Development of a multi-parametric model predictive control algorithm for insulin delivery in type 1 diabetes mellitus using clinical parameters

A multi-parametric model predictive control (mpMPC) algorithm for subcutaneous insulin delivery for individuals with type 1 diabetes mellitus (T1DM) that is computationally efficient, robust to variations in insulin sensitivity, and involves minimal burden for the user is proposed. System identification was achieved through impulse response tests feasible for ambulatory conditions on the UVa/Padova simulator adult subjects with T1DM. An alternative means of system identification using readily available clinical parameters was also investigated. A safety constraint was included explicitly in the algorithm formulation using clinical parameters typical of those available to an attending physician. Closed-loop simulations were carried out with daily consumption of 200 g carbohydrate. Controller robustness was assessed by subject/model mismatch scenarios addressing daily, simultaneous variation in insulin sensitivity and meal size with the addition of Gaussian white noise with a standard deviation of 10%. A second-order-plus-time-delay transfer function model fit the validation data with a mean (coefficient of variation) root-mean-square-error (RMSE) of 26 mg/dL (19%) for a 3 h prediction horizon. The resulting control law maintained a low risk Low Blood Glucose Index without any information about carbohydrate consumption for 90% of the subjects. Low-order linear models with clinically meaningful parameters thus provided sufficient information for a model predictive control algorithm to control glycemia. The use of clinical knowledge as a safety constraint can reduce hypoglycemic events, and this same knowledge can further improve glycemic control when used explicitly as the controller model. The resulting mpMPC algorithm was sufficiently compact to be implemented on a simple electronic device.     

A learning automata-based blood glucose regulation mechanism in type 2 diabetes

This paper proposes a learning automata-based mechanism for blood glucose regulation in type 2 diabetics. The proposed mechanism takes into account the past history of the blood glucose level to determine the correct dosage of the insulin. This method uses the learning automata theory to predict the required dosage of insulin and records the patient history in parameters of a Gaussian probability distribution function. The parameters of the distribution function are updated based on the difference between the actual glucose level regulated by the learning automata and the normal range in such a way that the gap between the actual glucose level and the normal one is minimized. As the proposed algorithm proceeds, it can be seen that it converges to the optimal insulin dosage that keeps the glucose level in normal range for a long time. Convergence of the proposed algorithm to the optimal insulin dosage is theoretically proven. A clinical study is conducted to show the performance of the proposed insulin therapy system for regulation of the blood glucose level of type 2 diabetics.     

An augmented subcutaneous type 1 diabetic patient modelling and design of adaptive glucose control

In the present work, an augmented subcutaneous (SC) model of type 1 diabetic patients (T1DP) is proposed first by estimating the model parameters with the aid of nonlinear least square method using the physiological data. Next, a nonlinear adaptive controller is proposed to tackle two important issues of intra-patient variability (IPV) and uncertain meal disturbance (MD). The proposed patient model agrees quite well with the responses of one of the most popular existing nonlinear model used in the research of artificial pancreas. Further, the developed adaptive control is shown to be capable of providing desired glycemic control without feed-forward action for meal compensation or safety algorithms to avoid hypoglycemia. Due to the simple structure and capability of handling intra-patient variability of the adaptive controller, it can find immediate applicability in the development of the in-silico artificial pancreas.     

数据挖掘在2型糖尿病数据处理中的应用

基于大量实测数据探索2型糖尿病的发病规律,寻求其有效的数据处理方法。将数据挖掘技术引入到2型糖尿病数据处理中得出决策分类树,再同医学认识相对照。利用11400条实测数据,采用C4．5算法得出分类树,经实验患病人群的正确识别率为80．90％,未患病人群的正确识别率为92．05％。给出的决策分类树同目前医学上认识的高危因素趋于一致,同时给出了血糖值等于5．85的临界性数值。数据挖掘方法的引入为2型糖尿病数据处理提供了一种新的方法,为其预警、干预和有效控制提供了一种新的解决方案。     

Entropy analysis of muscular near-infrared spectroscopy (NIRS) signals during exercise programme of type 2 diabetic patients: Quantitative assessment of muscle metabolic pattern

Diabetes mellitus (DM) is a metabolic disorder that is widely rampant throughout the world population these days. The uncontrolled DM may lead to complications of eye, heart, kidney and nerves. The most common type of diabetes is the type 2 diabetes or insulin-resistant DM.     

Proteomic analysis of early urinary biomarkers of renal changes in type 2 diabetic patients

Diabetic nephropathy (DN) is a complication associated with diabetes, leading to end-stage renal disease (ESRD). Despite significant progress in understanding DN, the cellular mechanisms leading to the renal damage are incompletely defined. In this study, with the aim to identify urine biomarkers for the early renal alterations in type 2 diabetes mellitus (T2D), we performed urinary proteomic analysis of 10 normoalbuminuric patients with T2D, 12 patients with type 2 DN (T2DN), and 12 healthy subjects. Proteins were separated by 2-DE and identified with ESI-Q-TOF MS/MS. Comparing the patients proteomic profiles with those of normal subjects, we identified 11 gradually differently changed proteins. The decreased proteins were the prostatic acid phosphatase precursor, the ribonuclease and the kallikrein-3. Eight proteins were progressively increased in both patients groups: transthyretin precursor, Ig κ chain C region, Ig κ chain V-II region Cum, Ig κ-chain V-III region SIE, carbonic anhydrase 1, plasma retinol-binding protein, β-2-microglobulin precursor, β-2-glycoprotein 1. The proteomic analysis allowed us to identify several increased urinary proteins, not only in T2DN but also in T2D patients in which the microalbuminuria was in the normal range. These patterns of urinary proteins might represent a potential tool for a better understanding of diabetic renal damage.     

Comparative assessment of statistical and machine learning techniques towards estimating the risk of developing type 2 diabetes and cardiovascular complications

The aim of the present study is to comparatively assess the performance of different machine learning and statistical techniques with regard to their ability to estimate the risk of developing type 2 diabetes mellitus (Case 1) and cardiovascular disease complications (Case 2). This is the first work investigating the application of ensembles of artificial neural networks (EANN) towards producing the 5‐year risk of developing type 2 diabetes mellitus and cardiovascular disease as a long‐term diabetes complication. The performance of the proposed models has been comparatively assessed with the performance obtained by applying logistic regression, Bayesian‐based approaches, and decision trees. The models' discrimination and calibration have been evaluated using the classification accuracy (ACC), the area under the curve (AUC) criterion, and the Hosmer–Lemeshow goodness of fit test. The obtained results demonstrate the superiority of the proposed models (EANN) over the other models. In Case 1, EANN with different topologies has achieved high discrimination and good calibration performance (ACC = 80.20%, AUC = 0.849, p value = .886). In Case 2, EANN based on bagging has resulted in good discrimination and calibration performance (ACC = 92.86%, AUC = 0.739, p value = .755).     

Comparison of interval and Monte Carlo simulation for the prediction of postprandial glucose under uncertainty in type 1 diabetes mellitus

In this paper, the problem of tackling uncertainty in the prediction of postprandial blood glucose is analyzed. Two simulation approaches, Monte Carlo and interval models, are studied and compared. Interval simulation is carried out using modal interval analysis. Simulation of a glucoregulatory model with uncertainty in insulin sensitivities, glucose absorption and food intake is carried out using both methods. Interval simulation is superior in predicting all severe and mild hyper- and hypoglycemia episodes. Furthermore, much less computational time is required for interval simulation than for Monte Carlo simulation.     

知识发现在2型糖尿病数据处理中的应用研究

目的:首次将知识发现理论引入到2型糖尿病发病相关因素数据处理中,从大量实测数据中识别出有效的、潜在的、有用的、可理解的发病规律。方法:根据2型糖尿病数据的特点,选用数据挖掘C4.5算法对17072条有效的整群抽样横断面健康调查数据进行决策树分类。结果:通过训练模型给出糖尿病患病与否的决策分类树,该决策树可以直观地给出发病相关因素的不同层次的相对影响,经实验测试结果对于未患病的正确识别率为92.05%,对于患病的正确识别率为80.90%,同时得出了血糖值为5.85的分类临界值。结论:决策分类树结果同目前认识的高危因素趋于一致,说明数据挖掘C4.5算法适用于2型糖尿病的发病相关因素数据分析处理,是2型糖尿病数据处理的一种新方法,其在疾病的宏观控制中有着广阔的应用前景。