Exhaled Gas Biomarkers of Glucose Metabolism in T2DM subjects

描述（由申请人提供）：在不到30年的时间里，预计将有3.5 - 4亿人受到2型糖尿病（T2 DM）的影响。疾病的管理取决于血糖，胰岛素，血脂和其他代谢变量的血液检查;不幸的是，这些检查通常是痛苦的，可能是不切实际的。我们提出了一种非侵入性的方法来监测血糖调节通过分析挥发性有机化合物（VOCs）在呼出气。我们的一般前提是，在T2 DM中，VOC的呼出模式可能发生重要变化，反映了组织和细胞水平的内源性代谢变化。我们的主要目标有两个方面：（1）在血糖、胰岛素和游离脂肪酸的实验性波动期间，确定健康和T2 DM个体之间呼出气体特征的差异，并推导出这些循环变量的基于呼吸的预测;（2）研究与糖尿病并发症发病机制、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对糖尿病人群产生切实的临床适用影响，因为我们的研究结果将构成将该技术转化为便携式呼吸分析仪的基础，该分析仪可以取代当前基于血液的生物测定，并提供对免疫功能和血糖调节的额外见解，这是现代临床方法学所不可能的。我们还设想，更容易的葡萄糖测试将导致更频繁的监测和更好的血糖控制在数百万糖尿病患者。还可以在难以抽血的人群中进行大规模人群筛查，包括对葡萄糖、胰岛素和脂质进行呼吸测试，从而能够更早地发现和制定更好的预防战略，最终降低与健康有关的总体成本。 公共卫生相关性：全世界糖尿病的患病率已从2000年的1.71亿患者迅速增加到预计到2030年的3.66亿患者（Diabetes Care 2004：1047）。我们建议呼吸气体分析可用于测量全身糖（以及其他关键变量，如胰岛素和胆固醇），并取代目前基于血液的方法，提高患者的依从性，改善疾病的预防和诊断。由于呼出的气体也可能反映细胞功能和代谢的变化，这些新的生物标志物也可以用于监测糖尿病的心血管和免疫系统并发症。

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. PUBLIC HEALTH RELEVANCE: The prevalence of diabetes mellitus worldwide has been rapidly increasing from 171 million patients in 2000 to a projected 366 million people by 2030 (Diabetes Care 2004:1047). We propose that breath gas analysis can be used to measure systemic sugar (and other crucial variables such as insulin and cholesterol) and replace current blood-based methodologies, increasing patient compliance and improve prevention and diagnosis of the disease. As exhaled gases may also reflect changes in cellular function and metabolism, these novel biomarkers may also allow for monitoring cardiovascular and immune system complications of diabetes.