Department of Paediatrics, University of Cambridge, Cambridge, UK.
Lancet. 2010 Feb 27;375(9716):743-51. doi: 10.1016/S0140-6736(09)61998-X. Epub 2010 Feb 4.
Closed-loop systems link continuous glucose measurements to insulin delivery. We aimed to establish whether closed-loop insulin delivery could control overnight blood glucose in young people.
We undertook three randomised crossover studies in 19 patients aged 5-18 years with type 1 diabetes of duration 6.4 years (SD 4.0). We compared standard continuous subcutaneous insulin infusion and closed-loop delivery (n=13; APCam01); closed-loop delivery after rapidly and slowly absorbed meals (n=7; APCam02); and closed-loop delivery and standard treatment after exercise (n=10; APCam03). Allocation was by computer-generated random code. Participants were masked to plasma and sensor glucose. In APCam01, investigators were masked to plasma glucose. During closed-loop nights, glucose measurements were fed every 15 min into a control algorithm calculating rate of insulin infusion, and a nurse adjusted the insulin pump. During control nights, patients' standard pump settings were applied. Primary outcomes were time for which plasma glucose concentration was 3.91-8.00 mmol/L or 3.90 mmol/L or lower. Analysis was per protocol. This trial is registered, number ISRCTN18155883.
17 patients were studied for 33 closed-loop and 21 continuous infusion nights. Primary outcomes did not differ significantly between treatment groups in APCam01 (12 analysed; target range, median 52% [IQR 43-83] closed loop vs 39% [15-51] standard treatment, p=0.06; <or=3.90 mmol/L, 1% [0-7] vs 2% [0-41], p=0.13), APCam02 (six analysed; target range, rapidly 53% [48-57] vs slowly absorbed meal 55% [37-64], p=0.97; <or=3.90 mmol/L, 0% [0-4] vs 0% [0-0], p=0.16]), and APCam03 (nine analysed; target range 78% [60-92] closed loop vs 43% [25-65] control, p=0.0245, not significant at corrected level; <or=3.90 mmol/L, 10% [2-15] vs 6% [0-44], p=0.27). A secondary analysis of pooled data documented increased time in the target range (60% [51-88] vs 40% [18-61]; p=0.0022) and reduced time for which glucose concentrations were 3.90 mmol/L or lower (2.1% (0.0-10.0) vs 4.1% (0.0-42.0); p=0.0304). No events with plasma glucose concentration lower than 3.0 mmol/L were recorded during closed-loop delivery, compared with nine events during standard treatment.
Closed-loop systems could reduce risk of nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.
Juvenile Diabetes Research Foundation; European Foundation for Study of Diabetes; Medical Research Council Centre for Obesity and Related Metabolic Diseases; National Institute for Health Research Cambridge Biomedical Research Centre.
闭环系统将连续血糖测量与胰岛素输送联系起来。我们旨在确定闭环胰岛素输送是否可以控制年轻人的夜间血糖。
我们在 19 名患有 1 型糖尿病的患者中进行了三项随机交叉研究，这些患者的糖尿病病程为 6.4 年（标准差 4.0）。我们比较了标准的连续皮下胰岛素输注和闭环输送（n=13；APCam01）；快速和缓慢吸收的餐后闭环输送（n=7；APCam02）；以及闭环输送和运动后的标准治疗（n=10；APCam03）。分配由计算机生成的随机代码进行。参与者对血浆和传感器葡萄糖进行了屏蔽。在 APCam01 中，研究人员对血浆葡萄糖进行了屏蔽。在闭环夜间，每 15 分钟将血糖测量值输入到计算胰岛素输注率的控制算法中，并由护士调整胰岛素泵。在对照夜间，患者的标准泵设置适用。主要结局是血浆葡萄糖浓度在 3.91-8.00 mmol/L 或 3.90 mmol/L 或更低的时间。分析按方案进行。这项试验已注册，编号为 ISRCTN85126658。
17 名患者接受了 33 次闭环和 21 次连续输注夜间的研究。在 APCam01 中，治疗组之间的主要结局没有显著差异（12 例分析；目标范围，中位数 52%[43-83]闭环与 39%[15-51]标准治疗，p=0.06；<or=3.90 mmol/L，1%[0-7]与 2%[0-41]，p=0.13），APCam02（6 例分析；目标范围，快速 53%[48-57]与缓慢吸收的餐 55%[37-64]，p=0.97；<or=3.90 mmol/L，0%[0-4]与 0%[0-0]，p=0.16）和 APCam03（9 例分析；目标范围 78%[60-92]闭环与 43%[25-65]对照，p=0.0245，在修正水平上无显著性；<or=3.90 mmol/L，10%[2-15]与 6%[0-44]，p=0.27）。对 pooled 数据的二次分析记录了目标范围内的时间增加（60%[51-88]与 40%[18-61]；p=0.0022）和血糖浓度低于 3.90 mmol/L 的时间减少（2.1%[0.0-10.0]与 4.1%[0.0-42.0]；p=0.0304）。与标准治疗相比，在闭环输送期间没有记录到血浆葡萄糖浓度低于 3.0 mmol/L 的事件，而在标准治疗期间记录到了 9 次事件。
闭环系统可以降低 1 型糖尿病儿童和青少年夜间发生低血糖的风险。
青少年糖尿病研究基金会；欧洲糖尿病研究基金会；医学研究委员会肥胖与相关代谢疾病中心；英国国家健康研究所剑桥生物医学研究中心。
