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Pediatric growth patterns in youth-onset type 2 diabetes mellitus: Implications for physiologically-based
Chelsea M Hosey1, Kelsee Halpin1,2, Valentina Shakhnovich1,2,3,4
1Children's Mercy Kansas City, Kansas City, Missouri, USA.
Insights
Children with type 2 diabetes exhibit distinct growth patterns, being heavier and shorter than typical norms. Disease-specific growth curves are crucial for accurate pediatric drug development models.
Area of Science:
- Pediatric Endocrinology
- Pharmacokinetics
- Biostatistics
Background:
- Accurate pediatric growth data is essential for physiologically-based pharmacokinetic (PBPK) models.
- Standard growth curves may not represent children with specific conditions like type 2 diabetes (T2D).
Purpose of the Study:
- To develop specific height and weight-for-age growth curves for youth diagnosed with T2D.
- To compare these disease-specific curves against established Centers for Disease Control and Prevention (CDC) norms.
Main Methods:
- Extracted data from electronic medical records of youth with T2D.
- Utilized robust nonlinear models to parameterize growth equations.
- Calculated CDC z-scores and compared growth curves to CDC standards.
Main Results:
- Youth with T2D showed increasing weight deviations above CDC norms from early childhood.
- On average, these youth were shorter than CDC norms, except around puberty, leading to shorter adult height.
- Significant growth deviations were observed in the T2D cohort compared to general population norms.
Conclusions:
- Growth patterns in youth with T2D differ significantly from general population standards.
- Disease-specific growth curves are necessary for accurate modeling in pediatric drug development.
- Consideration of condition-specific growth deviations is vital for model-informed pediatric drug development.
Abstract:
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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