Continuous Monitoring of Glycemic Oscillations in Interstitial Fluid

描述(申请人提供)：到目前为止，市场上销售的连续血糖监测系统(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。准确性的局限性，特别是在降糖范围内，以及低信噪比，阻碍了这项有前景的技术扩展到筛查应用，以便在疾病临床发作之前识别糖尿病的早期迹象，因此可能会采取预防措施。这项拟议的研究集中在利用酵母-生物传感器杂交技术开发酵母中血糖波动的体外模型。从这个模型得到的信息将被用来确定是否可以在人类的间质液体(ISF)中测量和表征血糖振荡的表现。到目前为止，体内组织间液血糖波动的现象尚未见报道。初步的活体间质液葡萄糖数据，在猪的真皮中测量，揭示了一种振荡现象，可能表明细胞内糖酵解。具体目标包括开发一种模拟体内ISF环境的体外酵母-生物传感器杂交系统。这一独特的混合、连续血糖监测系统将用于开发酵母中的血糖波动模型。来自体外模型的数据将用于开发模式识别算法，以在体内表征1型和2型糖尿病特有的ISF振荡。这项拟议研究的成功完成将提供连续血糖监测技术的进步，这些技术有可能解决使用CGMS的患者遇到的不准确问题。我们相信，拟议中的研究将打破技术障碍，排除将这项技术作为独立系统使用的可能性，扩大筛查和预防性应用的效用，使人工胰腺更接近现实。 公共卫生相关性：连续血糖监测系统(CGM)检测间质液体中血糖波动的潜力将使这项技术的使用进入预防医学领域，因为它提供了一种廉价的筛查工具，能够在明显的临床症状出现之前很久就识别出糖代谢异常的人。拟议的研究结果将使医生能够通过低成本的饮食和生活方式改变来早期干预糖尿病症状的发展，而不是高成本的治疗干预。早期干预将对减少美国医疗系统治疗糖尿病慢性并发症的每年超过2000亿美元的成本产生重大影响。

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.