Abstract
ObjectiveFamilial 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).Research Design and 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.ResultsOffspring 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).ConclusionsExcept 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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipedimia [1]
Offspring of long-lived siblings had higher nonfasting alanine transaminase (ALT) levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while aspartate transaminase (AST) and GGT levels were similar between the two groups
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 computed tomography (CT)
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipedimia [1]. Hepatocyte dysfunction due to liver fat accumulation may interfere with insulin action and cause hepatic insulin resistance [4]. The liver enzymes U-glutamyl transferase (GGT) and alanine aminotransferase (ALT) correlate with liver fat content, and have been shown to predict impaired glucose metabolism and type 2 diabetes mellitus incidence [5]. Secondary to insulin resistance, prolonged compensatory hyperinsulinemia may lead to the development of NAFLD [6]. From this point of view, NAFLD may be a consequence rather than a cause of age related insulin resistance
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