Abstract 1598: Hepatic Steatosis Does Not Result in Insulin Resistance in Subjects With Familial Hypobetalipoproteinaemia
Prelimenary data Background and aims: Hepatic steatosis is strongly associated with hepatic and whole body insulin resistance. Yet the causal relationship between hepatic steatosis and insulin resistance remains uncertain. Subjects with familial hypobetalipoproteinemia (FHBL) are characterized by low levels of apolipoprotein B and an increased risk of hepatic steatosis. However FHBL-patients are not characterized by disturbances in glucose metabolism. To investigate the role of liver fat in the development of insulin resistance we studied glucose metabolism in subjects with FHBL and matched controls.
Materials and methods: We measured endogenous glucose production (EGP) and hepatic and peripheral insulin sensitivity (Rd) in the basal state and during a two-step hyperinsulinemic euglycemic clamp using stable isotopes. We included 7 male subjects with established FHBL and 7 healthy controls, matched for sex, age, BMI, waist to hip ratio and physical activity. Hepatic triglyceride content (IHTG) was measured using magnetic resonance spectroscopy (STEAM, TE/TR=20/3000 ms, 6 acquisitions, voxel size 27 cm3). Intramyocellular lipid content (IMCL) was measured by magnetic resonance spectroscopic imaging (TE/TR=30/1100 ms, matrix size 32x32). Voxels inside the soleus muscle were selected for analysis. Data are presented as median [minimum-maximum].
Results: IHTG was significantly higher in patients compared to controls (29.8 % [0 – 82] vs. 0.82 % [0 –31] respectively, p= 0.045), while IMCL was similar in subjects with FHBL and controls (9.6 % [5.7–12.8] vs. 8.8 % [6.7–22.8] respectively). Basal EGP and basal insulin levels did not differ. Insulin-mediated suppression of EGP as well as Rd were not different between patients and controls (61.2% [17.7– 86.9] vs. 75.6% [43.6 – 82.8] respectively (p= 0.48) and 40.6 μmol/kg.min [35.0 – 42.6] vs. 48.7 μmol/kg.min [24.9 –71.8] respectively (p= 0.18)). Glucoregulatory hormones during the clamp were similar.
Conclusion: Subjects with FHBL and severe hepatic steatosis show no hepatic or peripheral insulin resistance. Our results indicate that hepatic steatosis per se is not sufficient to cause insulin resistance.