Background & aims: Aminotransferases are widely used for metabolic dysfunction-associated steatotic liver disease (MASLD) evaluation, especially in type 2 diabetes mellitus (T2DM). Whether within-person seasonal variation affects classification near commonly used thresholds or relates to long-term metabolic outcomes remains unclear.
Methods: This registry-based cohort analysed monthly aspartate aminotransferase (AST) and alanine aminotransferase (ALT) measurements from 6039 adults with T2DM in the Japan Diabetes Clinical Data Management registry (2014-2020). Classification discordance across the 30 IU/L threshold was compared between winter-mean and summer-mean values. Individual seasonal amplitude was derived from seasonal-trend decomposition of multiply imputed monthly time series. Final glycated haemoglobin (HbA1c) and non-achievement of HbA1c < 7% were analysed using multivariable regression.
Results: Both AST and ALT showed significant seasonal variation, with the highest values in late autumn to early winter and the lowest in summer (p < 0.001). Approximately one in nine patients with borderline ALT values showed discordant winter-summer classification. Each 1-SD increase in AST amplitude was associated with 0.06 percentage points higher final HbA1c (95% CI, 0.04-0.08) and higher odds of not achieving HbA1c < 7% (odds ratio, 1.14; 95% CI, 1.08-1.21; p < 0.001). ALT amplitude showed a similar but weaker, less consistent association.
Conclusions: AST and ALT exhibited reproducible seasonal variation peaking in late autumn to early winter, with approximately one in nine patients near the MASLD screening threshold reclassified depending on season. Greater seasonal amplitude, especially AST, was independently associated with poorer glycemic control, supporting season-aware interpretation in routine clinical practice.
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