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Metabolic Effect on Serum Mac-2 Binding Protein Glycan Isomer Level and Its Normal Range in the Health Checkup
Wataru Yoshioka1,2, Yoshihito Kubotsu1,2, Misa Norita1
1Department of Hepatology, Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, Japan.
Background:
Liver fibrosis is central to chronic liver disease prognosis, including metabolic dysfunction-associated steatotic liver disease (MASLD). Mac-2 binding protein glycan isomer (M2BPGi) is a recognized liver fibrosis marker, but lacks an established reference range in healthy populations, thereby limiting clinical use.
Methods:
This cross-sectional study analyzed 3623 Japanese adults undergoing routine health checks (2020-2021), excluding those with hepatitis B or C. Participants had physical and laboratory assessments, including serum M2BPGi, metabolic parameters, and liver indices. The fatty liver index (FLI) and Fibrosis-4 (FIB-4) index assessed hepatic steatosis and fibrosis. Multiple regression identified independent determinants of M2BPGi, and a normal reference range was established from participants with all metabolic and liver factors within normal limits.
Results:
Participants' mean age was 42.3 years (90.5% male). Median M2BPGi was 0.44 COI (IQR: 0.32-0.60). Higher M2BPGi correlated with increased BMI, waist circumference, glucose, lipid levels, liver enzymes, FLI and FIB-4. Regression analysis identified age, sex, BMI, waist, AST, GGT, HDL-C, fasting glucose, and FIB-4 as independent predictors of M2BPGi; alcohol intake was not significant. Females displayed significantly higher M2BPGi than males. Among 1350 participants with completely normal parameters, the reference M2BPGi was 0.41-0.43 COI in male and 0.46-0.54 COI in female.
Conclusions:
M2BPGi levels are independently influenced by metabolic factors and sex, and the study establishes sex-specific normal reference ranges in healthy Japanese adults. M2BPGi above these limits should prompt further metabolic and hepatic evaluation.
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