von Heimburg Philipp, Baber Ronny, Willenberg Anja, Wölfle Philip, Kratzsch Jürgen, Kiess Wieland, Vogel Mandy
LIFE Child - Leipzig Research Center for Civilization Diseases, Leipzig University, Leipzig, Germany.
Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics (ILM), Leipzig University, Leipzig, Germany.
Front Endocrinol (Lausanne). 2025 Feb 18;16:1470513. doi: 10.3389/fendo.2025.1470513. eCollection 2025.
Vitamin D binding protein (DBP) regulates the transport and availability of vitamin D. We aimed to establish age- and sex-specific reference ranges for serum concentrations of DBP in healthy infants, children, and adolescents. In addition, we investigated DBP's associations with age, sex, puberty, body mass index (BMI), and oral contraceptive use.
2,503 serum samples from children and adolescents aged 3 months to 17 years from the LIFE Child cohort were analyzed to study DBP levels in this population (49.3% female subjects, 50.7% male subjects). Age- and sex-dependent reference percentiles were established using generalized additive models. We used linear mixed effects models to assess DBP's associations with age, sex, pubertal status, the BMI standard deviation score (SDS), and oral contraceptives. To investigate associations between DBP and vitamin D metabolites, we applied univariate regression analysis. We used hierarchical regression models and linear mixed effects models to assess DBP's associations with bone parameters, hormones, and inflammatory markers.
Mean DBP values differed between males (347 mg/l) and females (366 mg/l) (p < 0.001). Age had no significant association with DBP levels. In both males and females, DBP levels remained relatively stable from infancy through late adolescence. Children and adolescents with obesity had lower mean DBP levels compared with normal-weight subjects (ß = -14.28, p < 0.001). The BMI-SDS was inversely associated with DBP levels in males (ß = -5.7, p < 0.001). Female subjects using oral contraceptives had higher levels of DBP (ß = 141.38, p < 0.001). DBP was positively associated with the vitamin D metabolites: 25(OH)D (females: ß = 0.8, p < 0.001; males: ß = 1.2, p < 0.001) and 1,25(OH)-D (females: ß = 0.3, p < 0.001; males: ß = 0.4, p < 0.001). An inverse association between osteocalcin and DBP (females: ß = -0.1, p < 0.022; males: ß = -0.1, p = 0.027) was found. CRP levels were also positively associated with DBP levels (females: ß = 2.8, p = 0.001; males: ß = 5.1, p < 0.001).
We established age- and sex-specific reference ranges for the serum concentration of DBP. We suggest that BMI, pubertal stages, oral contraceptive use, and inflammation markers need to be considered when interpreting DBP as a stabilizer and regulator of vitamin D metabolism and vitamin D status in children and adolescents.
ClinicalTrial.gov, identifier NCT02550236.
维生素D结合蛋白（DBP）调节维生素D的转运和可利用性。我们旨在建立健康婴儿、儿童和青少年血清DBP浓度的年龄和性别特异性参考范围。此外，我们研究了DBP与年龄、性别、青春期、体重指数（BMI）和口服避孕药使用之间的关联。
对来自LIFE儿童队列的2503份3个月至17岁儿童和青少年的血清样本进行分析，以研究该人群中的DBP水平（49.3%为女性受试者，50.7%为男性受试者）。使用广义相加模型建立年龄和性别依赖性参考百分位数。我们使用线性混合效应模型评估DBP与年龄、性别、青春期状态、BMI标准差评分（SDS）和口服避孕药之间的关联。为了研究DBP与维生素D代谢产物之间的关联，我们进行了单变量回归分析。我们使用分层回归模型和线性混合效应模型评估DBP与骨参数、激素和炎症标志物之间的关联。
男性（347mg/l）和女性（366mg/l）的DBP均值存在差异（p<0.001）。年龄与DBP水平无显著关联。在男性和女性中，从婴儿期到青春期后期，DBP水平相对稳定。与体重正常的受试者相比，肥胖儿童和青少年的DBP平均水平较低（β=-14.28，p<0.001）。BMI-SDS与男性的DBP水平呈负相关（β=-5.7，p<0.001）。使用口服避孕药的女性受试者DBP水平较高（β=141.38，p<0.001）。DBP与维生素D代谢产物呈正相关：25（OH）D（女性：β=0.8，p<0.001；男性：β=1.2，p<
