scholarly journals Identifiability Analysis of Three Control-Oriented Models for Use in Artificial Pancreas Systems

2018 ◽  
Vol 12 (5) ◽  
pp. 937-952 ◽  
Author(s):  
Jose Garcia-Tirado ◽  
Christian Zuluaga-Bedoya ◽  
Marc D. Breton
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Control ◽  
Minimal Model ◽  
Artificial Pancreas ◽  
Model Identification ◽  
Metabolic Effects ◽  
Identifiability Analysis ◽  
Practical Identifiability ◽  
Model Control

Objective: Our aim is to analyze the identifiability of three commonly used control-oriented models for glucose control in patients with type 1 diabetes (T1D). Methods: Structural and practical identifiability analysis were performed on three published control-oriented models for glucose control in patients with type 1 diabetes (T1D): the subcutaneous oral glucose minimal model (SOGMM), the intensive control insulin-nutrition-glucose (ICING) model, and the minimal model control-oriented (MMC). Structural identifiability was addressed with a combination of the generating series (GS) approach and identifiability tableaus whereas practical identifiability was studied by means of (1) global ranking of parameters via sensitivity analysis together with the Latin hypercube sampling method (LHS) and (2) collinearity analysis among parameters. For practical identifiability and model identification, continuous glucose monitor (CGM), insulin pump, and meal records were selected from a set of patients (n = 5) on continuous subcutaneous insulin infusion (CSII) that underwent a clinical trial in an outpatient setting. The performance of the identified models was analyzed by means of the root mean square (RMS) criterion. Results: A reliable set of identifiable parameters was found for every studied model after analyzing the possible identifiability issues of the original parameter sets. According to an importance factor ([Formula: see text]), it was shown that insulin sensitivity is not the most influential parameter from the dynamical point of view, that is, is not the parameter impacting the outputs the most of the three models, contrary to what is assumed in the literature. For the test data, the models demonstrated similar performance with most RMS values around 20 mg/dl (min: 15.64 mg/dl, max: 51.32 mg/dl). However, MMC failed to identify the model for patient 4. Also, considering the three models, the MMC model showed the higher parameter variability when reidentified every 6 hours. Conclusion: This study shows that both structural and practical identifiability analysis need to be considered prior to the model identification/individualization in patients with T1D. It was shown that all the studied models are able to represent the CGM data, yet their usefulness in a hypothetical artificial pancreas could be a matter of debate. In spite that the three models do not capture all the dynamics and metabolic effects as a maximal model (ie, our FDA-accepted UVa/Padova simulator), SOGMM and ICING appear to be more appealing than MMC regarding both the performance and parameter variability after reidentification. Although the model predictions of ICING are comparable to the ones of the SOGMM model, the large parameter set makes the model prone to overfitting if all parameters are identified. Moreover, the existence of a high nonlinear function like [Formula: see text] prevents the use of tools from the linear systems theory.

scholarly journals Free-living use of artificial pancreas for children with type 1 diabetes: systematic review

2018 ◽  
Vol 21 (3) ◽  
pp. 206-216
Author(s):  
Klemen Dovc ◽  
Gül Yeşiltepe Mutlu ◽  
Yury I. Philippov ◽  
Dmitry N. Laptev ◽  
Evgenia M. Patrakeeva ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 1 Diabetes ◽  
Control System ◽  
Glucose Control ◽  
Closed Loop ◽  
Artificial Pancreas ◽  
Hospital Environment ◽  
Time In Range ◽  
Randomized Control

BACKGRAUND: A closed-loop glucose control system or artificial pancreas consists of three components a Continuous Glucose Monitor (CGM), infusion pumps to deliver hormone(s) and a sophisticated dosing algorithm to control hormone delivery. In the past years, numerous studies with closed-loop system devices were conducted with gradual shift to out-of-hospital environment and with lengthening study duration. AIMS: To compare efficacy and safety of closed-loop insulin pump use in children with type 1 diabetes mellitus in compare with conventional insulin treatment (continuous subcutaneous insulin infusion (CSII) with our without CGM) based on randomized control trials data (RCT). METHODS: In the systematic review we have include 28 randomized controlled trials results indexed in PubMed, Medline databases published till 15 June 2017. The efficacy on metabolic control in this study evaluated by the proportion of time within target range (preferably 70 to 180 mg/dl if reported) and mean (median) glucose based on sensor measurements, and the safety evaluated by time in hypoglycemia (below 70 mg/dl if reported). RESULTS: Increased time in range in the night period was observed in all RCT. Only 3 RCT showed decrease of the time in range within 24 h evaluation period. In one RCT the significant positive differences have been shown in the time in range for dual hormone closed-loop glucose control system in compare with insulin-only artificial pancreas. Mean glycaemia and glucose variability changes were not in the same manner in different RCT, both in the night only and in 24 h estimation period. Night hypoglycemia duration decreased in most RCT with closed-loop control in compare with CSII, and increased only in 2 RCT. When all-day estimation period the time in hypoglycemia changed not in the same manner in different RCT. Valuable methodology differences of the glycaemic control estimation within observed RCT brought significant complications in the data analysis and made impossible the results quantitative estimation to prepare a metaanalysis. CONCLUSIONS: Much work has been done to develop effective and safe artificial pancreas, but not all RCTs confirmed advantages of closed-loop glucose control in compare with CSII in children and adolescents in real life. More research with prospective randomized control design required to prove benefits of closed-loop glucose control. Further RCTs should have an uniform methodology for glycemic control assessment and long duration that will allow to use cumulative measures in a closed-loop efficacy estimation (HbA1c).

scholarly journals Proposal for a Methodology to Create an Artificial Pancreas for the Control of Type 1 Diabetes using Machine Learning and Automated Insulin Dosing Systems (AID)

2021 ◽  
Author(s):  
Rodrigo Vilanova ◽  
Anderson Jefferson Cerqueira
Keyword(s):  
Type 1 Diabetes ◽  
Low Income ◽  
Glucose Control ◽  
Artificial Pancreas ◽  
Low Income Countries ◽  
Number Of Children ◽  
Adolescents And Adults ◽  
Medication Changes

The number of children, adolescents, and adults living with diabetes increases annually due to the lack of physical activity, poor diet habits, stress, and genetic factors, and there are greater numbers in low-income countries. Therefore, the aim of this article is to present a proposal for a methodology for developing a pancreas using artificial intelligence to control the required doses of insulin for a patient with type 1 diabetes (T1D), according to data received from monitoring sensors. The information collected can be used by physicians to make medication changes and improve patients’ glucose control using insulin pumps for optimum performance. Therefore, using the model proposed in this work, the patient is offered a gain in glucose control and, therefore, an improvement in quality of life, as well as in the costs related to hospitalization.

Feasibility Study of Automated Overnight Closed-Loop Glucose Control Under MD-Logic Artificial Pancreas in Patients with Type 1 Diabetes: The DREAM Project

2012 ◽  
Vol 14 (8) ◽  
pp. 728-735 ◽  
Author(s):  
Revital Nimri ◽  
Eran Atlas ◽  
Michal Ajzensztejn ◽  
Shahar Miller ◽  
Tal Oron ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Feasibility Study ◽  
Glucose Control ◽  
Closed Loop ◽  
Artificial Pancreas

scholarly journals Realizing a Closed-Loop (Artificial Pancreas) System for the Treatment of Type 1 Diabetes

2019 ◽  
Vol 40 (6) ◽  
pp. 1521-1546 ◽  
Author(s):  
Rayhan A Lal ◽  
Laya Ekhlaspour ◽  
Korey Hood ◽  
Bruce Buckingham
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Control ◽  
Closed Loop ◽  
Diabetes Management ◽  
Artificial Pancreas ◽  
Loop System ◽  
Closed Loop Control ◽  
Closed Loop System ◽  
Loop Control

Abstract Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an “artificial pancreas” that is better described as a closed-loop controller of insulin delivery. This review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short-term and long-term complications from diabetes and to decrease the daily burden of managing diabetes. The closed-loop systems are generally very effective and safe at night, have allowed for improved sleep, and have decreased the burden of diabetes management overnight. However, there are still significant barriers to achieving excellent daytime glucose control while simultaneously decreasing the burden of daytime diabetes management. These systems use a subcutaneous continuous glucose sensor, an algorithm that accounts for the current glucose and rate of change of the glucose, and the amount of insulin that has already been delivered to safely deliver insulin to control hyperglycemia, while minimizing the risk of hypoglycemia. The future challenge will be to allow for full closed-loop control with minimal burden on the patient during the day, alleviating meal announcements, carbohydrate counting, alerts, and maintenance. The human factors involved with interfacing with a closed-loop system and allowing the system to take control of diabetes management are significant. It is important to find a balance between enthusiasm and realistic expectations and experiences with the closed-loop system.

scholarly journals Current treatment options and challenges in patients with Type 1 diabetes: Pharmacological, technical advances and future perspectives

2021 ◽  
Author(s):  
Federico Boscari ◽  
Angelo Avogaro
Keyword(s):  
Quality Of Life ◽  
Type 1 Diabetes ◽  
Glucose Control ◽  
Diabetes Management ◽  
Treatment Options ◽  
Artificial Pancreas ◽  
Glucose Monitoring ◽  
Current Treatment

AbstractType 1 diabetes mellitus imposes a significant burden of complications and mortality, despite important advances in treatment: subjects affected by this disease have also a worse quality of life-related to disease management. To overcome these challenges, different new approaches have been proposed, such as new insulin formulations or innovative devices. The introduction of insulin pumps allows a more physiological insulin administration with a reduction of HbA1c level and hypoglycemic risk. New continuous glucose monitoring systems with better accuracy have allowed, not only better glucose control, but also the improvement of the quality of life. Integration of these devices with control algorithms brought to the creation of the first artificial pancreas, able to independently gain metabolic control without the risk of hypo- and hyperglycemic crisis. This approach has revolutionized the management of diabetes both in terms of quality of life and glucose control. However, complete independence from exogenous insulin will be obtained only by biological approaches that foresee the replacement of functional beta cells obtained from stem cells: this will be a major challenge but the biggest hope for the subjects with type 1 diabetes. In this review, we will outline the current scenario of innovative diabetes management both from a technological and biological point of view, and we will also forecast some cutting-edge approaches to reduce the challenges that hamper the definitive cure of diabetes.

scholarly journals Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial

2021 ◽  
Author(s):  
Helga Blauw ◽  
A. Joannet Onvlee ◽  
Michel Klaassen ◽  
Arianne C. van Bon ◽  
J. Hans DeVries
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Control ◽  
Closed Loop ◽  
Insulin Pump ◽  
Artificial Pancreas ◽  
Open Loop ◽  
Insulin Pump Therapy ◽  
Pump Therapy ◽  
Randomized Crossover Trial

OBJECTIVE <p>To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas in adults with type 1 diabetes.</p> <p> </p>RESEARCH DESIGN AND METHODS <p>In this outpatient, randomized, crossover trial, two-week fully closed loop glucose control (artificial pancreas therapy) was compared to two-week open loop control (patient’s normal insulin pump therapy with a glucose sensor if they had one). </p> <p> </p>RESULTS <p>Twenty three patients were included in the analysis. Median (IQR) time in range (70-180 mg/dL [3.9-10 mmol/L]) was significantly higher during closed loop (86.6% [84.9-88.5]) compared with open loop (53.9% [49.7-67.2]; p<0.0001).</p> <p> </p>CONCLUSIONS <p>Compared to insulin pump therapy, the bihormonal artificial pancreas provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.</p>

scholarly journals Effect of 6 months hybrid closed-loop insulin delivery in young people with type 1 diabetes: a randomised controlled trial protocol

BMJ Open ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. e020275 ◽  
Author(s):  
Martin de Bock ◽  
Sybil A McAuley ◽  
Mary Binsu Abraham ◽  
Grant Smith ◽  
Jennifer Nicholas ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Control ◽  
Standard Therapy ◽  
Closed Loop ◽  
Insulin Pump ◽  
Controlled Trial ◽  
Artificial Pancreas ◽  
Insulin Delivery ◽  
Randomised Controlled

IntroductionAutomated insulin delivery (also known as closed loop, or artificial pancreas) has shown potential to improve glycaemic control and quality of life in people with type 1 diabetes (T1D). Automated insulin delivery devices incorporate an insulin pump with continuous glucose monitoring(CGM) and an algorithm, and adjust insulin in real time. This study aims to establish the safety and efficacy of a hybrid closed-loop (HCL) system in a long-term outpatient trial in people with T1D aged 12 –<25 years of age, and compare outcomes with standard therapy for T1D as used in the contemporary community.Methods and analysisThis is an open-label, multicentre, 6-month, randomised controlled home trial to test the MiniMed Medtronic 670G system (HCL) in people with T1D aged 12 –<25 years, and compare it to standard care (multiple daily injections or continuous subcutaneous insulin infusion (CSII), with or without CGM). Following a run-in period including diabetes and carbohydrate counting education, dosage optimisation and baseline glucose control data collection, participants are randomised to either HCL or to continue on their current treatment regimen. The primary aim of the study is to compare the proportion of time spent in target sensor glucose range (3.9–10.0 mmol/L) on HCL versus standard therapy. Secondary aims include a range of glucose control parameters, psychosocial measures, health economic measures, biomarker status, user/technology interactions and healthcare professional expectations. Analysis will be intention to treat. A study in adults with an aligned design is being conducted in parallel to this trial.Ethics and disseminationEthics committee permissions were gained from respective institutional review boards. The findings of the study will provide high-quality evidence on the role of HCL in clinical practice.

scholarly journals Single- and Dual-Hormone Artificial Pancreas for Overnight Glucose Control in Type 1 Diabetes

2016 ◽  
Vol 101 (1) ◽  
pp. 214-223 ◽  
Author(s):  
Ahmad Haidar ◽  
Rémi Rabasa-Lhoret ◽  
Laurent Legault ◽  
Leif E. Lovblom ◽  
Rohan Rakheja ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Control ◽  
Artificial Pancreas
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