Non-Alcoholic Fatty Liver Disease and the Risk of Diabetes Mellitus by Menopausal Status: A Nationwide Cohort Study

Background: Non-alcoholic fatty liver disease (NAFLD) is regarded as a risk factor for type 2 diabetes mellitus (DM). Menopausal status also influences T2DM risk, where estrogen is presumed to play a protective role by decreasing insulin resistance. As such, we investigated the association between NAFLD and DM risk according to menopausal status. Objectives: We sought to examine the association between NAFLD and DM incidence in pre- and post-menopausal women. Methods: A total of 842,772 pre-menopausal and 1,074,767 post-menopausal women who underwent health examinations between 2009 and 2014 were included from the Korean National Health Insurance Service database. Multivariate Cox proportional hazard analyses were performed to evaluate the association between the risk of DM according to menopausal status and NAFLD, defined by a fatty liver index >60. Results: During the mean follow-up period (7.8 years), DM was diagnosed in 33,461 (4.0%) of pre-menopausal women and 121,102 (9.4%) post-menopausal women. A stronger association between NAFLD and the risk of DM was found in pre-menopausal women (multivariable-adjusted hazard ratio [aHR], 3.60; 95% confidence interval [CI], 3.48-3.71) than in post-menopausal women (aHR, 2.24; 95% CI, 2.21-2.28) (P-interaction < 0.01). Subgroup analyses among women aged 45 to 55 years also showed a stronger association in pre-menopausal (aHR, 3.35; 95% CI, 3.21-3.49) than in post-menopausal women (aHR, 2.83; 95% CI, 2.68-2.98) (P-interaction < 0.01). Conclusions: The association between NAFLD and DM was stronger in pre-menopausal women than in postmenopausal women. This might be due to the protective effect of estrogen, which is possibly in higher production in the peripheral fat tissue of post-menopausal women with NAFLD.