Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Wellcome Trust MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Lancet. 2015 Feb 26;385 Suppl 1:S96. doi: 10.1016/S0140-6736(15)60411-1.
The closed-loop system (artificial pancreas) delivers insulin in a glucose-responsive manner by the use of a control algorithm that automatically directs insulin delivery, based on real-time sensor glucose concentrations. Results from hospital-based studies have shown improved overnight glucose control and reduced risk of hypoglycaemia in type 1 diabetes. We aimed to assess whether unsupervised closed-loop systems can provide a realistic treatment option in patients with type 1 diabetes.
We combined data from two open-label, phase 2, randomised, cross-over, unsupervised home trials of people with type 1 diabetes, one in 24 adults (mean age 43 years [SD 12], HbA1c 8·0% [0·9]) and the other in 16 adolescents (15·6 [3·6], 8·1 [0·8]). In each trial, after training on study devices, participants were allocated to two periods of sensor-augmented pump therapy either with or without overnight closed loop that used a model predictive control algorithm to direct insulin delivery. Allocation sequence was done with a computer-generated random code. Each period lasted 4 weeks in adults and 3 weeks in adolescents. Primary outcome for both trials was time when sensor glucose was in the target range (3·9-8·0 mmol/L). Analysis was by intention to treat. Participants (or parents) gave written informed consent. The trials are registered with ClinicalTrials.gov, numbers NCT01440140 and NCT01221467.
Closed loop was started by participants on their own volition on 866 (89%) of 978 nights. The proportion of time when sensor glucose was in the target range between 0000 h and 0800 h was increased by a mean of 18·4% (95% CI 13·5-23·4, p<0·0001) during closed loop compared with no closed loop. Closed loop significantly reduced mean overnight sensor glucose by 0·9 mmol/L (95% CI 0·4-1·3, p=0·0001), and reduced the proportion of time when sensor glucose values were suggestive of hyperglycaemia (>8·0 mmol/L) (15·9%, 10·7-21·0; p<0·0001) and hypoglycaemia (<3·9 mmol/L) (median 0·9, IQR 0·2-2·2; p=0·014). Lower mean overnight glucose was associated with increased overnight insulin delivery (p<0·0001) without changing total daily insulin amount (p=0·84).
Extended use of overnight closed loop at home without supervision is feasible in adults and adolescents with type 1 diabetes. Clinically significant reduction in overnight glucose was observed accompanied by reduced time spent by patients in hypoglycaemia. To our knowledge, such combined effect has not been documented with any other means of intensified conventional insulin delivery. Longer term studies are warranted to assess its clinical potential.
Diabetes UK, Juvenile Diabetes Research Foundation, NIHR Cambridge Biomedical Research Centre.
闭环系统（人工胰腺）通过使用基于实时传感器葡萄糖浓度的自动指导胰岛素输送的控制算法，以葡萄糖反应的方式输送胰岛素。基于医院的研究结果表明，1 型糖尿病患者的夜间血糖控制得到改善，低血糖风险降低。我们旨在评估无监督闭环系统是否可以为 1 型糖尿病患者提供现实的治疗选择。
我们结合了两项针对 1 型糖尿病患者的开放标签、2 期、随机、交叉、无监督家庭试验的数据，一项针对 24 名成年人（平均年龄 43 岁[标准差 12]，HbA1c8.0%[0.9]），另一项针对 16 名青少年（15.6[3.6]，8.1[0.8]）。在每项试验中，在使用研究设备进行培训后，参与者被分配到两个具有或不具有夜间闭环的传感器增强型泵治疗期，其中闭环使用模型预测控制算法来指导胰岛素输送。分配顺序由计算机生成的随机代码完成。在成年人中，每个时期持续 4 周，在青少年中持续 3 周。两项试验的主要结果均为传感器葡萄糖处于目标范围内的时间（3.9-8.0mmol/L）。分析采用意向治疗。参与者（或其父母）给予书面知情同意。试验在 ClinicalTrials.gov 上注册，编号分别为 NCT01440140 和 NCT01221467。
在 978 个夜晚中的 866 个（89%），闭环是由参与者自愿启动的。与无闭环相比，在闭环期间，传感器葡萄糖在 00:00 至 08:00 之间处于目标范围内的时间比例平均增加了 18.4%（95%CI 13.5-23.4，p<0.0001）。闭环显著降低了平均夜间传感器葡萄糖 0.9mmol/L（95%CI 0.4-1.3，p=0.0001），并降低了传感器葡萄糖值提示高血糖（>8.0mmol/L）的时间比例（15.9%，10.7-21.0；p<0.0001）和低血糖（<3.9mmol/L）（中位数 0.9，IQR 0.2-2.2；p=0.014）。夜间平均葡萄糖降低与夜间胰岛素输送增加相关（p<0.0001），而不改变每日总胰岛素量（p=0.84）。
在没有监督的情况下，在家中长时间使用夜间闭环是可行的，适用于 1 型糖尿病的成年人和青少年。观察到夜间血糖显著降低，同时患者低血糖时间减少。据我们所知，这种综合效果以前没有通过任何其他强化常规胰岛素输送手段记录过。需要进行更长时间的研究来评估其临床潜力。
英国糖尿病协会、青少年糖尿病研究基金会、英国国家健康研究所剑桥生物医学研究中心。
