Cardiometabolic Index as a Mediator in the Association Between Estimated Glucose Disposal Rate and Depressive Symptoms: A Population‐Based Study

Mimi Li; Shujuan Wu; Xiaofang Ye; Binbin Yu; Wanli Huang; Lichao Ye; Chunnuan Chen

doi:10.1002/brb3.71247

journal article Open Access Feb 01, 2026

Cardiometabolic Index as a Mediator in the Association Between Estimated Glucose Disposal Rate and Depressive Symptoms: A Population‐Based Study

Mimi Li

Shujuan Wu Xiaofang Ye Binbin Yu

Wanli Huang Lichao Ye

Chunnuan Chen

Brain and Behavior Vol. 16 No. 2 · Wiley

View at Publisher Save 10.1002/brb3.71247

Abstract

ABSTRACT

Background
Estimated glucose disposal rate (eGDR) emerged as an innovative marker for insulin resistance, and this study was designed to investigate the connection between eGDR and depressive symptoms.

Methods
Information from the National Health and Nutrition Examination Survey (NHANES) was processed within the cross‐sectional research. Relationships between depressive symptoms and eGDR were examined using weighted logistic regression models, restricted cubic splines (RCS), sensitivity analyses, and subgroup comparisons. Receiver operating characteristic (ROC) curve analysis assessed the capacity for prediction of eGDR, relative to triglyceride‐glucose (TyG) index, Homeostasis Model Assessment of Insulin Resistance (HOMA‐IR), and glycated hemoglobin (HbA1c). Mediation analysis was also applied to assess cardiometabolic index (CMI)’s potential role in the eGDR‐depression relationship.

Results:

This analysis comprised 12,191 individuals stratified by eGDR tertiles (T1: <6.15; T2: 6.15–9.44; T3: ≥9.44 mg/kg/min). Multivariate logistic regression, adjusted for covariates, found that T3 had a significantly lower odds ratio for depressive symptoms than T1 (OR = 0.68, 95% CI: 0.48–0.97). RCS curves confirmed a linear trend (P for non‐linearity = 0.764). The negative association was particularly evident in participants under 60, non‐Hispanic Black individuals, those living alone, and those without cardiovascular disease. ROC analysis indicated that eGDR had better discriminative power for depressive symptoms than TyG, HOMA‐IR, and HbA1c (
p
< 0.05). Additionally, CMI mediated approximately 11.2% (95% CI: 4.2%–32.7%) of the total effect of eGDR on depressive symptoms.

Conclusions
Higher eGDR correlates with lower likelihood of depressive symptoms, with CMI acting as a mediator. Reducing insulin resistance and monitoring CMI could help decrease the occurrence of depression.

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Published: Feb 01, 2026
Vol/Issue: 16(2)
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Mimi Li