University of Virginia, Center for Diabetes Technology, Charlottesville, Virginia, USA.
Diabetes. 2012 Sep;61(9):2230-7. doi: 10.2337/db11-1445. Epub 2012 Jun 11.
Integrated closed-loop control (CLC), combining continuous glucose monitoring (CGM) with insulin pump (continuous subcutaneous insulin infusion [CSII]), known as artificial pancreas, can help optimize glycemic control in diabetes. We present a fundamental modular concept for CLC design, illustrated by clinical studies involving 11 adolescents and 27 adults at the Universities of Virginia, Padova, and Montpellier. We tested two modular CLC constructs: standard control to range (sCTR), designed to augment pump plus CGM by preventing extreme glucose excursions; and enhanced control to range (eCTR), designed to truly optimize control within near normoglycemia of 3.9-10 mmol/L. The CLC system was fully integrated using automated data transfer CGM→algorithm→CSII. All studies used randomized crossover design comparing CSII versus CLC during identical 22-h hospitalizations including meals, overnight rest, and 30-min exercise. sCTR increased significantly the time in near normoglycemia from 61 to 74%, simultaneously reducing hypoglycemia 2.7-fold. eCTR improved mean blood glucose from 7.73 to 6.68 mmol/L without increasing hypoglycemia, achieved 97% in near normoglycemia and 77% in tight glycemic control, and reduced variability overnight. In conclusion, sCTR and eCTR represent sequential steps toward automated CLC, preventing extremes (sCTR) and further optimizing control (eCTR). This approach inspires compelling new concepts: modular assembly, sequential deployment, testing, and clinical acceptance of custom-built CLC systems tailored to individual patient needs.
闭环整合控制（CLC），将连续血糖监测（CGM）与胰岛素泵（持续皮下胰岛素输注[CSII]）结合在一起，被称为人工胰腺，可帮助优化糖尿病患者的血糖控制。我们提出了 CLC 设计的基本模块化概念，通过在弗吉尼亚大学、帕多瓦大学和蒙彼利埃大学的 11 名青少年和 27 名成年人的临床研究中进行了说明。我们测试了两种模块化 CLC 结构：标准控制到范围（sCTR），旨在通过防止血糖剧烈波动来增强泵加 CGM；增强控制到范围（eCTR），旨在在接近 3.9-10mmol/L 的正常血糖范围内真正优化控制。CLC 系统使用自动数据传输 CGM→算法→CSII 实现了完全整合。所有研究均采用随机交叉设计，在包括进餐、夜间休息和 30 分钟运动的相同 22 小时住院期间比较 CSII 与 CLC。sCTR 将接近正常血糖的时间从 61%显著提高到 74%，同时将低血糖降低 2.7 倍。eCTR 将平均血糖从 7.73mmol/L 改善至 6.68mmol/L，同时不增加低血糖，达到 97%的接近正常血糖和 77%的严格血糖控制，夜间变异性降低。总之，sCTR 和 eCTR 代表了向自动化 CLC 的逐步发展，预防极端情况（sCTR）并进一步优化控制（eCTR）。这种方法激发了引人注目的新概念：模块化组装、顺序部署、测试以及基于个体患者需求定制的 CLC 系统的临床接受度。
