Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Paediatrics, University of Cambridge, Cambridge, UK.
Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; Department of Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Manchester University NHS Foundation Trust and University of Manchester, Manchester, UK.
Lancet. 2018 Oct 13;392(10155):1321-1329. doi: 10.1016/S0140-6736(18)31947-0. Epub 2018 Oct 3.
The achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.
In this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA] 7·5-10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9-10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.
From May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA was reduced from a screening value of 8·3% (SD 0·6) to 8·0% (SD 0·6) after the 4-week run-in, and to 7·4% (SD 0·6) after the 12-week intervention period. In the control group, the HbA values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The time spent with glucose concentrations below 3·9 mmol/L (mean difference in change -0·83 percentage points, -1·40 to -0·16; p=0·0013) and above 10·0 mmol/L (mean difference in change -10·3 percentage points, -13·2 to -7·5; p<0·0001) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change -0·4%, 95% CI -1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI -0·005 to 0·067; p=0·09) and bodyweight did not differ (mean difference in change 0·68 kg, 95% CI -0·34 to 1·69; p=0·19). No severe hypoglycaemia occurred. One diabetic ketoacidosis occurred in the closed-loop group due to infusion set failure. Two participants in each study group had significant hyperglycaemia, and there were 13 other adverse events in the closed-loop group and three in the control group.
Hybrid closed-loop insulin delivery improves glucose control while reducing the risk of hypoglycaemia across a wide age range in patients with suboptimally controlled type 1 diabetes.
JDRF, NIHR, and Wellcome Trust.
1 型糖尿病患者的血糖控制仍然具有挑战性。我们评估了日夜混合闭环胰岛素输注与传感器增强型胰岛素泵治疗在血糖控制不理想（糖化血红蛋白 [HbA] 7.5-10.0%）的 6 岁及以上 1 型糖尿病患者中的有效性。
这是一项开放标签、多中心、多国、单周期、平行随机对照试验，参与者来自英国四家医院和美国两家中心的糖尿病门诊。我们将接受胰岛素泵治疗且血糖控制不理想（HbA 7.5-10.0%）的 6 岁及以上的 1 型糖尿病患者随机分为混合闭环治疗组或传感器增强型胰岛素泵治疗组，在 12 周的自由生活中接受治疗。在 4 周的导入期内进行研究胰岛素泵和连续血糖监测的培训。使用中央随机软件进行合格受试者的随机分配。两组研究均为非盲法，按中心分层，低（<8.5%）或高（≥8.5%）HbA 分层。主要终点是随机分组后 12 周时葡萄糖浓度在 3.9-10.0mmol/L 目标范围内的时间比例。对主要结局和安全性措施的分析在所有随机患者中进行。该试验在 ClinicalTrials.gov 注册，编号为 NCT02523131，现已停止入组。
从 2016 年 5 月 12 日至 2017 年 11 月 17 日，共有 114 人接受了筛选，86 名符合条件的患者被随机分配接受混合闭环治疗组（n=46）或传感器增强型胰岛素泵治疗组（n=40；对照组）。闭环组葡萄糖浓度在目标范围内的时间比例明显高于对照组（65%，SD 8）（54%，SD 9；差值 10.8 个百分点，95%CI 8.2-13.5；p<0.0001）。在闭环组中，HbA 从筛查值 8.3%（SD 0.6）降至 4 周导入期后的 8.0%（SD 0.6），再降至 12 周干预期后的 7.4%（SD 0.6）。在对照组中，HbA 值在筛查时为 8.2%（SD 0.5），导入期后为 7.8%（SD 0.6），干预后为 7.7%（SD 0.5）；与对照组相比，闭环组的 HbA 百分比降低幅度明显更大（差值 0.36%，95%CI 0.19-0.53；p<0.0001）。闭环组血糖浓度低于 3.9mmol/L（差值-0.83 个百分点，-1.40 至-0.16；p=0.0013）和高于 10.0mmol/L（差值-10.3 个百分点，-13.2 至-7.5；p<0.0001）的时间比例明显短于对照组。传感器测量的血糖变异系数在两种干预措施之间没有差异（差值-0.4%，95%CI -1.4%至 0.7%；p=0.50）。同样，总日胰岛素剂量也没有差异（差值 0.031U/kg/天，95%CI -0.005 至 0.067；p=0.09），体重也没有差异（差值 0.68kg，95%CI -0.34 至 1.69；p=0.19）。没有发生严重的低血糖。由于输注套件故障，闭环组发生 1 例糖尿病酮症酸中毒。两组各有 1 名患者发生显著高血糖，闭环组有 13 例其他不良事件，对照组有 3 例。
混合闭环胰岛素输注可改善血糖控制，同时降低血糖控制不理想的 1 型糖尿病患者的低血糖风险，适用年龄范围较广。
JDRF、NIHR 和威康信托基金会。
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