Introduction:
Liver disease and diabetes often co-occur and have shared risk factors. We undertook this study to investigate which liver enzyme (alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT)) would be most strongly associated with incident diabetes in a large, community-based population.
Hypothesis:
We hypothesized that ALT, AST, and GGT would be independently associated with diabetes and that ALT would be most strongly associated with diabetes due to its liver specificity.
Methods:
We conducted a prospective analysis of 9,524 participants in the ARIC Study without diagnosed diabetes or a history of high alcohol consumption (>14 [women] and >21 [men] drinks/week). Enzymes were measured from stored plasma samples. We examined the association of sex-specific quartiles of liver enzymes with incident diagnosed diabetes using Cox proportional hazards models adjusted for demographic, lifestyle, and behavioral risk factors. Restricted cubic spline models were fit to model the continuous associations.
Results:
Median ALT, AST, and GGT were 13, 18, and 22 U/L, respectively. During a median follow-up of 11 years, there were 1,905 self-reported cases of diabetes. All three liver enzymes were significantly associated with diabetes, even after adjustment for all covariates (HRs (95% CIs): ALT, 1.63 (1.44, 1.85); AST, 1.23 (1.09, 1.40); GGT, 1.99 (1.71, 2.30) comparing Q4 versus Q1). The restricted cubic spline models show similar patterns (Figure). After simultaneously adjustment for the other liver enzymes, only ALT and GGT remained significantly associated with diabetes. In analyses further restricted to participants who reported never consuming alcohol only GGT remained significant.
Conclusion:
In this community-based population, GGT was more strongly associated with diabetes risk than ALT and AST. Although ALT and AST are considered to be more specific markers of liver disease, higher levels of GGT may be a more important risk factor for diabetes.
Isolated aspartate aminotransferase elevation: Is it liver disease or what else?
