Visceral adiposity (LAP) emerges as the principal metabolic correlate of hyperuricemia, and without concurrent visceral fat burden, insulin resistance alone is insufficient to maintain extreme serum uric acid elevations.
Key Findings
Results
Both LAP (visceral adiposity surrogate) and TyG index (insulin resistance surrogate) demonstrated independent associations with hyperuricemia risk.
The study included 60,516 participants (35,593 males, 24,923 females) from a large medical checkup cohort spanning January to December 2025.
Multivariable logistic regression was used to assess independent associations after adjustment for confounders.
Restricted cubic splines were utilized to assess non-linear dose-response relationships between each index and HUA risk.
Both markers showed statistically significant independent associations with hyperuricemia in the full cohort.
Results
LAP and TyG exhibited a significant synergistic (additive) interaction with hyperuricemia risk, but no significant multiplicative interaction.
The P-value for multiplicative interaction was 0.965, indicating no significant multiplicative synergy.
The Attributable Proportion due to additive interaction was 15.1%, indicating a significant synergistic effect on the additive scale.
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).
The Double-high phenotype (high both LAP and TyG) conferred the greatest overall HUA risk among the four groups.
Results
Among discordant metabolic phenotypes, Isolated High LAP demonstrated striking dominance over Isolated High TyG in association with hyperuricemia risk.
Participants with Isolated High LAP had substantially higher HUA risk compared to those with Isolated High TyG.
This finding suggests visceral adiposity exerts a stronger independent association with HUA than insulin resistance alone when the two are discordant.
The discordant phenotype analysis was a key analytical approach to disentangle the relative contributions of each metabolic factor.
This dominance of LAP over TyG persisted after multivariable adjustment.
Results
Without concurrent high LAP, extreme TyG elevations failed to sustain high hyperuricemia risk and exhibited a paradoxical decline.
Restricted cubic spline analysis revealed a non-linear dose-response relationship between TyG and HUA risk stratified by LAP status.
In the low-LAP stratum, the association between TyG and HUA risk showed a paradoxical attenuation or decline at extreme TyG values.
This paradoxical TyG attenuation was particularly pronounced in males and in individuals with BMI ≥24 kg/m².
These findings suggest that insulin resistance alone, absent the structural burden of visceral fat, may be insufficient to drive extreme uric acid elevations.
Results
Significant demographic heterogeneity was observed in the associations between metabolic phenotypes and hyperuricemia risk, with sex being a particularly important modifier.
The high LAP phenotype conferred the most pronounced relative risk in females, with an odds ratio of 2.45.
This elevated female risk was interpreted as effectively abrogating their inherent estrogenic urate-excretory protection.
The TyG paradoxical attenuation pattern was particularly pronounced in males and in individuals with BMI ≥24 kg/m².
Subgroup analyses were conducted to evaluate population heterogeneity across demographic and metabolic strata.
Conclusions
The study concludes that visceral fat reduction and agents with dual metabolic-uricosuric benefits should be prioritized over isolated glycemic control in hyperuricemia management.
The clinical implication drawn is that targeting visceral adiposity may be more impactful than targeting insulin resistance alone for HUA prevention.
The authors suggest that without the concurrent structural and metabolic burden of visceral fat, IR alone is insufficient to maintain extreme serum uric acid elevations.
This is a cross-sectional study, limiting causal inference.
The cohort was drawn from a medical checkup population, which may limit generalizability to the broader population.
What This Means
This research suggests that among two key metabolic risk factors — body fat accumulation around the organs (visceral adiposity, measured by the Lipid Accumulation Product or LAP) and insulin resistance (measured by the Triglyceride-Glucose or TyG index) — visceral adiposity plays a stronger and more dominant role in driving high uric acid levels (hyperuricemia) in the blood. The study analyzed over 60,000 adults who underwent medical checkups and found that when the two risk factors were considered separately, people with high visceral fat but normal insulin sensitivity had much higher hyperuricemia risk than people with high insulin resistance but low visceral fat. Interestingly, at very high levels of insulin resistance without accompanying visceral fat, the association with uric acid actually seemed to plateau or even decline — a counterintuitive finding the authors describe as a 'paradoxical decline.'
The study also found that both factors together were worse than either alone, with roughly 15% of the combined risk attributable to their synergistic interaction. Women with high visceral fat appeared especially vulnerable, with a roughly 2.5-fold increased odds of hyperuricemia, which the researchers suggest may override the natural uric acid-lowering effects of estrogen. The attenuation of insulin resistance's effect was most visible in men and in people who were overweight.
This research suggests that in efforts to prevent or manage hyperuricemia and its associated conditions (such as gout and kidney disease), reducing visceral (abdominal organ) fat may be more impactful than focusing solely on improving blood sugar control. The findings point to the potential value of therapies that address both metabolic dysfunction and uric acid excretion simultaneously, rather than targeting insulin resistance in isolation. As this was a cross-sectional (single point-in-time) study, it cannot prove cause and effect, and further longitudinal research would be needed to confirm these relationships.
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Li L, Yan J, Cai X, Pan J, Chen L. (2026). Independent and joint associations of visceral adiposity and insulin resistance with hyperuricemia: A large-scale cross-sectional study.. PloS one. https://doi.org/10.1371/journal.pone.0357105