Association of remnant cholesterol with depression, type 2 diabetes, and their coexistence

Depression and Type 2 Diabetes Mellitus (T2DM) represent significant public health challenges and share common pathogenic mechanisms. Previous studies have indicated a positive correlation between serum residual cholesterol (RC) and depression. However, further research is needed to understand the relationships between RC and depression, T2DM, and their coexistence. This study aims to assess the association between RC and depression, T2DM, and their comorbidities in a large sample of the U.S. population, while also exploring potential underlying mechanisms.

This is a cross-sectional study utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018 (N = 11,193). Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). We employed weighted univariate and multivariate logistic regression models, considering sampling weights, to explore the associations between serum RC and depression, T2DM and their coexistence. To assess model stability, we calculated unmeasured confounder E values. Restricted cubic spline regression models were used to reveal dose-response effects, and subgroup analyses were conducted.

Among the 11,193 participants, the weighted mean age was 45.24 years, with 49.0% being male. The prevalence of depression, T2DM, and their coexistence was 6.9%, 14.0%, and 1.4%, respectively (weighted percentages). In the multivariate regression model, higher serum RC levels were associated with an increased risk of depression, T2DM, and their coexistence. The adjusted odds ratios (ORs) per unit increase in RC were 1.39(1.06,1.82), 2.26(1.79,2.83), and 3.07(2.08,4.52), respectively. When considering only depression without T2DM, the association was not significant (OR: 1.23; 95% CI: 0.87-1.73). This nonlinear correlation between RC and depression, T2DM, and their coexistence was consistent across various participant characteristics.

The findings from this extensive cross-sectional study offer compelling evidence linking RC to the risk of depression, T2DM, and their coexistence. This implies that directing attention towards residual cholesterol could enhance research pertaining to the comorbidities of depression and type 2 diabetes.