Objective: We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods: In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results: Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [−29% (95% CI −36%, −20%); p < 0.0001], pubertal boys [−13% (95% CI −21%, −6%); p = 0.001], and pubertal girls [−16% (95% CI −24%, −6%); p = 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group Jin et al. A/G and Body Fat% as Cardiometabolic Predictors [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions: A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism.

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes (T1D), and a leading cause of death in children aged &lt;15 years with new-onset T1D.Aimsi) to assess the incidence of DKA in children and adolescents newly diagnosed with T1D over a 10-year period at a large regional center in China; and ii) to examine the clinical symptoms and demographic factors associated with DKA and its severity at diagnosis.MethodsWe carried out a retrospective audit of a regional center, encompassing all youth aged &lt;16 years diagnosed with T1D in 2009–2018 at the Children’s Hospital, Zhejiang University School of Medicine (Hangzhou, China). DKA and its severity were classified according to ISPAD 2018 guidelines.Results681 children were diagnosed with T1D, 50.1% having DKA at presentation (36.0% mild, 30.0% moderate, and 33.9% severe DKA). The number of patients diagnosed with T1D progressively rose from approximately 39 cases/year in 2009–2010 to 95 cases/year in 2017–2018 (≈2.5-fold increase), rising primarily among children aged 5–9 years. DKA incidence was unchanged but variable (44.8% to 56.8%). At T1D diagnosis, 89% of patients reported polyuria and 91% polydipsia. Children presenting with DKA were more likely to report vomiting, abdominal pain, and particularly fatigue. DKA was most common among the youngest children, affecting 4 in 5 children aged &lt;2 years (81.4%), in comparison to 53.3%, 42.7%, and 49.3% of patients aged 2–4, 5–9, and ≥10 years, respectively. Children with severe DKA were more likely to report vomiting, fatigue, and abdominal pain, but less likely to report polyuria, polydipsia, and polyphagia than those with mild/moderate DKA. Rates of severe DKA were highest in children aged &lt;2 years (51.1%).ConclusionsThe number of children diagnosed with T1D at our regional center increased over the study period, but DKA rates were unchanged. With 9 of 10 children reporting polyuria and polydipsia prior to T1D diagnosis, increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and thus potentially reduce rates of DKA at presentation.

IntroductionThis study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment.Research design and methodsA total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway.ResultsObese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells.ConclusionIncreased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

BackgroundTo evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China.MethodsThis study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS).Results△HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P &lt; 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P &lt; 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P &lt; 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P &lt; 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P &lt; 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related.ConclusionsDaily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile.Trial RegistrationClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580

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