Continuous Monitoring of Glycemic Oscillations in Interstitial Fluid

描述（由申请人提供）：迄今为止，市场上连续血糖监测系统（cgm）的使用仅限于胰岛素依赖型1型和2型糖尿病患者的血糖趋势分析。准确性的限制，特别是在低血糖范围内，低信噪比阻碍了这项有前途的技术扩展到筛查应用中，在疾病临床发作之前识别糖尿病的早期症状，因此可以采取预防措施。提出的研究重点是利用酵母-生物传感器杂交组合开发酵母血糖振荡的体外模型。从该模型中获得的信息将用于确定是否可以在人的间质液（ISF）中测量和表征血糖振荡的表现。到目前为止，体内间质液血糖振荡现象尚未见报道。在猪真皮中测量的初步体内间质液葡萄糖数据揭示了可能指示细胞内糖酵解的振荡现象。具体目标包括开发体外酵母-生物传感器混合系统，模拟体内ISF环境。这种独特的杂交，连续葡萄糖监测系统将用于开发酵母血糖振荡模型。来自体外模型的数据将用于开发模式识别算法，以表征1型和2型糖尿病特有的体内ISF振荡。该研究的成功完成将为连续血糖监测技术提供进步，有可能解决患者使用cgm时遇到的不准确问题。我们相信，拟议的研究将打破阻碍这项技术作为一个独立系统使用的技术障碍，扩大筛查和预防应用的实用性，这可能使人工胰腺更接近现实。

DESCRIPTION (provided by applicant): To date, the use of marketed continuous glucose monitoring systems (CGMs) are limited to glucose trend analysis by patients with insulin-dependent type 1 and type 2 diabetes. Accuracy limitations, particularly in the hypoglycemic range, and low signal-to-noise ratio have precluded expansion of this promising technology into screening applications to identify early signs of diabetes, prior to clinical onset of disease, so preventive measures may be taken. The proposed research is focused on developing an in vitro model of glycemic oscillations in yeast using a combined yeast-biosensor hybrid. The information derived from this model will be used to determine if manifestations of glycemic oscillations can be measured and characterized within the interstitial fluid (ISF) of humans. So far, the phenomenon of in vivo interstitial fluid glycemic oscillations has not been reported. Preliminary in vivo interstitial fluid glucose data, measured in the dermis of swine, revealed an oscillatory phenomenon that may be indicative of intracellular glycolysis. Included in the Specific Aims is the development of an in vitro yeast-biosensor hybrid system that models the in vivo ISF environment. This unique hybrid, continuous glucose monitoring system will be used to develop a model of glycemic oscillations in yeast. Data from the in vitro model will be used to develop pattern recognition algorithms to characterize in vivo ISF oscillations specific to type 1 and type 2 diabetes. Successful completion of the proposed research will provide advances in continuous glucose monitoring technology that have the potential to resolve inaccuracy issues encountered by patients using CGMs. It is our belief the proposed research will break-down technical barriers that preclude the use of this technology as a stand-alone system with expanded utility for screening and preventative applications that may bring the artificial pancreas on step closer to reality. PUBLIC HEALTH RELEVANCE: The potential for continuous glucose monitoring systems (CGMs) to detect glycemic oscillations in interstitial fluid will advance the use of this technology into the realm of preventative medicine by providing an inexpensive screening tool, capable of identifying people with abnormal glucose metabolism long before overt clinical symptoms are apparent. The outcomes of the proposed research will allow physicians to intervene early in the progression of diabetes symptoms with low cost diet and lifestyle changes as opposed to high cost therapeutic intervention. Early stage intervention will have a significant impact on reducing the over $200 billion annual cost to the US healthcare system to treat the chronic complications of diabetes.