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Title: Untargeted profiling of concordant/discordant phenotypes of high insulin resistance and obesity to predict the risk of developing diabetes
Author: Marco Ramell, Anna
Tulipani, Sara
Palau Rodríguez, Magalí
González-Domínguez, Raúl
Miñarro Alonso, Antonio
Jáuregui Pallarés, Olga
Sànchez, Àlex (Sànchez Pla)
Macias-Gonzalez, Manuel
Cardona, Fernando
Tinahones, Francisco J.
Andrés Lacueva, Ma. Cristina
Keywords: Diabetis no-insulinodependent
Marcadors bioquímics
Resistència a la insulina
Àcid úric
Non-insulin-dependent diabetes
Biochemical markers
Insulin resistance
Uric acid
Issue Date: 15-Jun-2018
Publisher: American Chemical Society
Abstract: 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.
Note: Versió postprint del document publicat a:
It is part of: Journal of Proteome Research, 2018, vol. 17, num. 7, p. 2307-2317
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ISSN: 1535-3893
Appears in Collections:Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)
Articles publicats en revistes (Institut de Recerca en Nutrició i Seguretat Alimentària (INSA·UB))

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