TY - JOUR
TI - Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification
Biomarkers of NAFLD
AU - Marques, Vanda
AU - Afonso, Marta B.
AU - Bierig, Nina
AU - Duarte-Ramos,
AU - Filipa
AU - Santos-Laso, Alvaro
AU - Jimenez-Aguero, Raul
AU - Eizaguirre,
AU - Emma
AU - Bujanda, Luis
AU - Pareja, Maria J.
AU - Luis, Rita
AU - Costa,
AU - Adilia
AU - Machado, V, Mariana
AU - Alonso, Cristina
AU - Arretxe, Enara
AU - and Alustiza, Jose M.
AU - Krawczyk, Marcin
AU - Lammert, Frank and
AU - Tiniakos, Dina G.
AU - Flehmig, Bertram
AU - Cortez-Pinto, Helena and
AU - Banales, Jesus M.
AU - Castro, Rui E.
AU - Normann, Andrea
AU - Rodrigues,
AU - Cecilia M. P.
JO - Frontiers in Cardiovascular Medicine
PY - 2021
VL - 8
TODO - null
SP - null
PB - Frontiers Media SA
SN - null
TODO - 10.3389/fmed.2021.683250
TODO - adiponectin; circulating biomarkers; fibrosis; IGF-1; leptin; lipid
metabolism; NAFLD
TODO - 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.
ER -