Unequal and Unique contribution of Different Adverse Childhood Experiences to Metabolic Disease Risk in a Multiracial Cohort

Abstract

Adverse childhood experiences (ACEs) are an independent risk factor for chronic disease, including obesity and metabolic syndrome. Therefore, we sought to determine the association of ACEs with BMI and plasma metabolic biomarkers affecting a multiracial cohort. Total ACE score was calculated in 38,353 non‐Hispanic Black and White men and women who participated in the second follow‐up of the Southern Community Cohort Study (2012‐2015). We used regression analyses to assess whether total ACE score or individual ACE components were associated with BMI and included interaction terms to evaluate if the association differed by sex or race, and for female participants, we accounted for menopause status. Total ACE score was associated with BMI (non‐linear p‐value=0.0026) and differed by sex and race (interaction p‐value<0.0001), but not menopause status. BMI steadily increased with cumulative ACEs among Black women. Among White women, BMI sharply increased from 0 to 1 ACEs, and steadily increased thereafter. In White men, BMI increased as ACEs increased from 0 to 3 and remained relatively stable among individuals with >4 ACEs. In Black men, BMI decreased with cumulative ACEs. Among Black women, emotional and sexual abuse were associated with higher BMI (p<0.05). Including both Black women and men, having an incarcerated family member was associated with lower BMI. Physical abuse was associated with increased BMI in Black and White men, while emotional neglect was associated with increased BMI in White women (p<0.05). In addition, regression analysis revealed an association between total ACE score and waist circumference, totalcholesterol, the ratio of leptin to adiponectin, HbA1c, and insulin. Furthermore, with increasing number of ACEs, Black men were the most affected in waist circumference, showing a 6 cm overall increase; however, they showed reduced BMI. This data indicates increased visceral fat deposition which is an indicator of metabolic syndrome and insulin resistance. Using a mouse model of postnatal neglect, and in line with this data, we have found that female mice, and not male mice, develop exacerbated adiposity. Specifically, female mice display increased whitening of adipose tissue via the actions of the mineralocorticoid receptor on lipid storage and adipocyte differentiation. Overall, ACEs are associated with BMI, but each ACE component has a unique contribution to this effect that varies based on sex and race. Future pre‐clinical studies should aim to model sex‐ and race‐specific effect of ACE on the development of obesity to provide insights on potential personalized therapies for people undergoing these health disparities.