Introduction

Hyperinsulinaemia 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.

Objectives

To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents.

Methods

81 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.

Results

Two 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).

Conclusions

Obesity 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.

中文翻译：

---

代谢组学分析揭示，与肥胖青少年相比，瘦人的代谢物发生了变化，以及肥胖青少年与高胰岛素血症和胰岛素抵抗相关的额外代谢变化：一项横断面研究

 介绍

高胰岛素血症和胰岛素抵抗 (IR) 与肥胖密切相关，是 2 型糖尿病的先兆。对于青少年肥胖、高胰岛素血症/IR 和糖耐量受损 (IGT) 分别相关的代谢改变知之甚少。

 目标

确定肥胖青少年与肥胖、高胰岛素血症/IR 和高胰岛素血症/IR 联合 IGT 相关的代谢改变。

 方法

81 名青少年根据体重指数（瘦与肥胖）、胰岛素反应（正常胰岛素 (NI) 与高胰岛素 (HI)）和葡萄糖反应（正常糖耐量 (NGT) 与 IGT）分为四组口服葡萄糖耐量试验（OGTT）。这些组包括：（1）具有 NI 和 NGT 的健康瘦身人群，（2）具有 NI 和 NGT 的肥胖人群，（3）具有 HI 和 NGT 的肥胖人群，以及（4）具有 HI 和 IGT 的肥胖人群。对禁食和 7 个 OGTT 后血浆样本进行基于核磁共振的靶向代谢组学分析，然后进行单变量和多变量统计分析。

 结果

确定了两组代谢物：（1）与胰岛素反应水平相关的代谢物：患有HI的青少年（第3-4组）具有较高浓度的支链氨基酸和酪氨酸，以及较低浓度的丝氨酸​​、甘氨酸、肌醇和二甲砜，优于患有 NI 的青少年（第 1-2 组）。 (2)与肥胖状态相关的代谢物：与瘦青少年（第1组）相比，肥胖青少年（第2-4组）的乙酰肉碱、丙氨酸、丙酮酸和谷氨酸浓度较高，而乙酸浓度较低。

 结论

肥胖与脂肪和能量代谢的变化有关。肥胖青少年的高胰岛素血症/IR也与支链氨基酸和芳香氨基酸的增加有关。