Glucose level control system with offline control based on preceding periods of online control

• US 10,543,313 B2
• Filed: 07/28/2016
• Issued: 01/28/2020
• Est. Priority Date: 01/31/2014
• Status: Active Grant

• Current Assignee: Trustees of Boston University
• Original Assignee: Boston University
• Inventors: Damiano, Edward R., El-Khatib, Firas H.
• Primary Examiner(s): Bosworth, Kami A
• Assistant Examiner(s): Swanson, Leah J
• Application Number:
  US15/221,871
• Publication Number:
  US 20160331898A1
• Time in Patent Office: 1,279 Days
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2005/14296 Pharmacokinetic models
• CPC Class Codes: A61M 2202/0486 Glucose
• CPC Class Codes: A61M 2202/07 Proteins
• CPC Class Codes: A61M 2205/3584 using modem, internet or bluetooth
• CPC Class Codes: A61M 2205/50 with microprocessors or computers
• CPC Class Codes: A61M 2205/502 User interfaces, e.g. screens or keyboards
• CPC Class Codes: A61M 2230/005 Parameter used as control input for the apparatus
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/16827 controlling delivery of multiple fluids, e.g. sequencing, mixing or via separate flow-paths infusion of multiple fluids without using a controller A61M5/1407
• 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: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 20/17 delivered via infusion or injection

Abstract

Apparatus and methods calculate and deliver doses of insulin and optionally glucagon into a subject. Online operation controls delivery of correction doses of insulin automatically in response to regular glucose measurements from a sensor, and offline operation calculates and delivers correction doses based on isolated glucose measurements and information gathered autonomously during preceding online operation. In another aspect, offline operation includes automatically calculating and administering meal doses based on information gathered autonomously during preceding periods of online operation. Both methods include generating relevant control parameters tailored to the individual and continually converged upon and potentially modulated during online operation. The control parameters are employed in real time during periods of offline operation to regulate glucose level without the need for user-provided control parameters such as correction factors and insulin-to-carbohydrate ratios.

Claims

1. A glucose level control system, comprising:

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

an insulin delivery device operative in response to an insulin dose control signal to infuse insulin into the subject; and

a controller having online operation and offline operation to generate the insulin dose control signal to achieve and maintain euglycemia in the subject, online operation employing a control algorithm including (i) regular administration of correction doses of insulin based on control parameters of the control algorithm and regular periodic sampling of glucose levels via the glucose sensor, and (ii) autonomously adjusting the control parameters to tailor the control parameters to the subject, offline operation including (iii) evolving a state of the control algorithm over time without sampling of glucose levels and without automatic administration of the correction doses of insulin, and (iv) correction dosing operations each including administration of a correction dose of insulin in response to an isolated glucose measurement provided to the controller, the correction dose being calculated by the controller based on the isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the correction dosing operation.

2. A glucose level control system according to claim 1, wherein the control algorithm employs regular periodic sampling intervals, and wherein evolving the control algorithm during the offline operation includes updating time effects of insulin previously administered to the subject.

3. A glucose level control system according to claim 2, wherein each correction dose during the offline operation includes calculating estimated glucose levels for immediately preceding offline sampling intervals using interpolation between a current isolated glucose measurement and a sample of glucose level from a most recent period of online operation.

4. A glucose level control system according to claim 1, wherein the correction dose is calculated by the controller during the offline operation assuming a first target glucose level or range higher than a second target glucose level or range assumed during online operation.

5. A glucose level control system according to claim 1, wherein the isolated glucose measurement is provided to the controller via a user interface used by the subject, and wherein each correction dosing operation includes use of one or more user interface functions selected from (i) the subject confirming that the correction dose is to be delivered, (ii) displaying a value of the correction dose to the subject, and (iii) accepting a modified value from the subject for use as the correction dose instead of the correction dose calculated by the controller.

6. A glucose level control system according to claim 1, wherein online operation of the control algorithm further includes regular administration of correction doses of a counter-regulatory agent based on the control parameters of the control algorithm and the regular periodic sampling of glucose levels, and wherein the offline operation further includes counter-regulatory agent dosing operations each including administration of a dose of a counter-regulatory agent in response to a second isolated glucose measurement provided to the controller and calculated by the controller based on the second isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the counter-regulatory agent dosing operation.

7. A glucose level control system according to claim 6, wherein the correction dose of insulin is calculated by the controller during periods when a counter-regulatory delivery channel or device is unavailable and assuming a first target glucose level or range higher than a second target glucose level or range assumed when the counter-regulatory delivery channel or device is available.

8. A glucose level control system according to claim 1, wherein in both the online and offline operations, the control algorithm allows the subject to issue a microburst or rescue dose of counter-regulatory agent, a value of the microburst or rescue dose being calculated by the controller.

9. A glucose level control system according to claim 1, wherein online operation of the control algorithm includes (v) administration of meal doses of insulin in response to a meal dose control input and automatically calculated by the controller based on preceding meal doses and corresponding prandial and post-prandial responses of the subject as reflected in the sampling of glucose levels via the glucose sensor and (vi) autonomously adjusting control parameters used to determine meal dose size to tailor the control parameters to the subject, and wherein offline operation including meal dosing operations each including administration of a meal dose of insulin in response to the meal dose control input and calculated by the controller based on a second isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the meal dosing operation.

10. A method of operating a controller for a glucose level control system having a glucose sensor and an insulin delivery device, the glucose sensor being operative to continually measure a glucose level of a subject and generate a corresponding glucose level signal, the insulin delivery device being operative in response to an insulin dose control signal to infuse insulin into the subject, comprising:

performing online operation employing a control algorithm including (i) regular administration of correction doses of insulin based on control parameters of the control algorithm and regular periodic sampling of glucose levels via the glucose sensor, and (ii) autonomously adjusting the control parameters to tailor the control parameters to the subject; and

performing offline operation including (iii) evolving a state of the control algorithm over time without sampling of glucose levels and without automatic administration of the correction doses of insulin, and (iv) correction dosing operations each including administration of a correction dose of insulin in response to an isolated glucose measurement provided to the controller, the correction dose being calculated by the controller based on the isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the correction dosing operation.

11. A method according to claim 10, wherein the control algorithm employs regular periodic sampling intervals, and wherein evolving the control algorithm during the offline operation includes updating time effects of insulin previously administered to the subject.

12. A method according to claim 11, wherein each correction dose during the offline operation includes calculating estimated glucose levels for immediately preceding offline sampling intervals using interpolation between a current isolated glucose measurement and a sample of glucose level from a most recent period of online operation.

13. A method according to claim 10, wherein the correction dose is calculated by the controller during the offline operation assuming a first target glucose level or range higher than a second target glucose level or range assumed during online operation.

14. A method according to claim 10, wherein the isolated glucose measurement is provided to the controller via a user interface used by the subject, and wherein each correction dosing operation includes use of one or more user interface functions selected from (i) the subject confirming that the correction dose is to be delivered, (ii) displaying a value of the correction dose to the subject, and (iii) accepting a modified value from the subject for use as the correction dose instead of the correction dose calculated by the controller.

15. A method according to claim 10, wherein online operation of the control algorithm further includes regular administration of correction doses of a counter-regulatory agent based on the control parameters of the control algorithm and the regular periodic sampling of glucose levels, and wherein the offline operation further includes counter-regulatory agent dosing operations each including administration of a correction dose of a counter-regulatory agent in response to a second isolated glucose measurement provided to the controller and calculated by the controller based on the second isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the counter-regulatory agent dosing operation.

16. A method according to claim 15, wherein the correction dose of insulin is calculated by the controller during periods when a counter-regulatory delivery channel or device is unavailable and assuming a first target glucose level or range higher than a second target glucose level or range assumed when the counter-regulatory delivery channel or device is available.

17. A method according to claim 10, wherein in both the online and offline operations, the control algorithm allows the subject to issue a microburst or rescue dose of counter-regulatory agent, a value of the microburst or rescue dose being calculated by the controller.

18. A method according to claim 10, wherein online operation of the control algorithm includes (v) administration of meal doses of insulin in response to a meal dose control input and automatically calculated by the controller based on preceding meal doses and corresponding prandial and post-prandial responses of the subject as reflected in the sampling of glucose levels via the glucose sensor and (vi) autonomously adjusting control parameters used to determine meal dose size to tailor the control parameters to the subject, and wherein offline operation including meal dosing operations each including administration of a meal dose of insulin in response to the meal dose control input and calculated by the controller based on a second isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the meal dosing operation.

19. A glucose level control system, comprising:

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

an insulin delivery device operative in response to an insulin dose control signal to infuse insulin into the subject; and

a controller having online operation and offline operation to generate the insulin dose control signal to achieve and maintain euglycemia in the subject, online operation employing a control algorithm including (i) administration of meal doses of insulin in response to a meal dose control input and automatically calculated by the controller based on preceding meal doses and corresponding prandial and post-prandial responses of the subject as reflected in sampling of glucose levels via the glucose sensor and (ii) autonomously adjusting control parameters used to determine meal dose size to tailor the control parameters to the subject, offline operation including (iii) evolving a state of the control algorithm over time without sampling of glucose levels, and (iv) meal dosing operations each including administration of a meal dose of insulin in response to the meal dose control input and calculated by the controller based on an isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the meal dosing operation.

20. A glucose level control system according to claim 19, wherein online operation of the control algorithm further includes (i) regular administration of correction doses of insulin based on control parameters of the control algorithm and regular periodic sampling of glucose levels via the glucose sensor, and (ii) autonomously adjusting the control parameters to tailor the control parameters to the subject, and wherein the offline operation further includes (iii) evolving the state of the control algorithm over time without sampling of glucose levels and without automatic administration of the correction doses of insulin, and (iv) correction dosing operations each including administration of a correction dose of insulin in response to a second isolated glucose measurement provided to the controller, the correction dose being calculated by the controller based on the second isolated glucose measurement, the control parameters, and the state of the control algorithm as evolved at the time of the correction dosing operation.