Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations
Introduction
Nonalcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of chronic liver disease in developed countries, with prevalence rates ranging from 15% to 39% in general population studies [1]. Although neither the exact etiology of NAFLD nor the factors responsible for its progression are completely understood, there is substantial evidence of a strong relationship between NAFLD and the presence of metabolic abnormalities typically associated with insulin resistance (IR) syndrome [2], [3], [4], [5], [6], [7], [8].
Because most studies examining the relationship between NAFLD and IR have been performed in patients with clinical evidence of liver disease [9], [10], there is relatively little information concerning a possible link between hepatic fat content and IR/hyperinsulinemia in apparently healthy individuals as defined by normal transaminase concentrations. The most common laboratory abnormality in patients with NAFLD is an increase in aminotransferase activity, particularly alanine transaminase (ALT), but the degree of enzyme elevation is not marked [2]. Furthermore, there is evidence that increases in hepatic fat content can occur in individuals without manifest liver disease, whose ALT concentrations are within the normal range [11], [12]. Thus, it seemed important to examine the role that IR/hyperinsulinemia might play in regulation of hepatic fat content in apparently healthy individuals with normal values for liver transaminase concentrations. The present study was initiated to address this issue and was based on the hypothesis that there would be a significant correlation between IR (assessed by the plasma insulin levels) and both hepatic fat content and ALT concentrations in apparently healthy individuals with ALT concentrations less than 30 U/L.
Section snippets
Materials and methods
The experimental population consisted of 69 individuals (39 women and 30 men) who volunteered to have an echographic study of their liver. They were recruited during a follow-up examination of participants in the Barilla Study of apparently healthy individuals, followed since 1981 to assess the impact of IR on human disease. To qualify, volunteers had to be free of a history or clinical evidence of diabetes, cardiovascular, or liver disease, and had to have a daily alcohol intake of less than
Results
Table 1 presents the clinical characteristics of the experimental population, subdivided into 3 groups on the basis of their degree of steatosis. These data indicate that 31 (45%) of these apparently healthy individuals had some degree of steatosis, which was considered to be moderate or severe in 12 (18%) of them. It can be seen that, although the 3 groups were of similar age, the greater the BMI and the larger the WC, the more severe the degree of steatosis. In addition, there was a
Discussion
The results presented indicate that the higher the FPI concentration is in apparently healthy individuals, the greater will be the amount of fat in the liver and the higher the ALT concentrations. As such, they support the hypothesis that the untoward effects of IR/hyperinsulinemia on hepatic fat content can be observed in individuals without clinical evidence of any liver abnormality. To put these findings into context, several issues must be addressed. Most fundamentally, care has been taken
Acknowledgment
The study was supported by a grant from Italian Ministry of University and Scientific Research (COFIN MIUR 2001–protocol no. 2001065732_003).
We thank Dr Luigi Ippolito, MD (biochemical analysis laboratory), and Dr Gianfranco Elia, MD (Division of Infectious Diseases), from Azienda Ospedaliera–Universitaria di Parma (Parma Hospital), Parma, Italy.
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