The Role of Neighborhood Socioeconomic Environment in the Association Between Glycemic Control and the Developing Brain

Objective: To investigate overall and neighborhood socioeconomic deprivation moderated associations between glycemic control and brain structure in youth. Research Design and Methods: This was a cross-sectional study of 705 healthy 11-12-year-olds across 21 study sites in the United States. Data was obtained from the Adolescent Brain and Cognitive Development (ABCD) Study(R). Glycemic control was assessed using hemoglobin A1c (HbA1c), brain structure was evaluated via MRI, and neighborhood deprivation was measured with the Area Deprivation Index (ADI). Mixed effects models were used to examine relationships between HbA1c, brain structure and ADI controlling for sociodemographic covariates. Stratified analysis was performed by tertiles of ADI. Results: Higher HbA1c was associated with lower mean cortical thickness (CT) and smaller total cortical gray matter volume (GMV). One percent increase in HbA1c corresponded to a 0.024 mm reduction in mean CT and a 9,611 mm3 reduction in total cortical GMV. Regionally, higher HbA1c was associated with thinner cortex and smaller gray matter volumes primarily in the frontal, cingulate and occipital areas. There was a significant interaction of HbA1c and ADI on total GMV, which was driven by significant negative associations of HbA1c with total GMV in the high ADI group, and medium ADI group, but not the low ADI group. Conclusions: Mild elevations in HbA1c, even within the non-diabetic range, are linked to early brain structural changes, particularly in youth from neighborhoods with greater socioeconomic deprivation. These results highlight the interplay between metabolic health and neighborhood deprivation on shaping brain development in youth.