Abstract
BackgroundThe association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. However, there is no information about the association of ALT with the Hepatic Insulin Resistance Index (HIRI). The aim of this study was to evaluate the association between serum ALT levels and HIRI in subjects with differing degrees of impaired glucose metabolism.MethodsThis cross-sectional study included subjects that had an indication for testing for type 2 diabetes mellitus (T2DM) with an oral glucose tolerance test (OGTT). Clinical and biochemical evaluations were carried out including serum ALT level quantification. HIRI was calculated for each participant. Correlation analyses and lineal regression models were used to evaluate the association between ALT levels and HIRI.ResultsA total of 324 subjects (37.6% male) were included. The mean age was 40.4 ± 14.3 years and the mean body mass index (BMI) was 32.0 ± 7.3 kg/m2. Individuals were divided into 1 of 5 groups: without metabolic abnormalities (n = 113, 34.8%); with the metabolic syndrome (MetS, n = 179, 55.2%), impaired fasting glucose (IFG, n = 85, 26.2%); impaired glucose tolerance (IGT, n = 91, 28.0%), and T2DM (n = 23, 7.0%). The ALT (p < 0.001) and HOMA2-IR (p < 0.001) values progressively increased with HIRI quartiles, while ISI-Matsuda (p < 0.001) progressively decreased. After adjustment for sex, age, and BMI, we identified a significant correlation between HIRI and ALT in persons with the MetS (r = 0.22, p = 0.003), IFG (r = 0.33, p < 0.001), IGT (r = 0.37, p < 0.001), and T2DM (r = 0.72, p < 0.001). Lineal regression analysis adjusting for age, HDL-C, TG and waist circumference (WC) showed an independent association between ALT and HIRI in subjects with the MetS (beta = 0.07, p = 0.01), IFG (beta = 0.10, p = 0.02), IGT (beta = 0.09, p = 0.007), and T2DM (beta = 0.31, p = 0.003). This association was not identified in subjects without metabolic abnormalities.ConclusionsALT levels are independently associated with HIRI in subjects with the MetS, IFG, IGT, and T2DM. The ALT value in these subjects may be an indirect parameter to evaluate hepatic IR.
Highlights
The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp
The metabolic syndrome (MetS) was defined as the presence of three or more of the following risk factors: 1) central obesity 2) hypertriglyceridemia (fasting triglycerides ≥150 mg/dl (≥1.69 mmol/l); 3) low HDL cholesterol (HDL cholesterol
The population was divided into 5 groups according to the degree of impaired glucose metabolism: 1) without metabolic abnormalities defined as a patient without the MetS, IFG, IGT or type 2 diabetes mellitus (T2DM); 2) with the MetS; 3) IFG; 4) IGT; and 5) T2DM
Summary
The association between serum alanine aminotransferase (ALT) levels and hepatic insulin resistance (IR) has been evaluated with the hyperinsulinemic-euglycemic clamp. Clinical studies have associated serum ALT levels with insulin resistance (IR), the MetS and the development of T2DM [13,14,15]. Accurate measurement of IR requires the use of techniques such as clamps that are costly, time-consuming, and invasive for use in large epidemiological or clinical studies. In this context, a number of simple indexes of IR have been proposed [18,19,20,21,22,23]. These indexes include HOMA-2, Matsuda-ISI, and QUICKI, among others
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