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

J Diabetes. 2023 Dec;15(12):1020-1028. doi: 10.1111/1753-0407.13460. Epub 2023 Aug 25.

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.

背景:儿童肥胖已成为严重的公共卫生挑战,胰岛素抵抗(IR)是其常见并发症之一。肥胖和IR都被认为是代谢紊乱的基础。然而,目前尚不清楚与儿童肥胖和IR相关的常见关键代谢物 方法:将儿童分为正常体重和超重/肥胖组。测量空腹血糖和空腹胰岛素,计算胰岛素抵抗稳态模型评估指数(HOMA-IR)。应用液相色谱-串联质谱进行代谢组学分析。通过多元线性回归分析和相关性分析探索肥胖、IR和代谢物之间的关系。使用随机森林(RF)对差异代谢物的重要性进行排序,并使用相对操作特征曲线进行预测 结果:共有88名正常体重儿童和171名肥胖/超重儿童参与了本研究。两组间有30种代谢物存在显著差异。儿童肥胖与10种氨基酸代谢物和20种脂肪酸代谢物显著相关。12种代谢物与IR显著相关。RF中代谢物的排名显示,谷氨酰胺、酪氨酸和丙氨酸在氨基酸中很重要,丙酮酸-2、乙基丙二酸-2和苯乳酸-2在脂肪酸中很重要。BMI-SDS曲线下面积与关键氨基酸代谢物和脂肪酸代谢物相结合,预测IR的准确率分别为80.0%和76.6% 结论:存在着与IR和肥胖儿童相关的关键代谢物,这些关键代谢物与BMI-SDS一起,可以有效预测IR风险.

Keywords: children; insulin resistance; metabolites; obesity; 代谢物; 儿童; 肥胖症; 胰岛素抵抗.

MeSH terms

  • Amino Acids
  • Blood Glucose / metabolism
  • Body Mass Index
  • Child
  • Fatty Acids
  • Humans
  • Insulin
  • Insulin Resistance*
  • Overweight / complications
  • Pediatric Obesity* / complications

Substances

  • Insulin
  • Amino Acids
  • Fatty Acids
  • Blood Glucose