Esther J. Kemper1, Michiel Adriaans2, Carla J.H. van der Kallen3,4, Annemarie Koster5,6, Martijn C.G.J. Brouwers3,7, Bastiaan E. de Galan3,7, Marleen van Greevenbroek3, Ellen E. Blaak1, Ruth C.R. Meex1
1: Department of Human Biology, Maastricht University 2: Maastricht Centre for Systems Biology (MaCSBio), Maastricht University 3: CARIM School for Cardiovascular Diseases, Maastricht University 4: Department of Internal Medicine, Maastricht University Medical Centre+ 5: CAPHRI Care and Public Health Research Institute, Maastricht University 6: Department of Social Medicine, Maastricht University 7: Division of Endocrinology and Metabolic Disease, Department of Internal Medicine, Maastricht University Medical Centre+
esther.kemper@maastrichtuniversity.nl
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disorder and is characterized by hepatic steatosis, excessive accumulation of lipids in the liver. Interestingly, women develop steatosis more slowly and experience less associated metabolic complications than men, but this protection diminishes after menopause. However, once steatosis occurs in women, MASLD progression seems to be associated with worse metabolic outcomes. Importantly, research is limited and often lacks age stratification and details on steatosis severity, limiting insights into how liver fat is related to metabolic health across sex and menopausal status.
Methods: We analyzed data from 1,835 participants of the Maastricht study, a large population-based cohort, to investigate sex and menopause-specific associations between liver fat and metabolic health. Stratified linear mixed-effect models were applied in premenopausal (n=242) and postmenopausal women (n=664) and age-matched men (n=201 and n=728 respectively), adjusting for age, BMI, alcohol consumption, smoking status and physical activity.
Results: Liver fat was lower in premenopausal women compared to the other groups (2.88%, 3.86%, 4.02% and 4.47% in pre- and postmenopausal women and age-matched men, respectively; p<0.05). Fasting glucose, insulin and HOMA-IR were higher in older men, compared to the other groups. Linear regression analyses showed that liver fat was positively associated with HOMA-IR and with fasting and 2h-OGTT insulin levels in all groups (β > 0.16, p<0.05 for all associations). In contrast, 2h-glucose levels were associated with liver fat in all groups (p<0.01), except in pre-menopausal women (β = 0.06, p=0.24).
Discussion/Conclusion: The relationship between liver fat and metabolic health differs across pre- and postmenopausal women. Notably, liver fat was not associated with 2h-glucose concentrations in premenopausal women, whereas such an association was observed in the other groups. Future analyses incorporating interaction effects may further clarify the nature and extent of sex- and menopause-related differences.