SLIDE 1 Lesson 15 Artificial pancreas: mathematical model of automatic blood glucose control.
Ettore Lanzarone April 29, 2020
MEDICAL SUPPORT SYSTEMS FOR CHRONIC DISEASES
Engineering and Management for Health University of Bergamo
LESSON 15
Physiological background
Insulin is a peptide hormone produced by beta cells of the pancreatic islets (or islets of Langerhans). It is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of carbohydrates, especially of glucose from the blood. In liver, fat and skeletal muscle cells, the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis,
- r, in the case of the liver, into both.
Glucose secretion and production is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins. It is therefore an anabolic hormone, promoting the conversion
- f small molecules in the blood into large molecules inside the cells.
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Physiological background
Low insulin levels in the blood promote widespread catabolism, especially of reserve body fat. Beta cells are sensitive to glucose concentrations:
- when glucose levels are high, the beta cells secrete insulin into the blood;
- when glucose levels are low, secretion of insulin is inhibited.
Their neighboring alpha cells, by receiving signals from the beta cells, secrete glucagon into the blood in the opposite manner:
- increased secretion when blood glucose concentration is low;
- decreased secretion when blood glucose concentration is high.
Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. Beta cells are destroyed by an autoimmune reaction. Thus, insulin can no longer be synthesized or be secreted into the blood. This results in the type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting.
Diabetes
Type 1 diabetes mellitus
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Lesson 15
In the type 2 diabetes mellitus, the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead, an accumulation of amyloid in the pancreatic islets disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but patients exhibit a reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance. Type 2 diabetes is characterized by high rates of glucagon secretion into the blood, unresponsive to the concentration of glucose in the blood. Insulin is still secreted into the blood in response to the blood glucose. However, insulin levels are much higher than in healthy persons even when the blood sugar level is normal.
Diabetes
Type 2 diabetes mellitus
The therapy consists of injecting insulin to compensate the lack of production or the insulin resistance. Two main approaches exists: 1) To inject insulin at discrete time instants, when a higher level is needed (e.g., after lunch or dinner)
Therapy
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The therapy consists of injecting insulin to compensate the lack of production or the insulin resistance. Two main approaches exists: 2) To continuously inject insulin (insulin pump), to guarantee an adequate average level
Therapy
First insulin pump, developed by Dr. Arnold Kadish in 1963. Insulin pump was considered experimental upon its introduction; it was seen as a more viable option in the 70s; it become a popular option for managing diabetes in the 90s.
The therapy consists of injecting insulin to compensate the lack of production or the insulin resistance. Two main approaches exists: 2) To continuously inject insulin (insulin pump), to guarantee an adequate average level
Therapy
Modern insulin pumps.
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Insulin pumps are nowadays coupled with a feedback mechanisms to regulate the insulin release based on the glucose level in blood. These systems avoid the high insulin peak after the single injection, while at the same time they allow to follow not only an average insulin level but also its temporal variations due to food and physical activity. These systems are called “artificial pancreas”.
Therapy
Alternative to the “artificial pancreas” there is the “bioartificial pancreas”, which consists of implanted islets: microencapsulation with perm-selective coating
- f islets in hydrogels for graft immunoisolation
Therapy
Pareta, RA, Farney, AC, and Opara, EC. Design of a bioartificial pancreas. Pathobiology 2013, 80(4): 194-202.
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For example, breathable insulin VIDEO
Therapy
Finally, there exist alternative solutions in the literature and in the practice.
Decision support tool
Artificial (and also bioartificial) pancreas needs to design the feedback control. How much insulin to release to face the current and the future level of glucose?
Body Artificial pancreas Blood glucose External insulin + Residual insulin (if any)
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Practical work
First step:
- Develop (based on a literature paper) a model of the body
Body Artificial pancreas Blood glucose External insulin + Residual insulin (if any)
Practical work
Second step:
- Design a control strategy
Body Artificial pancreas Blood glucose External insulin + Residual insulin (if any)
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Lesson 15
Body model
For the “body model”, we will refer to:
Wang, Q, et al. Personalized state-space modeling of glucose dynamics for type 1 diabetes using continuously monitored glucose, insulin dose, and meal intake: an extended Kalman filter approach. Journal of Diabetes Science and Technology 2014, 8(2): 331-345.
Body model
Dynamic discrete autoregressive system Added error term Consider 1 minute
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Body model Body model
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Body model
Assume them to be constant
Practical work
To code the model (simple model directly derived from the paper)
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Practical work
Tasks: 1) Implement the model in a language (matlab, excel, c, …) 2) Set the coefficients not detailed in the paper to replicate the trend 3) Look at the system behavior under:
- A spike of insulin injection
- A constant release
In both cases, the mean value of the release shoud be tailored in order to respect a cyclic behavior (e.g., end of day = begin of day).
