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Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

ABSTRACT: Background:The aim of this study was to determine whether insulin resistance, beta-cell function, and their associations with alanine aminotransferase (ALT) are affected by the functional variants of paraoxonase-2 (PON2) as an intracellular antioxidant in patients with type 2 diabetes (T2D). Materials and Methods:Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment for beta-cell function (HOMA-BCF) were assessed in T2D patients. Insulin levels were determined using ELISA. The variants PON2-A148G and PON2-S311C were genotyped using polymerase chain reaction-based restriction fragment length polymorphism. Results:According to the PON2-G148A variant, ALT was found to be significantly correlated with QUICKI (r = -0.616, P = 0.005) and HOMA-BCF (r = 0.573, P = 0.01) in the GA + GG group; however, the correlations were not statistically significant in the AA genotypes. Based on the genotypes of PON2-S311C, there was a significant correlation between ALT with QUICKI (r = -0.540, P = 0.031) and HOMA-BCF (r = 0.567, P = 0.022) in the SC + CC group. In the multiple adjusted logistic regression analyses, considering the variants PON2-G148A and PON2-C311S as independent variables and QUICKI and HOMA-BCF as the dependent variables, both variants were significantly associated with the QUICKI (P = 0.019 for PON2-G148A and P = 0.041 for PON2-C311S). Furthermore, PON2-C311S remained significantly associated with HOMA-BCF (P = 0.03). Conclusion:These data implicate a role for the functional variants of PON2 in insulin resistance and beta-cell function as well as underscore the effective role of these variants in the associations between them and ALT. Our data contribute to our understanding of the important physiologic functions of PON2 in glucose metabolism and its related metabolic diseases.

SUBMITTER: Qujeq D

PROVIDER: S-EPMC6327680 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

Qujeq Durdi D Mahrooz Abdolkarim A Mahrooz Abdolkarim A Alizadeh Ahad A Boorank Ruzbeh R

Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences 20181228

<h4>Background</h4>The aim of this study was to determine whether insulin resistance, beta-cell function, and their associations with alanine aminotransferase (ALT) are affected by the functional variants of paraoxonase-2 (PON2) as an intracellular antioxidant in patients with type 2 diabetes (T2D).<h4>Materials and methods</h4>Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment for beta-cell function (HOMA-BCF) were assessed in T2D patients. Insulin levels wer ...[more]

PMID: 30693042

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Project description:UnlabelledBackgroundThe 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.

Dataset Information

Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

Publications

Paraoxonase-2 variants potentially influence insulin resistance, beta-cell function, and their interrelationships with alanine aminotransferase in type 2 diabetes.

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