Continuous Monitoring of Glycemic Oscillations in Interstitial Fluid

描述(由申请人提供)：在第一阶段，完成了固定在葡萄糖传感器表面的酵母细胞中葡萄糖振荡的测量和表征。以此作为模型，假设在皮下环境中，细胞(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酵母细胞的体外环境。完成了一项12小时的临床研究，其中间质液中的血糖测量与参考血糖测量高度相关。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。第二阶段的进一步研究旨在建立一个更长时间段的测量数据库，以提供表征从正常到糖耐量受损到2型糖尿病的连续过程中不同血糖状态的手段。从第二阶段的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来控制胰岛素泵的方法，而不是仅仅依靠外周手指血糖测量来进行校准。持续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。为了充分发挥其潜力，需要更精确的设备，通过向胰岛素泵提供生理反馈来进行诊断和控制。测量皮下葡萄糖代谢波动可以为胰岛素泵反馈控制、更准确的血糖测量以及诊断糖耐量受损和胰岛素抵抗阶段的新方法提供缺失的一环。测量和表征组织液中葡萄糖代谢的异常，并将它们与已知的葡萄糖代谢缺陷联系起来，可能是糖尿病治疗的重大飞跃，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新工具。拟议的第二阶段研究可能会产生一种CGM系统，它可以减少频繁的手指血糖重新校准的需要，最终导致用户无需校准的CGM，它可以与胰岛素泵接口形成人工胰腺。

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.