El-Khatib Firas H, Jiang John, Damiano Edward R
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
J Diabetes Sci Technol. 2009 Jul 1;3(4):789-803. doi: 10.1177/193229680900300428.
We sought to test the feasibility and efficacy of bihormonal closed-loop blood glucose (BG) control that utilizes subcutaneous (SC) infusion of insulin and glucagon, a model-predictive control algorithm for determining insulin dosing, and a proportional-derivative control algorithm for determining glucagon dosing.
Thirteen closed-loop experiments (approximately 7-27 h in length) were conducted in six ambulatory diabetic pigs weighing 26-50 kg. In all experiments, venous BG was sampled through a central line in the vena cava. Efficacy was evaluated in terms of the controller's ability to regulate BG in response to large meal disturbances ( approximately 5 g of carbohydrate per kilogram of body mass per meal) based only on regular frequent venous BG sampling and requiring only the subject's weight for initialization.
Closed-loop results demonstrated successful BG regulation to normoglycemic range, with average insulin-to-carbohydrate ratios between approximately 1:20 and 1:40 U/g. The total insulin bolus doses averaged approximately 6 U for a meal containing approximately 6 g per kilogram body mass. Mean BG values in two 24 h experiments were approximately 142 and approximately 155 mg/dl, with the total daily dose (TDD) of insulin being approximately 0.8-1.0 U per kilogram of body mass and the TDD of glucagon being approximately 0.02-0.05 mg. Results also affirmed the efficacy of SC doses of glucagon in staving off episodic hypoglycemia.
We demonstrate the feasibility of bihormonal closed-loop BG regulation using a control system that employs SC infusion of insulin and glucagon as governed by an algorithm that reacts only to BG without any feed-forward information regarding carbohydrate consumption or physical activity. As such, this study can reasonably be regarded as the first practical implementation of an artificial endocrine pancreas that has a hormonally derived counterregulatory capability.
我们试图测试双激素闭环血糖（BG）控制的可行性和有效性，该控制方法利用皮下（SC）输注胰岛素和胰高血糖素、一种用于确定胰岛素剂量的模型预测控制算法以及一种用于确定胰高血糖素剂量的比例 - 微分控制算法。
在6头体重26 - 50 kg的非卧床糖尿病猪身上进行了13次闭环实验（时长约7 - 27小时）。在所有实验中，通过腔静脉的中心静脉导管采集静脉血中的血糖。仅基于定期频繁的静脉血糖采样且仅需受试者体重进行初始化，根据控制器应对大餐干扰（每餐每千克体重约5克碳水化合物）来调节血糖的能力评估有效性。
闭环结果表明成功将血糖调节至正常血糖范围，胰岛素与碳水化合物的平均比例约为1:20至1:40 U/g。对于每餐每千克体重约含6克碳水化合物的餐食，胰岛素总推注剂量平均约为6 U。两次24小时实验中的平均血糖值分别约为142和155 mg/dl，胰岛素每日总剂量（TDD）约为每千克体重0.8 - 1.0 U，胰高血糖素的TDD约为0.02 - 0.05 mg。结果还证实了皮下注射胰高血糖素在预防间歇性低血糖方面的有效性。
我们证明了使用一种控制系统进行双激素闭环血糖调节的可行性，该系统采用皮下输注胰岛素和胰高血糖素，由一种仅对血糖做出反应而无任何关于碳水化合物消耗或身体活动的前馈信息的算法控制。因此，本研究可合理地被视为具有激素衍生的反调节能力的人工内分泌胰腺的首次实际应用。
