LQG artificial pancreas control system and related method

• US 10,173,006 B2
• Filed: 06/20/2008
• Issued: 01/08/2019
• Est. Priority Date: 06/21/2007
• Status: Active Grant

• Current Assignee: University of Virginia
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Patek, Stephen D., Breton, Marc D.
• Primary Examiner(s): Natnithithadha, Navin
• Assistant Examiner(s): Messersmith, Eric
• Application Number:
  US12/665,420
• Publication Number:
  US 20100249561A1
• Time in Patent Office: 3,854 Days
• Field of Search: 600347, 600365
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 20/60 relating to nutrition control, e.g. diets
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

The invention relates to a methods and systems for determining an insulin dosing recommendation. The invention employs Linear Quadratic methodology to determine the insulin dosing recommendation based on a patient'"'"'s present physiological state, which is estimated by an adaptive filter methodology employing a dynamic model, which utilizes real-time measurements of blood glucose concentration.

Claims

1. A computer-implemented method for treating a patient with insulin, the patient suffering from diabetes mellitus (DM), by determining an insulin dosing recommendation to achieve an optimal glycemic control, the method comprising:

applying, by a processor, an adaptive observer scheme to estimate a present physiological state of a patient based on at least one measurement of blood glucose concentration in the patient, wherein the adaptive observer scheme models the present physiological state of the patient using a dynamic model that employs at least one physiological parameter;

applying, by a processor, the estimated physiological state to a Linear Quadratic regulator to determine an insulin dosing recommendation based on the present physiological state so estimated, and

outputting, by a processor, the insulin dosing recommendation to a user to determine an appropriate insulin injection to be administered to said patient; and

modifying, in the dynamic model, at least one physiological parameter based on an additional measurement of blood glucose concentration and blood insulin concentration from the patient to ensure absence of a bias between an estimated plasma glucose concentration and an actual plasma glucose concentration at steady state.

3. A method according to claim 1, wherein the method further comprises an initial step of customizing the dynamic model by fixing at least one physiological parameter.

4. A method according to claim 3, wherein at least one physiological parameter is fixed at an average value, wherein the average value represents an average of values measured for a plurality of subjects.

5. A method according to claim 1, further comprising determining an optimal gain for the dynamic model.

6. A method according to claim 1, wherein the dynamic model is optimized using a Kalman filter.

7. A method according to claim 1, wherein the dynamic model is optimized using an extended Kalman filter.

2. A computer-implemented method for determining an insulin dosing recommendation comprising:

applying, by a processor, an adaptive observer scheme to estimate a present physiological state of a patient based on at least one measurement of blood glucose concentration in the patient, wherein the adaptive observer scheme models the present physiological state of the patient using a dynamic model;

applying, by a processor, the estimated physiological state to a Linear Quadratic regulator to determine an insulin dosing recommendation based on the present physiological state so estimated, and

outputting, by a processor, the insulin dosing recommendation to a user to determine an appropriate insulin injection to be administered to said patient, wherein the dynamic model is one of;

a minimal model of glucose kinetics (MMGK), and wherein the MMGK is augmented to take into account transport of insulin from an injection site to central circulation, as well as transport of glucose from the patient'"'"'s stomach to central circulation;

a reduced meal model (RMM), and wherein the RMM is augmented using two subcutaneous insulin equations, an interstitial glucose equation, and modeling a meal via a single equation; and

an augmented meal model (AMM), which is augmented by two additional insulin states for transport and an additional glucose compartment (interstitium).

8. A computer-implemented method for treating a patient with insulin, the patient suffering from diabetes mellitus (DM), by determining an insulin dosing recommendation to achieve an optimal glycemic control, the method comprising:

taking a measurement of blood glucose concentration in a patient at each of a plurality of actuation times;

applying, by a processor, an adaptive filter scheme at each actuation time to generate an estimate of the patient'"'"'s present physiological state based on the most recent measurement of blood glucose concentration, wherein the adaptive filter scheme models the present physiological state of the patient using a dynamic model that employs at least one physiological parameter;

storing, by a processor, the estimate of the patient'"'"'s present physiological state;

using, by a processor, Linear Quadratic methodology to determine an insulin dosing recommendation based on the estimate of the patient'"'"'s present physiological state and based on any stored estimates of the patient'"'"'s physiological state,

outputting, by a processor, the insulin dosing recommendation to a user to determine an appropriate insulin injection to be administered to said patient;

modifying, in the dynamic model, at least one physiological parameter based on an additional measurement of blood glucose concentration and blood insulin concentration from the patient to ensure absence of a bias between an estimated plasma glucose concentration and an actual plasma glucose concentration at steady state.

9. A method according to claim 8, wherein the actuation times are spaced at regular intervals of less than 15 minutes.

10. An artificial pancreas control system for treating a patient with insulin, the patient suffering from diabetes mellitus (DM), by determining an insulin dosing recommendation to achieve an optimal glycemic control, the system comprising:

an observer, comprising a programmable computer controller programmed to receive real-time measurements of blood glucose concentration in a patient, and to apply an adaptive filter scheme to estimate a present physiological state of a patient based on the measurements of blood glucose concentration, wherein the adaptive filter scheme models the present physiological state of the patient using a dynamic model that employs at least one physiological parameter; and

an LQ Regulator, comprising a second programmable computer controller programmed to receive the present physiological state estimation from the observer, and to use Linear Quadratic methodology to determine the insulin dosing recommendation based on the present physiological state;

wherein the second programmable computer controller is further configured to present the insulin dosing recommendation;

modifying, in the dynamic model, at least one physiological parameter based on an additional measurement of blood glucose concentration and blood insulin concentration from the patient to ensure absence of a bias between an estimated plasma glucose concentration and an actual plasma glucose concentration at steady state.

11. An artificial pancreas control system according to claim 10, wherein the second programmable computer controller is programmed to present the insulin dosing recommendation to the patient in an open-loop application.

12. An artificial pancreas control system according to claim 10, wherein the second programmable computer controller is programmed to present the insulin dosing recommendation directly to an insulin pump in a closed-loop application.