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OBJECTIVE: Low birth weight (LBW), no early catch-up weight, and subsequent fat accumulation have been associated with increased risks of insulin resistance from childhood onward and later cardiovascular disease. We sought to clarify the effects of high birth weight (HBW) and postnatal weight gain on insulin resistance. RESEARCH DESIGN AND METHODS: A total of 117 obese children aged 10.4 +/- 2.4 years were divided into three groups according to fetal growth after exclusion of maternal diabetes. They were comparable for age, sex, puberty, and percent body fat. Customized French birth weight standards, adjusted for maternal characteristics and gestation number, identified subjects with true altered fetal growth: 32 had increased fetal growth according to customized standards (HBWcust), 52 were eutrophic, and 33 had restricted fetal growth according to customized standards (LBWcust). Fat distribution by dual-energy X-ray absorptiometry, insulin sensitivity indexes from an oral glucose tolerance test (OGTT), and leptin, adiponectin, and visfatin levels were compared between groups. RESULTS: The HBWcust subjects had a higher adiponectin level, higher whole-body insulin sensitivity index (WBISI), and lower hepatic insulin resistance index, lower insulin and free fatty acid concentrations during OGTT, and lower trunk fat percent than eutrophic (P < 0.05) and LBWcust subjects (P < 0.05). Besides birth weight, weight gain between 0 and 2 years was a positive predictor (P < 0.05) of WBISI, whereas weight gain after 4 years was a negative predictor (P < 0.05). CONCLUSIONS: HBW and early weight gain may program insulin sensitivity and adipose tissue metabolism and contribute to so-called metabolically healthy obesity. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of prolonged hybrid closed loop (HCL) use in children with type 1 diabetes (T1D) on glucose control and BMI throughout pubertal progression., Research Design and Methods: We used a prospective multicenter extension study following the Free-Life Kid AP (FLKAP) HCL trial. The 9-month previously reported FLKAP trial included 119 prepubertal children (aged 6-12 years). During the extension study, participants could continue to use HCL for 30 months (M9 to M39). HbA1c values were collected every 3 months up to M39, while continuous glucose monitoring metrics, BMI z scores, and Tanner stages were collected up to M24. Noninferiority tests were performed to assess parameter sustainability over time., Results: One hundred seventeen children completed the extension study, with mean age 10.1 years (minimum to maximum, 6.8-14.0) at the beginning. Improvement of HbA1c obtained in the FLKAP trial was significantly sustained during extension (median [interquartile range], M9 7.0% [6.8-7.4], and M39 7.0% [6.6-7.4], P < 0.0001 for noninferiority test) and did not differ between children who entered puberty at M24 (Tanner stage ≥2; 54% of the patients) and patients who remained prepubertal. BMI z score also remained stable (M9 0.41 [-0.29 to 1.13] and M24 0.48 [-0.11 to 1.13], P < 0.0001, for noninferiority test). No severe hypoglycemia and one ketoacidosis episode not related to the HCL system occurred., Conclusions: Prolonged use of HCL can safely and effectively mitigate impairment of glucose control usually associated with pubertal progression without impact on BMI in children with T1D., (© 2024 by the American Diabetes Association.)

Context: The increase in bone mineral content (BMC) and density (BMD) measured by dual-energy x-ray absorptiometry (DXA) in obese children may not sustain the mechanical load associated with weight, and the factors influencing bone mineralization are not well known., Objective: We described bone mineralization in boys with overweight/obesity and leanness in relation to body composition., Methods: Cross-sectional study in the Pediatric Endocrinology Unit of Angers University Hospital with 249 overweight/obese boys aged 8-18 who underwent DXA and insulin, testosterone, and IGF-1 measurements. Bone mineralization was compared with data from 301 lean boys of similar age and height from NHANES 2011-2015, using the same DXA model. Path analyses were performed to evaluate factors associated with total body less head (TBLH) BMC., Results: The mean age- and height-adjusted difference in TBLH BMC between obese and lean boys was 241 ± 20 g/cm2. Each 1 kg/m2 increase in BMI was associated with +39 ± 6 g of TBLH BMC in lean subjects vs + 25 ± 3 g in obese subjects (P < .05). Each 1 kg/m2 increase in lean BMI (LBMI) was associated with +78 ± 5 g of TBLH BMC in lean and obese boys, and each 1 kg/m2 increase in fat mass index (FMI) was associated with a decrease of 9 ± 3 g of TBLH BMC. The TBLH BMC was directly positively influenced by LBMI and indirectly and positively influenced by IGF-1, testosterone, and insulin (mediated through height and LBMI). FMI indirectly influenced TBLH BMC, both positively through LBMI and negatively through its negative impact on IGF-1 and testosterone., Conclusion: The increase in bone mineralization in obese children does not adapt to the increase in body mass., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Congenital hypothyroidism with gland-in-situ (CH-GIS) is usually attributed to mutations in the genes involved in thyroid hormone production. The diagnostic yield of targeted next-generation sequencing (NGS) varied widely between studies. We hypothesized that the molecular yield of targeted NGS would depend on the severity of CH., Methods: Targeted NGS was performed in 103 CH-GIS patients from the French national screening program referred to the Reference Center for Rare Thyroid Diseases of Angers University Hospital. The custom targeted NGS panel contained 48 genes. Cases were classified as solved or probably solved depending on the known inheritance of the gene, the classification of the variants according to the American College of Medical Genetics and Genomics, the familial segregation, and published functional studies. Thyroid-stimulating hormone at CH screening and at diagnosis (TSHsc and TSHdg) and free T4 at diagnosis (FT4dg) were recorded., Results: NGS identified 95 variants in 10 genes in 73 of the 103 patients, resulting in 25 solved cases and 18 probably solved cases. They were mainly due to mutations in the TG (n = 20) and TPO (n = 15) genes. The molecular yield was, respectively, 73% and 25% if TSHsc was ≥ and < 80 mUI/L, 60% and 30% if TSHdg was ≥ and < 100 mUI/L, and 69% and 29% if FT4dg was ≤ and > 5 pmol/L., Conclusion: NGS in patients with CH-GIS in France found a molecular explanation in 42% of the cases, increasing to 70% when TSHsc was ≥ 80 mUI/L or FT4dg was ≤ 5 pmol/L., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: It is unclear whether hybrid closed-loop (HCL) therapy attenuates the metabolic impact of missed or suboptimal meal insulin bolus compared with sensor-augmented pump (SAP) therapy in children with type 1 diabetes in free-living conditions. Methods: This is an ancillary study from a multicenter randomized controlled trial that compared 24/7 HCL with evening and night (E/N) HCL for 36 weeks in children between 6 and 12 years old. In the present study, the 60 children from the E/N arm underwent a SAP phase, an E/N HCL for 18 weeks, then a 24/7 phase for 18 weeks, extended for 36 more weeks. The last 28-30 days of each of the four phases were analyzed according to meal bolus management (cumulated 6817 days). The primary endpoint was the percentage of time that the sensor glucose was in the target range (TIR, 70-180 mg/dL) according to the number of missed boluses per day. Findings: TIR was 54% ± 10% with SAP, 63% ± 7% with E/N HCL, and steadily 67% ± 7% with 24/7 HCL. From the SAP phase to 72 weeks of HCL, the percentage of days with at least one missed meal bolus increased from 12% to 22%. Estimated marginal (EM) mean TIR when no bolus was missed was 54% (95% confidence intervals [CI] 53-56) in SAP and it was 13% higher (95% CI 11-15) in the 24/7 HCL phase. EM mean TIR with 1 and ≥2 missed boluses/day was 49.5% (95% CI 46-52) and 45% (95% CI 39-51) in SAP, and it was 15% (95% CI 14-16) and 17% higher (95% CI 6-28), respectively, in the 24/7 HCL phase ( P  < 0.05 for all comparisons vs. SAP). Interpretation: HCL persistently improves glycemic control compared with SAP, even in case of meal bolus omission. ClinicalTrials.gov (NCT03739099).