ArticleFrontiers in endocrinology2025
Association between the ratio of aspartate aminotransferase to alanine aminotransferase and risk of diabetes and the mediating effect of BMI: a comparative analysis in Chinese and Japanese populations.
Article in Frontiers in endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Objective: Despite the AST/ALT ratio emerging as a promising diabetes predictor, current research lacks comprehensive understanding of population-specific patterns and underlying mechanisms. This study aims to investigate the AST/ALT-diabetes risk relationship in Chinese and Japanese populations, specifically examining non-linear relationships, population-specific thresholds, and BMI's potential mediating role to address existing knowledge gaps. Methods: We performed a retrospective cohort analysis using data from the China Rich Healthcare Group (n=84,281) and Japanese NAGALA database (n=15,291). AST/ALT ratio was calculated by dividing AST concentration by ALT concentration. Diabetes was defined by fasting plasma glucose ≥7.00mmol/L or self-reported diagnosis. We employed Cox proportional hazards models, including restricted cubic splines to explore non-linear relationships, two-piecewise regression for identifying population-specific thresholds, and mediation analysis to quantify BMI's mediating effect on the AST/ALT-diabetes risk association. Results: In a cohort of 99,572 participants with 1,403 new diabetes cases, AST/ALT showed a significant negative association with diabetes risk across Chinese and Japanese populations (HR per unit increase: Chinese: 0.417, 95% CI: 0.341-0.510; Japanese: 0.631, 95% CI: 0.416-0.956). Country-specific variations were evident, with distinct non-linear relationships: Chinese participants exhibited risk reduction until AST/ALT reached 0.912, while Japanese participants showed an inflection point at 0.882. BMI's mediating effect differed markedly between populations, with a higher proportion in Japanese participants (32.22%), suggesting nuanced pathophysiological mechanisms underlying the AST/ALT-diabetes relationship. Conclusions: Our study unveils significant ethnic variations in the AST/ALT-diabetes interaction, highlighting population-specific diagnostic thresholds and mediation mechanisms. These insights advocate for customized screening approaches and suggest that AST/ALT and BMI-targeted interventions may yield differential outcomes across East Asian populations, emphasizing the critical need for precision-based medical strategies.
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