The interplay between birth weight and obesity in determining childhood and adolescent cardiometabolic risk
eBioMedicine, 2024
Stinson S., Kromann Reim P., Lund M., Lausten-Thomsen U., Aas Holm L., Huang Y., Brøns C., Vaag A., Thiele M., Krag A., Fonvig C., Grarup N., Pedersen O., Christiansen M., Ängquist L., Sørensen T., Holm J., Hansen T.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Metabolic Diseases CVD | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Background
Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations.
Methods
We used data from The cross-sectional HOLBAEK Study with 4263 participants (median [IQR] age, 11.7 [9.2, 14.3] years; 57.1% girls and 42.9% boys; 48.6% from an obesity clinic and 51.4% from a population-based group). We gathered information on BW and gestational age, anthropometrics, cardiometabolic risk factors, calculated a PGS for BW, and measured plasma proteins using Olink Inflammation and Cardiovascular II panels. We employed multiple linear regression to examine the associations with BW as a continuous variable and performed interaction analyses to assess the effect of childhood obesity on cardiometabolic risk and plasma protein levels.
Findings
BW and a PGS for BW associated with cardiometabolic risk and plasma protein levels in childhood and adolescence. Childhood obesity modified the associations between BW and measures of insulin resistance, including HOMA-IR (βadj [95% CI per SD] for obesity: −0.12 [−0.15, −0.08]; normal weight: −0.04 [−0.08, 0.00]; Pinteraction = 0.004), c-peptide (obesity: −0.11 [−0.14, −0.08]; normal weight: −0.02 [−0.06, 0.02]; Pinteraction = 5.05E-04), and SBP SDS (obesity: −0.12 [−0.16, −0.08]; normal weight: −0.06 [−0.11, −0.01]; Pinteraction = 0.0479). Childhood obesity also modified the associations between BW and plasma levels of 14 proteins (e.g., IL15RA, MCP1, and XCL1; Pinteraction < 0.05).
Interpretation
We identified associations between lower BW and adverse metabolic phenotypes, particularly insulin resistance, blood pressure, and altered plasma protein levels, which were more pronounced in children with obesity. Developing effective prevention and treatment strategies for this group is needed to reduce the risk of future CMD.