Department of Endocrinology, Grenoble University Hospital, INSERM U1055, Grenoble Alpes University, Grenoble, France.
Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes, France; Center for Study and Research for Improvement of the Treatment of Diabetes, Bioparc-Genopole Evry-Corbeil, Evry, France.
Lancet Digit Health. 2019 May;1(1):e17-e25. doi: 10.1016/S2589-7500(19)30003-2. Epub 2019 May 2.
Closed-loop insulin delivery systems are expected to become a standard treatment for patients with type 1 diabetes. We aimed to assess whether the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system improved glucose control compared with sensor-assisted pump therapy.
In this multicentre, open-label, randomised, crossover trial, we recruited adults (aged ≥18 years) with at least a 2 year history of type 1 diabetes, who had been treated with external insulin pump therapy for at least 6 months, had glycated haemoglobin (HbA) of 10% or less (86 mmol/mol), and preserved hypoglycaemia awareness. After a 2-week run-in period, patients were randomly assigned (1:1) with a web-based system in randomly permuted blocks of two, to receive insulin via the hybrid closed-loop system (DBLG1; using a machine-learning-based algorithm) or sensor-assisted pump therapy over 12 weeks of free living, followed by an 8-week washout period and then the other intervention for 12 weeks. The primary outcome was the proportion of time that the sensor glucose concentration was within the target range (3·9-10·0 mmol/L) during the 12 week study period. Efficacy analyses were done in the modified intention-to-treat population, which included all randomly assigned patients who completed both 12 week treatment periods. Safety analyses were done in all patients who were exposed to either of the two treatments at least once during the study. This trial is registered with ClinicalTrials.gov, number NCT02987556.
Between March 3, 2017, and June 19, 2017, 71 patients were screened, and 68 eligible patients were randomly assigned to the DBLG1 group (n=33) or the sensor-assisted pump therapy group (n=35), of whom five dropped out in the washout period (n=1 pregnancy; n=4 withdrew consent). 63 patients completed both 12 week treatment periods and were included in the modified intention-to-treat analysis. The proportion of time that the glucose concentration was within the target range was significantly higher in the DBLG1 group (68·5% [SD 9·4] than the sensor-assisted pump group (59·4% [10·2]; mean difference 9·2% [95% CI 6·4 to 11·9]; p<0·0001). Five severe hypoglycaemic episodes occurred in the DBLG1 group and three episodes occurred in the sensor-assisted pump therapy group, which were associated with hardware malfunctions or human error.
The DBLG1 system improves glucose control compared with sensor-assisted insulin pumps. This finding supports the use of closed-loop technology combined with appropriate health care organisation in adults with type 1 diabetes.
French Innovation Fund, Diabeloop.
闭环胰岛素输送系统有望成为 1 型糖尿病患者的标准治疗方法。我们旨在评估 Diabeloop Generation 1（DBLG1）混合闭环人工胰腺系统是否比传感器辅助泵治疗能更好地控制血糖。
在这项多中心、开放标签、随机、交叉试验中，我们招募了至少有 2 年 1 型糖尿病病史的成年患者（年龄≥18 岁），他们接受外部胰岛素泵治疗至少 6 个月，糖化血红蛋白（HbA）<10%（86mmol/mol），且保留低血糖意识。在 2 周的导入期后，患者通过基于网络的系统以 2 为基数的随机区组进行 1:1 随机分组，接受混合闭环系统（DBLG1；使用基于机器学习的算法）或传感器辅助泵治疗 12 周的自由生活，然后进行 8 周的洗脱期，随后进行 12 周的另一种干预。主要结局是传感器葡萄糖浓度在 12 周研究期间处于目标范围内（3.9-10.0mmol/L）的时间比例。在修改后的意向治疗人群中进行疗效分析，该人群包括所有完成两个 12 周治疗期的随机分配患者。在至少接受过研究中两种治疗之一的所有患者中进行安全性分析。这项试验在 ClinicalTrials.gov 注册，编号为 NCT02987556。
2017 年 3 月 3 日至 6 月 19 日，对 71 名患者进行了筛选，68 名符合条件的患者被随机分配到 DBLG1 组（n=33）或传感器辅助泵治疗组（n=35），其中 5 名在洗脱期脱落（1 例怀孕；4 例撤回同意）。63 名患者完成了两个 12 周的治疗期，并纳入修改后的意向治疗分析。DBLG1 组葡萄糖浓度处于目标范围内的时间比例显著高于传感器辅助泵组（68.5%[9.4]比 59.4%[10.2]；平均差异 9.2%[6.4 至 11.9]；p<0.0001）。DBLG1 组发生 5 例严重低血糖发作，传感器辅助泵治疗组发生 3 例，与硬件故障或人为错误有关。
DBLG1 系统与传感器辅助胰岛素泵相比，可改善血糖控制。这一发现支持在 1 型糖尿病成人中使用闭环技术和适当的医疗保健组织。
法国创新基金、Diabeloop。
