Depression, Systemic Inflammation, and Prevalent Diabetes: A Counterfactual Mediation Analysis

Depression and diabetes frequently co-occur, and chronic low-grade systemic inflammation has been proposed as one of many potential factors that may account for the association between these two conditions. This study aimed to empirically examine systemic inflammation as a potential mediator of the association between depression and prevalent diabetes. This study analyzed 2015–2018 NHANES data ( N = 7,583) using a counterfactual causal mediation approach. Depression was assessed via the Patient Health Questionnaire, systemic inflammation via high-sensitivity C-reactive protein, neutrophils-to-lymphocytes ratio, and platelet-to-lymphocytes ratio, and diabetes via HbA1c or self-report. Mediation effects were decomposed into natural direct effect (NDE), natural indirect effect (NIE), and total effect. Percentile bootstrapping with 1000 resampling was used to generate confidence intervals (CI). Depression was associated with 62% greater odds of prevalent diabetes (total effect: OR = 1.62, 95% CI: 1.20 – 2.24). There was a significant positive natural direct effect regarding the association between depression and prevalent diabetes (NDE: OR = 1.60, 95% CI: 1.18 – 2.19), and a positive but small natural indirect effect through systemic inflammation (NIE: OR = 1.02, 95% CI: 1.01 – 1.04). Similar findings were observed in the multiple imputed datasets. Depression is associated with greater odds of prevalent diabetes, with systemic inflammation contributing to a small but significant proportion of the observed association. Further research should assess other potential physiological or behavioral mediators that may account for the association between depression and prevalent diabetes.