Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.
Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.
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DOI：
10.1016/s0140-6736(16)32567-3
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发表时间：
2017-01-28
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通讯作者：
Russell SJ
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作者：
El-Khatib FH;Balliro C;Hillard MA;Magyar KL;Ekhlaspour L;Sinha M;Mondesir D;Esmaeili A;Hartigan C;Thompson MJ;Malkani S;Lock JP;Harlan DM;Clinton P;Frank E;Wilson DM;DeSalvo D;Norlander L;Ly T;Buckingham BA;Diner J;Dezube M;Young LA;Goley A;Kirkman MS;Buse JB;Zheng H;Selagamsetty RR;Damiano ER;Russell SJ
使用胰岛素和胰高血糖素的连续、昼夜自动血糖控制系统的安全性和有效性尚未在自由生活、家庭使用的环境中得到证实。我们的目的是评估仅以体重初始化的双激素仿生胰腺是否可以安全地降低1型糖尿病成人患者的平均血糖和低血糖，这些患者住在家里，没有饮食或身体活动的限制，参与正常的日常生活。我们对18岁以上的1型糖尿病患者进行了一项随机交叉研究，他们居住在距离美国四个地点30分钟车程的地方。参与者被随机分配（1:1）为两组，使用顺序编号的密封信封，首先使用双激素仿生胰腺或常规护理（传统或传感器增强胰岛素泵治疗）进行血糖调节，然后进行相反的干预。两个研究期都是11天，在此期间参与者继续进行所有正常活动，包括运动和驾驶。仿生胰腺的初始值仅为参与者的体重。自主自适应给药算法使用来自连续血糖监测仪的数据来控制胰岛素和胰高血糖素的皮下递送。主要结果是平均葡萄糖浓度和连续血糖监测（CGM）的时间，葡萄糖浓度低于3.3 mmol/L，在2-11天内分析完成两个阶段研究的参与者。该试验已在ClinicalTrials.gov注册，编号NCT02092220。我们在2014年5月6日至2015年7月3日期间随机分配了43名参与者，其中39人完成了研究：20人首先被分配到仿生胰腺组，19人首先被分配到比较组。仿生胰腺期CGM葡萄糖平均浓度为7.8 mmol/L (SD 0.6)，而对照组为9.0 mmol/L(1.6)（差异为1.1 mmol/L， 95% CI为0.7 - 1.6,p< 0.0001）；仿生胰腺期CGM葡萄糖浓度低于3.3 mmol/L的平均时间为0.6%(0.6)，对照组为1.9%(1.7)（差异为1.3%，95% CI为0.8 - 1.8,p< 0.0001）。仿生胰腺组恶心视觉模拟评分（0 - 10分）平均评分（0.52 [SD 0.83]）高于对照组（0.05[0.17]；差异0.47,95% CI 0.21 - 0.73; p= 0.0024）。不同时期的体重和实验室参数没有差异。在仿生胰腺研究期间未发生严重或意外的不良事件。相对于传统和传感器增强胰岛素泵治疗，双激素仿生胰腺，初始化仅与参与者的体重，能够实现优越的血糖调节，而不需要碳水化合物计数。需要更大规模和更长期的研究来确定使用双激素仿生胰腺进行自动血糖管理的长期益处和风险。美国国立卫生研究院糖尿病、消化和肾脏疾病研究所，以及美国国家促进转化科学中心。
The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant’s body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.