Insights into Central Congenital Hypothyroidism: A Multicenter Retrospective Analysis.

CONTEXT: Central congenital hypothyroidism (CCH) is a thyroid hormone deficiency at birth caused by inadequate pituitary stimulation of the thyroid gland. Although primary CH has been studied extensively, studies on CCH are sparse. OBJECTIVES: To assess the prevalence of CCH in Israel and describe its clinical features, neonatal screening results, and outcomes. DESIGN: Multicenter cross-sectional retrospective chart review. SETTING: Nine pediatric endocrine units throughout Israel. PATIENTS: Patients diagnosed with CCH in 1987-2021 were categorized into early (within 14 days of life) and late (after 14 days) diagnosis groups. Newborn screening (NBS) results were retrospectively retrieved from the national NBS program dataset. RESULTS: CCH prevalence in Israel was about 1:42,800 live births. Subjects were 94 patients (54 males), of these, 84% had multiple pituitary hormone deficiencies and 16% had isolated CCH. The median age at diagnosis was 50 days (range, 1-8760), with 66% having moderate to severe hypothyroidism. NBS detected only three infants. Early diagnosis occurred in 34% due to hypopituitarism, while 66% were diagnosed later due to growth and developmental delays. Neurodevelopmental sequelae included mental retardation (12%), learning difficulties (18%), delayed speech (27%), and motor clumsiness (19%), with no significant differences in outcomes between early and late diagnosis. CONCLUSIONS: Despite high rates of neurodevelopmental sequelae, no differences were found between early and late diagnosis groups. Further research is needed to assess the impact of delayed diagnosis on neurological outcomes in newborns with CCH. Improved strategies for detecting CHH in newborns are also necessary.

Heritability of Body Mass Index Among Familial Generations.

Importance: Studies on the familial effects of body mass index (BMI) status have yielded a wide range of data on its heritability. Objective: To assess the heritability of obesity by measuring the association between the BMIs of fathers, mothers, and their offspring at the same age. Design, Setting, and Participants: This cohort study used data from population-wide mandatory medical screening before compulsory military service in Israel. The study included participants examined between January 1, 1986, and December 31, 2018, whose both parents had their BMI measurement taken at their own prerecruitment evaluation in the past. Data analysis was performed from May to December 2023. Main Outcomes and Measures: Spearman correlation coefficients were calculated for offsprings' BMI and their mothers', fathers', and midparental BMI percentile (the mean of the mothers' and fathers' BMI cohort- and sex-specific BMI percentile) to estimate heritability. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% CIs of obesity compared with healthy BMI, according to parental BMI status. Results: A total of 447 883 offspring (235 105 male [52.5%]; mean [SD] age, 17.09 [0.34] years) with both parents enrolled and measured for BMI at 17 years of age were enrolled in the study, yielding a total study population of 1 343 649 individuals. Overall, the correlation between midparental BMI percentile at 17 years of age and the offspring's BMI at 17 years of age was moderate (ρ = 0.386). Among female offspring, maternal-offspring BMI correlation (ρ = 0.329) was somewhat higher than the paternal-offspring BMI correlation (ρ = 0.266). Among trios in which both parents had a healthy BMI, the prevalence of overweight or obesity in offspring was 15.4%; this proportion increased to 76.6% when both parents had obesity and decreased to 3.3% when both parents had severe underweight. Compared with healthy weight, maternal (OR, 4.96; 95% CI, 4.63-5.32), paternal (OR, 4.48; 95% CI, 4.26-4.72), and parental (OR, 6.44; 95% CI, 6.22-6.67) obesity (midparent BMI in the ≥95th percentile) at 17 years of age were associated with increased odds of obesity among offspring. Conclusions and Relevance: In this cohort study of military enrollees whose parents also underwent prerecruitment evaluations, the observed correlation between midparental and offspring BMI, coupled with a calculated narrow-sense heritability of 39%, suggested a substantive contribution of genetic factors to BMI variation at 17 years of age.

Stuttering in adolescence and the risk for dysglycemia in early adulthood.

AIMS: To investigate the association between stuttering during adolescence and the onset of dysglycemia (prediabetes or type 2 diabetes) in early adulthood among men and women. MATERIALS AND METHODS: This cohort study included Maccabi Health Services members assessed for mandatory military service at ages 16-19 during 1990-2019 and followed until 31 December 2020. Stuttering status was recorded in the baseline medical evaluation. Incident cases of dysglycemia were identified systematically using prediabetes and diabetes registries. Cox proportional hazard models were applied for men and women separately, adjusting for sociodemographics and medical status. RESULTS: The study cohort comprised 866,304 individuals (55% men; 0.21% with stuttering) followed for a total of 12,696,250 person-years. During the study period, 7.6% (n = 36,603) of men and 9.0% (n = 34,723) of women were diagnosed with dysglycemia. The mean ages at diagnosis were 34 and 32 years for men and women, respectively. Women with stuttering exhibited the highest dysglycemia incidence rate (102.3 per 10,000 person-years) compared with the other groups (61.4, 69.0, and 51.9 per 10,000 person-years for women without stuttering, men with stuttering, and men without stuttering, respectively). For both men and women, those with stuttering showed an increased risk of being diagnosed with dysglycemia compared with those without (adjusted hazard ratios 1.18 [1.01-1.38] and 1.61 [1.15-2.26], respectively). The associations persisted in extensive sub-analyses. CONCLUSIONS: Stuttering in adolescence is associated with a higher risk of dysglycemia in early adulthood for men and women. Screening and targeted prevention in this population, especially women, may be beneficial.

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.

Real-Life Achievements of MiniMed 780G Advanced Closed-Loop System in Youth with Type 1 Diabetes: AWeSoMe Study Group Multicenter 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 2-week 780G system data at five time points. 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 (interquartile range [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 hemoglobin A1c (HbA1c) (SE) was 8.65% (0.12) at baseline and dropped by >1% after 1 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 Advanced Hybrid Closed-Loop (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 health care professionals, youth, and caregivers.

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.