The link between obesity and insulin resistance among children: Effects of key metabolites.

ABSTRACT

BACKGROUND: Childhood obesity became a severe public health challenge, and insulin resistance (IR) was one of the common complications. Both obesity and IR were considered as the basis of metabolic disorders. However, it is unclear which common key metabolites are associated with childhood obesity and IR. METHODS: The children were divided into normal weight and overweight/obese groups. Fasting blood glucose and fasting insulin were measured, and homeostasis model assessment of insulin resistance was calculated. Liquid chromatography-tandem mass spectrometry was applied for metabonomic analysis. Multiple linear regression analysis and correlation analysis explored the relationships between obesity, IR, and metabolites. Random forests were used to rank the importance of differential metabolites, and relative operating characteristic curves were used for prediction. RESULTS: A total of 88 normal-weight children and 171 obese/overweight children participated in the study. There was a significant difference between the two groups in 30 metabolites. Childhood obesity was significantly associated with 10 amino acid metabolites and 20 fatty acid metabolites. There were 12 metabolites significantly correlated with IR. The ranking of metabolites in random forest showed that glutamine, tyrosine, and alanine were important in amino acids, and pyruvic-ox-2, ethylmalonic-2, and phenyllactic-2 were important in fatty acids. The area under the curve of body mass index standard deviation  score (BMI-SDS) combined with key amino acid metabolites and fatty acid metabolites for predicting IR was 80.0% and 76.6%, respectively. CONCLUSIONS: There are common key metabolites related to IR and obese children, and these key metabolites combined with BMI-SDS could effectively predict the risk of IR.