Temporal Relationship Between Hepatic Steatosis and Fasting Blood Glucose Elevation: a Longitudinal Analysis from China and UK

The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (βCMEC = 0.068, βUK−Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (βCMEC = 0.027, βUK−Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514