Fully automated control system for type 1 diabetes

• US 8,273,052 B2
• Filed: 07/30/2010
• Issued: 09/25/2012
• Est. Priority Date: 05/13/2005
• Status: Active Grant

• Current Assignee: Trustees of Boston University
• Original Assignee: Trustees of Boston University
• Inventors: Damiano, Edward, El-Khatib, Firas
• Primary Examiner(s): Koharski, Christopher D
• Assistant Examiner(s): PATEL, PRITESH ASHOK
• Application Number:
  US12/847,153
• Publication Number:
  US 20110106049A1
• Time in Patent Office: 788 Days
• Field of Search: 604/67, 604/65, 604/66, 604/131
• US Class Current: 604/67
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

An augmented, adaptive algorithm utilizing model predictive control (MPC) is developed for closed-loop glucose control in type 1 diabetes. A linear empirical input-output subject model is used with an MPC algorithm to regulate blood glucose online, where the subject model is recursively adapted, and the control signal for delivery of insulin and a counter-regulatory agent such as glucagon is based solely on online glucose concentration measurements. The MPC signal is synthesized by optimizing an augmented objective function that minimizes local insulin accumulation in the subcutaneous depot and control signal aggressiveness, while simultaneously regulating glucose concentration to a preset reference set point. The mathematical formulation governing the subcutaneous accumulation of administered insulin is derived based on nominal temporal values pertaining to the pharmacokinetics (time-course of activity) of insulin in human, in terms of its absorption rate, peak absorption time, and overall time of action. The MPC algorithm is also formulated to provide control action with an integral effect, and in essence minimizes overall drug consumption. When employed as a modulator in an automated integrated glucose-control system for type 1 diabetes, the control algorithm provides the system with self-learning capability that enables it to operate under unrestricted activity of the subject.

Claims

1. A system for automatic control of blood glucose level of a subject, comprising:

a glucose sensor operative to continually sense a glucose level of the subject and generate a corresponding glucose level signal;

a delivery device operative to deliver doses of insulin to the subject in response to an insulin dose control signal; and

a controller operative to generate the insulin dose control signal as a function of the weight of the subject and time-varying glucose levels of the subject as represented by the glucose level signal over time, the controller employing a control algorithm including;

generating the insulin dose control signal based on (a) the glucose level signal, and (b) accumulation of insulin in the subject due to finite rate of utilization.

2. A system according to claim 1 wherein the controller is further operative to generate the insulin dose control signal to provide a basal rate of delivery of insulin when the control algorithm reveals no need for a dose of insulin that exceeds a basal rate of delivery.

3. A system according to claim 2 wherein the basal rate is determined by a user-provided basal-rate value.

4. A system according to claim 3 wherein the controller employs a default basal-rate value based on the weight of the subject when the user-provided basal-rate value is either absent or greater than a predetermined maximum allowable value.

5. A system according to claim 4 wherein the controller adapts the basal rate online based on the glucose level signal over time.

6. A system according to claim 5 wherein the controller is operative to automatically impose respective constraints on the insulin dose control signal corresponding to a maximum allowable dose of insulin.

7. A system according to claim 1 wherein the glucose sensor is integrated with the delivery device.

8. A system according to claim 7 wherein the delivery device comprises a mechanically driven infusion mechanism and a cartridge for insulin.

9. A system according to claim 1, wherein delivery by the delivery device is to a subcutaneous space in the subject.

10. A system according to claim 1, wherein:

the delivery device is further operative to deliver doses of a counter-regulatory agent to the subject in response to a counter-regulatory-agent dose control signal; and

the controller is further operative to generate the counter-regulatory-agent dose control signal as a function of the weight of the subject and the time-varying glucose levels of the subject as represented by the glucose level signal over time.

11. A system according to claim 10 wherein the counter-regulatory agent comprises glucagon.

12. A system according to claim 10 wherein generating the counter-regulatory-agent dose control signal accounts for accumulation in the subject from past doses of the counter-regulatory agent.

13. A system according to claim 1 wherein the generating of the insulin dose control signal based on the accumulation of insulin in the subject provides a controlling effect on aggressiveness of the control algorithm.

14. A system according to claim 1 wherein generating the insulin dose control signal is performed based on a combination of one or more first mathematical expressions of a relationship between the insulin dose control signal and the glucose level signal and one or more second mathematical expressions of an estimation of the accumulation of insulin in the subject based on the insulin dose control signal.

15. A system according to claim 14 wherein generating the insulin dose control signal based on the glucose level signal includes scaled summations of past and ongoing components of the insulin dose control signal and the glucose level signal, and wherein the estimation of the accumulation of insulin in the subject is obtained based on a scaled summation of accumulation contributions based on the insulin dose control signal, including past, ongoing, and/or future components of the insulin dose control signal.

16. A system according to claim 14 wherein the estimation of the accumulation of insulin in the subject is obtained by feedback of the insulin dose control signal.

17. A system according to claim 14 wherein the first and second mathematical expressions are used to obtain a control objective.

18. A method for automatic control of the blood glucose level of a subject, comprising:

continually sensing a glucose level of the subject and generating a corresponding glucose level signal;

operating a delivery device to deliver doses of insulin to the subject in response to an insulin dose control signal; and

generating the insulin dose control signal as a function of the weight of the subject and time-varying glucose levels of the subject as represented by the glucose level signal over time, by a control algorithm including;

generating the insulin dose control signal based on (a) the glucose level signal, and (b) accumulation of insulin in the subject due to finite rate of utilization.

19. A method according to claim 18 further comprising generating the insulin dose control signal to provide a basal rate of delivery of insulin when the control algorithm reveals no need for a dose of insulin that exceeds a basal rate of delivery.

20. A method according to claim 19 wherein the basal rate is determined by a user-provided basal-rate value.

21. A method according to claim 20 wherein a default basal-rate value based on the weight of the subject is employed when the user-provided basal-rate value is either absent or greater than a predetermined maximum allowable value.

22. A method according to claim 21 wherein the basal rate is adapted online based on the glucose level signal over time.

23. A method according to claim 22 further comprising automatically imposing constraints on the insulin dose control signal corresponding to a maximum allowable dose of insulin.

24. A method according to claim 18 wherein delivery by the delivery device is to a subcutaneous space in the subject.

25. A method according to claim 18 further comprising:

operating the delivery device to deliver doses of a counter-regulatory agent to the subject in response to a counter-regulatory-agent dose control signal; and

generating the counter-regulatory-agent dose control signal as a function of the weight of the subject and the time-varying glucose levels of the subject as represented by the glucose level signal over time.

26. A method according to claim 25 wherein generating the counter-regulatory-agent dose control signal accounts for accumulation in the subject from past doses of the counter-regulatory agent.

27. A method according to claim 25 wherein the counter-regulatory agent comprises glucagon.

28. A method according to claim 18 wherein the generating of the insulin dose control signal based on (b) accumulation of insulin in the subject provides a controlling effect on aggressiveness of the control algorithm.

29. A method according to claim 18 wherein generating the insulin dose control signal is performed based on a combination of one or more first mathematical expressions of a relationship between the insulin dose control signal and the glucose level signal and one or more second mathematical expressions of an estimation of the accumulation of insulin in the subject based on the insulin dose control signal.

30. A method according to claim 29 wherein the relationship between the insulin dose control signal and the glucose level signal includes scaled summations of past and ongoing components of the insulin dose control signal and the glucose level signal, and wherein the estimation of the accumulation of insulin in the subject is obtained based on a scaled summation of accumulation contributions based on the insulin dose control signal, including past, ongoing, and/or future components of the insulin dose control signal.

31. A method according to claim 29 wherein the estimation of the accumulation of insulin in the subject is obtained by feedback of the insulin dose control signal.

32. A method according to claim 29 wherein the first and second mathematical expressions are used to obtain a control objective.

33. A controller for use in a system for automatic control of blood glucose level of a subject, the controller being operative to generate an insulin dose control signal as a function of the weight of the subject and time-varying glucose levels of the subject as represented by an glucose level signal over time, the glucose level signal being generated by a glucose sensor operative to continually sense a glucose level of the subject, the insulin dose control signal controlling the delivery of doses of insulin to the subject by a delivery device, the controller employing a control algorithm including:

generating the insulin dose control signal based on (a) the glucose level signal, and (b) accumulation of insulin in the subject due to finite rate of utilization.