RT Journal Article
T1 Untargeted Profiling of Concordant/Discordant Phenotypes of High Insulin Resistance and Obesity To Predict the Risk of Developing Diabetes.
A1 Marco-Ramell, Anna
A1 Tulipani, Sara
A1 Palau-Rodriguez, Magali
A1 Gonzalez-Dominguez, Raul
A1 Miñarro, Antonio
A1 Jauregui, Olga
A1 Sanchez-Pla, Alex
A1 Macias-Gonzalez, Manuel
A1 Cardona, Fernando
A1 Tinahones, Francisco J
A1 Andres-Lacueva, Cristina
K1 ROC curves
K1 adrenic acid
K1 diglycerides
K1 insulin resistance
K1 metabolic profiles
K1 metabolomics
K1 obesity
K1 observational study
K1 predictive model
K1 uric acid
AB This study explores the metabolic profiles of concordant/discordant phenotypes of high insulin resistance (IR) and obesity. Through untargeted metabolomics (LC-ESI-QTOF-MS), we analyzed the fasting serum of subjects with high IR and/or obesity ( n = 64). An partial least-squares discriminant analysis with orthogonal signal correction followed by univariate statistics and enrichment analysis allowed exploration of these metabolic profiles. A multivariate regression method (LASSO) was used for variable selection and a predictive biomarker model to identify subjects with high IR regardless of obesity was built. Adrenic acid and a dyglyceride (DG) were shared by high IR and obesity. Uric and margaric acids, 14 DGs, ketocholesterol, and hydroxycorticosterone were unique to high IR, while arachidonic, hydroxyeicosatetraenoic (HETE), palmitoleic, triHETE, and glycocholic acids, HETE lactone, leukotriene B4, and two glutamyl-peptides to obesity. DGs and adrenic acid differed in concordant/discordant phenotypes, thereby revealing protective mechanisms against high IR also in obesity. A biomarker model formed by DGs, uric and adrenic acids presented a high predictive power to identify subjects with high IR [AUC 80.1% (68.9-91.4)]. These findings could become relevant for diabetes risk detection and unveil new potential targets in therapeutic treatments of IR, diabetes, and obesity. An independent validated cohort is needed to confirm these results.
YR 2018
FD 2018-06-15
LK http://hdl.handle.net/10668/12596
UL http://hdl.handle.net/10668/12596
LA en
DS RISalud
RD Apr 10, 2025