BACKGROUND: Early prediabetes screening holds immense significance in decreasing the incidence of diabetes. Therefore, we aimed to evaluate the association of hepatic enzymes with prediabetes and diabetes in the Azar cohort population in Iran. METHODS: This cross-sectional study utilized data from the Azar cohort study, initiated in 2014, with 14,865 participants aged 35-70 years. This study defines prediabetes, according to the American Diabetes Association (ADA), as fasting blood sugar (FBS) of 100-125 mg/dl. An FBS ≥ 126 mg/dL or a history of diabetes indicates diabetes. Serum liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were measured, and associations with prediabetes and diabetes were analyzed using binary logistic regression. RESULTS: In a study of 14,865 participants, 16% had prediabetes and 14.1% had diabetes. The serum levels of ALT, AST, GGT, and ALP were significantly higher (P <
0.05) in the prediabetic and diabetic patients. The adjusted logistic regression model showed a dose-response increase for all hepatic enzymes, with the highest ORs in the fourth quartile for both prediabetes and diabetes. The highest OR for prediabetes and diabetes was in the fourth GGT quartile. CONCLUSION: Our findings suggest that serum ALT, GGT, and ALP levels are strongly associated with prediabetes and diabetes. These hepatic enzymes may be considered easy and valuable early indicators of diabetes risk, prompting timely interventions to slow disease progression.