The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes

Abstract

An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes.A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality.Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14-2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38-4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables.The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR.

Figure 1

In the upper part of the figure is reported the distribution of the AST/ALT ratio (AAR), showing that most of our type 2 diabetic patients had a ratio =1. In the lower part of the figure are reported the dispersion graphs of the relationship between the AAR and either ALT or AST levels. AAR = aspartate aminotransferase-to-alanine aminotransferase ratio, ALT = alanine aminotransferase, AST = aspartate aminotransferase.

Figure 2

Kaplan–Meier curves according to AAR categories in 2529 patients with type 2 diabetes. In the upper panel is reported the cumulative survival probability of all-cause mortality, whereas in the lower panel is reported the cumulative survival probability of CV mortality. The global statistical significance was estimated by log-rank test (P < 0.001 for both analyses). AAR = aspartate aminotransferase-to-alanine aminotransferase ratio, CV = cardiovascular.