title: Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.
abstract: OBJECTIVE
  Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT).
  
  
  METHODS
  We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship.
  
  
  RESULTS
  Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively).
  
  
  CONCLUSIONS
  Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and control subjects.
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Sala
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Lucia J M
authors.initials: LJ
authors.lastname: Kroft
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Röell
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: de Roos
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands; Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000378:metabolism; D005234:Fatty Liver / Q000201:enzymology*; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase