Elevated liver enzyme trajectories in early adulthood and persistently high levels predict type 2 diabetes risk in Japanese adults

This study examined long-term trajectories of liver enzyme levels and their associations with type 2 diabetes risk in Japanese adults. Data were analyzed from 24,380 individuals aged 30-64 years at baseline without type 2 diabetes, comprising 296,171 health check-up records from the Hitachi Cohort Study. Liver enzyme levels, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT), were measured annually. Over a mean follow-up of 12.8 years, 3,840 participants (15.8%) developed type 2 diabetes. Group-based trajectory modeling identified six ALT, three AST, and four GGT trajectory groups. Persistently elevated ALT levels and trajectories with early-adulthood elevation were strongly linked to increased type 2 diabetes risk. The persistently elevated ALT group (Group 6) exhibited an odds ratio (OR) of 7.97 (95% CI: 7.40-8.57), while the early-adulthood elevated group (Group 5) showed an OR of 4.23 (95% CI: 4.00-4.48) compared to the consistently low group (Group 1). Repeated exceedance of ALT and AST thresholds significantly increased type 2 diabetes risk, with higher thresholds and frequencies of exceedance showing stronger associations. Regular liver enzyme monitoring may help identify high-risk individuals, supporting early intervention strategies to mitigate type 2 diabetes incidence.