Parallel Control of an Artificial Pancreas with Coordinated Insulin, Glucagon, and Rescue Carbohydrate Control Actions

J Diabetes Sci Technol. 2019 Nov;13(6):1026-1034. doi: 10.1177/1932296819879093. Epub 2019 Oct 20.

Abstract

Background: An artificial pancreas with insulin and glucagon delivery has the potential to reduce the risk of hypo- and hyperglycemia in people with type 1 diabetes. However, a maximum dose of glucagon of 1 mg/d is recommended, potentially still requiring rescue carbohydrates in some situations. This work presents a parallel control structure with intrinsic insulin, glucagon, and rescue carbohydrates coordination to overcome glucagon limitations when needed.

Methods: The coordinated controller that combines insulin, glucagon, and rescue carbohydrate suggestions (DH-CC-CHO) was compared with the insulin and glucagon delivery coordinated controller (DH-CC). The impact of carbohydrate quantization for practical delivery was also assessed. An in silico study using the UVA-Padova simulator, extended to include exercise and various sources of variability, was performed.

Results: DH-CC and DH-CC-CHO performed similarly with regard to mean glucose (126.25 [123.43; 130.73] vs 127.92 [123.99; 132.97] mg/dL, P = .088), time in range (93.04 [90.00; 95.92] vs 92.91 [90.05; 95.75]%, P = .508), time above 180 mg/dL (4.94 [2.72; 7.53] vs 4.99 [2.93; 7.24]%, P = .966), time below 70 mg/dL (0.61 [0.09; 1.75] vs 0.96 [0.23; 2.17]%, P = .1364), insulin delivery (43.50 [38.68; 51.75] vs 42.86 [38.58; 51.36] U/d, P = .383), and glucagon delivery (0.75 [0.40; 1.83] vs 0.76 [0.43; 0.99] mg/d, P = .407). Time below 54 mg/dL was different (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.16]%, P = .036), although non-clinically significant. This was due to the carbs quantization effect in a specific patient, as no statistical difference was found when carbs were not quantized (0.00 [0.00; 0.05] vs 0.00 [0.00; 0.00]%, P = .265).

Conclusions: The new strategy of automatic rescue carbohydrates suggestion in coordination with insulin and glucagon delivery to overcome constraints on daily glucagon delivery was successfully evaluated in an in silico proof of concept.

Keywords: artificial pancreas; carbohydrate suggestion; coordinated control; dual hormone; glucagon limitation; parallel control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Blood Glucose / analysis*
  • Computer Simulation
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Glucagon / administration & dosage
  • Glucagon / therapeutic use*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / therapeutic use*
  • Pancreas, Artificial

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Glucagon