Sex Differences in the Association Between AST/ALT and Incidence of Type 2 Diabetes in Japanese Patients with Nonalcoholic Fatty Liver Disease: A Retrospective Cohort Study

ABSTRACTObjectives/Introduction The purpose of the current study was to investigate the association between Aspartate Transaminase (AST)/Alanine transaminase(ALT) and type 2 diabetes (T2DM) in nonalcoholic fatty liver disease (NAFLD) patients and to determine whether there were sex differences.Methods In the retrospective study, we collected data on NAFLD patients (1, 896 men and 465 women) at Murakami Memorial Hospital from 2004 to 2015. Data were stratified by sex to investigate the association between AST/ALT and T2DM incidence by sex. Multiple regression analysis, smooth curve fitting model and subgroup analysis were used to determine the correlation, non-linear relationship and threshold effect between AST/ALT and T2DM.Results In our study, 157 men and 40 women developed T2DM at follow-up. After adjusting for risk factors, AST/ALT was significantly associated with T2DM in men with NAFLD but not in women with NAFLD. The risk of T2DM increased as the AST/ALT ratio decreased. Besides, in male NAFLD patients, AST/ALT showed a non-linear relationship with T2DM, with an inflection point value of 0.964. When the AST to ALT ratio was below the threshold (AST/ALT <0.964), AST/ALT was significantly negatively associated with T2DM (HR = 0.177, 95% CI 0.055–0.568; P = 0.0036). In contrast, when AST/ALT >0.964, no significant association was found (HR = 3.174, 95% CI 0.345–29.167; P = 0.3074). Moreover, subgroup analysis showed that GGT could alter the relationship between AST/ALT and T2DM. In the group with GGT ≤ 40, AST/ALT was strongly associated with T2DM (HR = 0.24, 95% CI 0.09–0.66; P = 0.0059).Conclusions These results suggested that there were sex differences in the association between AST/ALT and T2DM in NAFLD participants. A non-linear association between AST/ALT and T2DM was observed in males. AST/ALT in the normal GGT group (GGT ≤40) might better facilitate the early screening of T2DM.KEYWORDS: AST/ALTnon-linear associationnonalcoholic fatty liver diseasesex differencestype 2 diabetes mellitus Disclosure statementNo potential conflict of interest was reported by the author(s).Authors' ContributionsCZ and MH contributed to the conception and design of the study. QX and CYX were responsible for data analysis, CZ was responsible for data interpretation. KY, TX, and WYHS wrote the original draft. MH and HYK verified the data. All authors were involved in the reviewing and editing of the manuscript. All authors read and approved the final manuscript.Availability of Data and MaterialsData can be downloaded from "DATADRYAD" database (https://datadryad.org/stash/dataset/doi:10.5061%2Fdryad.8q0p192).Ethics Approval and Consent to ParticipateIn the previously published article, Takuro Okamura et al. has clearly stated that: the study was approved by the ethics committee of Murakami Memorial Hospital, and written informed consent for their data to be used was obtained from each participant.Additional informationFundingThis research was supported by the National Natural Science Foundation of China (No. 81900742), the Key Program of Heilongjiang Province of China (No. 2022ZX06C09) , and The First Affiliated Hospital of Harbin Medical University. Foundation for Outstanding Young Scholars (No HYD2020YQ0006).