Martín-Rivada Álvaro, Martos-Moreno Gabriel Á, Guerra-Cantera Santiago, Campillo-Calatayud Ana, Oxvig Claus, Frystyk Jan, Chowen Julie A, Barrios Vicente, Argente Jesús
Department of Endocrinology, Hospital Infantil Universitario Niño Jesús, Madrid E-28009, Spain.
Research Institute "La Princesa", Madrid E-28009, Spain.
J Clin Endocrinol Metab. 2025 Feb 18;110(3):e622-e629. doi: 10.1210/clinem/dgae288.
Prepubertal children with obesity frequently have enhanced growth, accelerated skeletal maturation, and changes in the growth hormone-insulin-like growth factor (GH-IGF) axis. However, the involvement of pappalysins (PAPP-A, PAPP-A2) and stanniocalcins (STC1, STC2) as regulators of IGF bioavailability has not been studied in obesity.
We aimed to determine the effects of childhood obesity and weight reduction on serum levels of PAPP-A, PAPP-A2, STC1, and STC2 and their relationship with IGF bioavailability, growth, and other components of the GH-IGF system.
Prepubertal children with severe obesity (150, 50% males/females, age: 7.72 ± 2.05 years, BMI z-score: 4.95 ± 1.70, height z-score: 1.28 ± 1.04) were studied at diagnosis and after a minimum of 0.5 BMI z-score reduction. Two hundred and six healthy age- and sex-matched children were used as controls.
Children with obesity had decreased serum concentrations of PAPP-A, PAPP-A2 and STC2, but increased total and free IGF-I, intact IGFBP-3, acid-labile subunit (ALS), IGF-II, and insulin levels, with no difference in the free IGF-I/total IGF-I ratio. Neither the standardized body mass index (BMI) nor height correlated with any biochemical parameter analyzed. A decrease in IGF-II, insulin, and ALS with an increase in IGFBP-2 and -5, STC2, and PAPP-A were observed after weight loss.
Increased circulating total and free IGF-I, insulin, and IGF-II may all contribute to the increased rate of prepubertal growth and bone maturation observed in children with obesity, with STC2 possibly being involved.
青春期前肥胖儿童常常生长加快、骨骼成熟加速，生长激素 - 胰岛素样生长因子（GH - IGF）轴发生变化。然而，在肥胖症中，作为IGF生物利用度调节因子的妊娠相关血浆蛋白（PAPP - A、PAPP - A2）和鲟钙蛋白（STC1、STC2）的作用尚未得到研究。
我们旨在确定儿童肥胖及体重减轻对血清PAPP - A、PAPP - A2、STC1和STC2水平的影响，以及它们与IGF生物利用度、生长和GH - IGF系统其他成分的关系。
对青春期前重度肥胖儿童（150例，男女各占50%，年龄：7.72±2.05岁，BMI z评分：4.95±1.70，身高z评分：1.28±1.04）在诊断时及体重减轻至少0.5个BMI z评分后进行研究。206名年龄和性别匹配的健康儿童作为对照。
肥胖儿童血清PAPP - A、PAPP - A2和STC2浓度降低，但总IGF - I和游离IGF - I、完整IGFBP - 3、酸不稳定亚基（ALS）、IGF - II和胰岛素水平升高，游离IGF - I/总IGF - I比值无差异。标准化体重指数（BMI）和身高与所分析的任何生化参数均无相关性。体重减轻后，IGF - II、胰岛素和ALS降低，而IGFBP - 2和 - 5、STC2及PAPP - A升高。
循环中总IGF - I和游离IGF - I、胰岛素及IGF - II升高可能都导致了肥胖儿童青春期前生长速率加快和骨骼成熟加速，STC2可能参与其中。
