Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study

Elisabeth Müllner,Ali A Moazzami,Hanna E Röhnisch,Claudia Von Brömssen

doi:10.1007/s11306-020-01759-y

Elisabeth Müllner, Ali A Moazzami + Show 2 more

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https://doi.org/10.1007/s11306-020-01759-y

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Journal: Metabolomics	Publication Date: Jan 1, 2021
Citations: 16	License type: open-access

Affiliation: Swedish University of Agricultural Sciences

Abstract

IntroductionHyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents.ObjectivesTo identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents.Methods81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses.ResultsTwo groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3–4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1–2). (2) Metabolites associated with obesity status: obese adolescents (groups 2–4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1).ConclusionsObesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

Highlights

Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes
Our findings that branched-chain amino acids (BCAAs) are higher in obese adolescents with hyperinsulinaemia/IR are consistent with previous studies in adolescents showing higher BCAAs in obese compared with lean subjects (Butte et al 2015; Perng et al 2014; Short et al 2019) and positive associations between BCAAs and IR after adjustment for body mass index (BMI) (Suzuki et al 2019; Tricò et al 2017; Zhang et al 2019)
After selection and assignment of adolescents into groups, defined based on BMI, insulin secretory patterns and glucose tolerance, the present study revealed clusters of metabolites associated either with insulin response, or with obesity

Summary

Introduction

Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. 11 Page 2 of 13 depressed (compensatory increase in insulin secretion is incomplete) in IR individuals, impaired glucose tolerance (IGT) occurs, putting individuals at risk of developing type 2 diabetes (T2DM) (Arslanian 2005; Levy-Marchal et al 2010). The number of children developing obesityassociated complications (IR, IGT and T2DM) is increasing (Amed et al 2010) and healthcare costs related to overweight/obesity and its comorbidities are escalating (Lehnert et al 2013). To address this threat, there is an urgent need for research to identify pathophysiological disturbances associated with different stages on the pathway to T2DM

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Conclusion