Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children

Abstract

We hypothesised that ectopic fat deposition is present in liver and skeletal muscle before puberty and that both are potentially important factors in the early pathogenesis of insulin resistance. Proton magnetic resonance spectroscopy was used to evaluate intramyocellular and intrahepatic lipids in 50 male and 42 female multi-ethnic, prepubertal (Tanner < 2) children (8.1 ± 0.8 years; 35.4 ± 10.7 kg; 27.9 ± 8.3% body fat; means ± SD). Intramyocellular lipid was measured in soleus muscle and intrahepatic lipid in the middle right lobe. Abdominal fat was measured by magnetic resonance imaging, body fat by dual energy X-ray absorptiometry, and insulin resistance using homeostatic model assessment. Intrahepatic lipid ranged from 0.11% to 4.6% relative to the liver water signal (mean 0.79 ± 0.79%) whereas intramyocellular lipid ranged from 0.13% to 1.86% relative to the muscle water signal (mean 0.51 ± 0.28%). Intramyocellular and intrahepatic lipids were significantly correlated with total adiposity (r = 0.49 and 0.59), abdominal adiposity (r = 0.44 and 0.54), and each other (r = 0.39, p < 0.05, Spearman). Both intramyocellular and intrahepatic lipid were positively correlated with fasting insulin (r = 0.37 and 0.38 respectively) and insulin resistance (r = 0.37 and 0.37; p < 0.01). After adjustment for race and sex, the relations between ectopic fat and insulin resistance remained, whereas both disappeared when further adjusted for body fat or BMI z scores. These results suggest that typical relations between body composition, ectopic fat and insulin resistance are present in children before puberty. Thus, interventions aimed at reducing adiposity have the potential to decrease ectopic fat accumulation, delay the onset of insulin resistance and decrease the risk for development of type 2 diabetes in children.