Continuous Monitoring of Glycemic Oscillations in Interstitial Fluid

描述（由申请人提供）：在阶段1中，完成了对固定在葡萄糖传感器表面上的酵母细胞中葡萄糖振荡的测量和表征。使用此作为模型，假设在皮下环境中，细胞（例如，成纤维细胞、脂肪细胞）将非常接近葡萄糖传感器的表面，从而模拟葡萄糖传感器表面上的酵母细胞的体外环境。完成了一项12小时的临床研究，其中组织液中的葡萄糖测量值与参考葡萄糖测量值高度相关。此外，皮下组织内葡萄糖波动的测量显示正常受试者与1型和2型糖尿病患者之间存在明显差异。第2阶段的进一步研究旨在建立一个较长时间段内的测量数据库，以提供表征从正常到糖耐量受损再到2型糖尿病的连续体沿着不同糖尿病状态的方法。从2期人体研究中获得的信息可以提供基于细胞葡萄糖代谢的周期性变化控制胰岛素泵的方法，而不是仅依赖于外周手指针刺血糖测量用于校准目的。动态血糖监测是一项不断发展的革命性技术，有望改善数百万糖尿病患者的生活质量。为了实现其全部潜力，需要通过向胰岛素泵提供生理反馈来用于诊断和控制的更精确的装置。测量葡萄糖的皮下代谢振荡可以为胰岛素泵反馈控制、更准确的葡萄糖测量和诊断葡萄糖耐量受损和胰岛素抵抗阶段的新方法提供缺失的环节。测量和表征间质液中葡萄糖代谢的异常，并将其与已知的葡萄糖代谢缺陷相关联，可能是糖尿病管理的一个重大飞跃，并为发现胰岛素抵抗的遗传和分子起源提供了一种廉价的工具。拟议的2期研究可能会产生一种CGM系统，该系统减少了频繁的手指针刺血糖重新校准的需求，最终导致用户无需校准的CGM，该CGM可以与胰岛素泵连接以形成人工胰腺。

DESCRIPTION (provided by applicant): In Phase 1, measuring and characterizing glucose oscillations in yeast cells immobilized on the surface of a glucose sensor was completed. Using this as a model, it was postulated that within the subcutaneous environment, cells (e.g., fibroblasts, adipocytes) would be in close proximity to the surface of the glucose sensor thereby mimicking the in vitro environment of the yeast cells on the surface of the glucose sensor. A 12- hour clinical study was completed wherein glucose measurements within interstitial fluid were highly correlated with reference glucose measurements. Moreover, measurements of glucose oscillations within subcutaneous tissue showed clear differences between normal subjects and those with type 1 and type 2 diabetes. Further studies in Phase 2 are aimed at building a data base of measurements, over longer time periods, to provide the means for characterizing different states of glycemia along the continuum from normal to impaired glucose tolerance to type 2 diabetes. Information gained from human studies in Phase 2, could provide the means of controlling an insulin pump based on periodic changes in cellular glucose metabolism, rather than relying solely on peripheral fingerstick blood glucose measurements for calibration purposes. Continuous glucose monitoring is an evolving, revolutionary technology that promises to improve the quality of life for millions of people with diabetes. In order to realize its full potential, more accurate devices that can be used for diagnosis and control, by providing physiological feedback to an insulin pump, are required. Measuring subcutaneous metabolic oscillations of glucose could provide a missing link for insulin pump feedback control, more accurate glucose measurements and novel methods for diagnosing stages of impaired glucose tolerance and insulin resistance. Measuring and characterizing aberrations in glucose metabolism within interstitial fluid and correlating them to known defects in glucose metabolism could be a major leap forward in diabetes management and provide an inexpensive tool for discovering new insights into the genetic and molecular origins of insulin resistance. The proposed Phase 2 research may result in a CGM system that reduces the need for frequent fingerstick blood glucose re-calibration eventually leading to a user calibration-free CGM that can be interfaced with an insulin pump to form an artificial pancreas.