Branched-chain amino acids (BCAA) and aromatic AAs (AAA) are associated with increased risk for type 2 diabetes in adults. Studies in youth show conflicting results. We hypothesized that an AA metabolomic signature can be defined to identify youth at risk for β-cell failure and the development of type 2 diabetes. We performed targeted AA metabolomics analysis on 127 adolescents (65 females, 15.5±1.9 years old, Tanner stage II-V) with normal weight or obesity across the spectrum of glycemia, with assessment of AA concentrations by mass spectrometry, at fasting and steady-state (SS) of a hyperinsulinemic-euglycemic clamp, with determination of insulin sensitivity (ISFFM). We measured insulin secretion during a 2-hour hyperglycemic clamp and calculated the disposition index (DIFFM), a measure of β-cell function. Our results showed that Gly and Gln/Glu were lower, whereas BCAA, Tyr and Lys concentrations were higher in the groups with obesity and dysglycemia compared with those with normal weight. Gly and Gln/Glu were positively related to IS and DIFFM, with opposite relationships observed for BCAA, AAA and Lys. We conclude that a metabolic signature of low Gly, low Gln/Glu and elevated BCAA, AAA and Lys may constitute a biomarker to identify youth at risk for β-cell failure.

中文翻译：

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患有 2 型糖尿病或有患 2 型糖尿病风险的青少年具有独特的氨基酸特征

支链氨基酸 (BCAA) 和芳香族氨基酸 (AAA) 与成人 2 型糖尿病风险增加相关。对青少年的研究显示出相互矛盾的结果。我们假设可以定义 AA 代谢组学特征来识别有 β 细胞衰竭和 2 型糖尿病风险的青少年。我们对 127 名体重正常或肥胖的青少年（65 名女性，15.5±1.9 岁，Tanner II-V 期）的血糖谱进行了针对性的 AA 代谢组学分析，并通过质谱法评估了空腹和稳态时的 AA 浓度。高胰岛素正常血糖钳夹状态（SS），并测定胰岛素敏感性（ISFFM）。我们测量了 2 小时高血糖钳夹期间的胰岛素分泌情况，并计算了处置指数 (DIFFM)，这是衡量 β 细胞功能的指标。我们的结果显示，与正常体重组相比，肥胖和血糖异常组的 Gly 和 Gln/Glu 浓度较低，而 BCAA、Tyr 和 Lys 浓度较高。Gly 和 Gln/Glu 与 IS 和 DIFFM 呈正相关，而与 BCAA、AAA 和 Lys 呈相反关系。我们的结论是，低 Gly、低 Gln/Glu 和升高的 BCAA、AAA 和 Lys 的代谢特征可能构成识别有 β 细胞衰竭风险的青少年的生物标志物。