Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study

Abstract Background Accumulating evidence indicates a potential link between insulin resistance (IR) and depression, although the bidirectional nature and underlying mechanisms of this association remain poorly understood. This study aims to systematically investigate the associations between multip...

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Main Authors: Yueyu Zhang, Xinyi Chen, Yu Wang, Yi Tang, Kangrui Zhang, Juncang Wu
Format: Article
Language:English
Published: BMC 2025-06-01
Series:European Journal of Medical Research
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Online Access:https://doi.org/10.1186/s40001-025-02802-1
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author Yueyu Zhang
Xinyi Chen
Yu Wang
Yi Tang
Kangrui Zhang
Juncang Wu
author_facet Yueyu Zhang
Xinyi Chen
Yu Wang
Yi Tang
Kangrui Zhang
Juncang Wu
author_sort Yueyu Zhang
collection DOAJ
description Abstract Background Accumulating evidence indicates a potential link between insulin resistance (IR) and depression, although the bidirectional nature and underlying mechanisms of this association remain poorly understood. This study aims to systematically investigate the associations between multiple IR indices—specifically the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Lipid Accumulation Product (LAP), and Triglyceride-Glucose indice (TyG)—and the prevalence of depression. Methods Data from 12,011 participants in the National Health and Nutrition Examination Survey (NHANES) were analyzed. IR was quantified using three indices: HOMA-IR, LAP, and TyG. Baseline demographic and clinical characteristics were compared between participants with and without depression following stratification by depression status. Weighted multivariate logistic regression models were employed to evaluate the associations between IR indices (categorized into quartiles) and depression. Nonlinear relationships were explored using threshold effect analysis, restricted cubic spline (RCS) models, and smooth curve fitting. Subgroup analyses were performed to assess heterogeneity by age, gender, poverty level, and comorbidities (e.g., cardiovascular disease, hypertension). Results The depressed group (n = 971) exhibited significantly higher IR indices compared to the non-depressed group (n = 11,040). In the fully adjusted model (Model 3), both LAP (Q4 vs. Q1: OR = 1.569, 95% CI 1.234–1.998) and TyG (Q4 vs. Q1: OR = 1.497, 95% CI 1.182–1.896) were significantly associated with depression, whereas the association for HOMA-IR was attenuated (Q4 vs. Q1: OR = 1.310, p = 0.099). Threshold effect analysis revealed a nonlinear “inverted L-shaped” relationship between HOMA-IR, LAP, and depression, with effect modification observed at specific indice thresholds. Subgroup analyses demonstrated stronger associations in males (LAP: OR = 1.23, p < 0.01; TyG: OR = 1.31, p < 0.05), individuals with coronary heart disease (LAP: OR = 1.68, p < 0.001), and stroke survivors (LAP: OR = 1.42, p = 0.023 for interaction). Conclusions This study provides robust evidence of significant associations between IR indices (LAP and TyG) and depression, with a notable nonlinear “inverted L-shaped” relationship observed for LAP. Subgroup analyses highlighted stronger correlations in older adults (≥ 59 years), patients with coronary heart disease, stroke survivors, males, and individuals with hypertension. These findings enhance our understanding of the metabolic pathways underlying depression and emphasize the importance of integrating IR indices into mental health risk assessments. The results also offer a theoretical basis for personalized interventions targeting metabolic abnormalities in depression prevention and treatment.
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spelling doaj-art-4651f8e430db4e669646f07f1d69bd192025-08-20T03:27:11ZengBMCEuropean Journal of Medical Research2047-783X2025-06-0130111410.1186/s40001-025-02802-1Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional studyYueyu Zhang0Xinyi Chen1Yu Wang2Yi Tang3Kangrui Zhang4Juncang Wu5Anhui Medical UniversityAnhui Medical UniversityDepartment of Neurology, The Second People’s Hospital of HefeiAnhui Medical UniversityDepartment of Neurology, The Second People’s Hospital of HefeiAnhui Medical UniversityAbstract Background Accumulating evidence indicates a potential link between insulin resistance (IR) and depression, although the bidirectional nature and underlying mechanisms of this association remain poorly understood. This study aims to systematically investigate the associations between multiple IR indices—specifically the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Lipid Accumulation Product (LAP), and Triglyceride-Glucose indice (TyG)—and the prevalence of depression. Methods Data from 12,011 participants in the National Health and Nutrition Examination Survey (NHANES) were analyzed. IR was quantified using three indices: HOMA-IR, LAP, and TyG. Baseline demographic and clinical characteristics were compared between participants with and without depression following stratification by depression status. Weighted multivariate logistic regression models were employed to evaluate the associations between IR indices (categorized into quartiles) and depression. Nonlinear relationships were explored using threshold effect analysis, restricted cubic spline (RCS) models, and smooth curve fitting. Subgroup analyses were performed to assess heterogeneity by age, gender, poverty level, and comorbidities (e.g., cardiovascular disease, hypertension). Results The depressed group (n = 971) exhibited significantly higher IR indices compared to the non-depressed group (n = 11,040). In the fully adjusted model (Model 3), both LAP (Q4 vs. Q1: OR = 1.569, 95% CI 1.234–1.998) and TyG (Q4 vs. Q1: OR = 1.497, 95% CI 1.182–1.896) were significantly associated with depression, whereas the association for HOMA-IR was attenuated (Q4 vs. Q1: OR = 1.310, p = 0.099). Threshold effect analysis revealed a nonlinear “inverted L-shaped” relationship between HOMA-IR, LAP, and depression, with effect modification observed at specific indice thresholds. Subgroup analyses demonstrated stronger associations in males (LAP: OR = 1.23, p < 0.01; TyG: OR = 1.31, p < 0.05), individuals with coronary heart disease (LAP: OR = 1.68, p < 0.001), and stroke survivors (LAP: OR = 1.42, p = 0.023 for interaction). Conclusions This study provides robust evidence of significant associations between IR indices (LAP and TyG) and depression, with a notable nonlinear “inverted L-shaped” relationship observed for LAP. Subgroup analyses highlighted stronger correlations in older adults (≥ 59 years), patients with coronary heart disease, stroke survivors, males, and individuals with hypertension. These findings enhance our understanding of the metabolic pathways underlying depression and emphasize the importance of integrating IR indices into mental health risk assessments. The results also offer a theoretical basis for personalized interventions targeting metabolic abnormalities in depression prevention and treatment.https://doi.org/10.1186/s40001-025-02802-1Insulin resistanceDepressionNHANESNonlinear associationThreshold effect
spellingShingle Yueyu Zhang
Xinyi Chen
Yu Wang
Yi Tang
Kangrui Zhang
Juncang Wu
Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
European Journal of Medical Research
Insulin resistance
Depression
NHANES
Nonlinear association
Threshold effect
title Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
title_full Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
title_fullStr Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
title_full_unstemmed Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
title_short Analysis of the nonlinear relationships between insulin resistance indicators such as LAP and TyG and depression, and population characteristics: a cross-sectional study
title_sort analysis of the nonlinear relationships between insulin resistance indicators such as lap and tyg and depression and population characteristics a cross sectional study
topic Insulin resistance
Depression
NHANES
Nonlinear association
Threshold effect
url https://doi.org/10.1186/s40001-025-02802-1
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