Clinical studies of a bionic pancreas for automated glucose management in cystic fibrosis-related diabetes mellitus

项目摘要 囊性纤维化是最常见的常染色体隐性遗传病，影响高加索人群和 导致进行性肺功能衰退和多器官疾病，导致过早死亡。囊性纤维化- 相关糖尿病(CFRD)影响多达一半的成人CF。CFRD的发展与临床相关 恶化包括肺功能下降、营养状况受损和死亡率增加。 胰岛素是唯一推荐的治疗CFRD的方法，并已被证明可以改善临床状况。 并降低死亡率。CF患者已经背负着管理肺部的重大医疗负担 他们的疾病表现，以及频繁的血糖监测和胰岛素的额外责任 伴随着CFRD的注射通常会导致生活质量的下降和不坚持。其中一个 改善1型糖尿病(T1D)患者血糖调节的最有希望的策略是自动化 使用人工胰腺(AP)设备进行血糖调节。我们已经测试了一种名为仿生的AP设备 T1D受试者的胰腺广泛存在，并已表明它同时降低了两个人的平均血糖 和低血糖，同时减少糖尿病管理所需的工作和提高生活质量。 仿生胰腺有几个独特的特征，使其非常适合AP系统使用 在面板堆石坝人口中。仿生胰腺能快速、自动地适应多种胰岛素 需求，使其非常适合于解决CFRD患者胰岛素需求的波动 在慢性萎缩性胃炎急性加重和糖皮质激素治疗期间。此外，没有必要 计算碳水化合物或通知仿生胰腺何时进餐以达到良好的血糖水平 对照，这对于经常需要高热量、高热量、高热量的CF患者特别有用 碳水化合物餐和零食，以保持足够的营养状态。此外，两种激素 仿生胰腺的配置，可以使用微量的胰高血糖素来预防低血糖时 暂停胰岛素给药不足，可能对预防低血糖特别有用 患有CFRD的患者，由于胰腺纤维化导致低血糖的风险已经很高， 胰升糖素缺乏症。在这项计划中，我们将测试仿生胰腺控制血糖的能力。 CFRD受试者的水平有以下三个目标：(1)我们将测试 两种结构的仿生胰腺，双激素(胰岛素/高血糖素)和仅胰岛素，而不是通常的护理 (2)我们将比较仿生胰腺的长期门诊表现与 常规护理超过6个月，并寻找非血糖改善的初步证据 结果，如肺功能、体重和CF恶化的次数；以及(3)我们将比较 慢性阻塞性肺疾病患者住院期间仿生胰腺对常规血糖的处理 病情恶化，往往与血糖控制困难有关。

Project Summary Cystic fibrosis (CF) is the most common autosomal recessive disease affecting Caucasian populations and causes progressive pulmonary decline and multi-organ disease leading to premature death. Cystic fibrosis- related diabetes (CFRD) affects up to half of adults with CF. Development of CFRD is associated with clinical deterioration including decline in pulmonary function, compromised nutritional status, and increased mortality. Insulin is the only recommended treatment for CFRD and has been demonstrated to improve clinical status and decrease mortality. Patients with CF already carry a significant medical burden managing the pulmonary manifestations of their disease, and the additional onus of frequent blood sugar monitoring and insulin injections that accompanies CFRD often leads to a decline in quality of life and non-adherence. One of the most promising strategies to improve glycemic regulation in people with type 1 diabetes (T1D) is automation of glycemic regulation with artificial pancreas (AP) devices. We have tested an AP device called the bionic pancreas extensively in subjects with T1D and have shown that it simultaneously reduces both mean glucose and hypoglycemia while reducing the work required for diabetes management and improving quality of life. There are several unique features of the bionic pancreas that make it ideally suited among AP systems for use in the CFRD population. The bionic pancreas rapidly and automatically adapts to a wide range of insulin needs, making it well suited to address fluctuations in insulin requirements of those with CFRD that occur during acute CF exacerbations and treatment with glucocorticoids. In addition, it is not necessary to carbohydrate count or inform the bionic pancreas when a meal is going to be eaten to achieve good glycemic control, which will be particularly useful for patients with CF who require frequent high calorie, high carbohydrate meals and snacks to maintain an adequate nutritional status. Moreover, the bihormonal configuration of the bionic pancreas, which can use micro-dose glucagon to prevent hypoglycemia when suspension of insulin delivery is insufficient, may be particularly useful for prevention of hypoglycemia in patients with CFRD, who are already at high risk for hypoglycemia due to pancreatic fibrosis leading to glucagon deficiency. In this proposal we will test the ability of the bionic pancreas to control blood glucose levels in subjects with CFRD with the following three aims: (1) We will test the short-term safety and efficacy of two configurations of the bionic pancreas, bihormonal (insulin/glucagon) and insulin-only, versus usual care in subjects with CFRD; (2) we will compare the long-term outpatient performance of the bionic pancreas versus usual care over a period of 6 months and look for preliminary evidence of improvement in non-glycemic outcomes such as pulmonary function, weight, and number of CF exacerbations; and (3) we will compare the bionic pancreas to usual glycemic inpatient management in patients with CFRD during hospitalizations for CF exacerbations, which are often associated with difficulty in glycemic management.