Participants with higher estimated glucose disposal rates demonstrated significantly lower odds of depression, according to a population-based study of U.S. adults published in BMC Psychiatry. 

Researchers analyzed data from 28,444 participants in the National Health and Nutrition Examination Survey (1999–2018). Depression was assessed using Patient Health Questionnaire-9 (PHQ-9) scores, with a threshold of ≥10 indicating depression.

Multivariate logistic regression revealed a linear, inverse association between estimated glucose disposal rates (eGDR) and depression (OR: 0.913; 95% CI: 0.875–0.953). Restricted cubic spline analysis confirmed this relationship, with participants in eGDR categories of 6–8 mg/kg/min and >8 mg/kg/min exhibiting a 25.4% (OR: 0.746; 95% CI: 0.562–0.990) and 41.5% (OR: 0.585; 95% CI: 0.431–0.795) lower likelihood of depression, respectively, compared to those with eGDR <4 mg/kg/min.

Subgroup analyses indicated the association was stronger among participants with obesity, where each unit increase in eGDR corresponded to a 15.2% reduction in depression risk (OR: 0.848; 95% CI: 0.780–0.922). Mediation analysis further identified the atherogenic index of plasma (AIP) as accounting for 9.6% of the eGDR-depression association, emphasizing the role of lipid metabolism.

Baseline characteristics highlighted that participants with depression had higher BMIs, larger waist circumferences, and more comorbidities, including hypertension, diabetes, and chronic kidney disease. Depression prevalence was 8.5%, with women and individuals with lower physical activity levels being disproportionately affected.

eGDR, a measure combining hypertension, waist circumference, and HbA1c, serves as a surrogate for insulin resistance. The study suggests insulin resistance could influence depression through mechanisms such as HPA axis dysregulation, inflammation, and lipid metabolism disturbances.

While the large, nationally representative sample strengthens generalizability, the study's cross-sectional design limits causal interpretations. Future longitudinal research is necessary to further clarify the observed relationships and assess potential intervention strategies targeting metabolic health to mitigate depression risk.

Full disclosures can be found in the published study.