title: Longitudinal effects of MRI-measured hepatic steatosis on biomarkers of glucose homeostasis and hepatic apoptosis in obese youth.
abstract: OBJECTIVE
  We used fast-gradient magnetic resonance imaging (MRI) to determine the longitudinal associations between the hepatic fat content (HFF), glucose homeostasis, and a biomarker of hepatocellular apoptosis in obese youth.
  
  
  METHODS
  Baseline and longitudinal liver and abdominal MRI were performed with an oral glucose tolerance test in 76 obese youth followed for an average of 1.9 years. Cytokeratin-18 (CK-18) was measured at baseline and follow-up as a biomarker of hepatic apoptosis. The relationship between baseline HFF and metabolic parameters and circulating levels of CK-18 at follow-up were assessed using a bivariate correlation.
  
  
  RESULTS
  At baseline, 38% had hepatic steatosis based on %HFF ≥5.5% with alterations in indices of insulin sensitivity and secretion. At follow-up, BMI increased in both groups and baseline %HFF correlated strongly with the follow-up %HFF (r = 0.81, P < 0.001). Over time, markers of insulin sensitivity and 2-h glucose improved significantly in the group without fatty liver, in contrast with the persistence of the insulin resistance and associated correlates in the fatty liver group. Baseline HFF correlated with 2-h glucose (r = 0.38, P = 0.001), whole-body insulin sensitivity (r = -0.405, P = 0.001), adiponectin (r = -0.44, P < 0.001), CK-18 levels, (r = 0.63, P < 0.001), and disposition index (r = -0.272, P = 0.021) at follow-up. In a multivariate analysis, we showed that baseline HFF is an independent predictor of 2-h glucose and whole-body insulin sensitivity.
  
  
  CONCLUSIONS
  In obese youth, the phenotype of MRI-measured hepatic steatosis is persistent. Baseline HFF strongly modulates longitudinally 2-h blood glucose, biomarkers of insulin resistance, and hepatocellular apoptosis.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Kim
authors.forename: Cosimo
authors.initials: C
authors.lastname: Giannini
authors.forename: Bridget
authors.initials: B
authors.lastname: Pierpont
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.forename: Nicola
authors.initials: N
authors.lastname: Santoro
authors.forename: Romy
authors.initials: R
authors.lastname: Kursawe
authors.forename: Melissa
authors.initials: M
authors.lastname: Shaw
authors.forename: Elvira
authors.initials: E
authors.lastname: Duran
authors.forename: Rachel
authors.initials: R
authors.lastname: Goldberg
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.forename: Sonia
authors.initials: S
authors.lastname: Caprio
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism*; D002648:Child; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D015999:Multivariate Analysis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005947:Glucose