Advanced Artificial Pancreas Systems to Enable Fully Automated Glycemic Control in Type 1 Diabetes Mellitus

项目摘要 尽管自动胰岛素递送系统的进步显示出优越的血糖 结果，具有挑战性的临床问题仍然是对准确碳水化合物的持续需求 计数和进餐通知结合慢效皮下胰岛素 会导致反复出现的餐后高血糖。这一血糖水平的临床差距 拟议的项目解决了控制问题。我们打算利用我们现有的进步 在模式识别和预期中，改进和测试一种全自动闭环系统，该闭环系统 不需要用餐通知。这个系统的独特之处在于它依赖于模式 以预期的方式识别，特别是周围的食物，以便胰岛素的作用是 在预期的用餐前服用，而不是主要的反应性解决方案 经常被提议。我们打算在加速的背景下进一步测试和调整这一系统 胰岛素通过以下方式进一步改善血糖结果并消除使用这些系统的障碍 减轻疾病管理负担。 我们已经开发了全自动闭环系统所需的基础工具，并 将计划通过利用我们积累的临床研究数据库中的数据来进一步完善。 我们计划进行2项试点研究，然后进行为期7个月的更大规模的主要研究，以评估 本提案的具体目标如下： 1)我们假设，新的快速起作用的胰岛素类似物可以安全地用于提供更多 有效的全自动闭环控制。我们的第一个飞行员将测试FIAsp和 以及监督试验中天冬氨酸的新配方(AT247)。这一试验结果将通知 后续试验中使用的胰岛素的选择。 2)我们假设，通过适应这些新的胰岛素配方的设计，完全自动化 闭环控制是混合闭环系统的一种有效的临床替代方案，目前的状态- 最先进的系统。 3)最后，我们假设进一步增加血糖紊乱预期(例如，一般 到这个全自动的闭环控制系统将会进一步改进 与无干扰的全自动闭环系统的血糖结果比较 期待。

PROJECT ABSTRACT Despite advancements in automated insulin delivery systems that demonstrate superior glycemic outcomes, challenging clinical issues remain with the continued need for accurate carbohydrate counting and meal announcement combined with slow-acting subcutaneous insulin that contribute to repeated occurrences of postprandial hyperglycemia. This clinical gap in glycemic control is addressed by the proposed project. We intend to leverage our existing advancements in pattern recognition and anticipation to refine and test a fully automated closed-loop system that does not require meal announcements. This system is unique in that it relies on pattern recognition, particularly surrounding meals, in an anticipatory manner so that insulin action is taken in advance of an expected meal rather than the predominantly reactive solutions that are often proposed. We intend to further test and tune this system within the context of accelerated insulins to further improve glycemic outcomes and remove barriers to use of these systems by lowering burden of disease management. We have already developed the foundational tools needed for a fully automated closed-loop and will plan for further refinement by leveraging data from our accumulated clinical studies database. We plan to conduct 2 pilots studies followed by a larger, 7-month main study to evaluate the following specific aims of this proposal: 1) We hypothesize that novel faster acting insulin analogs can be safely used to provide more effective fully automated closed-loop control. Our first pilot will test the differences between Fiasp and a novel formulation of aspart (AT247) in a supervised trial. This trial results will inform the selection of the insulin used in the subsequent trials. 2) We hypothesize that, with a design adapted to these new insulin formulations, fully automated closed-loop control is a valid clinical alternative to hybrid closed-loop systems, the current state- of-the-art systems. 3) Lastly, we hypothesize that further adding glycemic disturbance anticipation (e.g. generally surrounding meals) to this fully automated closed-loop control system will further improve glycemic outcomes compared with a fully automated closed-loop system without disturbance anticipation.