Independent and joint associations of visceral adiposity and insulin resistance with hyperuricemia: A large-scale cross-sectional study
- 1Department of General Practice, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Abstract
Background: Driven by rapid lifestyle transitions, hyperuricemia (HUA) has evolved into a formidable public health challenge. While insulin resistance (IR) and visceral adiposity are core pathophysiological factors associated with HUA, their relative dominance under discordant metabolic phenotypes remains unclear. We aimed to evaluate the joint and discordant associations of the triglyceride-glucose (TyG) index (surrogate for IR) and lipid accumulation product (LAP) (surrogate for visceral adiposity) with HUA risk. Methods: This cross-sectional study included 60,516 participants (35,593 males, 24,923 females) from a large medical checkup cohort (January to December 2025). Participants were cross-classified into four metabolic phenotypes based on TyG and LAP medians: Double-low (N = 26,023), Double-high (N = 25,998), Isolated High LAP (N = 4,236), and Isolated High TyG (N = 4,259). Multivariable logistic regression and restricted cubic splines were utilized to assess risk stratifications and non-linear dose-response relationships. Additionally, additive interactions and subgroup analyses were conducted to evaluate synergistic effects and population heterogeneity. Results: LAP and TyG exhibited independent and additive associations with HUA, exhibiting no significant multiplicative interaction (P for interaction = 0.965) but a significant synergistic effect on the additive scale (Attributable Proportion: 15.1%). Among discordant phenotypes, Isolated High LAP demonstrated a striking dominance over Isolated High TyG in its association with HUA risk. Spline curves revealed that without concurrent high LAP, extreme TyG elevations failed to sustain a high HUA risk, exhibiting a paradoxical decline. Subgroup analysis unmasked crucial demographic heterogeneities: this TyG attenuation was particularly pronounced in males and individuals with a BMI ≥ 24 kg/m². Conversely, the high LAP phenotype conferred the most pronounced relative risk in females (OR: 2.45), effectively abrogating their inherent estrogenic urate-excretory protection. Conclusions: Visceral adiposity, represented by LAP, emerges as the principal metabolic correlate of HUA. Without the concurrent structural and metabolic burden of visceral fat, IR alone is insufficient to maintain extreme serum uric acid elevations. These findings suggest the clinical importance of prioritizing visceral fat reduction and agents with dual metabolic-uricosuric benefits over isolated glycemic control in HUA management.
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BibTeX
@article{li2026independent,
title = {{Independent and joint associations of visceral adiposity and insulin resistance with hyperuricemia: A large-scale cross-sectional study}},
author = {Lusha Li and Jingkai Yan and Xixuan Cai and Jianjiang Pan and Liying Chen},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357105},
url = {https://doi.org/10.1371/journal.pone.0357105},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Independent and joint associations of visceral adiposity and insulin resistance with hyperuricemia: A large-scale cross-sectional study
AU - Lusha Li
AU - Jingkai Yan
AU - Xixuan Cai
AU - Jianjiang Pan
AU - Liying Chen
PY - 2026
DA - 2026/09/22
JO - PLOS One
DO - 10.1371/journal.pone.0357105
UR - https://doi.org/10.1371/journal.pone.0357105
AB - Background: Driven by rapid lifestyle transitions, hyperuricemia (HUA) has evolved into a formidable public health challenge. While insulin resistance (IR) and visceral adiposity are core pathophysiological factors associated with HUA, their relative dominance under discordant metabolic phenotypes remains unclear. We aimed to evaluate the joint and discordant associations of the triglyceride-glucose (TyG) index (surrogate for IR) and lipid accumulation product (LAP) (surrogate for visceral adiposity) with HUA risk. Methods: This cross-sectional study included 60,516 participants (35,593 males, 24,923 females) from a large medical checkup cohort (January to December 2025). Participants were cross-classified into four metabolic phenotypes based on TyG and LAP medians: Double-low (N = 26,023), Double-high (N = 25,998), Isolated High LAP (N = 4,236), and Isolated High TyG (N = 4,259). Multivariable logistic regression and restricted cubic splines were utilized to assess risk stratifications and non-linear dose-response relationships. Additionally, additive interactions and subgroup analyses were conducted to evaluate synergistic effects and population heterogeneity. Results: LAP and TyG exhibited independent and additive associations with HUA, exhibiting no significant multiplicative interaction (P for interaction = 0.965) but a significant synergistic effect on the additive scale (Attributable Proportion: 15.1%). Among discordant phenotypes, Isolated High LAP demonstrated a striking dominance over Isolated High TyG in its association with HUA risk. Spline curves revealed that without concurrent high LAP, extreme TyG elevations failed to sustain a high HUA risk, exhibiting a paradoxical decline. Subgroup analysis unmasked crucial demographic heterogeneities: this TyG attenuation was particularly pronounced in males and individuals with a BMI ≥ 24 kg/m². Conversely, the high LAP phenotype conferred the most pronounced relative risk in females (OR: 2.45), effectively abrogating their inherent estrogenic urate-excretory protection. Conclusions: Visceral adiposity, represented by LAP, emerges as the principal metabolic correlate of HUA. Without the concurrent structural and metabolic burden of visceral fat, IR alone is insufficient to maintain extreme serum uric acid elevations. These findings suggest the clinical importance of prioritizing visceral fat reduction and agents with dual metabolic-uricosuric benefits over isolated glycemic control in HUA management.
SN - 1932-6203
ER -