Synergistic Associations of Depressive Symptoms and Executive Functions With Longitudinal Trajectories of Diabetes Biomarkers Among Urban-Dwelling Adults Without Diabetes

Objective Depressive symptoms and executive functions (EFs) have recently emerged as novel risk factors for type 2 diabetes, but it is unknown if these factors interact to influence diabetes pathophysiology across the life span. We examined the synergistic associations of depressive symptoms and EFs with longitudinal trajectories of diabetes diagnostic criteria among middle-aged and older adults without diabetes. Methods Participants were 1257 African American and White, urban-dwelling adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span study who were assessed up to three times over a 13-year period (2004–2017). At baseline, participants completed the Center for Epidemiological Studies—Depression scale and measures of EFs—Trail Making Test Part B, verbal fluency, and Digit Span Backward—for a composite EFs score, and provided blood samples at each follow-up for glycated hemoglobin and fasting serum glucose. Results A total of 155 and 220 individuals developed diabetes or prediabetes at wave 3 and wave 4, respectively. Linear mixed-effects regression models adjusting for sociodemographic factors, diabetes risk factors, and antidepressant medications revealed significant three-way interactions of Center for Epidemiological Studies—Depression, EFs, and age on change in glycated hemoglobin (b = −0.0001, p = .005) and in fasting serum glucose (b = −0.0004, p < .001), such that among individuals with lower but not higher EFs, elevated depressive symptoms were associated with steeper age-related increases in diabetes biomarkers over time. Conclusions Depressive symptoms and lower EFs may interactively accelerate trajectories of key diagnostic criteria, thereby increasing the risk for earlier diabetes incidence. Identifying individuals in this high-risk group may be an important clinical priority for earlier intervention, which has the promise of preventing or delaying this debilitating disease.