Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)

Abstract Objective This study analyzes data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between the Aggregate Index of Systemic Inflammation (AISI), also referred to as the pan-immune-inflammation value (PIV), and Type 2 Diabetes Mellitus...

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Main Authors: Ziying Su, Lei Cao, Hailong Chen, Peng Zhang, Chunwei Wu, Jing Lu, Ze He
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Lipids in Health and Disease
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Online Access:https://doi.org/10.1186/s12944-025-02589-4
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author Ziying Su
Lei Cao
Hailong Chen
Peng Zhang
Chunwei Wu
Jing Lu
Ze He
author_facet Ziying Su
Lei Cao
Hailong Chen
Peng Zhang
Chunwei Wu
Jing Lu
Ze He
author_sort Ziying Su
collection DOAJ
description Abstract Objective This study analyzes data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between the Aggregate Index of Systemic Inflammation (AISI), also referred to as the pan-immune-inflammation value (PIV), and Type 2 Diabetes Mellitus (T2DM) among adults in the United States. Furthermore, it evaluates the mediating effect of obesity indicators on this association. Methods This study included 9,947 individuals from NHANES and applied appropriate weighting techniques. To examine the relationship between AISI and T2DM, we used various statistical models, including weighted multivariable logistic regression, smooth curve fitting, threshold effect analysis, subgroup analysis, trend tests, mediation analysis, and Shapley additive explanations (SHAP) models. Results This research included a total of 9,947 participants, with 3,220 diagnosed with T2DM, while 6,727 remained undiagnosed. Weighted multiple logistic regression with all covariates adjusted indicated that with every one-unit increment in AISI/1000, there was an 88.3% likelihood of T2DM occurrence (OR: 1.883, 95% CI: 1.378–2.571). The stratified analysis identified significant differences in this association based on age, biological sex, level of education, poverty-income ratio (PIR), tobacco consumption status, and body mass index (BMI). Interaction tests revealed a positive association between AISI and T2DM, apart from PIR, BMI, age, education attainment, race, gender, tobacco use status, Estimated Glomerular Filtration Rate(eGFR), platelet count, and high blood pressure, with none of the interaction p-values falling below 0.05. Nevertheless, the occurrence of cardiovascular disease (CVD) among participants may affect the strength of this relationship, where an interaction p-value was less than 0.05. Additionally, smoothing curve fitting revealed a nonlinear relationship between AISI and T2DM, marking a significant change at AISI/1000 of 0.21. Mediation analysis indicated that five obesity-related indicators—LAP, VAI, WHtR, WWI and ABSI — partly mediated the association between AISI/1000 and T2DM. Conclusion An increase in AISI is associated with an elevated probability of T2DM, with obesity indicators potentially mediating this relationship. Reducing AISI and managing obesity may help prevent T2DM. However, with the cross-sectional design of this study, causal relationships cannot be established. Future research should utilize longitudinal studies to confirm these findings. Graphical Abstract
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spelling doaj-art-bc494272392c419ca2d9930234039cc32025-08-20T03:10:31ZengBMCLipids in Health and Disease1476-511X2025-05-0124111510.1186/s12944-025-02589-4Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)Ziying Su0Lei Cao1Hailong Chen2Peng Zhang3Chunwei Wu4Jing Lu5Ze He6Changchun University of Traditional Chinese MedicineThe Affiliated Hospital of Changchun University of Traditional Chinese MedicineChangchun University of Traditional Chinese MedicineThe Affiliated Hospital of Changchun University of Traditional Chinese MedicineThe Affiliated Hospital of Changchun University of Traditional Chinese MedicineThe Affiliated Hospital of Changchun University of Traditional Chinese MedicineThe Affiliated Hospital of Changchun University of Traditional Chinese MedicineAbstract Objective This study analyzes data from the 2009–2018 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between the Aggregate Index of Systemic Inflammation (AISI), also referred to as the pan-immune-inflammation value (PIV), and Type 2 Diabetes Mellitus (T2DM) among adults in the United States. Furthermore, it evaluates the mediating effect of obesity indicators on this association. Methods This study included 9,947 individuals from NHANES and applied appropriate weighting techniques. To examine the relationship between AISI and T2DM, we used various statistical models, including weighted multivariable logistic regression, smooth curve fitting, threshold effect analysis, subgroup analysis, trend tests, mediation analysis, and Shapley additive explanations (SHAP) models. Results This research included a total of 9,947 participants, with 3,220 diagnosed with T2DM, while 6,727 remained undiagnosed. Weighted multiple logistic regression with all covariates adjusted indicated that with every one-unit increment in AISI/1000, there was an 88.3% likelihood of T2DM occurrence (OR: 1.883, 95% CI: 1.378–2.571). The stratified analysis identified significant differences in this association based on age, biological sex, level of education, poverty-income ratio (PIR), tobacco consumption status, and body mass index (BMI). Interaction tests revealed a positive association between AISI and T2DM, apart from PIR, BMI, age, education attainment, race, gender, tobacco use status, Estimated Glomerular Filtration Rate(eGFR), platelet count, and high blood pressure, with none of the interaction p-values falling below 0.05. Nevertheless, the occurrence of cardiovascular disease (CVD) among participants may affect the strength of this relationship, where an interaction p-value was less than 0.05. Additionally, smoothing curve fitting revealed a nonlinear relationship between AISI and T2DM, marking a significant change at AISI/1000 of 0.21. Mediation analysis indicated that five obesity-related indicators—LAP, VAI, WHtR, WWI and ABSI — partly mediated the association between AISI/1000 and T2DM. Conclusion An increase in AISI is associated with an elevated probability of T2DM, with obesity indicators potentially mediating this relationship. Reducing AISI and managing obesity may help prevent T2DM. However, with the cross-sectional design of this study, causal relationships cannot be established. Future research should utilize longitudinal studies to confirm these findings. Graphical Abstracthttps://doi.org/10.1186/s12944-025-02589-4Cross-sectional studyNHANESAggregate index of systemic inflammationType 2 diabetes mellitusMediation analysisShapley additive explanations (SHAP)
spellingShingle Ziying Su
Lei Cao
Hailong Chen
Peng Zhang
Chunwei Wu
Jing Lu
Ze He
Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
Lipids in Health and Disease
Cross-sectional study
NHANES
Aggregate index of systemic inflammation
Type 2 diabetes mellitus
Mediation analysis
Shapley additive explanations (SHAP)
title Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
title_full Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
title_fullStr Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
title_full_unstemmed Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
title_short Obesity indicators mediate the association between the aggregate index of systemic inflammation (AISI) and type 2 diabetes mellitus (T2DM)
title_sort obesity indicators mediate the association between the aggregate index of systemic inflammation aisi and type 2 diabetes mellitus t2dm
topic Cross-sectional study
NHANES
Aggregate index of systemic inflammation
Type 2 diabetes mellitus
Mediation analysis
Shapley additive explanations (SHAP)
url https://doi.org/10.1186/s12944-025-02589-4
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