Investigating the Role of Childhood Adiposity in the Development of Adult Type 2 Diabetes in a 64-year Follow-up Cohort: An Application of the Parametric G-formula Within an Agent-based Simulation Study.

Abstract

The contribution of childhood obesity to adult type 2 diabetes (T2DM), not through adult adiposity, as well as the causal pathways through which childhood obesity increases adult T2DM risk are not well understood. This study investigated the contribution of childhood obesity to incident T2DM including pathways not through adult adiposity, and explored whether race modified this contribution. We used data from the Virtual Los Angeles Cohort, an agent-based longitudinal birth cohort composed of 98,230 simulated individuals born in 2009 and followed until age 65 years. We applied the parametric mediational g-formula to the causal mediation analysis investigating the impact of childhood obesity on the development of adult T2DM. The marginal adjusted odds ratio (aOR) for the total effect of childhood obesity on adult T2DM was 1.37 (95% CI = 1.32, 1.46). Nearly all the effect of childhood obesity on adult T2DM was mostly attributable to pathways other than through adult obesity; the aOR for the pure direct effect was 1.36 (95% CI = 1.31, 1.41). In all racial subpopulations, a similar 3% of the total effect of childhood obesity on adult T2DM was attributable to its effect on adult obesity. Childhood obesity remains a risk factor for adult T2DM separate from its effects on adult obesity. This study emphasizes the potential benefits of early interventions and illustrates that agent-based simulation models could serve as virtual laboratories for exploring mechanisms in obesity research.