Insulin resistance mediates the relationship between cardiovascular-kidney-metabolic syndrome and depression: A cross-sectional analysis.

BACKGROUND: To date, no studies have examined the role of insulin resistance (IR) in the relationship between depression and cardiovascular-kidney-metabolic (CKM) syndrome. OBJECTIVES: This study aims to explore the association between CKM and depression, and to determine whether IR mediates this relationship. METHODS: A total of 8584 participants were included in the analysis. CKM was categorized according to the 2023 American Heart Association guidelines. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score ≥10 indicating the presence of depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations, and mediation analysis was performed to evaluate the potential mediating effect of IR biomarkers. RESULTS: Of the participants, 675 exhibited clinically significant depressive symptoms. After adjusting for confounders, compared with participants in CKM stage 0, those in CKM stages 1, 2, and advanced CKM exhibited increases in PHQ-9 scores of 0.41, 0.68, and 1.82, respectively (all p < 0.05). Among the core depressive symptoms, fatigue showed the strongest association with advanced CKM (β = 0.45, 95% CI: 0.32-0.57, p < 0.001). Additionally, all IR biomarkers demonstrated significant partial mediation effects (p < 0.05), with the estimated glucose disposal rate (eGDR) showing the largest mediation effect (7.04%). CONCLUSION: Advanced CKM is positively associated with depressive symptoms, and IR partially mediates this relationship. These findings highlight the importance of enhanced mental health screening in patients with advanced CKM and suggest that improving IR may be a potential therapeutic target for future interventions.