Elsevier

Metabolism

Volume 54, Issue 12, December 2005, Pages 1566-1570
Metabolism

Hyperinsulinemia predicts hepatic fat content in healthy individuals with normal transaminase concentrations

https://doi.org/10.1016/j.metabol.2005.05.027Get rights and content

Abstract

Although the prevalence of insulin resistance (IR) and compensatory hyperinsulinemia (CH) is increased in patients with nonalcoholic fatty liver disease, the role of IR/CH in regulation of hepatic fat content in healthy volunteers with normal concentrations of alanine transaminase (ALT) has not been defined. To address this issue, hepatic fat content was quantified by ultrasound in 69 (30 men, 39 women) healthy individuals, without known risk factors for liver disease and with plasma ALT concentrations of less than 30 U/L. Experimental variables quantified included body mass index, waist circumference, systolic and diastolic blood pressures, and fasting plasma glucose, fasting plasma insulin (FPI), and lipid concentrations. Subjects were classified as having no (55%), mild (27%), or moderate to severe (18%) hepatic steatosis on the basis of the ultrasound results. Statistically significant (P < .05-.001) correlations (Spearman ρ values) existed between liver fat content and ALT (0.26), body mass index (0.52), waist circumference (0.50), systolic blood pressure (0.28), diastolic blood pressure (0.27), fasting plasma glucose (0.47), FPI (0.56), triglycerides (0.30), and high-density lipoprotein cholesterol (−0.35). Multivariate general discriminant analysis and multiple linear regression analysis indicated that FPI was the only independent predictor (P < .001) of both liver fat content and ALT concentrations. Fasting plasma insulin (a surrogate estimate of IR/CH) predicts hepatic fat content and ALT in healthy volunteers with normal transaminase concentrations, independently of the other anthropometric and metabolic variables measured.

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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