Publications | Poster sessions | Presentations

A new animal model of insulin-glucose dynamics in the intraperitoneal space enhances closed-loop control performance

Journal of Process Control Volume 76, April 2019, Pages 62-73
Ankush Chakrabarty, Justin M.Gregory, L. Merkle Moore, Philip E. Williams, Ben Farmer, Alan D. Cherrington, Peter Lord, Brian Shelton, Don Cohen, Howard C.Zisse,
Francis J.Doyle III, Eyal Dassau
https://doi.org/10.1016/j.jprocont.2019.01.002

ABSTRACT

Current artificial pancreas (AP) systems operate via subcutaneous (SC) glucose sensing and SC insulin delivery. Due to slow diffusion and transport dynamics across the interstitial space, even the most sophisticated control algorithms in on-body AP systems cannot react fast enough to maintain tight glycemic control under the effect of exogenous glucose disturbances caused by ingesting meals or performing physical activity. Recent efforts made towards the development of an implantable AP have explored the utility of insulin infusion in the intraperitoneal (IP) space: a region within the abdominal cavity where the insulin-glucose kinetics are observed to be much more rapid than the SC space. In this paper, a series of canine experiments are used to determine the dynamic association between IP insulin boluses and plasma glucose levels. Data from these experiments are employed to construct a new mathematical model and to formulate a closed-loop control strategy to be deployed on an implantable AP. The potential of the proposed controller is demonstrated via in-silico experiments on an FDA-accepted benchmark cohort: the proposed design significantly outperforms a previous controller designed using artificial data (time in clinically acceptable glucose range: 97.3 ± 1.5% vs. 90.1 ± 5.6%). Furthermore, the robustness of the proposed closed-loop system to delays and noise in the measurement signal (for example, when glucose is sensed subcutaneously) and deleterious glycemic changes (such as sudden glucose decline due to physical activity) is investigated. The proposed model based on experimental canine data leads to the generation of more effective control algorithms and is a promising step towards fully automated and implantable artificial pancreas systems.

2019

He, J., Renard, E., Lord, P., Cohen, D., Burgess, D.J. 2019. “Impact of Insulin Stability on Intraperitoneal Insulin Catheter Obstruction: A Comprehensive Analysis in Rodents and Type 1 Diabetic Patients.” Poster. 2019 Diabetes Technology Meeting. North Bethesda, MD, US. November 2019.

He, J., Renard, E., Lord, P., Cohen, D., Burgess, D.J. 2019. “Size and Tip Configuration-dependent Foreign Body Reaction to Intraperitoneal Insulin Catheters.” Poster. 2019 Diabetes Technology Meeting. North Bethesda, MD, US. November 2019.

He, J., Renard, E., Lord, P., Burgess, D.J. 2019. “Investigations of Catheter Obstructions from Materials Collected in Patients with Type 1 Diabetes Treated by Intraperitoneal Insulin Infusion.” Poster. 2019 AAPS PharmaSci 360. San Antonio, TX, US. November, 2019.

He, J., Renard, E., Lord, P., Burgess, D.J. 2019. “Root Cause Determination of Catheter Obstruction for Type 1 Diabetes.” Selected Presentation. 2019 2nd Annual UConn/URI-AAPS Symposium. Kingston, RI, US. September 2019.

He, J., Renard, E., Lord, P., Burgess, D.J. 2019. “Comprehensive Analysis of Intraperitoneal Insulin Catheter Obstructions in Patients with Type 1 Diabetes.” Selected Presentation. 2019 Annual Meeting, AAPS Northeast Regional Discussion Group (NERDG). Farmington, CT, US. April, 2019.

2018

He, J., Renard, E., Lord, P., Burgess, D.J. 2018. “Root Cause Determination of Obstruction in Insulin Pump.” Invited presentation. 2018 Peking University, Beijing, China

He, J., Renard, E., Lord, P., Burgess, D.J. 2018. “Long-term in vitroStability Test of Insulin for Implantable Devices.” Poster. 2018 CRS. New York, NY, US. July 2018

He, J., Renard, E., Lord, P., Burgess, D.J. 2018. “Histological Evaluation of Obstructed Insulin Pump Catheters Explanted from Patients.” Poster. 2018 AAPS. Washington DC, US. November 2018. Best Poster Award