Real-life Achievements of MiniMed™ 780G Advanced Closed Loop System in Youth With Type 1 Diabetes: AWeSoMe Study Group Multi-Center Prospective Trial.

BACKGROUND: We assessed real-life glycemic outcomes and predictors of composite measures of optimal glycemic control in children and adolescents with type 1 diabetes (T1D) during their initial 12 months of the MiniMed™ 780G use. METHODS: This prospective observational multicenter study collected demographic, clinical, and two-week 780G system data at five timepoints. Optimal glycemic control was defined as a composite glycemic control (CGC) score requiring the attainment of four recommended continuous glucose monitoring (CGM) targets, as well as the glycemia risk index (GRI) of hypoglycemia and hyperglycemia and composite CGM index (COGI). Outcome measures included longitudinal changes in multiple glycemic parameters and CGC, GRI, and COGI scores, as well as predictors of these optimal measures. RESULTS: The cohort included 93 children, 43% girls, with a median age of 15.1 years [IQR 12.9,17.0]. A longitudinal analysis adjusted for age and socioeconomic index yielded a significant improvement in glycemic control for the entire cohort (ptime<0.001) after the transition to 780G. The mean HbA1c (SE) was 8.65%(0.12) at baseline and dropped by more than 1% after one year to 7.54%(0.14) (ptime<0.001). Optimal glycemic control measures improved at 12 months post 780G; CGC improved by 5.6-fold (p<0.001) and was attained by 24% of the participants, the GRI score improved by 10-fold (p=0.009) and was achieved by 10% of them, and the COGI improved by 7.6-fold (p<0.001) and was attained by 20% of them. Lower baseline HbA1c levels and increased adherence to AHCL usage were predictors of achieving optimal glycemic control. CONCLUSIONS: The AHCL 780G system enhances glycemic control in children and adolescents with T1D, demonstrating improvements in HbA1c and CGM metrics, albeit most participants did not achieve optimal glycemic control. This highlights yet ongoing challenges in diabetes management, emphasizing the need for continued proactive efforts on the part of healthcare professionals, youth, and caregivers.

An "out of the box" approach for prevention of ketoacidosis in youth with poorly controlled type 1 diabetes: combined use of insulin pump and long-acting insulin.

BACKGROUND: Poorly controlled adolescents living with type 1 diabetes (T1D) and pump failure of insulin delivery leading to diabetic ketoacidosis (DKA) are still challenging in the western world. AIM: To investigate the effect of a combination modality of long-acting insulin for basal coverage and a pump for boluses, on the incidence of DKA and glycemic parameters in pediatric and young adults with poorly controlled T1D. METHODS: This multicenter, observational retrospective study included 55 patients (age range 3-25 years, 52.7% males) who were treated with the combination modality for a median of 18 months [(IQR)12,47], as part of their clinical care. Data were retrieved at initiation of the combined modality, after 6 months, and at last visit. RESULTS: Cohort's median age at combination modality initiation was 14.5 years [IQR12.4,17.3], and its median HbA1c level was 9.2% [IQR 8.2,10.2]. The main reasons for combination modality initiation were: (a) concern about sustained hyperglycemia on current management in 41.8%, (b) previous DKA episodes in 30.8%, and (c) refusal to wear a pump continuously in 14.6%. The percent of patients experiencing DKA who used the modality till end decreased from 25.4 to 8.8%. The frequency of DKA events per patient month decreased after 6 months from 0.073 (min 0, max 0.5) to 0.020 (min 0, max 0.5), p = 0.01, and at end to 0.016 (min 0, max 0.25), p = 0.007. CONCLUSIONS: The combination modality of once-daily long-acting insulin and pump for boluses is safe, feasible, and effective in preventing DKA among poorly controlled young people living with T1D, unable or un-willing to use advanced closed pumps.

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.

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.

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.

Gynecomastia: A systematic review of pharmacological treatments.

Background: Pubertal gynecomastia (PG), a benign condition with varied reported prevalence, typically appears at 13-14 years-old and is mostly idiopathic and self-limited. Psychologic impairments are common among adolescents with gynecomastia. Surgical intervention is reserved to severe cases and is offered towards the end of puberty. Pharmacological treatment is seldom given by clinicians mainly due to insufficient published data. We conducted this systematic literature review to assess the efficacy, safety, side effects, and complications of pharmacological treatments published. Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched for the terms "gynecomastia", "pubertal", and "adolescent" in conjunction with medications from the Selective Estrogen Receptor Modulator (SERM), aromatase inhibitors (AI), and androgens groups in different combinations to optimize the search results. Exclusion criteria included: studies based on expert opinion, similar evidence-based medicine levels studies, and studies which discuss gynecomastia in adults. Selected articles were assessed by two authors. Data collected included: the level of evidence, population size, treatment regimen, follow-up, outcomes, complications, and side effects. Results: Of 1,425 published studies found and examined meticulously by the authors, only 24 publications met all the study research goals. These were divided into 16 publications of patients treated with SERM, of whom four had AI and four androgens. In general, the data regarding pharmacologic therapy for PG is partial, with insufficient evidence-based research. Tamoxifen and SERM drugs have long been used as treatments for PG. Tamoxifen was the chosen drug of treatment in most of the reviewed studies and found to be effective, safe, and with minimal side effects. Conclusions: Pharmacological treatment as a new standard of care has an advantage in relieving behavioral and psychological distress. Although high quality publications are lacking, pharmacological intervention with tamoxifen is appropriate in select patients. Conduction large-scale high-quality studies are warranted with various drugs.

Epidemiologic, microbiologic and imaging characteristics of urinary tract infections in hospitalized children < 2 years of age diagnosed with anatomic abnormalities of the urinary tract.

BACKGROUND: To compare the epidemiologic, microbiologic and imaging characteristics of urinary tract infections (UTI) in children <2 years of age with and without anatomic urinary tract abnormalities (AA). METHODS: All children hospitalized with UTI during 1.1.2005-31.12.2018 were included. The study group (patients with AA) included 76 patients. The control group (99 patients) included patients without AA. RESULTS: 1163 children were hospitalized. Age at diagnosis was younger in the study group vs. controls (5.2 ± 6.0 vs. 7.9 ± 7.5 months, P = 0.038). Uropathogens distribution was different (P = 0.007), with lower Escherichia coli (Ec) and Proteus mirabilis (Pm) percentages in the study group and higher percentages of Enterococcus spp. (Ent) in controls. In the study group, Ec nonsusceptibility rates to ampicillin, amoxicillin/clavulanic acid, cefazolin, cefuroxime, TMP/SMX and ceftriaxone were 58%, 40%, 14%, 14%, 12% and 10%, respectively, with no differences vs. controls. Ultrasound (US) was performed in 69/76 (98%) patients with AA (84.1%, abnormal); bilateral (39.7%) and unilateral (32.7%) ureteral dilatation were the most frequent findings. Voiding cystourethrography was performed in 46 patients (pathologic in 35, 76%); 31 (81.6%) patients had vesicoureteral reflux (VUR) (bilateral in 11, 35.5%; grade 4/5 in 7 patients). Uropathogens distribution in VUR patients differed between study and control groups, with lower Ec and Pm in the first group and higher Pseudomonas aeruginosa and Ent percentages in the control group. CONCLUSION: Age at diagnosis was lower and pathogen distribution was different in patients with AA. Antibiotic susceptibility patterns of the main uropathogens were similar between patients with or without AA.

Attention-Deficit/Hyperactivity Disorder and Obesity: A National Study of 1.1 Million Israeli Adolescents.

PURPOSE: The incidences of obesity and attention-deficit/hyperactivity disorder (ADHD) have increased in parallel over recent decades. We assessed the association between obesity and ADHD in a national sample of adolescents. METHOD: In a nationwide population-based study of 1 118 315 adolescents (57% males; mean age 17 years), risks of obesity were compared between individuals with severe and mild ADHD and those without ADHD. Diagnoses of ADHD were confirmed by specialists in either neurology or psychiatry. Adolescents requiring regular and continuous treatment with stimulants with no improvement of symptoms under treatment were classified as having severe ADHD; data were available from 2004 to 2019. During 2015 to 2019, the diagnosis of ADHD was defined, and 65 118 (16.76%) of 388 543 adolescents with mild symptoms who required medications only for learning or who used stimulants irregularly were defined as having mild ADHD. RESULTS: The prevalence of severe and mild ADHD was 0.3% and 20.1%, respectively. Obesity was more prevalent among adolescents with severe ADHD than among those without ADHD (13.5% vs 7.5%). In the mild ADHD group 12.6% of males and 8.4% of females were diagnosed with obesity compared to 9.7% and 6.4%, respectively, in the non-ADHD group. The adjusted odds of severe ADHD for males and females with obesity were 1.77 (1.56-2.02) and 2.09 (1.63-2.66) times the odds for males and females with low-normal body mass index, respectively, and 1.42 (1.37-1.48) and 1.42 (1.34-1.50) for males and females with mild ADHD, respectively. The elevated risk persisted in several sensitivity analyses. CONCLUSIONS: Both adolescents with severe and mild ADHD are at increased risk for obesity.

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.

Real-World Treatment Patterns and Outcomes of Growth Hormone Treatment Among Children in Israel Over the Past Decade (2004-2015).

Objective: To assess a decade of growth hormone (GH) treatment patterns and outcomes in a real-world setting in Israel using a state-of-the-art computerized database. Methods: This large retrospective database study included 2,379 children initiating GH treatment in Maccabi Healthcare Services (between January 2004 and December 2014). Good adherence with therapy (proportion of days covered >80%) was assessed during follow-up. Results: At GH treatment initiation: 62.1% were boys; height standard deviation score (SDS) was -2.36 ± 0.65 (mean ± SD); age was 9.8 ± 3.1 years; and time from short stature diagnosis to first GH purchase was 4.8 ± 3.3 years. Mean treatment period was 3.5 ± 0.95 years; 79.4% of children were treated for more than 3 years. The two main indications for GH therapy were idiopathic short stature (ISS) (n = 1,615, 67.9%) and GH deficiency (GHD) (n = 611, 25.7%). Children in the highest socio-economic-status (SES) tertile comprised 61.3% of ISS and 59.7% of GHD. After 3 years, mean height gain SDS was 1.09 ± 0.91 for GHD and 0.96 ± 0.57 for ISS (p = 0.0004). Adult height (age 15 for girls and 17 for boys) was recorded for 624 patients (26.2%) with better outcomes for GHD than ISS (-1.0±0.82 vs. -1.28±0.93, respectively; p = 0.0002). Good adherence was achieved in 78.2% of the cohort during the first year and declined thereafter to 68.1% during the third year of the treatment. Conclusions: Children who initiate GH therapy are predominantly male, belong mainly to the upper SES, commence treatment a long period after initial recognition of short stature, and have suboptimal adherence. Appropriate referral, diagnosis, and follow-up care may result in better treatment outcomes with GH therapy.

Serum from type 2 diabetes patients consuming a three-meal diet resets circadian rhythms in cultured hepatocytes.

AIMS: Feeding regimens alter circadian rhythms in peripheral tissues, but the mechanism is not understood. We aimed to study whether soluble factors, rather than neuronal-based communication, directly influence circadian rhythms in the liver, in response to a nutritional treatment in type 2 diabetes (T2D) patients. METHODS: Cultured hepatocytes were treated with serum of insulin-treated T2D patients following either a three-meal diet (3Mdiet) or six-meal diet (6Mdiet) and the circadian expression of clock and metabolic genes was measured. RESULTS: Serum of the 3Mdiet group led to increased amplitudes and daily mRNA levels of the positive limb of the circadian clock (Clock, Bmal1, Rorα). In parallel, serum of the 3Mdiet group led to the downregulation of the negative limb of the circadian clock (Cry1 and Per1), compared to both baseline and 6Mdiet. In contrast, serum of the 6Mdiet group led to a more distorted expression pattern. The catabolic genes Sirt1 and Ampk were significantly upregulated only by serum of the 3Mdiet group. CONCLUSIONS: Our results show that serum of type 2 diabetes patients consuming the 3Mdiet contains soluble factors that reset circadian rhythms leading to an expression pattern similar to that of healthy people. This clock pattern contributes to improved glucose metabolism.

Role of High Energy Breakfast "Big Breakfast Diet" in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes.

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of ß-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., ß-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.

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.

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.

Renin-aldosterone system evaluation over four decades in an extended family with autosomal dominant pseudohypoaldosteronism due to a deletion in the NR3C2 gene.

Renal pseudohypoaldosteronism (PHA1) is a mild form of an aldosterone-resistance syndrome caused by mutations in the NR3C2 gene that codes for the mineralocorticoid receptor (MR). The disease is inherited as an autosomal dominant trait characterized by signs and symptoms of salt-losing in infancy. Disease manifestations could be severe in infancy but improve after the age of 1-3 years. Some affected members are asymptomatic and remain so life-long. In this study, we report the identification of a large deletion in the NR3C2 gene (c.1897+1_1898-1)_(c.*2955+?)del in renal PHA1 patients from an extended family spanning four generations. We prospectively evaluated the plasma renin activity and serum aldosterone profiles over four decades in symptomatic and asymptomatic affected family members. The benefits of early diagnosis on the clinical outcome were assessed as well. The long-term follow-up showed an age-dependent decrease in both plasma renin activity and serum aldosterone levels over the years. However, aldosterone levels remain high life-long. Thus, levels of aldosterone are a reliable marker to detect asymptomatic family members. The diagnosis of the proposita led to early diagnosis and therapy in other affected family members, significantly mitigating the clinical course. Despite the extremely elevated serum aldosterone levels during pregnancy, affected pregnant women did not experience any ill effects. However, this should be verified by observations in other adult 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.

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.

Primary Ovarian Insufficiency Nationwide Incidence Rate and Etiology Among Israeli Adolescents.

PURPOSE: The aim of the study was to estimate the current incidence and the distribution of etiologies of primary ovarian insufficiency (POI) in a nationwide study. The prevalence of POI in young adult women has recently increased, but the data cited for adolescents are more than three decades old. METHODS: Data regarding females aged <21 years diagnosed with POI during the years 2000-2016 were collected from all the pediatric endocrinology units in Israel. POI was defined by at least 4 months of amenorrhea in association with menopausal levels of follicle-stimulating hormone. Iatrogenic cases were excluded. RESULTS: For the 130 females aged <21 years included in the study, the distribution of POI etiologies was Turner syndrome/mosaicism in 56 (43%), idiopathic in 35 (27%), and other (developmental, genetic, metabolic, adrenal, and autoimmune) in 39 (30%) females. During the years 2009-2016, compared with 2000-2008, the incidence rate of new POI diagnoses per 100,000 person-years doubled (4.5 vs. 2.0; p value <.0001), and incidence rates of idiopathic and other etiologies increased by 2.6 (p value = .008) and 3.0 (p value = .002), respectively. In contrast, the incidence of Turner syndrome was constant (p value = .2). In the age group of 15-21 years, the current incidence of non-Turner POI in adolescents is one per 100,000 person-years. CONCLUSIONS: In this nationwide study, the incidence rate of POI in youth aged <21 years was one tenth of the rate that is commonly cited. A significant increase in the rate of POI in non-Turner females was observed over the last decade. Contributions of environmental and epigenetic factors should be studied.