The role of neighborhood socioeconomic environment in the association between glycemic control and the developing brain

Abstract Metabolic health and socioeconomic environments may jointly shape neurodevelopment during adolescence, a sensitive period of brain maturation. This cross-sectional study investigated overall and neighborhood socioeconomic deprivation moderated associations between glycemic control and brain structure in youth. Data were analyzed from 705 healthy 10–13-year-olds participating in the Adolescent Brain and Cognitive Development (ABCD) Study® across 21 sites in the United States. Glycemic control was assessed using hemoglobin A1c (HbA1c), brain structure was evaluated via magnetic resonance imaging (MRI), and neighborhood deprivation was measured with the Area Deprivation Index (ADI). Mixed-effects models examined associations between HbA1c and brain structural measures while controlling for sociodemographic covariates, with additional analyses stratified by ADI tertiles. Higher HbA1c was associated with lower mean cortical thickness and smaller total cortical gray matter volume. Each one percent increase in HbA1c corresponded to a 0.024 mm reduction in mean cortical thickness and a 9,611 mm 3 reduction in total cortical gray matter volume. Regionally, higher HbA1c was associated with thinner cortex and smaller gray matter volumes primarily within frontal, cingulate and occipital areas. Exploratory analysis found that higher HbA1c was associated with lower total cortical gray matter volume among youth living in medium and high ADI neighborhoods, but not low ADI neighborhoods, whereas higher HbA1c was associated with lower mean cortical thickness only among youth living in high ADI neighborhoods. These findings highlight the interplay between metabolic health and neighborhood deprivation, supporting a model in which socioeconomic disadvantage may magnify the neurodevelopmental impact of metabolic variation, even within the non-diabetic range.