Hepatic steatosis is associated with impaired hepatic glucose uptake under hyperglycemic conditions, a dynamic whole-body 18F-FDG PET approach

Objective Accumulation of fat in the liver is associated with hepatic insulin resistance, as evidenced by a reduced insulin-induced suppression of endogenous glucose production (EGP). However, suppression of EGP has been proposed to be mainly a reflection of indirect insulin action.Hepatic glucose uptake in the postprandial state is another aspect of hepatic insulin sensitivity, which is seldom investigated. Here we sought to examine if hepatic steatosis is associated with a reduced hepatic glucose uptake under conditions of hyperglycemia and hyperinsulinemia. Methods In this cross-sectional study, 15 participants with a range of liver fat content (0.9–18 %) as assessed by 1H-MRSwere recruited. Whole-body insulin sensitivity and insulin-induced suppression of EGP were measured by a two-step euglycemic-hyperinsulinemic clamp. A hyperglycemic-hyperinsulinemic clamp was used to measure hepatic and tissue-specific glucose uptake using a dynamic whole-body 18F-FDG PET protocol. Results Under conditions of hyperglycemic-hyperinsulinemia, hepatic glucose uptake correlated strongly and inversely with liver fat content (r = -0.756, p < 0.001). Hepatic glucose uptake also correlated with insulin-stimulated EGP suppression (r = 0.616, p = 0.015). Adipose tissue insulin sensitivity was negatively associated with liver fat content and positively with hepatic, skeletal muscle, and adipose tissue glucose uptake. Conclusion We show that another aspect of hepatic insulin resistance, namely the ability of insulin to stimulate hepatic glucose uptake under hyperglycemic conditions, is negatively associated with hepatic fat content. This suggests that hepatic glucose uptake is another factor that may be important in Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) and the risk for type 2 diabetes, and needs further investigation.