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The use of insulin pumps in pediatric patients with type 1 diabetes (T1D) has expanded; however, data comparing devices remain scarce. We compared glycemic control, technical difficulties, and quality of life (QOL) between pump devices of three companies.This prospective observational trial is based on clinical data retrieved during 12 months of follow-up of pediatric patients who started pump therapy as part of their clinical care in four medical centers. The devices fully reimbursed by the national health insurance are as follows: MiniMed™ 640G, MiniMedOf 113 children (mean age 9.1 ± 4.1 years, 46% females), 68 (60%) used Medtronic devices, 33 (29%) OmniPod, and 12 (11%) Animas devices. Twelve percent of the cohort stopped using the pump during the study period, with no difference according to device. There were no differences between groups regarding mean SMBG values (P = 0.86), insulin TDD (P = 0.24), BMI (P = 0.87), level of insertion site pain or local reaction (P = 0.51), technical problems (P = 0.66), and QOL (P = 0.38). Changes in HbA1c from study initiation to end were also not statistically significant for any of the devices: from 7.99% ± 1.14% to 7.93% ± 0.99% for Medtronic, from 7.71% ± 1.29% to 7.92% ± 1.38% for OmniPod, and from 8.75% ± 1.3% to 7.70% ± 1.33% for Animas (P = 0.63).Pump devices were comparable regarding glycemic control, weight gain, and satisfaction among pediatric patients with T1D.

To examine the effectiveness and safety over a 12-month period of a telemedicine intervention in adults with type 1 diabetes (T1D) treated with insulin pumps. 74 T1D patients on insulin pumps for at least 1 year (mean 19.5 [11.5] years) and HbA1c ≥ 6.5% (≥ 48 mmol/mol) were randomized to the telemedicine (n = 37) or the standard care group (n = 37). The intervention group was instructed to download data from insulin pumps and glucometers monthly. They received immediate phone feedback and recommendations for insulin dose adjustment; and face-to-face visits once in 6 months, compared to once every 3 months for the standard care group. Satisfaction with treatment, quality of life and frequency of hypoglycemic events was evaluated. The mean changes in HbA1c adjusted to baseline were − 0.08% (0.25 mmol/mol) vs. − 0.01% (0.03 mmol/mol), in the intervention and control groups, respectively (p = 0.18) at 12 months, without an increased frequency of hypoglycemia. Patients in the intervention group felt satisfied and interested in continuing with the treatment (p = 0.04). The quality of life scores were similar in both groups. Direct total costs were 24% less in the intervention group, and indirect total costs decreased by 22% compared to the year preceding the study. Internet-based insulin dose adjustment is as effective and safe as routine care in adults with type 1 diabetes treated by insulin pumps. For suitable patients, some of the time-consuming routine visits may be replaced by user-friendly digital medicine. Clinical Trial.gov Identifier NCT01887431.

To compare clinical outcomes of 3 treatment regimens-glucocorticoids (GCs), oral contraceptives (OCs), or a combination of both-administered to adolescents and young women diagnosed in childhood with nonclassical congenital adrenal hyperplasia (NCCAH), who had been treated with GCs until their adult height was achieved.A retrospective study of medical records of 53 female patients with NCCAH followed in 3 tertiary pediatric endocrinology institutes. The 3 treatment groups were compared for the prevalence of hirsutism and acne, standardized body mass index (BMI)-standard deviation score (SDS), and androgen levels at the attainment of adult height (baseline), 1-year later, and at the last documented visit.At baseline, there were no significant differences among groups in BMI-SDS, androgen levels, hirsutism prevalence, acne, or irregular menses. From baseline to the last visit, the rate of hirsutism declined significantly only in the OC group (37.5% vs 6.2%, respectively; P = .03). The rate of acne declined in the combined group (50% vs 9%, respectively; P = .03) with a similar tendency in the OC group (50% vs 12.5%, respectively; P = .05). No significant changes were observed in BMI-SDS for the entire cohort or any subgroup during follow-up. A significant rise in androstenedione (P.001), testosterone (P.01), and 17-hydroxyprogesterone (P.01) levels was observed only in the OC group.In girls diagnosed in childhood with NCCAH, who require treatment for hyperandrogenism following completion of linear growth, management should be tailored individually using a patient-centered approach. Treatment with OCs might be better than that with GCs for regression of hirsutism and acne. The long-term effects of elevated levels of androgens associated with this treatment regimen should be further studied.

Background and Purpose: There is a continuous rise in the prevalence of adolescent obesity and incidence of stroke among young adults in many Western countries, but the association between them is unclear. Methods: A nationwide population-based study of 1 900 384 Israeli adolescents (58% men; mean age, 17.3 years) who were evaluated before mandatory military service during 1985 and 2013. Body mass index was classified according to the US Center for Disease Control and Prevention percentiles. Primary outcome was a first stroke event as recorded by the Israeli National Stroke Registry between 2014 and 2018. Cox proportional hazard models were applied. Results: There were 1088 first stroke events (921 ischemic and 167 hemorrhagic; mean diagnosis age, 41.0 years). Adolescent body mass index was significantly associated with a graded increase in the risk for any stroke, ischemic stroke, but less so with hemorrhagic stroke. The hazard ratios for the first ischemic stroke event were 1.4 (95% CI, 1.2–1.6), 2.0 (95% CI, 1.6–2.4), and 3.4 (95% CI, 2.7–4.3) for the 50th to 84th percentile, overweight and obese groups, respectively, after adjustment for sex, age, and sociodemographic confounders with the 5th to 49th body mass index percentile group as the reference. The respective hazard ratios after further adjustment for diabetes status were 1.3 (1.1–1.5), 1.6 (1.3–2.0), and 2.4 (1.9–3.1). Results persisted when the cohort was divided by diabetes status and when ischemic stroke before age 30 was the outcome. Conclusions: High adolescent body mass index was associated with ischemic stroke in young adults with or without diabetes. The rising prevalence of adolescent obesity may increase the future burden of stroke in young adults.

Multiple sclerosis (MS) is a chronic disease marked by progressive disability and decreased mobility over time. We studied whether individuals with MS of higher disability levels will be more overweight/obese as a result of their immobility and/or recurrent steroid treatments. In a prospective study, 130 individuals with MS and significant disability were classified according to the Expanded Disability Status Scale (EDSS) score as belonging to four groups: EDSS 3.0–4.0 (n = 31, 24%), EDSS 4.5–5.5 (n = 24, 18%), EDSS = 6.0 (n = 44, 34%) and EDSS ≥ 6.5 (n = 31, 24%). Medical history, body mass index (BMI), waist circumference and the level of engagement in physical activity were obtained. The mean ± standard error age was 55.8 ± 0.5 years, disease duration 18.2 ± 1.0 years and EDSS score 5.5 ± 0.1. Disease duration, the number of steroid courses per disease duration, weight, BMI and physical activity did not differ according to the four disability groups. The mean waist circumference increased significantly with increased severity of EDSS, p = 0.03. Increased disability in individuals with MS was not correlated with disease duration, lifestyle habits or overweight/obesity. However, increased disability was associated with central obesity.

Context Thyroid hormones play a key role in systemic metabolism, yet the relationship between thyroid dysfunction and risk for type 2 diabetes is unclear. Objective To assess type 2 diabetes risk in adulthood among adolescents with thyroid disorders. Design and Setting A nationwide, population-based study of Israeli adolescents who were examined before military recruitment during 1988 to 2007 and were followed until December 31, 2016. Participants 1 382 560 adolescents (mean age 17.3 years). Interventions The diagnosis of thyroid disorders was based on recent thyroid function tests. Data were linked to the Israeli National Diabetes Registry. Cox proportional hazard models were applied. Main Outcome Measures Type 2 diabetes incidence. Results During a mean follow-up of 18.5 years, 1.12% (69 of 6,152) of adolescents with thyroid disorders were diagnosed with type 2 diabetes vs 0.77% of adolescents without thyroid disorders. The hazard ratio (HR) for type 2 diabetes was 2.3 (95% CI, 1.8-2.9) among those with thyroid disorders, after adjustment for sex, birth-year, body mass index, and sociodemographic confounders. The increased diabetes risk was observed in both men and women, with the presence or absence of obesity, and in the absence of other health conditions and was associated with different types of thyroid disorders. It was also similar when the outcome was defined as type 2 diabetes diagnosed at or before the age of 30 years (HR 2.3, 95% CI, 1.5-3.5). Conclusions Thyroid disorders diagnosed in adolescence are a risk factor for early-onset type 2 diabetes in both men and women.

Background The prevalence of both asthma and early-onset diabetes is on the rise; however, the association between them remains unclear. We examined a possible association of asthma at adolescence with type 2 diabetes in young adulthood. Methods This is a nationwide, population-based study of 1 718 541 Israeli adolescents (57% males; mean age 17.3 years; range 16-19 years), examined before compulsory military service between 1992 and 2016, with data linked to the Israeli National Diabetes Registry. Asthma diagnosis and severity were determined by a board-certified pulmonologist and based on spirometry tests. Results Type 2 diabetes developed in 58/9090 (0.64%), 507/97 059 (0.52%), 114/23 332 (0.49%), and 7095/1 589 060 (0.44%) persons with moderate-to-severe, mild, inactive, and no history of asthma, respectively, during a mean follow-up >13 years. The respective odds ratios (ORs) were 1.33 (95% CI, 1.02-1.74), 1.17 (1.06-1.28), and 1.09 (0.9-1.31), considering those without asthma history as the reference, in a model adjusted for birth year, sex, body mass index, and other sociodemographic variables. The association persisted when the analysis accounted for coexisting morbidities, and when persons without asthma, individually matched by age, sex, birth year, and body mass index were the reference. Both mild and moderate-to-severe asthma were associated with type 2 diabetes before age 35 years: ORs 1.18 (1.05-1.34) and 1.44 (1.05-2.00), respectively. The strength of the association was accentuated over time. The effect was unchanged when adjusted for oral and inhaled glucocorticoid use. Conclusion Adolescents with active asthma have higher risk to develop type 2 diabetes. This seems related to disease severity, independent of adolescent obesity status, apparent before age 35 years, and more pronounced in recent years.

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 ( 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 3%) were significantly older than patients with stable or worse TIR (P = 0.028). Children aged

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.

Among adults with type 2 diabetes (T2D), cognitive behavioral therapy (CBT), acceptance and commitment therapy, and mindfulness interventions have demonstrated improvement in depression, anxiety, and glycemic control. We assessed whether these treatment modalities have shown usefulness in adolescents with T2D or at risk for T2D. Data are limited on the use of the abovementioned therapeutic interventions and include only adolescent girls at risk for T2D. CBT was as useful as health education sessions. At 1 year, greater decreases in depression, insulin resistance, and BMI were observed in girls randomized to mindfulness compared with CBT groups. Given the positive outcome of mindfulness intervention in adults and in adolescent girls at risk for T2D, future studies should involve males at risk for T2D, and adolescents diagnosed with T2D. Longer interventions and booster meetings for maintenance should be studied.

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

Background We assessed in a nationwide cohort the association between adolescent BMI and early-onset ( Methods Normoglycemic adolescents (range 16–20 years old), including 93,806 native Israelis (≥ 3rd generation in Israel) and 27,684 Israelis of Ethiopian origin, were medically assessed for military service between 1996 and 2011. Weight and height were measured. Data were linked to the Israeli National Diabetes Registry. Incident type 2 diabetes by December 31, 2016 was the outcome. Cox regression models stratified by sex and BMI categories were applied. Results 226 (0.29%) men and 79 (0.18%) women developed diabetes during 992,980 and 530,814 person-years follow-up, respectively, at a mean age of 30.4 and 27.4 years, respectively. Among native Israeli men with normal and high (overweight and obese) BMI, diabetes incidence was 9.5 and 62.0 (per 105 person-years), respectively. The respective incidences were 46.9 and 112.3 among men of Ethiopian origin. After adjustment for sociodemographic confounders, the hazard ratios for type 2 diabetes among Ethiopian men with normal and high BMI were 3.4 (2.3–5.1) and 15.8 (8.3–30.3) respectively, compared to third-generation Israelis with normal BMI. When this analysis was limited to Israeli-born Ethiopian men, the hazard ratios were 4.4 (1.7–11.4) and 29.1 (12.9–70.6), respectively. Results persisted when immigrants of other white Caucasian origin were the reference; and among women with normal, but not high, BMI. Conclusions Ethiopian origin is a risk factor for early-onset type 2 diabetes among young men at any BMI, and may require selective interventions.

Introduction In a nationwide population of adolescents, we investigated the sex-specific association of socioeconomic position (SEP) with severe obesity, and trends over time. Methods The cohort comprises all Israeli adolescents (mean ± SD age 17.3 ± 0.5 years) who were medically examined, before mandatory military service during 2000 to 2015. Of 1 120 362 adolescents, 239 816 (21.4%) were classified with overweight or with obesity classes I to III using the International Obesity Task Force criteria. Data were compared between 2000 to 2009 and 2010 to 2015. Results Considering more advantaged residential SEP as the reference group, the respective odds ratios (ORs ± 95%CI) of less advantaged SEP for obesity classes I to III in 2010 to 2015 were 1.48 (1.40-1.56), 1.66 (1.51-1.83), and 1.73 (1.45-2.08) for males; and 1.72 (1.60-1.84), 1.89 (1.66-2.15), and 2.62 (2.04-3.37) for females. All point estimates were higher than in the preceding decade. Considering female inductees from the more advantaged SEP as the reference group, ORs were higher for males in the more advantaged SEP group, for overweight, 1.31 (1.27-1.36); class I obesity, 1.29 (1.20-1.38); class II obesity, 1.34 (1.18-1.53); and class III obesity, 1.60 (1.24-2.07). Similarly, in the less and medium advantaged SEP groups, increased ORs for males compared with females were observed in all obesity groups. Results persisted using United States Centers for Disease Control and Prevention growth charts. Conclusions Adolescents with less rather than more advantaged residential SEP are at greater risk of severe obesity. Adolescent males, of all residential SEP groups had higher odds than females for all classes of obesity.

A 22-year old female with type 1 diabetes (T1DM) presented with generalized rash. She was diagnosed at the age of 9 years and is treated with insulin pump and CGMS (continues glucose monitoring sensors), her recent HbA1c was 7.4%. Four weeks prior to her rash presentation she started a low carbohydrate diet (50 gr of carbs per day) in order to improve her glycemic control. Pruritic erythematous papules, papulovesicular, and vesicles appeared on her axillary region, upper back and groins. Lesions were associated with severe pruritus and negatively affected her quality of life. Various therapies were initiated by dermatologist as: antifungal agent, Itraconazole, and Betamethasone Esters, without any improvement. Her serum beta-hydroxybutyrate levels were between 1.1-1.2 mmol/l. Prurigo pigmentosa, a rare pruritic inflammatory dermatosis secondary to her high ketones levels was diagnosed. Her condition resolved after she increased her carbohydrate intake to 75 gr per day. Beta-hydroxybutyrate level decreased concomitantly to 0.1-0.2 mmol/l. When carbohydrate restriction was rechallenged, she again entered ketosis, followed by recurrence of the pruritic lesions. Carbohydrate intake was increased and subsequently all lesions resolved with remaining reticular hyperpigmentation. During the last few years low carb diets have gained popularity among patients with T1DM. This case illustrates the rare side effect of high ketones body levels. Health care providers should be familiar with this side effect. Disclosure N. levran: None. K. Mazor-Aronovitch: None. S. Grenberger: None. N. Levek: None. B. Sher: None. E. Mauda: None. Z. Landau: None. E. Monsonego-Ornan: None. O. Pinhas-Hamiel: None.

OBJECTIVE Type 2 diabetes (T2D) is increasingly diagnosed at younger ages. We investigated the association of adolescent obesity with incident T2D at early adulthood. RESEARCH DESIGN AND METHODS A nationwide, population-based study evaluated 1,462,362 adolescents (59% men, mean age 17.4 years) during 1996–2016. Data were linked to the Israeli National Diabetes Registry. Weight and height were measured at study entry. Cox proportional models were applied. RESULTS During 15,810,751 person-years, 2,177 people (69% men) developed T2D (mean age at diagnosis 27 years). There was an interaction among BMI, sex, and incident T2D (Pinteraction = 0.023). In a model adjusted for sociodemographic variables, the hazard ratios for diabetes diagnosis were 1.7 (95% CI 1.4–2.0), 2.8 (2.3–3.5), 5.8 (4.9–6.9), 13.4 (11.5–15.7), and 25.8 (21.0–31.6) among men in the 50th–74th percentile, 75th–84th percentile, overweight, mild obesity, and severe obesity groups, respectively, and 2.2 (1.6–2.9), 3.4 (2.5–4.6), 10.6 (8.3–13.6), 21.1 (16.0–27.8), and 44.7 (32.4–61.5), respectively, in women. An inverse graded relationship was observed between baseline BMI and mean age of T2D diagnosis: 27.8 and 25.9 years among men and women with severe obesity, respectively, and 29.5 and 28.5 years among low-normal BMI (5th–49th percentile; reference), respectively. The projected fractions of adult-onset T2D that were attributed to high BMI (≥85th percentile) at adolescence were 56.9% (53.8–59.9%) and 61.1% (56.8–65.2%) in men and women, respectively. CONCLUSIONS Severe obesity significantly increases the risk for incidence of T2D in early adulthood in both sexes. The rise in adolescent severe obesity is likely to increase diabetes incidence in young adults in coming decades.

ObjectiveThe number of transgender and gender non-conforming children is on the rise. For these children, the timing of medical intervention is crucial, yet transgender children report poorer overall physical and mental health outcomes compared with their cisgender peers. We aim to describe how paediatricians perceive transgender people.SettingThe ‘Transgender Attitudes and Beliefs Scale’, which consists of 29 items in three domains—human value, interpersonal comfort and sex/gender beliefs—was administered to 391 senior and resident paediatricians in Israel. The responses on a 7-point Likert scale were collapsed into two categories: a mean score of ≥6 for each domain was a ‘Favourable’ perception and ResultsOf 355 respondents (91% response rate), 221 (62%) were females, 132 (37%) were males and 2 identified as ‘other’; 290 (82%) were born in ‘trans-respect countries’, 274 (77%) identified as secular, 223 (63%) were senior physicians and 132 (27%) were residents. Overall, 90% of the cohort scored favourably on the ‘Human value’ domain, 68% on ‘Interpersonal comfort’ and 40% on ‘Sex/gender beliefs’. In the ‘Interpersonal comfort’ domain, being a man, birthplace in a transphobic country, identification as religious and being a senior physician were all associated with increased ORs for an unfavourable score: 2.1 (95% CI 1.3 to 3.4), 3.4 (95% CI 1.9 to 6.3), 2.4 (95% CI 1.4 to 4.2) and 1.8 (95% CI 1.1 to 3.0), respectively. In the ‘Sex/gender beliefs’ domain, being a man and identifying as religious had significantly increased ORs for unfavourable scores: 2.2 (95% CI 1.3 to 3.5) and 10.6 (95% CI 4.7 to 24.1), respectively.ConclusionsNegative attitudes towards transgender people are still widespread among paediatricians. Interventions are warranted to positively impact these attitudes.

Severe obesity is rising among adolescents, but data on the prevalence of metabolic abnormalities among this group are limited. We assessed the secular trend of severe obesity and its association with major cardio-metabolic morbidities. A total of 2,785,227 Israeli adolescents (aged 17.2 ± 0.5 years) who underwent a pre-recruitment medical examination including routine measurements of weight, height and blood pressure between 1967 and 2015 were included. In all, 230,639 adolescents with abnormally excessive BMI were classified into overweight, classes I, II, and III (severe) obesity. Logistic regression was applied to determine the association between BMI groups and prehypertension, high blood pressure and type 2 diabetes (T2DM). There was 45-fold increase in the prevalence of class III obesity during study period. Severe obesity was recorded in 2060 males and 1149 females, in whom nearly 35 and 43% had prehypertension or high blood pressure, respectively. Compared with adolescents with overweight, the odds ratios (ORs) for high blood pressure in classes II and III obesity groups, respectively, were 2.13 (95% CI, 2.04–2.23) and 2.86 (2.60–3.15) in males, and 2.59 (2.43–2.76) and 3.44 (3.04–3.90) in females, whereas the ORs for T2DM were 19.1 (12.3–29.6) and 38.0 (22.6–64.0) in males, and 15.1 (11.4–20.0) and 24.8 (17.2–35.7) in females. Results persisted in extensive sensitivity analyses including a longitudinal follow-up (median: males, 3.4 years; females, 4.9 years). Severe obesity showed a marked secular increase and was associated with significantly higher risk for abnormal blood pressure and T2DM than lower degrees of obesity, in both males and females.

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 pediatric individuals with type 1 diabetes (T1D). Methods: An observational multicenter 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, 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 Conclusions: Pediatric patients with T1D benefited from a telehealth visit during COVID-19. This modality and its benefit should be employed, and used in the future as well. However, this modality is not yet suitable for a considerable proportion of patients.

Background: Pregestational excessive body mass index (BMI) is linked to an increased risk for gestational diabetes mellitus (GDM), but less is known on the effect of adolescent BMI on GDM occurrence. The study aimed to investigate possible associations of adolescent BMI and changes in BMI experienced before first pregnancy, with gestational diabetes risk. Methods: This retrospective study was based on linkage of a military screening database of adolescent health status (Israel Defence Forces) including measured height and weight, with medical records (Maccabi Healthcare Services, MHS) of a state-mandated health provider. The latter covers about 25% of the Israeli population; about 90% of pregnant women undergo screening by the two-step Carpenter-Coustan method. Adolescent BMI was categorized according to Center of Disease Control and Prevention percentiles. Only first documented pregnanies were analyzed and GDM was the outcome. Findings: Of 190,905 nulliparous women, 10,265 (5.4%) developed GDM. Incidence proportions of GDM were 5.1%, 6.1%, 7.3%, and 8.9% among women with adolescent normal BMI, underweight, overweight, and obesity (p

22q11.2 deletion syndrome (22q11.2DS) has a wide range of clinical features including endocrine abnormalities. We aimed to characterize growth patterns, hypoparathyroidism, and thyroid dysfunction of individuals with 22q11.2DS. Anthropometric and laboratory measurements were obtained from the charts of 48 individuals (males=28, 8.0±6.8 visits/participant) followed at a national 22q11.2DS clinic between 2009 and 2016. Age at diagnosis was 4.3±4.9 years and age at last evaluation 11.2±7.2 years. Median height-SDS was negative at all ages. Height-SDS at last visit was correlated to the midparental height-SDS (r=0.52 P=0.002). Yet, participants did not reach their target height, with a difference of 1.06±1.07 SD (P

Prevalence studies from around the world have established a substantial increase in the prevalence of celiac disease (CD) in patients with type 1 diabetes mellitus (T1DM). Approximately two-thirds of patients with T1DM and CD are asymptomatic for CD at diagnosis. We aim to provide an up-to-date state-of-the-art summary of the recommendations for serologic testing for CD in patients with T1DM and to clarify the debate on the need for screening and interventions. We searched Medline and Cochrane databases for studies of celiac autoimmunity and biopsy-proven CD in people with T1DM between January 1, 2000 and December 1, 2015. CD was found to be an independent risk factor for micro- and macrovascular complications, as well as for increased morbidity in patients with T1DM. Publications, however, reveal controversy regarding the benefits of a gluten-free diet (GFD) on glycemic control, bone health, and quality of life in individuals with T1DM and asymptomatic CD. A multicenter, prospective randomized controlled trial aimed to investigate this issue is currently ongoing. Until resolution of the pros and cons of screening for CD, and of the benefit versus burden of GFD treatment in T1DM patients with asymptomatic CD, we recommend repeated screening for CD during childhood and adulthood, and treatment with GFD for those with biopsy-proven CD, even if asymptomatic.

Background Gilbert syndrome (GS) is a common hereditary condition, characterized by intermittent unconjugated hyperbilirubinemia. In adults with type 2 diabetes and GS, a markedly lower prevalence of nephropathy was documented, suggesting a beneficial effect of hyperbilirubinemia. We investigated the prevalence of GS among individuals with type 1 diabetes mellitus (T1DM), and the prevalence of microalbuminuria. Methods The prevalence of GS was assessed in 401 (204 female) patients with T1DM, median age 21.0 years, (interquartile range [IQR], 15.7-27.9), median disease duration 10.8 years (IQR, 5.7-15.8); and was compared with GS prevalence in 181 children (control). The prevalence of microalbuminuria was assessed in patients with T1DM and GS (group I) and compared with that of patients with T1DM alone (group II), in a ratio of 1:2 matched by gender, age, and duration of diabetes. Results The prevalence of GS in TIDM patients was significantly higher than in the control group (10.7% vs 3.3% respectively, p = .004), with no gender difference. Patients with T1DM and GS had significantly lower HbA1c levels than did those with T1DM alone 7.3 ± 1.2 vs 7.9 ± 1.3% respectively (56 ± 13 vs 63 ± 14 mmol/mol), p = .02. The rate of microalbuminuria was 14.0% vs 11.0% for patients with T1DM and GS, compared with those with T1DM alone (p = .6). Conclusions The occurrence of GS was 3-fold higher among individuals with T1DM than in a healthy control group. Despite better glycemic control, the rate of microalbuminuria was similar among young individuals with T1DM and GS, and those with T1DM alone, suggesting no protective value to elevated bilirubin.

Patients with chronic diseases may develop, in addition to their underlying disease, insulin resistance, and the metabolic syndrome (MetS). The MetS is a cluster of conditions—hypertension, central obesity, dyslipidemia, and insulin resistance—that increases the risk for coronary heart disease, type 2 diabetes, and stroke. In this chapter, we aim to review the prevalence of the MetS in several chronic diseases and its impact on long-term morbidity. Bidirectional relationships between obesity and chronic diseases may exist, such as obesity predating the development of the disease, while medications and disability further increase the risk of developing the MetS. Patients with chronic disease may develop components of the MetS, even with normal body mass index (BMI). Patients with chronic disease carry an increased risk of morbidity due to coronary heart disease. A beneficial effect of metformin on glycemic control has been demonstrated, and this may be a promising drug for preventing metabolic side effects in some chronic diseases.

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.Data regarding females aged21 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.For the 130 females aged21 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.In this nationwide study, the incidence rate of POI in youth aged21 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.

To present current data on the coexistence of attention deficit hyperactivity disorder (ADHD) and the metabolic syndrome and type 2 diabetes mellitus in adults and children and to discuss possible mechanisms. Emerging data suggest that risk factors for obesity and insulin resistance such as diabetes during pregnancy and intrauterine growth failure may also have a role in the development of ADHD. Furthermore, ADHD and obesity share lifestyle factors, such as abnormal eating patterns, binge eating, and a sedentary lifestyle. ADHD is a risk factor for components of the metabolic syndrome, particularly obesity and type 2 diabetes mellitus, and also hypertension, both in adults and youth. Associations of ADHD with obesity, diabetes, and hypertension have been ascertained, and various mechanisms have been proposed. Research is needed to decipher the shared genetic, pharmacological, and lifestyle risk factors. Individuals with ADHD should be treated as a high-risk group for cardiometabolic complications.

Background: The MiniMed™ 670G system is FDA-approved and CE-marked for patients with T1D aged ≥7 years. Glycemic outcomes of patients aged 2-75 years with T1D using the system at home for 3 months were evaluated and compared. Methods: Data from 151 children (n=46, 2-6 years and n=105, 7-13 years) enrolled at 9 sites; and 124 adolescents and adults (n=30, 14-21 years and n=94, 22-75 years) enrolled at 10 sites, during 2-week Manual Mode use (run-in phase) followed by 3-month Auto Mode use (study phase) were analyzed. Glycemic outcomes (HbA1c, time spent at sensor glucose [SG] ranges, SG, and SG variability, etc.) were compared across age groups. Results: Data from run-in and study phases are shown (Table). Across age groups there was a 0.4% to 0.5% decrease in HbA1c and a 5.5% to 8.8% increase in time in range. During the study phases of the pediatric (2-13 years) and older cohort (14-75 years) trials, there were no episodes of severe hypoglycemia or DKA, and no serious device-related adverse events. Conclusions: These findings indicate that 3-month MiniMed™ 670G Auto Mode use in patients as young as two years of age with T1D, similar to older cohorts using the system, can safely improve glycemic outcomes compared to 2-week open-loop Manual Mode. Disclosure T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. G.P. Forlenza: Advisory Panel; Self; Dexcom, Inc. Consultant; Self; Medtronic MiniMed, Inc., Tandem Diabetes Care. Research Support; Self; Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. O. Pinhas-Hamiel: None. K.K. Kaiserman: Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Medtronic MiniMed, Inc. Speaker's Bureau; Self; Medtronic MiniMed, Inc. D.R. Liljenquist: None. D.I. Shulman: None. M.A. Wood: None. X. Chen: None. J. Shin: Employee; Self; Medtronic. T.L. Cordero: Employee; Self; Medtronic. S.W. Lee: Employee; Self; Medtronic. F.R. Kaufman: Employee; Self; Medtronic.

Objectives: It is unclear whether adolescence obesity is associated with limited linear growth. We assessed this association in a nationwide cohort of adolescents. Methods: We conducted a nationwide, population-based, cohort study of 2,785,227 Israeli adolescents (60% males) who were examined before military service in 1967 through 2015; Height and weight were measured along with assessment of medical status at age 17.4±0.4 years. The secular trend of height was plotted for US-CDC age- and sex-adjusted BMI percentiles groups. We accounted for health status at enrolment and computed the expected height based on parental data that was available for 512,978 examinees. Results: Mean height has increased by 3.1 cm among males, but remained unchanged among females over five decades. Among males, gain in height was mostly attained during the first 25 years and has stabled since. Obese males were taller than their normal-weight and underweight counterparts. Underweight girls had a prominent increase in mean height during the first 2 decades exceeding by over 2 cm the mean height of their obese counterparts. There was a gradual decrease in the difference between measured and expected height in males and females regardless of BMI status, with the exception of underweight females who achieved consistently higher stature than expected (≥3 cm). Conclusions: During five decades excessive BMI was not a limiting factor in growth potential compared to normal BMI in both sexes. Underweight females with unimpaired health are the sole group that has yet realized its growth potential even when accounting parental height.

Background: The incidence of both the survival of premature infants and type 1 diabetes (T1D) is rising worldwide. The pathophysiology of T1D depends on the differentiation of cellular and humoral immune systems recognition of the self, which occurs during the neonatal period and is influenced by environmental exposures. Aim: To assess the association between nutritional, antibiotic and parenteral exposures during the neonatal period and the development of pediatric T1D. Methods: a multicenter, paired case-control study. Preterm subjects who were born between 1990-2013, and developed T1D before the age of 18 years (T1D group), were paired with subjects who didn't develop TID (Control group) at a ratio of 1:3 by: gender, gestational age (GA), month of birth and birth medical center . This preterm population is a model of a neonatal population with strictly meticulous follow up data available in all medical centers in Israel. Data retrieved from charts included maternal history, delivery method, ethnic origin, weight for GA, NICU length of hospitalization, medications, parenteral fluid types, feeding modes and their timing. Univariate and multivariate analysis via Generalized Estimating Equations (GEE) using a binary logistic regression model were performed to evaluate the association between T1D and the assessed exposures. Results: T1D group included 52 subjects, 26 males, median GA 35 (26-36), mean BW 2307.6±534.5. Control group included 133 subjects, 69 males. median GA 35 (27-36), mean BW 2094.5±484.1. In univariate analysis, the odds ratio (OR) for T1D increased with each extra 100 grams in BW (OR 1.13, 95%CI 1.057-1.206, p < 0.001), later day of parenteral glucose initiation (OR 1.61, 95%CI 1.05-2.48, p 0.03), and parenteral cephalosporines initiated beyond the first week of life (OR 3.25, 95%CI 1.504-7.04, p 0.003). Treatment with narrow spectrum beta-lactam antibiotics during the first week of life was associated with lower risk for T1D development (OR 0.23, 95%CI 0.12-0.47, p < 0.001). Multivariate analysis revealed significant association between both treatment with cephalosporins beyond the first week of life and later day of parenteral glucose initiation and the development of pediatric T1D (OR 6.49, 95%CI 1.54-27.44, p 0.011 and OR 1.61, 95%CI 1.05-2.48, p 0.002, respectively). No association with feeding modality (oral/nasogastric), timing and type of feeding (breast or bottle) was found. Conclusions: This is the first report indicating a significant association between parenteral exposure and timing of variable antibiotic treatments and glucose solution administration during the neonatal period with development of T1D. This report indicates the need for a larger study to conclude clinical implications of management and exposure to these substances during the neonatal period and its relevance to the neonatal microbiome.

Objective: We examined short and long-term outcomes of bariatric surgery in patients with obesity and type 1 diabetes mellitus (T1DM). Methods: We reviewed the records of all adults insured by Maccabi Healthcare Services during 2010 -2015, with body mass index (BMI) ⩾30 kg/m2 and T1DM; and compared weight reduction and glucose control according to the performance of bariatric surgery. BMI and glycated hemoglobin (HbA1c) levels were extracted for baseline and every 6 months, for a mean 3.5 years. Results: Of 52 patients, 26(50%) underwent bariatric surgery. Those who underwent surgery were more often female and with a longer duration of diabetes. Immediately postoperative, 4(15%) developed diabetic ketoacidosis, while 6(23%) experienced severe hypoglycemic episodes. The mean BMI decreased among surgery patients: from 39.5±4.4 to 30.1±5.0 kg/m2 ( p < 0.0001); and increased among those who did not undergo surgery: from 33.6±3.9 to 35.1±4.4 kg/m2 ( p = 0.49). The mean HbA1c level decreased during the first 6 months postoperative: from 8.5±0.9% to 7.9±0.9%; however, at the end of follow-up, was similar to baseline, 8.6±2.0% (p = 0.87). For patients who did not undergo surgery, the mean HbA1c increased from 7.9±1.9% to 8.6±1.5% ( p = 0.09). Conclusions: Among individuals with obesity and T1DM, weight loss was successful after bariatric surgery, but glucose control did not improve. The postoperative risks of diabetic ketoacidosis and severe hypoglycemic episodes should be considering when performing bariatric surgery in this population.

Objective: To evaluate the safety of in-home use of the MiniMed™ 670G system with SmartGuard™ technology in children with type 1 diabetes (T1D). Methods: Participants (N = 105, ages 7–13 years, mean age 10.8 ± 1.8 years) were enrolled at nine centers (eight in the United States and one in Israel) and completed a 2-week baseline run-in phase in Manual Mode followed by a 3-month study phase with Auto Mode enabled. Sensor glucose (SG), glycated hemoglobin (HbA1c), percentage of SG values across glucose ranges, and SG variability, during the run-in and study phases were compared. Participants underwent frequent sample testing with i-STAT® venous reference measurement during a hotel period (6 days/5 nights) to evaluate the system's continuous glucose monitoring performance. Results: Auto Mode was used a median of 81% of the time. From baseline to end of study, overall SG dropped by 6.9 ± 17.2 mg/dL (P

Context Congenital adrenal hyperplasia (CAH) was among the first genetic disorders included in newborn screening (NBS) programs worldwide, based on 17α-hydroxyprogesterone (17-OHP) levels in dried blood spots. However, the success of NBS for CAH is hampered by high false positive (FP) rates, especially in preterm and low-birthweight infants. Objective To establish a set of cutoff values adjusting for both gestational age (GA) and birthweight (BW), with the aim of reducing FP rates. Design This cross-sectional, population-based study summarizes 10 years of experience of the Israeli NBS program for diagnosis of CAH. Multitiered 17-OHP cutoff values were stratified according to both BW and GA. Participants A total of 1,378,132 newborns born between 2008 and 2017 were included in the NBS program. Results Eighty-eight newborns were ultimately diagnosed with CAH; in 84 of these, CAH was detected upon NBS. The combined parameters-adjusted approach significantly reduced the recall FP rate (0.03%) and increased the positive predictive value (PPV) (16.5%). Sensitivity among those referred for immediate attention increased significantly (94%). There were four false negative cases (sensitivity, 95.4%), all ultimately diagnosed as simple-virilizing. Sensitivity and specificity were 95.4% and 99.9%, respectively, and the percentage of true-positive cases from all newborns referred for evaluation following a positive NBS result was 96%. Conclusions The use of cutoff values adjusted for both GA and BW significantly reduced FP rates (0.03%) and increased overall PPV (16.5%). Based on our 10 years of experience, we recommend the implementation of this two parameter-adjusted approach for NBS of classic CAH in NBS programs worldwide.

It is unclear whether adolescent obesity is associated with limited linear growth. We assessed this association in a nationwide sample of adolescents.We conducted a population-based, study of 2,785,227 Israeli adolescents (60% males) who were examined before military service since 1967 through 2015. Height and weight were measured along with assessment of medical status at age 17.4 ± 0.4 years. The secular trend of height was plotted using United States Center for Disease Control (US CDC) age- and sex-adjusted BMI percentile groups. We accounted for health status at enrollment and computed the expected height based on parental data that was available for 512,978 examinees.Over five decades, the mean height increased by 3.1 cm among males, but remained unchanged among females. Among males, gain in height was attained predominantly during the first 25 years and has stabilized since. Males with obesity were taller than their normal-weight and underweight counterparts. Underweight girls had a prominent increase in mean height during the first two decades, exceeding the mean height of their counterparts with obesity by over 2 cm. There was a gradual decrease in the difference between measured and expected height in males and females regardless of BMI status, with the exception of the underweight females who achieved consistently higher stature than expected (≥3 cm).During five decades, excessive BMI was not a limiting factor in growth potential compared with normal BMI in both sexes. The only group that exceeded its growth potential, when accounting for expected mid-parental height, were underweight females with unimpaired health.

The Medtronic predictive low-glucose management (PLGM) algorithm automatically stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low-glucose value within the next 30 min, and resumes delivery after hypoglycemia recovery. The present study evaluated the PLGM algorithm performance of the MiniMed™ 670G system SmartGuard™ "suspend before low" feature in children aged 7-13 years with type 1 diabetes (T1D).Participants (N = 105, mean ± standard deviation of 10.8 ± 1.8 years) underwent an overnight in-clinic evaluation of the "suspend before low" feature with a preset low limit of 65 mg/dL. After exercise, frequent sample testing (FST) was conducted every 5 min if values were70 mg/dL; every 15 min if 70-80 mg/dL; and every 30 min if80 mg/dL. First-day performance of the Guardian™ Sensor 3 glucose sensor and continuous glucose monitoring system was also evaluated.Activation of the "suspend before low" feature occurred in 79 of the 105 participants, 79.7% (63/79) did not result in SG falling below 65 mg/dL. Mean glucose at activation was 102 ± 19 mg/dL and the initial insulin suspension duration was 87.5 ± 32.7 min. Four hours after insulin resumption, mean reference glucose was 130 ± 42 mg/dL. Mean absolute relative difference between the FST reference glucose and SG values on the first day of sensor wear was 11.4%. For the 26 participants in whom the "suspend before low" feature did not activate, none involved a reference glucose value ≤65 mg/dL, suggesting that the PLGM algorithm performed as intended.In children aged 7-13 years with T1D, the "suspend before low" feature of the MiniMed 670G system demonstrated a hypoglycemia prevention rate of nearly 80% after exercise and did not involve rebound hyperglycemia. There were no events of severe hypoglycemia during the evaluation.

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.

Unfortunately, the co-author name was misspelled as "Avivit Brenner" instead of "Avivit Brener" in the original publication and the correct author name is updated here.

The occurrence of type 2 diabetes (T2DM) in youth has been established and numerous reports about prevalence, incidence, and clinical characteristics of these adolescents are continuously documented from all over the world [1]. The highlights of this year’s section include: population genetics studies shedding light on both susceptibility to develop T2DM and on novel disease mechanisms; new data on complications of T2DM in youth, and the outcome of a new treatment modality – bariatric surgery in adolescents with T2DM. Several works have aimed to identify children and adolescents who are at increased risk of developing T2DM. The impact of intrauterine exposure to both maternal obesity and maternal diabetes and the impact of medications such as atypical antipsychotic drugs and valproic acid, on impaired glucose metabolism, the metabolic syndrome and T2DM are reviewed. In parallel the reliability of our diagnostic methods for impaired glucose metabolism in obese children is highlighted as well. In addition, evidence for the efficacy and side effects of various pharmacologic medications in obese children and in adolescents with polycystic ovary syndromes (PCOS) is reviewed. The last section reviews clinical practice recommendations for children with diabetes and dyslipidemia for children with elevated LDL cholesterol and with hypertriglyceridemia.

At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.

Context Most studies linking long-term consequences of adolescent underweight and obesity are limited to men. Objective To assess the sex-specific association of adolescent BMI with cardiovascular- and non-cardiovascular-related mortality in young adulthood and midlife. Setting A nationwide cohort. Participants 927,868 women, 1,366,271 men. Interventions Medical examination data at age 17, including BMI, were linked to the national death registry. Main outcomes Death attributed to cardiovascular (CVD) and non-CVD causes. Results During 17,346,230 women-years and 28,367,431 men-years of follow-up, there were 451 and 3208 CVD deaths, respectively, and 6235 and 22,223 non-CVD deaths, respectively. Compared to low-normal BMI (18.5–22.0 kg/m2), underweight women had a lower adjusted risk for CVD mortality (Cox hazard ratio (HR) = 0.68; 95% CI 0.46–0.98) in contrast to underweight men (HR = 0.99; 0.88–1.13). The latter were at higher risk for non-CVD mortality (HR = 1.04; 1.00–1.09), unlike underweight women (HR = 1.01; 0.93–1.10). Findings, which persisted when the study sample was limited to those with unimpaired health, were accentuated for the obese with ≥ 30 years follow-up. Both sexes exhibited similarly higher risk estimates already in the high-normal BMI range (22.0 ≤ BMI

Background & Aims : To assess the prevalence of biopsy-confirmed celiac disease (CD) among ch il dren and youth with type 1 diabetes mellitus, and the implications of CD on metabolic control, nutritional status, and physical growth in type 1 diabetes patients. Methods : A retrospective study of type 1 diabetes patients at Maccabi Juvenile Diabetes Center. Those diagnosed with CD based on positive intestinal biopsy were compared to a control group compromising two patients matched by sex, age, and duration of diabetes for each CD patient. Results : Of 316 type 1 diabetes patients, 294 (93%) were screened for CD, and eleven (3.7%) diagnosed. There was no statistically significant difference in mean HbA1c levels between the CD and control groups. However, CD patients with good adherence to gluten-free diet (GFD) (n=7), had better metabolic control than those with poor adherence (n=4), without statistical significance. For patients with both type 1 diabetes and CD, and not for the control group, mean final height was significantly lower than target height (p=0.01). Among those with poor adherence to GFD, growth impairment was severe. Conclusions : Patients with both type 1 diabetes and CD had significant growth impairment; more pronounced impairment was observed in ch il dren with poor adherence to GFD.

Frequent glucose testing is required for optimal management of type 1 diabetes (T1D). Limited data are available regarding real-world experience of the novel technology for monitoring by continuous interstitial fluid glucose (IFG), using flash glucose-sensing technology (FSL-CGM). We aimed to assess the effect of FSL-CGM in a real-life clinical setting on glycemic control parameters, compliance, and adverse events among pediatric and young adult T1D patients.This observational multi-center study assessed FSL-CGM use (6-12 months) in T1D patients (mean ± SD age 13.4 ± 4.9 years) who purchased the device out-of-pocket. Outcome measures included HbA1c, mean IFG levels, CGM metrics [time in hypoglycemia ( 54 mg/dL; 3 mmol/L), in target range (70-180 mg/dL; 3.9-10 mmol/L), and in hyperglycemia 240 mg/dL; 13.3 mmol/L)], frequency of self-monitoring of blood glucose, acute complications, skin reactions, and reasons for initiation/discontinuation.Among patients with regular use of the FSL-CGM (n = 59), mean HbA1c decreased from 8.86 ± 0.23 to 8.05 ± 0.2% (73.3-64.5 mmol/mol) in 3 months (p = 0.0001) and plateaued thereafter. A clinically significant reduction in HbA1c (defined as a decrease of ≥ 0.5%) was associated with shorter diabetes duration. Of 71 patients who initiated use of the FSL-CGM, 12 (16.9%) discontinued during the study period. No statistically significant changes were found after FSL-CGM use, in mean and standard deviation IFG levels, and in time of glucose levels in target, hypoglycemia, and hyperglycemia ranges. One patient with hypoglycemia unawareness was found dead-in-bed while using FSL-CGM.Real-life observational data in a self-selected young T1D population demonstrated a significant and sustained reduction in HbA1c with FSL-CGM in one-third of the participants. Surveillance of glucose monitoring should be individualized, especially for patients with hypoglycemia unawareness.

A growing number of pediatric acute lymphoblastic leukemia (ALL) and hematopoietic stem cell transplantation (HSCT) survivors reach adulthood and face long-term health-related problems. We review risk factors and the prevalence of the metabolic syndrome (MetS), a cluster of obesity-related comorbidities, including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, impaired glucose metabolism, and type 2 diabetes in ALL and HSCT survivors. Components of the MetS are already detected during the first year of ALL maintenance therapy and significantly worsen over time. The prevalence of MetS increases at a faster rate in this setting than in the general population. Factors found to be of the greatest potential risk to the development of the MetS are central obesity, increased BMI, irradiation therapy, older age, poor diet, and low level of physical activity. The early onset of MetS and its components among ALL and HSCT survivors calls for early and continuous screening to identify those at risk and to implement preventive measures.

Celiac disease (CD) is a chronic immune-mediated systemic disease characterized by inflammation and villous atrophy of the small intestine. A strict, lifelong gluten-free diet (GFD) is the only treatment for CD. Disordered eating behaviors (DEBs) prevail in adolescence and young adulthood, and confer a risk of developing into full-blown eating disorders. The aims of the current study were to assess the incidence and risk factors for DEBs among individuals with CD, and to examine an association between adherence to GFD and DEBs. A cohort of 136 individuals with CD responded to a web-mediated survey that assessed DEBs and adherence to a GFD. The survey included demographic data (gender, age, weight, disease duration) and two self-rating questionnaires: the Eating Attitudes Test-26 and the gluten-free diet questionnaire. DEBs were found in 19% of female and 7% of male responders. These individuals were characterized by being overweight (p = 0.02), of an older age (p = 0.04) and female sex (p = 0.06). Strict adherence to a GFD was reported by 32% of the responders and was not correlated with age, disease duration, age at diagnosis of CD and with being overweight. Caregivers should be aware of the increased occurrence of DEBs in adolescents with CD, especially those who are overweight, older and of a female gender. Level V, cross-sectional descriptive study.

In this study, we examined early growth characteristics among small-for-gestational-age (SGA) preterm twins compared to their appropriate-for-gestational-age (AGA) counterparts. A retrospective study evaluated all consecutive twins born between 2008 and 2015 at a tertiary referral center whose gestational age ranged from 30.0 to 34.86 weeks. Included were twins in which one twin was AGA and the other SGA at birth. Changes of ≥2, 1–1.99, and 0–0.99 in z-score between births and 36 weeks post menstrual age (PMA) were respectively defined as severe, moderate, and mild postnatal growth failure (PNGF) in weight or head circumference (HC). Early neonatal morbidities were documented. Multiple logistic regression analysis was applied to determine conditions associated with PNGF and its severity. Out of 666 sets of twins, 83 met the inclusion criteria. Weight PNGF was similar and mild among the SGA and the AGA groups (0.9 ± 0.46 vs. 0.96 ± 0.44 z-score, respectively, p = 0.24). At 36 weeks PMA, a significantly larger proportion of SGAs were below −2 z-scores in weight (84.3%) compared to birth (31.3%) or to the AGAs (8.4%). In both groups, weight PNGF correlated with the time needed to regain birth weight. HC PNGF was mild among both groups, yet significantly more prominent among the AGAs (0.39 ± 0.72 z-score) vs. SGAs (0.75 ± 0.65 z-score, p = 0.001). We suggest that among preterm SGA infants, the absolute z-score should be used to assess the severity of weight PNGF. Individual nutritional strategies to decrease time to regain birth weight may mitigate severe malnutrition among SGAs.

Background and purpose Information about metabolic comorbidities in patients with multiple sclerosis (MS) is scarce. Our aim was to examine the prevalence of the metabolic syndrome (MetS) and its components in patients with long duration of MS and significant disability. Methods Demographic and clinical data, weight, height, waist circumference, blood pressure, and levels of fasting glucose, triglycerides and high density lipoprotein cholesterol (HDL-C) were obtained from 130 MS patients with Extended Disability Status Scale (EDSS) score ≥3.0. Results Seventy-two percent were female, mean ± SD age 55.8 ± 6.0, range 45–65 years, disease duration 18.2 ± 10.1 years, EDSS 5.5 ± 1.0. Obesity [body mass index (BMI) ≥ 30 kg/m2] was present in 18.5% and overweight (BMI 25.0–29.9 kg/m2) in 34.6%. The prevalence of the MetS was 30% with no gender difference. Fifty-six percent had central obesity by waist circumference, 28% treated hypertension, 45.8% elevated blood pressure, 11% type 2 diabetes mellitus, 31.4% treated dyslipidemia, 28.8% elevated triglyceride levels and 31.4% had low HDL-C. MS patients with MetS were significantly older (59.0 ± 5.5 vs. 53.8 ± 5.5, P

Emerging adulthood is a challenging period for diabetes management. Our aim was to determine whether a dedicated transition clinic for emerging adults with type 1 diabetes can improve glycemic control and visit attendance. An observational study of 53 emerging adults (30 males) treated during 2010–2014 in a newly established transition clinic. The clinic was operated jointly by pediatric and adult endocrinologists and included a transition coordinator. Data collected included the source of referral, HbA1c levels, frequency of visit attendance, and acute complications. For 27 patients who had attended the pediatric clinic at the same medical center, data from up to 2 years preceding the transition were also collected. Patients filled the Diabetes Quality of Life–Youth questionnaire at the transition and 1 year later. Mean ± SD age at the transfer to the transition clinic was 22.1 ± 2.7 years; mean disease duration was 8.4 ± 5.0 years. Follow-up duration at the transition clinic was 1.2 ± 1.1 years. Mean HbA1c levels decreased from 67 mmol/mol (95 % CI 63–72) [8.3 % (95 % CI 7.9–8.7)] at transfer to 57 mmol/mol (95 % CI 52–63) [7.4 % (95 % CI 6.9–7.9)] after 1 year (p

Background We aimed to determine the prevalence of overweight and obesity among children, adolescents and young adults with type 1 diabetes mellitus (T1DM), and to assess the prevalence of the metabolic syndrome and its components. Methods The study cohort comprised 326 (168 women) consecutive patients aged 5 to 30 years diagnosed with T1DM and followed up in the Juvenile Diabetes Clinic, Maccabi Health Care Services. Anthropometric measurements, blood pressure, presence of additional diseases, other medications, HbA1c, triglycerides and high density lipoprotein cholesterol levels were obtained. Results The mean age in the study group was 18.5 ± 6.0 years, and the mean diabetes duration was 8.7 ± 5.0 years. Mean HbA1c level was 8.1 ± 1.3%. Nineteen per cent of the study population was overweight (85th > body mass index