Consumption of cow's milk formula in the nursery and the development of milk allergy.

BACKGROUND: The effect of the amount of transient cow's milk formula (CMF) consumed during the first days of life on IgE-cow's milk allergy (IgE-CMA) is unknown. METHODS: A cohort of 58 patients with IgE-CMA was identified from a large scale population-based study of 13,019 infants followed from birth. A group of 116 infants matched for sex and breastfeeding only duration (beyond the nursery period), and another random group of 259 healthy infants were used as controls. Parents were interviewed and the infants' medical records were searched to assess CMF consumption in the nursery. RESULTS: While 96% of the mothers of the 174 infants (58 with Cow's milk allergy and 116 controls) reported on exclusive breastfeeding during the stay in the nursery, CMF consumption was documented in 96 (55%) of the infants. Of those, most (57; 59%) received one to three feedings, 20 (21%) received four to nine feedings, and 19 (20%) received ≥10 feedings. Fewer formula feeds (1-3) were significantly more common in the allergic group than ≥4 feeds (p = 0.0003) and no feeds at all (p = 0.02) compared to controls (n = 116). Of those exclusively breastfed in the nursery, 13/23 allergic infants (57%) introduced CMF at age 105-194 days (the period with highest-risk for IgE-CMA) compared to 33/98 (34%) from the random control group (n = 259) (p = 0.04). CONCLUSIONS: Most infants end up receiving few CMF feeds in the nursery. Transient CMF in the nursery is associated with increased risk of IgE-CMA.

A comparison of the usage of an open-source automated insulin delivery system and the MiniMed™ 780 G system in children and adolescents with type 1 diabetes in real-world settings: the AWeSoMe study group.

PURPOSE: In recent years there has been a noticeable increase in the use of advanced hybrid closed-loop systems (AHCLs) for managing type 1 diabetes (T1D) among youth. However, there is a lack of comparison between the open-source automated insulin delivery (AID) system and the MiniMed™ 780 G system (780 G). METHODS: In this multi-center study, we retrospectively compared selected glycemic ranges of 26 individuals who used open-source AID and 20 individuals who used 780 G (age 11.3 years [IQR 9.3, 12.9] and 13.4 years [IQR 10.9, 16.5], respectively, p = 0.069) from system initiation to the most recent visit. RESULTS: At baseline, the median HbA1c was significantly lower and the time below range (TBR)<54mg/dL was significantly higher in the open-source AID group compared to the 780 G group (6.8% [IQR 6.4, 7.1] vs. 7.4% [IQR 6.9, 8.6], p = 0.006 and (1.0% [IQR 0.5, 2.8] vs. 0.0% [0.0, 1.0], p = 0.014), respectively; the median time in range (TIR70-180mg/dL) was similar (p = 0.068). After a median duration of 10.9 months on AHCLs the reduction of HbA1c was similar ( ~ 0.3%). The time spent in the hypoglycemic ranges was longer among users of the open-source AID compared to 780 G (TBR54-70mg/dL 4.2% [IQR 2.6, 7.3] vs. 2.0% [1.0, 4.0], p = 0.005) and TBR<54mg/dL 1.1% [IQR 0.4, 2.3] vs. 0.0 [0.0, 1.0], p = 0.001). CONCLUSIONS: Both AHCLs similarly improved HbA1c and TIR70-180mg/dL. The open-source AID youth had better glycemic control but spent longer time in the hypoglycemic range. These findings must be considered when choosing the use of AHCL technologies.

Sexually dimorphic anthropometric measurements in patients with hypospadias and cryptorchidism.

Background: Inappropriate exposure or activity of sex hormones in-utero has been postulated as a leading cause for the development of hypospadias and cryptorchidism. Anthropometric sexually dimorphic traits such as the 2nd to 4th digit ratio (2D:4D), anogenital distance (AGD) and the stretched penile length (SPL), have been associated with androgen and estrogen activity in-utero. Purpose: Evaluate anthropometric parameters in patients with hypospadias or cryptorchidism compared with healthy controls. Materials and methods: This is a case control study of male patients operated on between 2019 and 2020. Three groups were included: Hypospadias, cryptorchidism and a demographically similar control group. Anthropometric parameters 2D:4D, AGD and SPL were measured intra-operatively and compared between the groups. Results: Included in the study were 179 pediatric patients between the ages of 9-15 months (58 patients with hypospadias, 69 with cryptorchidism and 47 controls). There was no difference in AGD, 2D:4D and SPL between patients with cryptorchidism, hypospadias and controls. Conclusions: Anthropometric characteristics associated with androgen activity in utero were not different in patients with hypospadias and cryptorchidism compared with controls.

Open-source automated insulin delivery systems (OS-AIDs) in a pediatric population with type 1 diabetes in a real-life setting: the AWeSoMe study group experience.

PURPOSE: The use of open-source automated insulin delivery systems (OS-AIDs), for the management of type 1 diabetes (T1D), has increased over recent years in all age groups. Real-life data has demonstrated the safety and efficacy of these systems, however, studies in the pediatric population remain limited. In this study, we aimed to examine the effect of transition to an OS-AIDs on glycemic parameters, and on several aspects related to quality of life. In addition, we aimed to characterize the socioeconomic position of families who chose this treatment modality, assess their motivations to do so, and evaluate treatment satisfaction. METHODS: In this multi-center observational real-life study from the AWeSoMe Group, we compared glycemic parameters of 52 individuals with T1D (56% males, mean diabetes duration 4.2 ± 3.9 years), from the last clinic visit prior to OS-AIDs initiation to the most recent clinic visit while using the system. Socioeconomic position (SEP) index was retrieved from the Israel Central Bureau of Statistics. Caregivers completed questionnaires assessing reasons for system initiation and treatment satisfaction. RESULTS: Mean age at OS-AIDs initiation was 11.2 ± 4 years, range 3.3-20.7 years with a median usage duration of 11.1 months (range 3-45.7). Mean SEP Index was 1.033 ± 0.956 (value range: -2.797 to 2.590). Time in range (TIR) of 70 to 180 mg/dl increased from 69.0 ± 11.9 to 75.5 ± 11.7%, (P < 0.001), and HbA1c decreased from 6.9 ± 0.7 to 6.4 ± 0.6%, (P < 0.001). Time in tight range (TITR) of 70 to 140 mg/dl increased from 49.7 ± 12.9 to 58.8 ± 10.8% (P < 0.001). No episodes of severe hypoglycemia or DKA were reported. Reduction in diabetes burden and sleep quality improvement were the main reasons for OS-AID initiation. CONCLUSIONS: In our cohort of youth with T1D, the transition to an OS-AID resulted in greater TIR and less severe hypoglycemia regardless of age, diabetes duration or SEP, which was found to be above average. The overall improvement in glycemic parameters in our study population with excellent baseline glycemic control, provides additional evidence of beneficence and efficacy of OS-AIDs in the pediatric population.

MiniMed 780G Advanced Hybrid Closed-Loop System Outcomes According to Pubertal Status: Awesome Study Group Real-Life Experience.

Background and Aims: Achieving good glycemic control is a major challenge for adolescents with type 1 diabetes (TID). The introduction of the MiniMed 780G system, an advanced hybrid closed-loop (AHCL) that enables an automatic correction of insulin, gave hope for improved glycemic outcomes in adolescents. We assessed specific characteristics associated with glycemic measures in youth with T1D switching to Minimed 780G. Methods: This retrospective observational real-life multicenter study from the AWeSoMe Group assessed continuous glucose monitoring (CGM) metrics of 22 patients (59% females, median age 13.9 interquartile range [IQR 11,18] years), from a high socioeconomic background. CGM metrics were recorded for 2-week periods before AHCL, after 1, 3, 6 months, and at the end of follow-up (median 10.9 [IQR 5.4, 17.4] months). Delta-variables (Δ) were calculated as the difference between the end of follow-up and baseline. Results: Time in range (TIR)70-180mg/dL increased from 65% [52, 72] to 75% [63, 80], P = 0.008, from baseline to end of follow-up. Time above range>180mg/dL decreased from 28% [20, 46] to 22% [14, 35], P = 0.047. Advanced pubertal stage was correlated with less improvement in ΔTAR>180mg/dL, r = 0.47, P = 0.05, and less CGM usage r = -0.57, P = 0.05. A longer disease duration was associated with less improvement in ΔTAR180-250mg/dL, r = 0.48, P = 0.05. Lower pump site change frequency was associated with higher glucose management indicator, r = 0.5, P = 0.03, and lower TIR70-180mg/dL r = -0.52, P = 0.08. Conclusion: The use of AHCL enabled improvements in TIR70-180mg/dL in youth with T1D. More advanced pubertal stages, longer disease duration, and less compliance were associated with less improvement, stressing the need for continuous support, and re-education in this age group.

Missed meal boluses and poorer glycemic control impact on neurocognitive function may be associated with white matter integrity in adolescents with type 1 diabetes.

Background: The notion that pediatric type 1 diabetes impacts brain function and structure early in life is of great concern. Neurological manifestations, including neurocognitive and behavioral symptoms, may be present from childhood, initially mild and undetectable in daily life. Despite intensive management and technological therapeutic interventions, most pediatric patients do not achieve glycemic control targets for HbA1c. One of the most common causes of such poor control and frequent transient hyperglycemic episodes may be lifestyle factors, including missed meal boluses. Objective: The aim of this study was to assess the association between specific neurocognitive accomplishments-learning and memory, inhibition ability learning, and verbal and semantic memory-during meals with and without bolusing, correlated to diffusion tensor imaging measurements of major related tracts, and glycemic control in adolescents with type 1 diabetes compared with their healthy siblings of similar age. Study design and methods: This is a case-control study of 12- to 18-year-old patients with type 1 diabetes (N = 17, 8 male patients, diabetes duration of 6.53 ± 4.1 years) and their healthy siblings (N = 13). All were hospitalized for 30 h for continuous glucose monitoring and repeated neurocognitive tests as a function of a missed or appropriate pre-meal bolus. This situation was mimicked by controlled, patient blinded manipulation of lunch pre-meal bolus administration to enable capillary glucose level of <180 mg/dl and to >240 mg/d 2 hours after similar meals, at a similar time. The diabetes team randomly and blindly manipulated post-lunch glucose levels by subcutaneous injection of either rapid-acting insulin or 0.9% NaCl solution before lunch. A specific neurocognitive test battery was performed twice, after each manipulation, and its results were compared, along with additional neurocognitive tasks administered during hospitalization without insulin manipulation. Participants underwent brain imaging, including diffusion tensor imaging and tractography. Results: A significant association was demonstrated between glycemic control and performance in the domains of executive functions, inhibition ability, learning and verbal memory, and semantic memory. Inhibition ability was specifically related to food management. Poorer glycemic control (>8.3%) was associated with a slower reaction time. Conclusion: These findings highlight the potential impairment of brain networks responsible for learning, memory, and controlled reactivity to food in adolescents with type 1 diabetes whose glycemic control is poor.

The Effect of a Nutritional Supplement on Growth and Body Composition in Short and Lean Preadolescent Boys following One Year of Intervention.

INTRODUCTION: Adequate nutrition plays an important role in linear growth throughout childhood, including puberty. However, not all children are willing or able to consume an adequate and balanced diet daily. We aimed to evaluate the 1-year effectiveness and safety of nutritional supplementation on linear growth, weight gain, and changes in body composition in short and lean peripubertal boys. METHODS: A 1-year, 2-phase multicenter interventional study comprising 1-6 months of a double-blinded intervention with nutritional formula or placebo, followed by 6-12 months of an open-label extension with the nutritional formula for all participants. RESULTS: The outcomes of the double-blinded intervention were reported previously. A total of 79/98 (81%) boys, aged ≥10 years, Tanner stages 1-3, completed the open-labeled extension phase. For this phase, a significant dose-response correlation (p < 0.05) was found of the consumption of the formula with Δ height-SDS, Δ weight-SDS, and Δ muscle mass (crude correlations and after adjustment for baseline age and end-of-study Tanner stage). In the extension phase and in the 12-month analysis, participants who were good formula consumers (intake ≥50% of the recommended dose) maintained their height-SDS, while poor consumers had a significant decline in their height-SDS (p = 0.028 and p = 0.009, between group difference in the extension phase and 12-month analysis, respectively). Between-group differences were not observed in the Tanner stage at any point of the study. No serious adverse events were reported. CONCLUSIONS: An intervention in healthy peripubertal boys suggests that 1-year consumption of a multi-nutrient, protein-rich nutritional supplement is efficacious and safe. The induced changes in growth and body composition, although modest, may be clinically significant. The effect of the formula on growth parameters was not mediated by enhancement of the pubertal tempo.

Early exposures and inherent factors in premature newborns are associated with type 1 diabetes.

BACKGROUND: Pathophysiology of type 1 diabetes (T1D) involves immune responses that may be associated with early exposure to environmental factors among preterm newborns. The aim of this work was to evaluate for association between T1D and maternal, nutritional, and medical exposures during the neonatal period among premature newborns. METHODS: This is a multicenter, matched case-control study. Preterm newborns, who developed T1D before 18 years, were matched by sex, gestational age (GA), birth date, and medical center of birth with newborns who did not develop TID. Data included maternal medical history, birth weight (BW), length of hospitalization, enteral and parenteral medications, fluid administration, and feeding modalities during hospitalization. RESULTS: Fifty-two patients with T1D, 26 males, median age at T1D diagnosis 8.17 years (5.92-9.77), median GA 34 weeks (33-m36), and 132 matched controls, were included. Multivariate-conditional-regression demonstrated a significant association between T1D and any maternal illness (23.1% vs. 9.1%, OR = 4.99 (1.69-14.72), p = 0.004), higher BW-SDS (0.07 ± 0.95 vs. -0.27 ± 0.97, OR = 2.03 (1.19-3.49), p = 0.01), longer duration of glucose infusion (3 (1-5) days vs. 2 (0-4), OR = 1.23 (1.03-1.46), p = 0.02), and antibiotic therapy beyond the first week of life (19.2% vs. 6.9%, OR = 5.22 (1.32-20.70), p = 0.019). Antibiotic treatment during the first week of life was negatively associated with T1D (51.9% vs. 67.2%, OR 0.31 (0.11-0.88), p = 0.027). CONCLUSIONS: A novel association was demonstrated between the development of T1D and early interventions and exposures among preterm newborns. IMPACT: Type 1 diabetes mellitus during childhood may be associated with early exposures during the neonatal period, in addition to known maternal and neonatal metabolic parameters. Early exposure to intravenous antibiotics, differing between the first week of life and later, and longer parenteral glucose administration to preterm newborns were associated with childhood type 1 diabetes. This is in addition to familiar maternal risk factors. Future prospective studies should examine the microbial changes and immune system characteristics of preterm and term neonates exposed to parenteral antibiotics and glucose treatment, in order to validate our exploratory findings.

Youth-onset type 2 diabetes in Israel: A national cohort.

BACKGROUND: Prevalence of youth-onset type 2 diabetes (T2D) has increased worldwide, paralleling the rise in pediatric obesity. Occurrence and clinical manifestations vary regionally and demographically. OBJECTIVES: We assessed the incidence, and clinical and demographic manifestations of youth-onset T2D in Israel. METHODS: In a national observational study, demographic, clinical, and laboratory data were collected from the medical records of children and adolescents, aged 10-18 years, diagnosed with T2D between the years 2008 and 2019. RESULTS: The incidence of youth-onset T2D in Israel increased significantly from 0.63/100,000 in 2008 to 3.41/100,000 in 2019. The study cohort comprised 379 individuals (228 girls [59.7%], 221 Jews [58.3%], mean age 14.7 ± 1.9 years); 73.1% had a positive family history of T2D. Mean body mass index (BMI) z-score was 1.96 ± 0.7, higher in Jews than Arabs. High systolic (≥ 130 mmHg) and diastolic blood pressure (≥ 85 mmHg) were observed in 33.7% and 7.8% of patients, respectively; mean glycosylated hemoglobin (A1c) level at diagnosis was 8.8 ± 2.5%. Dyslipidemia, with high triglyceride (>150 mg/dl) and low HDL-c (<40 mg/dl) levels, was found in 45.6% and 56.5%, respectively. Microalbuminuria and retinopathy were documented at diagnosis, 15.2% and 1.9%, respectively) and increased (36.7% and 4.6%, respectively) at follow-up of 2.9 ± 2.1 years. Criteria of metabolic syndrome were met by 224 (62.2%) patients, and fatty liver documented in 65%, mainly Jews. Psychosocial comorbidity was found in 31%. Treatment with metformin (45.6%), insulin (20.6%), and lifestyle modification (18%) improved glycemic control. CONCLUSION: Youth-onset T2D in Israel has increased significantly and presents a unique profile.

Symptoms and Glycemic Control in Young People With Type 1 Diabetes Following SARS-CoV-2 Infection: An Observational Study.

CONTEXT: Data is needed regarding the effect of SARS-CoV-19 infection on young people with established type 1 diabetes. Identifying the disease outcomes, short and long-term sequelae may help to establish an evidence-based prevention and education policy for sick days management and DKA prevention. OBJECTIVE: This work aims to describe clinical manifestations of SARS-CoV-2 infection in children, adolescents, and young adults with established type 1 diabetes (T1D) and explore the effects of COVID-19 on glycemic control and disease course. METHODS: An observational study was conducted at 3 pediatric diabetes clinics in Israel between mid-March 2020 and mid-March 2021. Included were young people with established T1D, age younger than 30 years, who tested positive for SARS-CoV-2 (quantitative real-time polymerase chain reaction). Data were collected from medical files, diabetes devices, and COVID-19 questionnaire. Outcome measures were analyzed by the presence/absence of clinical symptoms (symptomatic/asymptomatic) and by age group (pediatric, < 19 years/young adults, 19-30 years). RESULTS: Of 132 patients, mean age 16.9 ±â€…5.3years, with COVID-19-confirmed infection, 103 (78%) had related symptoms; the most common were headaches, fatigue, fever, and loss of sense of smell. All had a mild disease course, but 4 required hospitalization and 2 cases were directly related to COVID-19 infection (pleuropneumonia in a patient with immunodeficiency syndrome, 1 case of diabetic ketoacidosis). Logistic regression analysis showed that age (odds ratio [OR] = 1.11; 95% CI, 1.01-1.23; P = .033), elevated glucose levels (OR = 5.23; 95% CI, 1.12-24.41; P = .035), and comorbidities (OR = 8.21; 95% CI, 1.00-67.51; P = .050) were positively associated with symptomatic infection. Persistent symptoms occurred in 16.5% of the cohort over a median of 6.7 months; age (OR = 1.14; 95% CI, 1.01-1.29; P = .030) and elevated glucose levels (OR = 3.42; 95% CI, 1.12-10.40; P = .031) were positively associated with persistent symptoms. Usually, no change was reported in glucose levels (64%) except for a temporary deterioration in glycemic control during the short infection period. CONCLUSION: Young people with established T1D experience mild COVID-19 infection. Elevated glucose levels during COVID-19 infection and older age were associated with prolonged disease course.

The Gut Microbiome of Adults With Type 1 Diabetes and Its Association With the Host Glycemic Control.

OBJECTIVE: Previous studies have demonstrated an association between gut microbiota composition and type 1 diabetes (T1D) pathogenesis. However, little is known about the composition and function of the gut microbiome in adults with longstanding T1D or its association with host glycemic control. RESEARCH DESIGN AND METHODS: We performed a metagenomic analysis of the gut microbiome obtained from fecal samples of 74 adults with T1D, 14.6 ± 9.6 years following diagnosis, and compared their microbial composition and function to 296 age-matched healthy control subjects (1:4 ratio). We further analyzed the association between microbial taxa and indices of glycemic control derived from continuous glucose monitoring measurements and blood tests and constructed a prediction model that solely takes microbiome features as input to evaluate the discriminative power of microbial composition for distinguishing individuals with T1D from control subjects. RESULTS: Adults with T1D had a distinct microbial signature that separated them from control subjects when using prediction algorithms on held-out subjects (area under the receiver operating characteristic curve = 0.89 ± 0.03). Linear discriminant analysis showed several bacterial species with significantly higher scores in T1D, including Prevotella copri and Eubacterium siraeum, and species with higher scores in control subjects, including Firmicutes bacterium and Faecalibacterium prausnitzii (P < 0.05, false discovery rate corrected for all). On the functional level, several metabolic pathways were significantly lower in adults with T1D. Several bacterial taxa and metabolic pathways were associated with the host's glycemic control. CONCLUSIONS: We identified a distinct gut microbial signature in adults with longstanding T1D and associations between microbial taxa, metabolic pathways, and glycemic control indices. Additional mechanistic studies are needed to identify the role of these bacteria for potential therapeutic strategies.

Prediction of Personal Glycemic Responses to Food for Individuals With Type 1 Diabetes Through Integration of Clinical and Microbial Data.

OBJECTIVE: Despite technological advances, results from various clinical trials have repeatedly shown that many individuals with type 1 diabetes (T1D) do not achieve their glycemic goals. One of the major challenges in disease management is the administration of an accurate amount of insulin for each meal that will match the expected postprandial glycemic response (PPGR). The objective of this study was to develop a prediction model for PPGR in individuals with T1D. RESEARCH DESIGN AND METHODS: We recruited individuals with T1D who were using continuous glucose monitoring and continuous subcutaneous insulin infusion devices simultaneously to a prospective cohort and profiled them for 2 weeks. Participants were asked to report real-time dietary intake using a designated mobile app. We measured their PPGRs and devised machine learning algorithms for PPGR prediction, which integrate glucose measurements, insulin dosages, dietary habits, blood parameters, anthropometrics, exercise, and gut microbiota. Data of the PPGR of 900 healthy individuals to 41,371 meals were also integrated into the model. The performance of the models was evaluated with 10-fold cross validation. RESULTS: A total of 121 individuals with T1D, 75 adults and 46 children, were included in the study. PPGR to 6,377 meals was measured. Our PPGR prediction model substantially outperforms a baseline model with emulation of standard of care (correlation of R = 0.59 compared with R = 0.40 for predicted and observed PPGR respectively; P < 10-10). The model was robust across different subpopulations. Feature attribution analysis revealed that glucose levels at meal initiation, glucose trend 30 min prior to meal, meal carbohydrate content, and meal's carbohydrate-to-fat ratio were the most influential features for the model. CONCLUSIONS: Our model enables a more accurate prediction of PPGR and therefore may allow a better adjustment of the required insulin dosage for meals. It can be further implemented in closed loop systems and may lead to rationally designed nutritional interventions personally tailored for individuals with T1D on the basis of meals with expected low glycemic response.

Are current cut-off values of 11-DOC in children useful for assessing suspected nonclassical congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency?

OBJECTIVE: A nonclassic form of 11ß-hydroxylase deficiency (NC11ß-OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11-deoxycortisol (11-DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11-DOC level cutoffs. One of the accepted references for 11-DOC levels for the paediatric population was published in 1991 by Lashansky et al. AIM: To determine the correlation between 11-DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11ß-OHD. DESIGN: A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients' medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11-DOC cut-off levels according to Lashansky for sex and age, and according to commercial kit cut-offs. RESULTS: Data were complete at presentation for 136 patients. Long-term clinical data were documented for 98 patients, mean follow-up duration of 3.1 years (1.37-5.09). There was no statistically significant difference in the number of cases with elevated 11-DOC according to both cut-offs and early puberty, premature adrenarche nor acne. Follow-up data demonstrated no statistically significant difference in the number of cases with elevated 11-DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism. CONCLUSIONS: Basal and corticotropin stimulated 11-DOC levels were not significantly elevated above the 1.5 times cut-offs according to paediatric-specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11ß-OHD.

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.

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.

Novel perspectives of super-high dose sulfonylurea and high-dose oral prednisolone in an infant with DEND syndrome due to V64M heterozygote KCNJ11 mutation.

AIMS: To report a novel mutation associated with developmental delay, epilepsy, and neonatal diabetes-DEND Syndrome, responsive to a novel management combination. METHODS: We describe the investigation, treatment, and genetic diagnosis of a newborn diagnosed with DEND syndrome. RESULTS: The patient was found to be de-novo heterozygous for pathogenic KCNJ11 missense variant: c.190G > A, p. (Val64Met), associated with DEND syndrome, responsive to a combination of super high doses of sulfonylurea (SU) and oral high-dose steroids. A single case was reported so far due to this mutation, presenting with severe DEND syndrome, treated by insulin only. His phenotypic description and management during 18 months, demonstrates this mutation is responsive to super-high doses of SU combined with high dose 6 weeks steroids protocol. CONCLUSIONS: We have identified a heterozygous missense mutation as the etiology for severe DEND syndrome in a one-day old neonate, presenting with asymptomatic hyperglycemia, responsive to a novel management combination.

Glycaemic control in the paediatric and young adult population with type 1 diabetes following a single telehealth visit - what have we learned from the COVID-19 lockdown?

AIMS: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of paediatric individuals with type 1 diabetes (T1D). METHODS: An observational multicentre real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e. change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100). RESULTS: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6 ± 5.3 years, and diabetes duration 6.0 ± 4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9 ± 16.0, p < 0.001 vs. 59.0 ± 17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180-250 mg/dl range, higher daily insulin dose, and single-parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively. CONCLUSIONS: Paediatric and young adult patients with T1D benefited from a telehealth visit during COVID-19. However, this modality is not yet suitable for a considerable proportion of patients.

Lessons learned from the continuous glucose monitoring metrics in pediatric patients with type 1 diabetes under COVID-19 lockdown.

AIMS: Billions of people have been under lockdown in an attempt to prevent COVID-19 spread. Lifestyle changes during lockdown could lead to deterioration of glycemic control in type 1 diabetes (T1D). We aimed to assess the impact of COVID-19 lockdown on the glycemic control of pediatric patients with T1D. METHODS: This observational real-life study from the AWeSoMe Group assessed continuous glucose monitoring (CGM) metrics of 102 T1D patients (52.9% males, mean age 11.2 ± 3.8 years, mean diabetes duration 4.2 ± 3.8 years) who used  Dexcom G5. The data were accessed without any interface between patients, caregivers, and the diabetes team. Study variables from CGM metrics were: mean glucose level, time-in-range (TIR, 70-180 mg/dL; 3.9-10 mmol/L), hypoglycemia (< 54 mg/dL; < 3 mmol/L), hyperglycemia (> 250 mg/dL; > 13.3 mmol/L), coefficient of variation (CV), and time CGM active before and during lockdown. Delta-variable = lockdown variable minus before-lockdown variable. RESULTS: The mean TIR was 60.9 ± 14.3% before lockdown, with no significant change during lockdown (delta-TIR was 0.9 ± 7.9%). TIR during lockdown was significantly correlated with TIR before lockdown (r = 0.855, P < 0.001). Patients with improved TIR (delta-TIR > 3%) were significantly older than patients with stable or worse TIR (P = 0.028). Children aged < 10 years had a significantly higher CV before lockdown and during lockdown than children aged ≥ 10 years (P = 0.02 and P = 0.005, respectively). Among children aged < 10 years, a multiple linear regression model revealed associations of age and lower socioeconomic cluster with delta-TIR (F = 4.416, P = 0.019) and with delta-mean glucose (F = 4.459, P = 0.018). CONCLUSIONS: CGM metrics in pediatric patients with T1D were relatively stable during a nationwide lockdown. Intervention plans should focus on younger patients with lower socioeconomic position.