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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2025-06-01
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| 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 |
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| 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. |
| format | Article |
| id | doaj-art-4651f8e430db4e669646f07f1d69bd19 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | European Journal of Medical Research |
| 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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