Abstract
BACKGROUND: Metabolic syndrome (MetS) is a major global health concern that increases morbidity and mortality from cardiometabolic diseases. We refined the rationale to highlight the mechanistic involvement of the liver in metabolic dysregulation. METHODS: This population-based study was conducted on 3896 adults aged between 35 and 70 (57.2% female) who participated in the Bandare-Kong Non-Communicable Diseases (BKNCD) cohort study. Participants were categorized into normal quartiles and abnormal levels of liver enzymes including gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). MetS was defined based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for Iranian population. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and p values, adjusting for age, sex, residence, BMI, physical activity, energy intake, and financial status. RESULTS: The prevalence of MetS was 36.6%. After multivariable adjustment, abnormal levels of GGT (OR = 1.91, 95% CI: 1.61-2.28, p < 0.001), ALT (OR = 1.60, 95% CI: 1.34-1.90, p < 0.001), ALP (OR = 1.48, 95% CI: 1.07-2.03, p = 0.01), and AST (OR = 1.39, 95% CI: 1.09-1.77, p = 0.007) were significantly associated with higher odds of MetS. Within normal ranges, the highest quartile of GGT (OR = 2.81, 95% CI: 2.22-3.56, p < 0.001), ALT (OR = 2.39, 95% CI: 1.89-3.03, p < 0.001), and ALP (OR = 1.63, 95% CI: 1.30-2.04, p < 0.001) showed significant associations, while AST did not. CONCLUSION: Serum liver enzyme levels, including those within normal range, were strongly associated with MetS. GGT showed relatively stronger associations compared with other enzymes; however, these findings should not be interpreted as diagnostic superiority because no performance metrics (AUC, PPV, and NPV) were evaluated. ALT and ALP also showed meaningful associations. Future studies should assess diagnostic accuracy before considering clinical implementation.