Pediatric growth patterns in youth-onset type 2 diabetes mellitus: Implications for physiologically-based pharmacokinetic models.
Pediatric growth patterns in youth-onset type 2 diabetes mellitus: Implications for physiologically-based pharmacokinetic models.
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DOI：
10.1111/cts.13207
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发表时间：
2022-04
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准确了解儿童身高和体重随年龄的变化对于开发预测儿童药物浓度的模型（即基于生理的药代动力学模型）至关重要。然而，描述典型儿童群体生长的曲线可能不能准确地描述患有各种疾病（如肥胖）的儿童的生长。因此，为了建立诊断为2型糖尿病的青少年的身高和体重与年龄的增长曲线，我们从电子医疗记录中提取数据。鲁棒非线性模型被参数化到描述身高和体重与年龄的方程中，这是由疾病控制和预防中心（CDC）定义的。CDC z - score使用内部程序计算。将生长曲线和z -分数与CDC标准进行比较。青少年2型糖尿病患者的体重从儿童早期就超过了疾病控制与预防中心的标准。除了青春期前后的一段时间外，患有2型糖尿病的青少年平均身高低于疾病控制与预防中心的标准，这导致他们成年后的平均身高更短。青少年2型糖尿病患者的生长差异明显；这种偏差也可能出现在其他疾病中，在针对儿科疾病的模型知情药物开发过程中，应考虑疾病特异性生长曲线。
An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically‐based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for Disease Control and Prevention (CDC). CDC z‐scores were calculated using an internal program. The growth curves and z‐scores were compared to CDC norms. Youth with type 2 diabetes were increasingly heavier than CDC norms from early childhood. Except for a period around puberty, youth with type 2 diabetes were, on average, shorter than CDC norms, resulting in shorter average adult height. Deviations in growth were apparent in youth who develop type 2 diabetes; such deviations may be expected for other conditions as well, and disease‐specific growth curves should be considered during development of model‐informed drug development for pediatric conditions.
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