Higher HbA1c linked to reduced cortical thickness, gray matter in youth; effect stronger in deprived neighborhoods

This cross-sectional observational analysis used data from 705 healthy 11-12-year-olds across 21 U.S. sites in the Adolescent Brain and Cognitive Development (ABCD) Study. It examined associations between glycemic control (measured by hemoglobin A1c), neighborhood socioeconomic deprivation (measured by the Area Deprivation Index), and brain structure via MRI. No comparator group was explicitly reported.

Higher HbA1c was associated with lower mean cortical thickness, with a 1% increase in HbA1c corresponding to a 0.024 mm reduction. Higher HbA1c was also associated with smaller total cortical gray matter volume, with a 1% increase corresponding to a 9,611 mm3 reduction. Regional analyses showed these associations primarily involved thinner cortex and smaller gray matter volumes in frontal, cingulate, and occipital areas.

A key finding was a significant interaction between HbA1c and neighborhood deprivation on total gray matter volume. The negative association of HbA1c with total gray matter volume was significant in the high and medium neighborhood deprivation groups, but not in the low deprivation group. Safety and tolerability data were not reported for this observational analysis.

Major limitations include the cross-sectional design, which cannot establish causality or temporal sequence. The analysis reports effect sizes per 1% HbA1c increase but does not provide absolute numbers, p-values, or confidence intervals in the available abstract. Funding and conflicts of interest were not reported. For clinicians, this adds to observational evidence that glycemic markers, even in a non-diabetic pediatric range, may correlate with early neuroanatomical differences, with socioeconomic context appearing to modify this relationship.