Finan Daniel A, Doyle Francis J, Palerm Cesar C, Bevier Wendy C, Zisser Howard C, Jovanovic Lois, Seborg Dale E
Department of Chemical Engineering, University of California, Santa Barbara, California, USA.
J Diabetes Sci Technol. 2009 Sep 1;3(5):1192-202. doi: 10.1177/193229680900300526.
A model-based controller for an artificial beta cell requires an accurate model of the glucose-insulin dynamics in type 1 diabetes subjects. To ensure the robustness of the controller for changing conditions (e.g., changes in insulin sensitivity due to illnesses, changes in exercise habits, or changes in stress levels), the model should be able to adapt to the new conditions by means of a recursive parameter estimation technique. Such an adaptive strategy will ensure that the most accurate model is used for the current conditions, and thus the most accurate model predictions are used in model-based control calculations.
In a retrospective analysis, empirical dynamic autoregressive exogenous input (ARX) models were identified from glucose-insulin data for nine type 1 diabetes subjects in ambulatory conditions. Data sets consisted of continuous (5-minute) glucose concentration measurements obtained from a continuous glucose monitor, basal insulin infusion rates and times and amounts of insulin boluses obtained from the subjects' insulin pumps, and subject-reported estimates of the times and carbohydrate content of meals. Two identification techniques were investigated: nonrecursive, or batch methods, and recursive methods. Batch models were identified from a set of training data, whereas recursively identified models were updated at each sampling instant. Both types of models were used to make predictions of new test data. For the purpose of comparison, model predictions were compared to zero-order hold (ZOH) predictions, which were made by simply holding the current glucose value constant for p steps into the future, where p is the prediction horizon. Thus, the ZOH predictions are model free and provide a base case for the prediction metrics used to quantify the accuracy of the model predictions. In theory, recursive identification techniques are needed only when there are changing conditions in the subject that require model adaptation. Thus, the identification and validation techniques were performed with both "normal" data and data collected during conditions of reduced insulin sensitivity. The latter were achieved by having the subjects self-administer a medication, prednisone, for 3 consecutive days. The recursive models were allowed to adapt to this condition of reduced insulin sensitivity, while the batch models were only identified from normal data.
Data from nine type 1 diabetes subjects in ambulatory conditions were analyzed; six of these subjects also participated in the prednisone portion of the study. For normal test data, the batch ARX models produced 30-, 45-, and 60-minute-ahead predictions that had average root mean square error (RMSE) values of 26, 34, and 40 mg/dl, respectively. For test data characterized by reduced insulin sensitivity, the batch ARX models produced 30-, 60-, and 90-minute-ahead predictions with average RMSE values of 27, 46, and 59 mg/dl, respectively; the recursive ARX models demonstrated similar performance with corresponding values of 27, 45, and 61 mg/dl, respectively. The identified ARX models (batch and recursive) produced more accurate predictions than the model-free ZOH predictions, but only marginally. For test data characterized by reduced insulin sensitivity, RMSE values for the predictions of the batch ARX models were 9, 5, and 5% more accurate than the ZOH predictions for prediction horizons of 30, 60, and 90 minutes, respectively. In terms of RMSE values, the 30-, 60-, and 90-minute predictions of the recursive models were more accurate than the ZOH predictions, by 10, 5, and 2%, respectively.
In this experimental study, the recursively identified ARX models resulted in predictions of test data that were similar, but not superior, to the batch models. Even for the test data characteristic of reduced insulin sensitivity, the batch and recursive models demonstrated similar prediction accuracy. The predictions of the identified ARX models were only marginally more accurate than the model-free ZOH predictions. Given the simplicity of the ARX models and the computational ease with which they are identified, however, even modest improvements may justify the use of these models in a model-based controller for an artificial beta cell.
用于人工β细胞的基于模型的控制器需要1型糖尿病患者葡萄糖 - 胰岛素动力学的精确模型。为确保控制器在变化条件下(例如,由于疾病导致的胰岛素敏感性变化、运动习惯改变或压力水平变化)的鲁棒性,该模型应能够通过递归参数估计技术适应新条件。这种自适应策略将确保在当前条件下使用最准确的模型,从而在基于模型的控制计算中使用最准确的模型预测。
在一项回顾性分析中,从9名1型糖尿病患者动态条件下的葡萄糖 - 胰岛素数据中识别出经验动态自回归外生输入(ARX)模型。数据集包括从连续血糖监测仪获得的连续(5分钟)血糖浓度测量值、从受试者胰岛素泵获得的基础胰岛素输注速率以及胰岛素推注的时间和剂量,以及受试者报告的用餐时间和碳水化合物含量估计值。研究了两种识别技术:非递归或批处理方法以及递归方法。批处理模型从一组训练数据中识别,而递归识别的模型在每个采样时刻进行更新。两种类型的模型都用于对新的测试数据进行预测。为了进行比较,将模型预测与零阶保持(ZOH)预测进行比较,ZOH预测是通过将当前血糖值在未来p步保持恒定来进行的,其中p是预测时域。因此,ZOH预测是无模型的,并为用于量化模型预测准确性的预测指标提供了一个基础情况。理论上,仅当受试者存在需要模型适应的变化条件时才需要递归识别技术。因此,识别和验证技术使用“正常”数据以及在胰岛素敏感性降低条件下收集的数据进行。后者通过让受试者连续3天自行服用泼尼松药物来实现。递归模型被允许适应这种胰岛素敏感性降低的情况,而批处理模型仅从正常数据中识别。
分析了9名1型糖尿病患者动态条件下的数据;其中6名受试者也参与了研究的泼尼松部分。对于正常测试数据,批处理ARX模型提前30、45和60分钟的预测的平均均方根误差(RMSE)值分别为26、34和40mg/dl。对于以胰岛素敏感性降低为特征的测试数据,批处理ARX模型提前30、60和90分钟的预测的平均RMSE值分别为27、46和59mg/dl;递归ARX模型表现出类似的性能,相应值分别为27、45和61mg/dl。所识别的ARX模型(批处理和递归)产生的预测比无模型的ZOH预测更准确,但只是略微更准确。对于以胰岛素敏感性降低为特征的测试数据,批处理ARX模型预测的RMSE值在预测时域为30、60和90分钟时分别比ZOH预测准确9%、5%和5%。就RMSE值而言,递归模型提前30、60和90分钟的预测分别比ZOH预测准确10%、5%和2%。
在本实验研究中,递归识别的ARX模型对测试数据的预测与批处理模型相似,但并不更优。即使对于以胰岛素敏感性降低为特征的测试数据,批处理和递归模型也表现出相似的预测准确性。所识别的ARX模型的预测仅比无模型的ZOH预测略微更准确。然而,鉴于ARX模型的简单性以及识别它们的计算简便性,即使是适度的改进也可能证明在用于人工β细胞的基于模型的控制器中使用这些模型是合理的。