Valentina Canonico

Bio: Valentina Canonico is an academic researcher from University of Perugia. The author has contributed to research in topics: Artificial pancreas & Insulin. The author has an hindex of 5, co-authored 7 publications receiving 1375 citations.

Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes

Abstract: A nonlinear model predictive controller has been developed to maintain normoglycemia in subjects with type 1 diabetes during fasting conditions such as during overnight fast. The controller employs a compartment model, which represents the glucoregulatory system and includes submodels representing absorption of subcutaneously administered short-acting insulin Lispro and gut absorption. The controller uses Bayesian parameter estimation to determine time-varying model parameters. Moving target trajectory facilitates slow, controlled normalization of elevated glucose levels and faster normalization of low glucose values. The predictive capabilities of the model have been evaluated using data from 15 clinical experiments in subjects with type 1 diabetes. The experiments employed intravenous glucose sampling (every 15 min) and subcutaneous infusion of insulin Lispro by insulin pump (modified also every 15 min). The model gave glucose predictions with a mean square error proportionally related to the prediction horizon with the value of 0.2 mmol L(-1) per 15 min. The assessment of clinical utility of model-based glucose predictions using Clarke error grid analysis gave 95% of values in zone A and the remaining 5% of values in zone B for glucose predictions up to 60 min (n = 1674). In conclusion, adaptive nonlinear model predictive control is promising for the control of glucose concentration during fasting conditions in subjects with type 1 diabetes.

Closing the loop: the adicol experience.

Abstract: The objective of the project Advanced Insulin Infusion using a Control Loop (ADICOL) was to develop a treatment system that continuously measures and controls the glucose concentration in subjects with type 1 diabetes. The modular concept of the ADICOL's extracorporeal artificial pancreas consisted of a minimally invasive subcutaneous glucose system, a handheld PocketPC computer, and an insulin pump (D-Tron, Disetronic, Burgdorf, Switzerland) delivering subcutaneously insulin lispro. The present paper describes a subset of ADICOL activities focusing on the development of a glucose controller for semi-closed-loop control, an in silico testing environment, clinical testing, and system integration. An incremental approach was adopted to evaluate experimentally a model predictive glucose controller. A feasibility study was followed by efficacy studies of increasing complexity. The ADICOL project demonstrated feasibility of a semi-closed-loop glucose control during fasting and fed conditions with a wearable, m...

Control oriented model of insulin and glucose dynamics in type 1 diabetics

Abstract: The aim of the study was to realize a mathematical model of insulin–glucose relationship in type I diabetes and test its effectiveness for the design of control algorithms in external artificial pancreas. A new mathematical model, divided into glucose and insulin sub-models, was developed from the so-called “minimal model”. The key feature is the representation of insulin sensitivity so as to permit the personalisation of the parameters. Real-time applications are based on an insulin standardised model. Clinical data were used to estimate model parameters. Root mean square error between simulated and real blood glucose profiles (Grms) was used to evaluate system efficacy. Results from parameter estimation and insulin standardisation showed a good capability of the model to identify individual characteristics. Simulation results with a Grms 1.30 mmol/l in the worst case testified the capacity of the model to accurately represent glucose–insulin relationship in type 1 diabetes allowing self tuning in real time.

Clinical validation of a new control-oriented model of insulin and glucose dynamics in subjects with type 1 diabetes.

Abstract: Background: The development of an artificial pancreas requires an accurate representation of diabetes pathophysiology to create effective and safe control systems for automatic insulin infusion regulation. The aim of the present study is the assessment of a previously developed mathematical model of insulin and glucose metabolism in type 1 diabetes and the evaluation of its effectiveness for the development and testing of control algorithms. Methods: Based on the already existing “minimal model” a new mathematical model was developed composed of glucose and insulin submodels. The glucose model includes the representation of peripheral uptake, hepatic uptake and release, and renal clearance. The insulin model describes the kinetics of exogenous insulin injected either subcutaneously or intravenously. The estimation of insulin sensitivity allows the model to personalize parameters to each subject. Data sets from two different clinical trials were used here for model validation through simulation studies. Th...

Early detection of insulin deprivation in continuous subcutaneous insulin infusion-treated patients with type 1 diabetes.

Abstract: Background: This study was performed to define the clinical relevance of early changes of capillary 3β-hydroxybutyrate (3βOHB), for detection of metabolic deterioration before occurrence of overt diabetic ketoacidosis following interruption of continuous subcutaneous insulin infusion (CSII). Methods: An open clinical trial was performed with eight patients with type 1 diabetes on CSII therapy. After an overnight fast, at 8 a.m. (T0) CSII was interrupted for 4 h. At noon (T240) CSII was re-established, and at 4 p.m. (T480) the study was ended. Blood glucose (BG) and capillary and plasma 3βOHB were measured at 30-min intervals, plasma insulin at 60-min intervals, and urinary ketones at 120-min intervals. Results: After CSII interruption mean BG increased from 149.8 ± 54.4 mg/dL at T0 to 224.8 ± 56.2 mg/dL at T240 (P < 0.05), and mean capillary 3βOHB increased from 0.1 ± 0.1 mmol/L at T0 to 0.9 ± 0.6 mmol/L at T240 (P < 0.001). The rate of increase of capillary 3βOHB was faster and significantly more relevan...

Feedback Systems: An Introduction for Scientists and Engineers

Abstract: This book provides an introduction to the mathematics needed to model, analyze, and design feedback systems. It is an ideal textbook for undergraduate and graduate students, and is indispensable for researchers seeking a self-contained reference on control theory. Unlike most books on the subject, Feedback Systems develops transfer functions through the exponential response of a system, and is accessible across a range of disciplines that utilize feedback in physical, biological, information, and economic systems. Karl strm and Richard Murray use techniques from physics, computer science, and operations research to introduce control-oriented modeling. They begin with state space tools for analysis and design, including stability of solutions, Lyapunov functions, reachability, state feedback observability, and estimators. The matrix exponential plays a central role in the analysis of linear control systems, allowing a concise development of many of the key concepts for this class of models. strm and Murray then develop and explain tools in the frequency domain, including transfer functions, Nyquist analysis, PID control, frequency domain design, and robustness. They provide exercises at the end of every chapter, and an accompanying electronic solutions manual is available. Feedback Systems is a complete one-volume resource for students and researchers in mathematics, engineering, and the sciences.Covers the mathematics needed to model, analyze, and design feedback systems Serves as an introductory textbook for students and a self-contained resource for researchers Includes exercises at the end of every chapter Features an electronic solutions manual Offers techniques applicable across a range of disciplines

Analyte Monitoring Device And Methods Of Use

Abstract: An analyte monitor includes a sensor, a sensor control unit, and a display unit. The sensor has, for example, a substrate, a recessed channel formed in the substrate, and conductive material disposed in the recessed channel to form a working electrode. The sensor control unit typically has a housing adapted for placement on skin and is adapted to receive a portion of an electrochemical sensor. The sensor control unit also includes two or more conductive contacts disposed on the housing and configured for coupling to two or more contact pads on the sensor. A transmitter is disposed in the housing and coupled to the plurality of conductive contacts for transmitting data obtained using the sensor. The display unit has a receiver for receiving data transmitted by the transmitter of the sensor control unit and a display coupled to the receiver for displaying an indication of a level of an analyte. The analyte monitor may also be part of a drug delivery system to alter the level of the analyte based on the data obtained using the sensor.

Transcutaneous analyte sensor

Abstract: The present invention relates generally to systems and methods for measuring an analyte in a host. More particularly, the present invention relates to systems and methods for transcutaneous measurement of glucose in a host.

Meal Simulation Model of the Glucose-Insulin System

Abstract: A simulation model of the glucose-insulin system in the postprandial state can be useful in several circumstances, including testing of glucose sensors, insulin infusion algorithms and decision support systems for diabetes. Here, we present a new simulation model in normal humans that describes the physiological events that occur after a meal, by employing the quantitative knowledge that has become available in recent years. Model parameters were set to fit the mean data of a large normal subject database that underwent a triple tracer meal protocol which provided quasi-model-independent estimates of major glucose and insulin fluxes, e.g., meal rate of appearance, endogenous glucose production, utilization of glucose, insulin secretion. By decomposing the system into subsystems, we have developed parametric models of each subsystem by using a forcing function strategy. Model results are shown in describing both a single meal and normal daily life (breakfast, lunch, dinner) in normal. The same strategy is also applied on a smaller database for extending the model to type 2 diabetes.

In Silico Preclinical Trials: A Proof of Concept in Closed-Loop Control of Type 1 Diabetes

Abstract: Arguably, a minimally invasive system using subcutaneous (s.c.) continuous glucose monitoring (CGM) and s.c. insulin delivery via insulin pump would be a most feasible step to closed-loop control in type 1 diabetes mellitus (T1DM). Consequently, diabetes technology is focusing on developing an artificial pancreas using control algorithms to link CGM with s.c. insulin delivery. The future development of the artificial pancreas will be greatly accelerated by employing mathematical modeling and computer simulation. Realistic computer simulation is capable of providing invaluable information about the safety and the limitations of closed-loop control algorithms, guiding clinical studies, and out-ruling ineffective control scenarios in a cost-effective manner. Thus computer simulation testing of closed-loop control algorithms is regarded as a prerequisite to clinical trials of the artificial pancreas. In this paper, we present a system for in silico testing of control algorithms that has three principal components: (1) a large cohort of n = 300 simulated “subjects” (n = 100 adults, 100 adolescents, and 100 children) based on real individuals’ data and spanning the observed variability of key metabolic parameters in the general population of people with T1DM; (2) a simulator of CGM sensor errors representative of Freestyle Navigator™, Guardian RT, or Dexcom™ STS™, 7-day sensor; and (3) a simulator of discrete s.c. insulin delivery via OmniPod Insulin Management System or Deltec Cozmo ® insulin pump. The system has been shown to represent adequate glucose fluctuations in T1DM observed during meal challenges, and has been accepted by the Food and Drug Administration as a substitute to animal trials in the preclinical testing of closed-loop control strategies.