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- Title
Identifying metabotypes of insulin resistance severity in children with metabolic syndrome.
- Authors
González-Domínguez, Álvaro; Domínguez-Riscart, Jesús; Savolainen, Otto; Lechuga-Sancho, Alfonso; Landberg, Rikard; González-Domínguez, Raúl
- Abstract
Background: Insulin 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. Methods: The 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. Results: Children 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. Conclusions: Altogether, 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.
- Subjects
INSULIN resistance; DIETARY patterns; METABOLIC syndrome; GLUCOSE tolerance tests; METABOLIC disorders
- Publication
Cardiovascular Diabetology, 2024, Vol 23, Issue 1, p1
- ISSN
1475-2840
- Publication type
Article
- DOI
10.1186/s12933-024-02412-x