Dataset Information

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD.

ABSTRACT: Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p < 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.

SUBMITTER: Marques V

PROVIDER: S-EPMC8260936 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD.

Marques Vanda V Afonso Marta B MB Bierig Nina N Duarte-Ramos Filipa F Santos-Laso Álvaro Á Jimenez-Agüero Raul R Eizaguirre Emma E Bujanda Luis L Pareja Maria J MJ Luís Rita R Costa Adília A Machado Mariana V MV Alonso Cristina C Arretxe Enara E Alustiza José M JM Krawczyk Marcin M Lammert Frank F Tiniakos Dina G DG Flehmig Bertram B Cortez-Pinto Helena H Banales Jesus M JM Castro Rui E RE Normann Andrea A Rodrigues Cecília M P CMP

Frontiers in medicine 20210623

<b>Background:</b> Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. <b>Materials and Methods:</b> Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-pro ...[more]

PMID: 34249975

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Project description:BackgroundAdiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to provide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.MethodsIn this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.ResultsThe AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955.ConclusionsThe novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.

Dataset Information

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD.

Publications

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD.

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