Noninvasive Blood Glucose Monitoring Using Otoacoustic Emissions

描述（由申请人提供）：项目摘要拟议研究的长期目标是为糖尿病患者开发一种新的方法，以无痛和非侵入性地监测他们的血糖水平。有令人信服的证据表明，当糖尿病患者积极监测和控制他们的血糖水平时，可以避免长期并发症，包括视网膜病变和神经病变。目前的监测技术需要患者刺破手指以提取血液，这可能会阻止患者主动监测其葡萄糖水平。在这个探索性的项目中，提出了一种新的方法用于无创血糖监测。该方法是基于耳声发射（OAE）的测量和分析。OAE是由耳蜗响应于声学刺激而产生的低强度声音。诱发和测量耳声发射是使用一个微型扬声器和麦克风，适合紧贴在耳朵内。文献中有证据表明OAE的时间和光谱分量与血管葡萄糖水平相关。这在一项使用兔子的动物研究中得到了证实。然而，一项调查糖尿病患者OAE和血糖之间联系的研究并未显示出显著相关性。然而，尚未进行考虑抑制OAE的研究。OAE反应可以通过对侧（对耳）、同侧（同耳）或两者同时提供竞争性声刺激而被部分抑制或掩蔽。这种抑制效应已被证明是来自大脑的神经传出反馈的结果。已知神经效应包括诱发反应和轴突传递延迟与葡萄糖相关。这表明，受抑制的OAE可能与葡萄糖具有稳健的相关性，因为抑制是外周神经反馈的结果，并且神经活动受葡萄糖水平的影响。这里提出的初步实验提供了强有力的证据来支持这一假设。该补助金提出了更多更详细的实验和评估。具体目标包括（1）确定诱发和测量与糖尿病和非糖尿病受试者血糖最相关的受抑制OAE的最佳程序，（2）开发参数和非参数模型以预测血糖水平，以及（3）基于临床准确性测量评价预测模型。研究方法包括许多实验，其中糖尿病和非糖尿病受试者将进行葡萄糖耐量试验，同时测量抑制和未抑制的OAE。信号处理算法将应用于OAE波形，以评价测试期间时间和光谱模式与血糖的相关性。将进行对照实验，并独立评估潜在干扰化合物。这项研究的结果最终可能导致未来开发出一种低成本的手持设备，糖尿病患者可以使用这种设备来无痛和无创地监测他们的血糖水平。 项目叙述/相关性：研究表明，糖尿病患者可以通过积极监测血糖水平来显著降低与疾病相关的并发症的风险。然而，许多糖尿病患者无法监测他们的血糖，主要原因是手指酸痛，疼痛，不便或害怕针头。在这个项目中，提出了一种新的方法，使糖尿病患者能够无痛和非侵入性地监测他们的葡萄糖水平，该方法使用从耳朵发出的低强度声音。

DESCRIPTION (provided by applicant): Project Summary The long term objective of the proposed research is to develop a new means for diabetic patients to painlessly and non-invasively monitor their blood glucose levels. There is convincing evidence that when diabetes patients actively monitor and control their blood glucose levels, long term complications including retinopathy and neuropathy can be avoided. Current monitoring technologies require the patient to prick their finger to extract blood, which can discourage a patient from actively monitoring their glucose levels. In this exploratory project, a novel method is proposed for noninvasive glucose monitoring. The method is based on the measurement and analysis of otoacoustic emissions (OAE). The OAE is a low-intensity sound generated by the cochlea in response to acoustic stimuli. Evoking and measuring an OAE is done using a tiny speaker and microphone that fits snugly inside of the ear. There is evidence from the literature that the temporal and spectral components of an OAE correlate with vascular glucose levels. This was confirmed in an animal study using rabbits. A single study investigating the link between OAEs and glucose in human diabetic subjects, however, did not show significant correlation. However, no studies have been performed which considered suppressed OAEs. The OAE response can be partially suppressed or masked by presenting a competing acoustic stimulus either contralaterally (opposite ear), ipsilaterally (same ear), or both. This suppression effect has been shown to be a result of neural efferent feedback from the brain. Neural effects including evoked responses and axonal transmission latencies are known to correlate with glucose. This suggests that suppressed OAEs may provide a robust correlation with glucose since the suppression is a result of peripheral neural feedback, and neural activity is affected by glucose levels. Preliminary experiments presented here provide strong evidence to support this hypothesis. This grant proposes additional more detailed experiments and evaluations. Specific aims include (1) determining optimal procedures for evoking and measuring suppressed OAEs that best correlate with blood glucose in diabetic and nondiabetic subjects, (2) developing parametric and non-parametric models to predict blood glucose levels, and (3) evaluating the prediction models based on clinical accuracy measures. Research methods include a number of experiments in which diabetic and non-diabetic subjects will be given a glucose tolerance test while suppressed and unsuppressed OAEs are measured. Signal processing algorithms will be applied to the OAE waveforms to evaluate how well temporal and spectral patterns correlate with blood glucose during the test. Control experiments will be done and potential interfering compounds will be independently assessed. The outcome from this research could ultimately lead to the future development of a low-cost, hand-held device that would be used by diabetic patients to painlessly and noninvasively monitor their glucose levels. Project Narrative/Relevance:Studies have shown that persons with diabetes can reduce the risk of complications associated with the disease significantly by actively monitoring their blood sugar levels. However, many diabetic patients fail to monitor their blood sugar for the primary reasons of finger soreness, pain, inconvenience, or fear of needles. In this project, a new method for enabling diabetic patients to painlessly and non-invasively monitor their glucose levels is proposed which uses low intensity sounds emitted from the ears.