RT journal article
T1 Identifying metabotypes of insulin resistance severity in children with metabolic syndrome
A1 González Domínguez, Alvaro
A1 Domínguez Riscart, Jesús
A1 Savolainen, Otto
A1 Lechuga Sancho, Alfonso María
A1 Landberg, Rikard
A1 González-Domínguez, Raúl
A2 Materno-Infantil y Radiología
K1 Childhood obesity
K1 Insulin resistance
K1 Metabolic flexibility
K1 Metabolomics
AB BackgroundInsulin resistance is a frequent precursor of typical obesity and metabolic syndrome complications. However, accurate diagnosis remains elusive because of its pathophysiological complexity and heterogeneity. Herein, we have explored the utility of insulin secretion dynamics in response to an oral glucose tolerance test as a surrogate marker to identify distinct metabotypes of disease severity.MethodsThe study population consisted of children with obesity and insulin resistance, stratified according to the post-challenge insulin peak timing (i.e., early, middle, and late peak), from whom fasting and postprandial plasma and erythrocytes were collected for metabolomics analysis.ResultsChildren with late insulin peak manifested worse cardiometabolic health (i.e., higher blood pressure, glycemia, and HOMA-IR scores) than early responders. These subjects also showed more pronounced changes in metabolites mirroring failures in energy homeostasis, oxidative stress, metabolism of cholesterol and phospholipids, and adherence to unhealthy dietary habits. Furthermore, delayed insulin peak was associated with impaired metabolic flexibility, as reflected in compromised capacity to regulate mitochondrial energy pathways and the antioxidant defense in response to glucose overload.ConclusionsAltogether, these findings suggest that insulin resistance could encompass several phenotypic subtypes characterized by graded disturbances in distinctive metabolic derangements occurring in childhood obesity, which serve as severity predictive markers.
PB BMC
SN 1475-2840
YR 2024
FD 2024-08-27
LK http://hdl.handle.net/10498/35664
UL http://hdl.handle.net/10498/35664
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 10-nov-2026