Exhaled Gas Biomarkers of Glucose Metabolism in T2DM subjects

描述(申请人提供)：在不到30年的时间里，预计将有3.5亿-4亿人受到2型糖尿病(T2 DM)的影响。这种疾病的治疗取决于血糖、胰岛素、血脂和其他代谢变量的血液测试；不幸的是，这些测试通常是痛苦的，而且可能不切实际。我们提出了一种非侵入性的方法，通过分析呼气中的挥发性有机化合物(VOCs)来监测血糖调节。我们的总前提是，在T2 DM中，VOCs的呼出模式可能会发生重要的变化，反映组织和细胞水平的内源性代谢变化。 我们的主要目标将有两个：(1)确定健康人和T2 DM患者在血糖、胰岛素和游离脂肪酸实验性波动期间呼出气体的差异，并得出基于呼吸的这些循环变量的预测；(2)研究与糖尿病并发症、VOC排放和中性粒细胞功能反应模式相关的气体-细胞相互作用的新机制。 该项目的下游发展可能会对糖尿病人群产生切实的、临床适用的影响，因为我们的发现将构成将这项技术转化为便携式呼吸分析仪的基础，该分析仪可以取代目前基于血液的生物分析，并提供现代临床方法无法提供的关于免疫功能和糖调节的更多见解。我们还设想，更容易的血糖测试将导致数百万糖尿病患者更频繁的监测和更好的血糖控制。还可以在抽血困难的人群中进行大规模人群筛查，不仅包括血糖的呼气测试，还包括胰岛素和血脂的呼气测试，从而能够更早地发现并制定更好的预防策略，最终降低与健康相关的总体成本。

DESCRIPTION (provided by applicant): In less than 30 years, 350-400 million people are projected to be affected by Type 2 Diabetes Mellitus (T2DM). Management of the disease hinges on blood tests for glucose, insulin, lipids, and other metabolic variables; unfortunately, these tests are often painful and may be impractical. We propose a non-invasive approach to monitoring glucose regulation via the analysis of volatile organic compounds (VOCs) in exhaled breath. Our general premise is that in T2DM, important changes may occur in the exhaled patterns of VOCs, reflecting endogenous metabolic changes at the tissue and cellular levels. Our main objectives will be two-fold: (1) define differences in exhaled breath gas profiles between healthy and T2DM individuals during experimental fluctuations of plasma glucose, insulin, and free fatty acids and derive breath-based predictions of these circulating variables; (2) investigate novel mechanisms of gas-cell interactions relevant to the pathogenesis of diabetes complications, VOC emission and functional response patterns in neutrophils. The downstream evolution of this project may have a tangible, clinically applicable impact on diabetic populations, as our findings will constitute the basis for the translation of this technology into portable breath analyzers that could replace current blood-based bioassays and provide additional insight on immunofunctionality and glucoregulation that is not possible with modern clinical methodologies. We also envision that easier glucose testing will result in more frequent monitoring and better glycemic control in millions of diabetic patients. Large population screenings, including breath tests for not only glucose but also insulin and lipids, could also be conducted in populations for which blood draws would be difficult, allowing earlier detection and better prevention strategies to ultimately reduce overall health-related costs.