# Association between metabolic syndrome, fatty liver disease, and gastrointestinal tumors: a population-based study with external validation

## TL;DR

This study finds that metabolic syndrome is strongly linked to fatty liver disease and gastrointestinal tumors, suggesting early metabolic intervention could help prevent these conditions.

## Contribution

The study provides population-based validation of the association between metabolic syndrome, fatty liver disease, and gastrointestinal tumors using a large U.S. cohort and an external validation set.

## Key findings

- MetS is independently associated with increased risk of fatty liver disease (OR = 3.889) and gastrointestinal tumors (OR = 2.456).
- MetS significantly reduces overall survival, with elevated risks for all-cause, cancer-specific, and cardiovascular mortality.
- Findings were validated in an external cohort, confirming the robustness of the associations.

## Abstract

Metabolic Syndrome (MetS), defined by central obesity and disturbances in glucose and lipid metabolism, has not been extensively validated in large national cohorts concerning its association with fatty liver disease (FLD), gastrointestinal tumors (GIT), and prognostic outcomes.

A total of 24,434 adults from the 2003–2018 cycles of The National Health and Nutrition Examination Survey (NHANES) were included as the development cohort, with a validation cohort of 365 adults to verify key associations. MetS was diagnosed per NCEP-ATP III criteria across both cohorts. Weighted multivariate regression models assessed associations between MetS and FLD/GIT incidence, and Cox proportional hazards models evaluated survival risks. Three hierarchical models were constructed: Model 1 (unadjusted), Model 2 (adjusted for demographic confounders), and Model 3 (further adjusted for laboratory parameters).

In the development cohort, MetS patients exhibited a higher FLD prevalence (16.2% vs. 4.6%) and GIT incidence (1.25% vs. 0.57%). After full adjustment in Model 3, MetS remained a strong independent risk factor for FLD (OR = 3.889, 95% CI: 3.529–4.307) and GIT (OR = 2.456, 95% CI: 1.832–3.292). These associations were corroborated in the validation cohort, with adjusted ORs of 4.760 for FLD and 4.395 for GIT. Survival analysis indicated that MetS significantly reduced overall survival in the development cohort, with HRs for all-cause, cancer-specific, and cardiovascular mortality of 2.146, 1.941, and 2.572, respectively. Furthermore, the mortality risk was further elevated in FLD patients with MetS (all-cause mortality HR = 1.823). In the validation cohort, cardiovascular mortality risk was significant (HR = 3.902), while other survival outcomes did not reach statistical significance due to the small sample size. Sensitivity analysis using IDF criteria confirmed the robustness of these findings.

This study confirms that MetS is strongly associated with FLD risk and GIT incidence, supporting early metabolic intervention to interrupt the progression of liver disease and tumors.