A JAPANESE cohort study has found having persistently elevated liver enzyme levels in early adulthood can increase the risk of type 2 diabetes. Data from annual health check records of 24,380 individuals aged 30-64 was used to track the long-term trajectories of their liver enzyme levels. The liver enzyme levels tracked in the study were alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT).
Strong predictor of type 2 diabetes risk
Group-based trajectory modelling identified six ALT, three AST, and four GGT liver enzyme groups. Repeated exceedance of ALT and AST liver enzyme threshold levels significantly increased type 2 diabetes risk, the study found.
When participants had persistently high liver enzyme levels present in early adulthood, researchers found this was a strong predictor of type 2 diabetes risk, even when enzyme levels normalised later in life. The persistently elevated ALT group exhibited an odds ratio (OR) of 7.97 (95% CI: 7.40-8.57), while the early-adulthood elevated group showed an OR of 4.23 (95% CI: 4.00-4.48) compared to the consistently low group.
Over a mean follow-up period of 12.8 years, the study found a total of 3,840 participants (15.8%) developed type 2 diabetes. Those diagnosed with the condition were significantly older, had higher BMI, and higher blood pressure, lipid levels, liver function markers, and blood glucose levels.
Lifestyle factors such as smoking and alcohol consumption were also more common in those who developed the condition, compared to participants without type 2 diabetes.
Liver enzyme monitoring beneficial
In summary, the study identified distinct liver enzyme trajectories that are strongly associated with increased type 2 diabetes risk, particularly when levels are persistently elevated in early adolescence. Regular liver enzyme monitoring may help to identify high-risk patients at an earlier stage, and support intervention strategies to mitigate type 2 diabetes incidence, the study authors suggested.
Reference
Fukai K et al. Elevated liver enzyme trajectories in early adulthood and persistently high levels predict type 2 diabetes risk in Japanese adults. Sci Rep. 2025;DOI:10.1038/s41598-025-30591-4.
