ABSTRACT Background: Insulin Resistance (IR) affects a quarter of the world's adult population and is a major factor in the pathogenesis of cardio-metabolic disease. Non-invasive sampling of exhaled breath contains metabolic markers indicative of underlying systemic metabolic abnormality. Method: In this pilot study, we implemented a non-invasive breathomics approach, combined with random forest machine learning, to investigate metabolic markers from pre-diabetic Hispanic adolescents with obesity as indicators of abnormal metabolic regulation. Findings: Exhaled breath collection using the ReCIVA breathalyzer is feasible in an adolescent population. We have identified a signature of breath metabolites (breath-IR model) which correlates with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R = 0.95, p <0.001). A strong correlation was also observed between the breath-IR model and the blood glycemic profile (fasting insulin R=0.91, p <0.001 and fasting glucose R=0.80, p <0.001). Among tentatively identified metabolites, limonene, undecane, and 2,7-dimethyl-undecane, significantly cluster individuals based on HOMA-IR (p =0.003, p =0.002, and p<0.001, respectively). Our breath-IR model differentiates between adolescents with and without IR with an area under the receiver operating characteristic curve of 0.87, after cross-validation. Interpretation: Identification of a breath metabolite signature indicative of IR in prediabetic Hispanic adolescents with obesity provides evidence of the utility of exhaled breath metabolomics for assessing systemic metabolic dysregulation. A simple and non-invasive breath-based test has utility as a diagnostic tool for monitoring IR progression, potentially allowing for earlier detection of IR and implementation of early interventions to prevent onset of type 2 diabetes mellitus.

中文翻译：

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糖尿病前期西班牙裔肥胖青少年胰岛素抵抗的呼吸生物标志物

摘要背景：胰岛素抵抗 (IR) 影响世界四分之一的成年人口，是心脏代谢疾病发病机制的主要因素。呼出气的非侵入性采样包含指示潜在全身代谢异常的代谢标志物。方法：在这项试点研究中，我们实施了一种非侵入性呼吸组学方法，结合随机森林机器学习，研究了肥胖症前期糖尿病西班牙裔青少年的代谢标志物，作为异常代谢调节的指标。结果：使用 ReCIVA 呼气分析仪收集呼气在青少年人群中是可行的。我们已经确定了与胰岛素抵抗的稳态模型评估 (HOMA-IR) 相关的呼吸代谢物的特征（呼吸 IR 模型）（R = 0.95，p <0.001）。在呼吸 IR 模型和血糖曲线之间也观察到了很强的相关性（空腹胰岛素 R=0.91，p <0.001 和空腹血糖 R=0.80，p <0.001）。在初步鉴定的代谢物中，柠檬烯、十一烷和 2,7-二甲基十一烷，基于 HOMA-IR 显着地将个体聚类（分别为 p =0.003、p =0.002 和 p<0.001）。在交叉验证后，我们的呼吸 IR 模型区分了有和没有 IR 的青少年，受试者操作特征曲线下的面积为 0.87。解释：在患有肥胖症的前驱糖尿病西班牙裔青少年中鉴定出指示 IR 的呼吸代谢物特征提供了呼气代谢组学用于评估全身代谢失调的效用的证据。