Association between liver fibrosis severity and impaired myocardial glucose metabolism in subjects with different degrees of glucose tolerance

Introduction: Increasing evidence suggests that liver fibrosis is an independent risk factor for cardiovascular disease. However, the mechanisms underlying this increased risk are still unsettled. The aim of this study was to explore the relationship between myocardial glucose metabolism and the severity of liver fibrosis. Research design and methods: We evaluated insulin-stimulated myocardial glucose metabolic rate (MrGlu) using cardiac dynamic positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) combined with a euglycemic-hyperinsulinemic clamp and liver fibrosis severity, estimated by the fibrosis-4 (FIB-4) index, in 57 individuals with varying degrees of glucose tolerance. According to the FIB-4 index, subjects were stratified into three groups: low risk of fibrosis (<1.3; n=37), intermediate risk of fibrosis (≥1.3 to <2.67; n=16), and high risk of fibrosis (≥2.67; n=4). Results: Subjects with a high risk of advanced fibrosis exhibited an age-adjusted decrease of myocardial MrGlu compared with both individuals with a low FIB-4 index category (4.6±4.3 µmol/min/100 g vs 21.7±11.2 µmol/min/100 g; p=0.009) and intermediate FIB-4 index category (20.±11.03 µmol/min/100 g; p=0.01, respectively). No significant differences in glycemic and anthropometric parameters, whole-body insulin sensitivity, or blood pressure were found between groups.In a multivariable regression analysis, the only variable significantly associated with advanced liver fibrosis risk was myocardial MrGlu (β=-0.286; p=0.003), explaining 28.6% of the variation. Conclusions: These data suggest that impairment of insulin-stimulated myocardial glucose metabolism is associated with a high risk of advanced liver fibrosis in individuals with varying degrees of glucose tolerance.