Impact of increasing alanine aminotransferase levels within normal range on incident diabetes

Abnormal alanine aminotransferase level (ALT) levels might be associated with type 2 diabetes, but whether higher ALT levels within the normal range predict the risk is unknown.

We followed a community-based cohort of 3446 individuals who were ≥35 years old without diabetes and hepatitis B or C in southern Taiwan for 8 years (1997-2004) to study the risk for type 2 diabetes with different normal ALT levels.

Among the 337 incident diabetes cases, 16.0% were from those with ALT levels <10 IU/L, 44.5% with ALT levels 10-19 IU/L, 30.0% with ALT levels 20-39 IU/L, and only 9.5% with ALT levels ≥40 IU/L. A cumulative hazard function test showed that the higher the ALT levels, the greater the cumulative incidence rate of diabetes (p < 0.001, log-rank test). A multiple Cox proportional hazards analysis showed that increasing age, lower educational levels, higher body mass index levels (≥25 vs. <25), and higher ALT levels (vs. the reference group, ALT <10 IU/L), from hazard ratio (HR) = 1.8, for ALT = 10-19, HR = 3.7 for ALT = 20-39, to HR = 4.5 for ALT ≥40, were significant factors for developing diabetes (p < 0.001). The hazard ratios of higher ALT levels in the participants without alcohol consumption were similar to or higher than those in the total cohort.

Higher ALT levels, even within the normal range, are strong predictors of type 2 diabetes independently of body mass index levels with a dose-response relationship.