Incidence and causes of mildly to moderately elevated aminotransferase in Japanese patients with type 2 diabetes

  • Chia-Hsien ChangEmail author
  • Motonobu Sakaguchi
Original Article



To identify the association of type 2 diabetes (T2DM) and liver disease with elevated ALT and factors associated with increased ALT in patients with and without T2DM.

Design and setting

We performed a retrospective study in adults with ≥ 2 claims for blood tests recorded in the Medical Data Vision claims database between 2010 and 2016.


Patients were entered into T2DM and non-DM groups based on diagnosis and medication claim codes.

Primary outcome measure

The primary endpoint was the first follow-up ALT elevation over three times the normal value, and etiologies were categorized by subsequent diagnoses. We estimated the ALT elevation incidence and association with T2DM using Poisson regression and Cox proportional hazard models.


We identified 3161 cases of elevated ALT in 104,903 patients (follow-up, 280,659 patient-years). The age- and sex-adjusted incidence of elevated ALT in the T2DM group (13.47 per 1000 patient-years; 95% confidence interval (CI) 12.53–14.48) was significantly higher than that in the non-DM group (8.43 per 1000 patient-years; 95% CI 7.72–9.20, p < 0.0001). Compared to the non-DM group, the T2DM group had an approximately 3.5 times higher risk of fatty liver-related ALT elevation (adjusted hazard ratio (HR), 3.54; 95% CI 1.90–6.58). T2DM was not associated with an increased incidence of jointly elevated ALT and total bilirubin (adjusted HR, 0.94; 95% CI 0.77–1.15).


T2DM is strongly associated with increased liver enzymes secondary to fatty liver. The causes of liver enzyme abnormalities were not fully characterized due to a high proportion of unexplained ALT elevation.


Alanine transaminase Diabetes mellitus Epidemiology Japan Liver diseases 



We would like to thank Editage ( for editing and reviewing this manuscript for English language.

Author contribution

All authors contributed to the conceptualization of the study and preparation of the manuscript, including literature review (CHC), data analysis (CHC) and result interpretation (CHC and MS), and are responsible for the reported research. All the authors have read the manuscript and approved its submission.


This work was supported by Takeda, Japan.

Compliance with ethical standards

Conflicts of interest

CHC and MS are employees of Takeda. The authors declare they have no conflict of interest with respect to this research study and paper. The funder (Takeda, Japan) provided support in the form of salaries for authors (CHC, MS) and research materials only, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Ethics policy

As secondary database we used for research purposes contained anonymized data only, this article does not contain any studies with human or animal subjects performed by any of the authors. Patient informed consent was not required, because it is impossible to link the identifiers with external information.

Supplementary material

13340_2019_405_MOESM1_ESM.docx (39 kb)
Supplementary material 1 Table. S1 Disease categories and diagnosis codes used to determine the causes of ALT elevation identified in the Medical Data Vision database (DOCX 38 kb)


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Copyright information

© The Japan Diabetes Society 2019

Authors and Affiliations

  1. 1.Global Patient Safety Evaluation JapanTakeda Pharmaceutical Company LimitedOsakaJapan

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