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Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72).

Abstract：

BACKGROUND:While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. METHODS:The Earlybird cohort is a well-characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. RESULTS:IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched-chain amino acids (BCAA), 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. CONCLUSIONS:Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.

journal_name

Pediatr Diabetes

journal_title

Pediatric diabetes

authors

Hosking J,Pinkney J,Jeffery A,Cominetti O,Da Silva L,Collino S,Kussmann M,Hager J,Martin FP

doi

10.1111/pedi.12884

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

832-841

issue

eissn

1399-543X

issn

1399-5448

journal_volume

pub_type

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Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72).