Reducing risk of closed loop control of blood glucose in artificial pancreas using fractional calculus

Automated closed-loop control of blood glucose concentration is a daily challenge for type 1 diabetes mellitus, where insulin and glucagon are two critical hormones for glucose regulation. According to whether glucagon is included, all artificial pancreas (AP) systems can be divided into two types: unihormonal AP (infuse only insulin) and bihormonal AP (infuse both insulin and glucagon). Even though the bihormonal AP is widely considered a promising direction, related studies are very scarce due to this system’s short research history. More importantly, there are few studies to compare these two kinds of AP systems fairly and systematically. In this paper, two switching rules, P-type and PD-type, were proposed to design the logic of orchestrates switching between insulin and glucagon subsystems, where the delivery rates of both insulin and glucagon were designed by using IMC-PID method. These proposed algorithms have been compared with an optimal unihormonal system on virtual type 1 diabetic subjects. Thein silicoresults demonstrate that the proposed bihormonal AP systems have outstanding superiorities in reducing the risk of hypoglycemia, smoothing the glucose level, and robustness with respect to insulin/glucagon sensitivity variations, compared with the optimal unihormonal AP system.

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Comparison of Algorithms for the Closed-Loop Control of Blood Glucose Using the Artificial Beta Cell

IEEE Transactions on Biomedical Engineering ◽

10.1109/tbme.1981.324661 ◽

1981 ◽

Vol BME-28 (10) ◽

pp. 678-687 ◽

Cited By ~ 47

Author(s):

Henry M. Broekhuyse ◽

Hill D. Nelson ◽

Bernard Zinman ◽

A. M. Albisser

Keyword(s):

Blood Glucose ◽

Beta Cell ◽

Closed Loop ◽

Closed Loop Control ◽

Loop Control ◽

Comparison Of Algorithms ◽

Artificial Beta Cell

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Dual-hormone closed loop system using a liquid stable glucagon formulation versus insulin-only closed loop system compared to a predictive low glucose suspend system: an open label, outpatient, single center, crossover, randomized control trial

10.2337/figshare.12815861 ◽

2020 ◽

Cited By ~ 1

Author(s):

Leah M. Wilson ◽

Peter G. Jacobs ◽

Katrina L. Ramsey ◽

Navid Resalat ◽

Ravi Reddy ◽

...

Keyword(s):

Closed Loop ◽

Artificial Pancreas ◽

Loop System ◽

Target Range ◽

Closed Loop Control ◽

Closed Loop System ◽

Entire Study ◽

Loop Control ◽

Study Duration ◽

Low Glucose

Objective: To assess the efficacy and feasibility of a dual-hormone closed loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed loop system and a predictive low glucose suspend system. Research Design and Methods: In a 76-hour, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: (1) dual-hormone (DH) closed loop control, (2) insulin-only single-hormone (SH) closed loop control and (3) predictive low glucose suspend (PLGS). The primary endpoint was percent time in hypoglycemia (<70 mg/dL) from start of in-clinic aerobic exercise (45mins at 60% VO2max) to 4 hours after. Results: DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [0.0-4.2], SH 8.3% [0.0-12.5], p=0.025). There was an increased time in hyperglycemia (>180mg/dL) during and after exercise for DH vs SH (20.8% DH vs. 6.3% SH, p=0.038). Mean glucose during the entire study duration was: DH 159.2, SH 151.6, PLGS 163.6 mg/dL. Across the entire study duration, DH resulted in 7.5% more time in target range (70-180 mg/dL) compared with the PLGS system (71.0% vs. 63.4%, p=0.044). For the entire study duration, DH had 28.2% time in hyperglycemia versus 25.1% for SH (p=0.044) and 34.7% for PLGS (p=0.140). Four participants experienced nausea related to glucagon leading 3 to withdraw from the study. Conclusions: The glucagon formulation demonstrated feasibility in a closed loop system. The dual-hormone system reduced hypoglycemia during and after exercise with some increase in hyperglycemia.

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