Fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease: A prospective study

The association between sugar-sweetened beverages and metabolic disorders has been well studied. However, it has not been determined whether fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease (MAFLD).

Participants were enrolled from 2011 to 2012 in Shanghai. Fasting serum fructose concentration was measured with a validated liquid chromatography-tandem mass spectrometry method.

A total of 954 participants without diabetes were included. They were followed for an average of 3.5 years. A total of 320 (33.5%) participants had MAFLD at baseline. With the increase in fasting serum fructose level by quartile, the MAFLD prevalence was increased by 27.0%, 25.0%, 37.4%, and 44.5%, respectively (p < 0.001). Each SD increase in fasting serum fructose level was associated with a 60% increased risk of MAFLD (odds ratio 1.60; 95% confidence interval [CI], 1.36-1.88; p < 0.001). Fasting serum fructose levels were more closely associated with four components of MAFLD (hepatic steatosis, prediabetes, insulin resistance, and low high-density lipoprotein). We built a diagnostic model named the fructose fat index (FFI). The area under the receiver operating characteristic curve of the FFI was 0.879 (95% CI, 0.850-0.908) in the derivation cohort and 0.827 (95% CI, 0.776-0.878) in the validation cohort. Subsequent prospective studies found that the incidence risk of MAFLD was 2.26 times higher in the high-fructose group than in the low-fructose group among female participants (95% CI, 1.46-3.49; p < 0.001).

Fasting serum fructose concentration, which mostly reflects endogenous fructose, was associated with a higher risk of MAFLD. The FFI derived from fasting serum fructose could be used to predict MAFLD.