Distinct Liver Enzyme Profiles in Non-Diabetic Obesity: Associations with Obesity Severity and Metabolic Dysfunction

Background: Obesity is a heterogeneous condition encompassing metabolically healthy and metabolically unhealthy phenotypes. Routine liver enzymes may reflect metabolic heterogeneity among individuals with obesity, yet their metabolic relevance in non-diabetic obesity remains incompletely characterized, particularly in Arab populations. This study examined the associations of routine liver enzymes with obesity severity and metabolic abnormalities in Saudi adults with non-diabetic obesity. Methods: This cross-sectional study included 168 non-diabetic adults with obesity. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were evaluated in relation to obesity severity, prediabetes, hypercholesterolemia, hypertriglyceridemia and metabolic syndrome (MetS). Correlation, multivariable linear regression, and receiver operating characteristic (ROC) analyses were performed to examine associations with obesity severity, prediabetes, hypercholesterolemia, and hypertriglyceridemia. Results: ALT, AST, and GGT generally increased with obesity severity, with ALT and GGT significantly higher in Class III than Class I obesity. GGT showed the most consistent differences across metabolic abnormalities, with higher concentrations in participants with prediabetes (20.0 vs. 16.0 U/L), hypercholesterolemia (21.0 vs. 16.0 U/L), and hypertriglyceridemia (22.0 vs. 17.0 U/L). GGT was also higher in participants with MetS (20.0 vs. 16.0 U/L). After multivariable adjustment, GGT remained positively associated with HbA1c (β = 0.031) and triglycerides (β = 0.188), while ALT was associated with BMI (β = 0.04). ROC analyses showed modest, outcome-specific discrimination, with GGT showing the highest discrimination for hypertriglyceridemia (AUC = 0.68). Conclusions: Liver enzyme profiles, particularly GGT and ALT, are associated with distinct dimensions of metabolic dysfunction in non-diabetic adults with obesity. GGT demonstrated the most consistent metabolic relationships with glycemic and lipid abnormalities, although the modest discriminatory performance supports its potential role as a complementary rather than standalone metabolic indicator.