Dataset Information

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study.

ABSTRACT:

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Background

The 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.

Methods

This 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.

Results

A 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?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.

SUBMITTER: Gomez-Samano MA

PROVIDER: S-EPMC3515498 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study.

Gómez-Sámano Miguel Angel MA Cuevas-Ramos Daniel D Mehta Roopa R Brau-Figueroa Hasan H Meza-Arana Clara Elena CE Gulias-Herrero Alfonso A

BMC endocrine disorders 20120904

<h4>Unlabelled</h4><h4>Background</h4>The 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.<h4>Methods</h4>This cross-se ...[more]

PMID: 22947097

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Project description:The changing epidemiology of liver disease, and modifications in the recommended analytical methodology call for a re-evaluation of the upper reference limits (URLs) of alanine aminotransferase (ALT) levels. Using the same approach consolidated 20 years ago to define the healthy population, we defined the URL for the newly recommended International Federation of Clinical Chemistry (IFCC) standardized test. In a cross-sectional study, we examined 21,296 apparently healthy blood donors (age 18-65 years) and calculated the sex-specific URL by the 95th percentile in individuals without risk factors for liver disease. These were tested for the ability to predict liver damage in a subset of 745 participants with dysmetabolism, in an independent cohort of 977 unselected donors, and in 899 patients with chronic liver disease. ALT levels were measured by the IFCC test. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and younger age were independent ALT predictors (P < 0.001). Updated URLs were identified at 42/30 U/L in males/females, approximately 30% lower than those currently recommended by the IFCC. Due to improved sensitivity, they conferred the ability to detect steatosis and significant fibrosis in individuals with dysmetabolism (odds ratio [OR] = 2.31, range 1.40-3.80, P = 0.001; and OR = 3.35, range 1.19-9.42, P = 0.021; respectively), although with a limited accuracy, and significant fibrosis in unselected donors (OR = 2.32, 1.02-5.31, P = 0.045). Updated URLs had a moderate to high accuracy to discriminate liver conditions (area under the receiver operating characteristic curve = 0.81, range 0.78-0.91). Conclusion: Updated URLs by the IFCC method were lower than those calculated in initial studies, but higher than those in use with the recommended old, nonstandardized method, and were able to better predict liver disease. The limited awareness that different techniques are still in use should be regarded as a possible source of medical errors.

Project description:Interpretations of elevated blood levels of alanine aminotransferase (ALT) for drug-induced liver injury often assume that the biomarker is released passively from dying cells. However, the mechanisms driving that release have not been explored experimentally. The usefulness of ALT and related biomarkers will improve by developing mechanism-based explanations of elevated levels that can be expanded and elaborated incrementally. We provide the means to challenge the ability of closely related model mechanisms to generate patterns of simulated hepatic injury and ALT release that scale (or not) to be quantitatively similar to the wet-lab validation targets, which are elevated plasma ALT values following acetaminophen (APAP) exposure in mice. We build on a published model mechanism that helps explain the generation of characteristic spatiotemporal features of APAP hepatotoxicity within hepatic lobules. Discrete event and agent-oriented software methods are most prominent. We instantiate and leverage a small constellation of concrete model mechanisms. Their details during execution help bring into focus ways in which particular sources of uncertainty become entangled with cause-effect details within and across several levels. We scale ALT amounts in virtual mice directly to target plasma ALT values in individual mice. A virtual experiment comprises a set of Monte Carlo simulations. We challenge the sufficiency of four potentially explanatory theories for ALT release. The first of the tested model theories failed to achieve the initial validation target, but each of the three others succeeded. Results for one of the three model mechanisms matched all target ALT values quantitatively. It explains how ALT externalization is the combined consequence of lobular-location-dependent drug-induced cellular damage and hepatocyte death. Falsification of one (or more) of the model mechanisms provides new knowledge and incrementally shrinks the constellation of model mechanisms. The modularity and biomimicry of our explanatory models enable seamless transition from mice to humans.

Project description:BackgroundWe aimed to determine the prevalence of elevated alanine aminotransferase (eALT) in employees of a German chemical company, and analyze its association with sociodemographic, work- and lifestyle-related factors.MethodsThe cross-sectional study is based on data surveyed from occupational health check-ups between 2013 and 2018 at the site clinic of a chemical company based in Ludwigshafen, Germany. We used logistic regression analyses to assess the association between sociodemographic, work- and lifestyle-related characteristics and eALT. Quantile regression technique was applied to investigate if associations vary across different quantiles of the ALT distribution.ResultsParticipants (n = 15,348) were predominantly male (78.3%) with a mean age of 42.2 years (SD 10.7). The prevalence of eALT was 18.5% (21.6% in men/7.2% in women) with a geometric mean of 28.9 U/L (32.8 U/L in men/18.5 U/L in women). In the multivariable logistic regression model, odds of eALT were significantly higher for males (OR 2.61; 95%-CI 2.24-3.05), manual workers (OR 1.23; 95%-CI 1.06-1.43), overweight (OR 2.66; 95%-CI 2.36-3.00) or obese respondents (e.g. OR 7.88; 95%-CI 5.75-10.80 for obesity class III), employees who consume any number of alcoholic drinks/week (e.g. OR 1.32; 95%-CI 1.16-1.49 for ≥ 3 drinks per week) and diabetics (OR 1.47; 95%-CI 1.22-1.78). Additionally, season of participation was significantly associated with eALT, with odds being higher for participation in spring, fall or winter, as compared to summer. A significant interaction between age and gender (pInteraction < 0.001) was found, showing approximately a u-shaped age/ALT relationship in women and an inversely u-shaped relationship in men. Quantile regression showed an increasing positive effect of male gender, overweight/obesity, and for diabetics on ALT level when moving from the lowest (q0.1) to the highest (q0.9) considered quantile. Additionally, from the lowest to the highest quantile an increasing negative effect on ALT for older age was observed.ConclusionsPrevalence of eALT in our sample of employees can be considered as high, with almost one in five participants affected. Identification of risk groups allows the implementation of targeted preventive measures in order to avoid transition to severe morbidity.

Dataset Information

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study.

Unlabelled

Background

Methods

Results

Publications

Association of Alanine Aminotransferase Levels (ALT) with the Hepatic Insulin Resistance Index (HIRI): a cross-sectional study.

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