.19], P = 0.015) and 2017 (aOR, 2.73 [95% CI, 1.28-5.82], P = 0.009). In 2020, admissions and duration of stay in the intensive care unit were higher than in previous years (P = 0.001). During the COVID-19 pandemic, children aged 6-11 years had higher incidences of DKA (61.3% vs. 34.0%, 40.6%, and 45.1%, respectively, P = 0.012), and severe DKA (29.3% vs. 15.1%, 10.9%, and 5.9%, respectively, P = 0.002). CONCLUSIONS: The dramatic increase in DKA at presentation of childhood-onset type 1 diabetes during the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.

Effect of a nutritional supplementation on growth and body composition in short and lean preadolescent boys: A randomised, double-blind, placebo-controlled study.

AIM: To evaluate the effect of nutritional supplementation on height, weight and body composition in short and lean male preadolescents. METHODS: A randomised, double-blinded, placebo-controlled trial of nutritional supplementation of short and lean prepubertal 10-14.5-year-old boys. Primary outcomes included Δheight-SDS and Δweight-SDS. Secondary outcomes included changes in body composition and BMI-SDS. RESULTS: Of 160 boys enrolled, 126 (80%) completed 6 months' intervention. Baseline age, height-SDS, weight-SDS, BMI-SDS, body composition and dietary intake were similar in the formula and placebo groups. 'Good' formula consumers (intake of ≥50% of the recommended dose, n = 30) gained significantly more in weight-SDS, BMI-SDS, fat-free-mass and muscle mass (p < 0.05) than did 'poor' consumers (n = 35) and the placebo group (n = 61). Only in the formula group, positive dose-response correlations were found between consumption of the formula and changes in the outcome parameters examined, including Δheight-SDS (r = 0.301, p = 0.015). Boys aged >11.4 years who were 'good' formula consumers maintained their Δheight-SDS, while Δheight-SDS declined in 'poor' consumers and the placebo group of the same age (p = 0.033). CONCLUSION: Intervention with a multi-nutrient, protein-rich formula was effective in increasing weight-SDS, fat-free-mass, muscle mass and BMI-SDS in short and lean prepubertal male adolescents. Good consumption of the formula prevented Δheight-SDS decline in the older participants.

The impact of preoperative vitamin administration on skeletal status following sleeve gastrectomy in young and middle-aged women: a randomized controlled trial.

BACKGROUND: The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG). METHODS: Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA). RESULTS: Sixty-two females (median age 29.7 years and median BMI 43.4 kg/m2) were recruited, 87% completed the 12-month follow-up. For the intervention and control arms, significant and similar reductions at 12-months post-surgery were observed in BMD of the hip (-6.8 ± 3.7% vs. -6.0 ± 3.6%; P = 0.646) and of the femoral neck (-7.1 ± 5.8% vs. -7.2 ± 5.5%; P = 0.973). For the intervention compared to the control arm, the 25 hydroxyvitamin D (25(OH)D) increment was greater after 2 months treatment, and vitamin D deficiency rates were lower at 3 and 6-months follow-up (P < 0.016). However, at 12-months postoperative, 25(OH)D values and vitamin D deficiency were comparable between the arms (P > 0.339). Predictors for BMD decline in the total hip were the percentage of excess weight-loss, age>50 years, and lower initial BMI (P ≤ 0.003). CONCLUSIONS: SG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline.

Sex-Specific Long-Term Height and Body Mass Index Trajectories of Children Diagnosed with Attention-Deficit/Hyperactivity Disorder and Treated with Stimulants.

OBJECTIVES: To evaluate the sex-specific effects of stimulants in children with attention-deficit/hyperactivity disorder (ADHD) on body mass index (BMI) z and height z trajectories. STUDY DESIGN: A retrospective cohort study using the database of Israel Clalit Health Services was performed. Participants included 5- to 18-year-old insured patients with documentation of at least 2 consecutive prescriptions of stimulant drugs for ADHD. Participants were further compared with sex- and age-matched insured control patients without ADHD. RESULTS: A total of 4561 (66% boys) participants with ADHD were included. Of these, 2151 (70% boys) had follow-up data for ≥2 years of treatment. A decline of ≥1 SD in height and BMI z score was observed in 10.1% and 13.2% of the cohort, respectively. During ≥2 years follow-up, boys had a greater decline in height z score (~0.2 SD) than girls (~0.06 SD). Boys' height z score continued to decline after 1 and ≥2 years, and girls' height z score declined after 1 year, and then stabilized. The trajectory of BMI z score of boys and girls was similar, showing a greater decline after 1 year, followed by an incline after ≥2 years. Younger age at stimulants initiation, better adherence, longer treatment duration, and lower socioeconomic status were correlated with a greater impact on growth attenuation. The non-ADHD group (n = 4561, 66% boys) had baseline height z score and BMI z score similar to those in children with ADHD before treatment initiation. Height z score and BMI z score were greater in children without ADHD compared with children with ADHD following 1 year of treatment (P < .001). CONCLUSIONS: These findings highlight the importance of growth monitoring accompanied with dietary counseling in children with ADHD treated with stimulants.

Dual diagnosis of type 1 diabetes mellitus and attention deficit hyperactivity disorder.

BACKGROUND: Data regarding glycemic control in children and adolescents with a dual diagnosis of type 1 diabetes mellitus (T1DM) and attention-deficit/hyperactivity disorder (ADHD) are limited. OBJECTIVE: To compare various aspects of diabetes control among youth with T1DM, between those with and without ADHD. METHODS: In this cross-sectional study of youth with T1DM, 39 had ADHD (mean age 14.1 ± 2.8 years) and 82 did not (control group, mean age 12.6 ± 3.3 years). Health-related quality of life was assessed by a Diabetes Quality of Life (DQOL) questionnaire submitted to their parents. Glycemic data were downloaded from glucometers, pumps, and continuous glucose monitoring systems. HbA1c levels, hospitalizations, and severe hypoglycemic and diabetes ketoacidosis events were retrieved from the medical files. RESULTS: Compared to the control group mean HbA1c level of the ADHD group was higher: 8.3 ± 1.1% versus 7.7 ± 1.0% (p = 0.005) and the percent of time that glucose level was in the target range (70-180 mg/dl) was lower: 48 ± 17% versus 59 ± 14% (p = 0.006). Mean glucose and glucose variability were higher in the ADHD group. Youth with ADHD who were not pharmacologically treated had worse HbA1c and more hospitalizations than those who were treated. DQOL did not differ between the control group, the treated ADHD group, and the untreated ADHD-Group. CONCLUSIONS: Dual diagnosis of T1DM and ADHD during childhood leads to worse diabetes control, which is more pronounced in the context of untreated ADHD. Healthcare providers should be aware of the difficulties facing youth with T1DM and ADHD in coping with the current intensive treatment of diabetes.

Cardiometabolic outcomes in children and adolescents with West syndrome.

BACKGROUND: West syndrome is a convulsive disorder of infancy with unique seizures and a characteristic background electroencephalograph pattern. Adrenocorticotropic hormone (ACTH) is effective in spasm cessation, yet metabolic consequences of this therapeutic agent in childhood have not been published. METHODS: In this observational study we explored the cardiometabolic outcomes of 117 children with West syndrome (78 ACTH-treated and 39 non-ACTH-treated) monitored at a single medical center from 1995 to 2019 (median follow-up 7.2 years). Outcomes included the prevalence of cardiometabolic derangements (obesity, hypertension, and dyslipidemia) during infancy (< 2 years), early childhood (2-6 years), and childhood/adolescence (6-18 years). RESULTS: The rates of metabolic derangements during infancy in the West syndrome cohort were high compared to childhood/adolescence (obesity 27.3 % vs. 3.3 %, [p = 0.010], diastolic hypertension 48.8 % vs. 5.1 % [p < 0.001], hypertriglyceridemia 71 % vs. 40 % [p = 0.008], low high-density lipoprotein cholesterol [HDL-c] 54.2 % vs. 12.9 % [p = 0.001], and elevated triglycerides/HDL-c ratios 62.5 % vs. 12.9 % [p < 0.001]). The proportion of systolic and/or diastolic blood pressure levels categorized as hypertensive was 58.5 % during infancy, 48.1 % during early childhood, and 26.3 % during childhood/adolescence. ACTH-treated patients had higher weight and weight-to-length z-scores and higher triglyceride levels during infancy compared to non-ACTH-treated patients (p = 0.008, p = 0.001, and p = 0.037, respectively), and higher triglyceride levels during early childhood (p = 0.050), with no significant group differences during childhood/adolescence. CONCLUSIONS: Children with West syndrome apparently have an increased prevalence of cardiometabolic derangements more pronounced in infants and in ACTH-treated patients. These findings highlight the need to monitor these children for cardiometabolic derangements, even though these cardiometabolic abnormalities are transitory and tend to decrease with time. The health implications of cardiometabolic derangements during critical windows of growth and development warrant further investigation.

Growth hormone therapy and short stature-related distress: A randomized placebo-controlled trial.

CONTEXT: Growth hormone (GH) treatment of short healthy children is based on the belief that short stature is associated with psychosocial problems and a diminished quality of life. OBJECTIVE: To determine the impact of GH therapy on psychosocial well-being and the ability of psychological metrics to define short stature-related distress. METHODS: Sixty prepubertal boys with idiopathic short stature (age: 10.0 ± 1.4 years, height-SDS: -2.38 ± 0.3) were enrolled in this 4-year intervention study (1-year double-blinded, randomized, placebo-controlled [GH/placebo-2:1] and 3-year open-labelled GH therapy). Explicit (conscious/voluntary) psychological metrics (Pediatric Quality of Life Inventory [PedsQL], Silhouette Apperception Test [SAT], Rosenberg Self-Esteem Scale [RSES], Child Behavior Checklist [CBCL]) and implicit (unconscious/involuntary) psychological metrics (Single-Category Implicit Association Test for height [SC-IAT-H], Height Perception Picture Test [HPPT]). Psychosocial evaluations were performed at study entry, after 1 and 4 years. RESULTS: At study entry, PedsQL of boys with idiopathic short stature was lower than Israeli norms (P = 0.001). After 1-year blinded intervention, only the GH-treated boys improved their actual and anticipated adult height perception (SAT, P < 0.001 and P = 0.022) with reduced short stature-related distress (SC-IAT-H, P < 0.001). At study end, RSES and SC-IAT-H improved significantly (P < 0.001), with no change in PedsQL and CBCL. CONCLUSIONS: Our finding of improved psychosocial functioning only in the GH-treated boys after 1-year blinded intervention suggests that it was the GH therapy, rather than being enrolled in a clinical trial, which contributed to the outcome. Long-term open-labelled GH treatment significantly improved height perception and self-esteem. Future studies are needed to fully assess the relevance of complementing the routinely used explicit self-report measures with the implicit measures.

Growth hormone therapy in children with idiopathic short stature - the effect on appetite and appetite-regulating hormones: a pilot study.

AIM: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE). METHODS: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months. RESULTS: Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p < .05). Significant changes in appetite-regulating hormones included a decrease in postprandial AUC ghrelin levels (p = .045) and fasting GLP-1 (p = .038), and an increase in fasting insulin (p = .043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r = .667, p = .05; AUC: r = .788, p = .012) and REE (fasting: r = .866, p = .005; AUC: r = .847, p = .008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r = .741, p = .022) and fat-free-mass (r = .890, p = .001) at 12 months of GH treatment. CONCLUSIONS: The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated. ABBREVIATIONS: SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range.

Adjusting insulin doses in patients with type 1 diabetes who use insulin pump and continuous glucose monitoring: Variations among countries and physicians.

AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Randomised study found that improved nutritional intake was associated with better sleep patterns in prepubertal children who were both short and lean.

AIMS: Nutrition and sleep are prerequisites for linear growth and we addressed the under-researched role of sleep in this equation. METHODS: This was a prospective randomised, double-blinded, placebo-controlled study of nutritional supplements in 164 healthy lean, short, prepubertal children with 83 in the supplement group and 81 in the placebo group. From November 2010 to November 2013, we focussed on children aged three to nine years referred for specialist growth assessments to the Schneider Children's Medical Center, Israel. Progress was assessed using anthropometric measurements, sleep questionnaires and three-day food diaries at baseline and after the six-month intervention. RESULTS: Children in the supplement group who took at least 50% of the recommended dose had shorter sleep latency than those who did not (p = 0.046). Children who fell asleep in less than 15 minutes had significantly improved standard deviation scores for weight (0.25 ± 0.34 versus 0.07 ± 0.36, p = 0.044) and height (0.09 ± 0.13 versus 0.03 ± 0.13, p = 0.057) than those who took longer to fall asleep. Positive correlations were found between mean sleep duration and caloric and macronutrient intake per kilogram. CONCLUSION: Adequate nutritional intake was associated with better sleep patterns and may enhance linear growth.