Obesity is positively associated with sexual maturation in both boys and girls, and the association does not differ by gender, but the association is stronger in girls than in boys.

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.

Background To investigate the clinical and molecular characteristics of Chinese children with maturity onset diabetes of the young (MODY). Methods A total of 42 Chinese patients suspected MODY referred to our unit from 2014 to 2018 were enrolled. Mutational analysis of monogenic diabetes mellitus genes was performed by next-generation sequencing and confirmed by Sanger sequencing. Results There were 28 males (66.7%) and 14 females (33.3%) with a mean age of 9.49 ± 3.46 years (range, 1.4–15.3 years) and a mean birth weight of 3.38 ± 0.49 kg (range, 2.55–4.90 kg). Among these patients, 15 patients had polyuria, polydipsia or weight loss. Two patients (4.8%) were obese and six (14.3%) were overweight. Moreover, 13 patients (30.9%) had a family history of diabetes. Thirty variants were identified in 28 patients. Twenty-six variants in 25 patients were pathogenic or likely pathogenic genes (59.5%, 25/42), including 15 patients (60.0%, 15/25) with GCK mutation, four (16.0%, 4/25) with PAX4 mutation, three (12.0%, 3/25) with HNF4A mutation, one (4.0%, 1/25) with INS mutation, one (4.0%, 1/25) with NEUROD1 mutation and one (4.0%, 1/25) with HNF1A mutation. Nine mutations (36.0%, 9/25) were novel. There was no difference between mutation-suspected patients and MODY-confirmed patients except for a 2-h glucose increment in an oral glucose tolerance test (OGTT), while the GCK-MODY had lower glycated hemoglobin (HbA1c) and a significantly smaller 2-h glucose increment in an OGTT compared with transcription factor MODYs. The GCK-MODY was identified by incidental hyperglycemia without glycosuria. GCK-MODY without drug management and hepatocyte nuclear factor-1 alpha (HNF4A) or HNF1A-MODY with sulfonylurea therapy obtained good glucose controlling. Conclusions Mutation of the GCK gene is the most common in MODY patients in China followed by PAX4. The screening criteria can improve the cost-effectiveness of disease diagnosis and treatment. A precise molecular diagnosis would lead to optimal treatment of the patients.

ObjectiveThis study aims to outline the clinical characteristics of pediatric NAFLD, as well as establish and validate a prediction model for the disease.Materials and methodsThe retrospective study enrolled 3216 children with obesity from January 2003 to May 2021. They were divided into obese without NAFLD, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH) groups. Clinical data were retrieved, and gender and chronologic characteristics were compared between groups. Data from the training set (3036) were assessed using univariate analyses and stepwise multivariate logistic regression, by which a nomogram was developed to estimate the probability of NAFLD. Another 180 cases received additional liver hydrogen proton magnetic resonance spectroscopy (1H-MRS) as a validation set.ResultsThe prevalence of NAFLD was higher in males than in females and has increased over the last 19 years. In total, 1915 cases were NAFLD, and the peak onset age was 10-12 years old. Hyperuricemia ranked first in childhood NAFLD comorbidities, followed by dyslipidemia, hypertension, metabolic syndrome (MetS), and dysglycemia. The AUROC of the eight-parameter nomogram, including waist-to-height ratio (WHtR), hip circumference (HC), triglyceride glucose-waist circumference (TyG-WC), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1(ApoA1), insulin sensitivity index [ISI (composite)], and gender, for predicting NAFLD was 0.913 (sensitivity 80.70%, specificity 90.10%). Calibration curves demonstrated a great calibration ability of the model.Conclusion and relevanceNAFLD is the most common complication in children with obesity. The nomogram based on anthropometric and laboratory indicators performed well in predicting NAFLD. This can be used as a quick screening tool to assess pediatric NAFLD in children with obesity.

Background Prader–Willi syndrome (PWS) is a rare and multisystemic genetic disorder that is characterized by severe hypotonia, hyperphagia, short stature, and global developmental delay. Although early recombinant human growth hormone (rhGH) treatment has been proven to rescue some symptoms and bring additional benefits to PWS patients, studies in patients under 2 years old are scarce. Thus, this study aims to investigate the effectiveness and safety of rhGH treatment for young children. Methods A total of 96 genetically confirmed Chinese PWS infants or toddlers (47 males) followed between 2013 and 2022 were retrospectively analyzed. Sixty-five infants (early treatment group) started rhGH treatment during their first year, and 31 toddlers (later treatment group) started at the age of 1–2 years. Auxological parameters, carbohydrate metabolism parameters, thyroid function, liver function, insulin-like growth factor-1 (IGF-1), and radiographs were acquired before the initiation of the treatment and every 3–6 months thereafter. Height/length, weight, and weight for height were expressed as standard deviation scores (SDSs) according to WHO child growth standards. Results The mean SDS of length/height in the early treatment group was significantly higher than that in the later treatment group throughout the observation period (all P < 0.001). The change in the length SDS between the two groups at 1 year old and 4 years old was 1.50 (95% CI, 0.88–2.13) and 0.63 (95% CI, 0.16–1.10), respectively. Compared to the later treatment group, the weight SDS in the early treatment group increased by 0.94 (95% CI, 0.37–1.52) at 1 year old and 0.84 (95% CI, 0.28–1.39) at 2 years old. No statistical significance was found after 2.5 years of age. No significant differences were observed in IGF-1, incidence of liver dysfunction, hypothyroidism or spinal deformity between the two groups. Conclusions rhGH treatment improved growth and body composition in infants and toddlers. Furthermore, an early start of rhGH treatment is expected to have more efficacy than the later treatment group without an increase in adverse effects.

The present data provide further evidence to support the role of WT1 in diverse cellular functions.

No abstract

Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on chromosome15q11.2-q13.1. The clinical manifestations of PWS vary with age. It is characterized by severe hypotonia with poor suck and feeding difficulties in the early infancy, followed by overeating in late infancy or early childhood and progressive development of morbid obesity unless the diet is externally controlled. Compared to Western PWS patients, Chinese patients have a higher ratio of deletion type. Although some rare disease networks, including PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Zhejiang Expert Group for PWS, were established recently, misdiagnosis, missed diagnosis and inappropriate intervention were usually noted in China. Therefore, there is an urgent need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy. Our purpose is to evaluate the current literature and evidences on diagnosis and management of PWS in order to provide evidence-based guidelines for this disease, specially from China.