Generation of target glucose values for a closed-loop operating mode of an insulin infusion system

• US 9,878,096 B2
• Filed: 08/13/2013
• Issued: 01/30/2018
• Est. Priority Date: 08/30/2012
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Roy, Anirban, Keenan, Desmond Barry, Mastrototaro, John J., Grosman, Benyamin, Parikh, Neha J.
• Primary Examiner(s): Lubin, Valerie
• Application Number:
  US13/966,101
• Publication Number:
  US 20140066886A1
• Time in Patent Office: 1,631 Days
• Field of Search: None
• 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 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 40/40 for the management of medical equipment or devices, e.g. scheduling maintenance or upgrades
• CPC Class Codes: G16H 50/00 ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

A controller for an insulin infusion device includes at least one processor device and at least one memory element that cooperate to provide a processor-implemented closed-loop start-up module. The start-up module is operated to initiate a closed-loop mode of the infusion device and to obtain a most recent sensor glucose value for the user. The start-up module also calculates a difference between the most recent sensor glucose value and a target glucose setpoint value. When the difference is less than or equal to a threshold value, the closed-loop insulin infusion rate is adjusted over time, based on a fixed final target glucose value that is derived from the target glucose setpoint value. When the difference is greater than the threshold, the infusion rate is adjusted over time, based on a dynamic final target glucose value that decreases over time toward the target glucose setpoint value.

Claims

1. An insulin infusion device comprising:

an insulin reservoir for insulin to be delivered from the insulin infusion device to a body of a user;

a processor architecture comprising at least one processor device; and

at least one memory element associated with the processor architecture, the at least one memory element storing processor-executable instructions that, when executed by the processor architecture, perform a method of controlling delivery of insulin from the insulin reservoir to the body of the user, the method comprising;

initiating a closed-loop operating mode of the insulin infusion device, wherein during the closed-loop operating mode the insulin infusion device receives sensor glucose values from a continuous glucose sensor, and automatically controls delivery of insulin to the body of the user in response to at least the received sensor glucose values;

in response to initiating the closed-loop operating mode, obtaining a most recent sensor glucose value for the user;

calculating a difference between the most recent sensor glucose value and a target glucose setpoint value;

when the calculated difference is less than or equal to a minimum threshold value, adjusting a closed-loop insulin infusion rate over time, based on a fixed final target glucose value that is derived from the target glucose setpoint value, and operating the insulin infusion device over time to deliver insulin from the insulin reservoir in accordance with the adjusted closed-loop insulin infusion rate; and

when the calculated difference is greater than the minimum threshold value, adjusting the closed-loop insulin infusion rate over time by;

calculating a dynamic glucose setpoint value for a current sampling point, wherein the dynamic glucose setpoint value is calculated in accordance with the expression DynSP(n)=cd₁·

DynSP(n−

1)+cd₂·

DynSP(n−

2)+cn₀·

DeltaGlu(n)+cn₁·

DeltaGlu(n−

1), where cd₁, cd₂, cn₀, and cn₁ are coefficients of the discretized second order transfer function model, and for an initial calculation of the dynamic glucose setpoint value, DeltaGlu(n) is the difference, at the current sampling point, between the most recent sensor glucose value and the target glucose setpoint value;

for the current sampling point, adding the calculated dynamic glucose setpoint value to the target glucose setpoint value to obtain a dynamic final target glucose value, wherein the dynamic final target glucose value is calculated in accordance with the expression FinalTarget(n)=Setpoint+DynSP(n), where n represents a current sampling point, FinalTarget(n) is the dynamic final target glucose value at the current sampling point, Setpoint is the target glucose setpoint value, and DynSP(n) is the dynamic glucose setpoint value at the current sampling point;

for the current sampling point, adjusting the closed-loop insulin infusion rate in accordance with the obtained dynamic final target glucose value;

for the current sampling point, operating the insulin infusion device to deliver insulin from the insulin reservoir in accordance with the adjusted closed-loop insulin infusion rate; and

repeating, for subsequent sampling points, the steps of calculating a dynamic glucose setpoint value, adding the calculated dynamic glucose setpoint value to the target glucose setpoint value, adjusting the closed-loop insulin infusion rate, and operating the insulin infusion device, wherein the method decreases the calculated dynamic glucose setpoint value over time such that the obtained dynamic final target glucose value approaches the target glucose setpoint value.

2. The insulin infusion device of claim 1, wherein the fixed final target glucose value is equal to the target glucose setpoint value.

3. The insulin infusion device of claim 1, wherein adjusting the closed-loop insulin infusion rate over time is performed in accordance with a proportional-integral-derivative insulin feedback (PID-IFB) control algorithm that calculates the closed-loop insulin infusion rate based on a proportional component, an integral component, and a derivative component, and further based on states of an insulin pharmacokinetic model corresponding to subcutaneous, plasma, and effective site compartments.

4. The insulin infusion device of claim 1, wherein each of cd₁, cd₂, and cn₁ is based on two time constants of the discretized second order transfer function model.

5. The insulin infusion device of claim 1, wherein:

DynSP(n−

1) is equal to zero for an initial calculation of the dynamic glucose setpoint value;

DynSP(n−

2) is equal to zero for the initial calculation of the dynamic glucose setpoint value; and

DeltaGlu(n−

1) is equal to zero for the initial calculation of the dynamic glucose setpoint value.

6. A closed-loop insulin infusion system comprising:

a continuous glucose sensor that generates sensor data indicative of sensor glucose values for a user; and

an insulin infusion device coupled to receive the sensor data generated by the continuous glucose sensor, the insulin infusion device comprising an insulin reservoir for insulin to be delivered from the insulin infusion device to the user, a processor architecture comprising at least one processor device and further comprising at least one memory element associated with the processor architecture, the at least one memory element storing processor-executable instructions that, when executed by the processor architecture, cause the insulin infusion device to perform a method comprising;

initiating a closed-loop operating mode of the insulin infusion device, wherein during the closed-loop operating mode the insulin infusion device receives sensor glucose values from the continuous glucose sensor, and automatically controls delivery of insulin to the body of the user in response to at least the received sensor glucose values;

in response to initiating the closed-loop operating mode, obtaining a most recent sensor glucose value for the user;

calculating a difference between the most recent sensor glucose value and a target glucose setpoint value;

when the calculated difference is less than or equal to a minimum threshold value, adjusting a closed-loop insulin infusion rate over time, based on a fixed final target glucose value that is derived from the target glucose setpoint value, and operating the insulin infusion device over time to deliver insulin from the insulin reservoir in accordance with the adjusted closed-loop insulin infusion rate;

when the calculated difference is greater than the minimum threshold value, adjusting the closed-loop insulin infusion rate over time by;

calculating a dynamic glucose setpoint value for a current sampling point, wherein the dynamic glucose setpoint value is calculated in accordance with the expression DynSP(n)=cd₁·

DynSP(n−

1)+cd₂·

DynSP(n−

2)+cn₀·

DeltaGlu(n)+cn₁·

DeltaGlu(n−

1), where cd₁, cd₂, cn₀, and cn₁ are coefficients of the discretized second order transfer function model, and for an initial calculation of the dynamic glucose setpoint value, DeltaGlu(n) is the difference, at the current sampling point, between the most recent sensor glucose value and the target glucose setpoint value;

for the current sampling point, adding the calculated dynamic glucose setpoint value to the target glucose setpoint value to obtain a dynamic final target glucose value, wherein the dynamic final target glucose value is calculated in accordance with the expression FinalTarget(n)=Setpoint+DynSP(n), where n represents a current sampling point, FinalTarget(n) is the dynamic final target glucose value at the current sampling point, Setpoint is the target glucose setpoint value, and DynSP(n) is the dynamic glucose setpoint value at the current sampling point;

for the current sampling point, adjusting the closed-loop insulin infusion rate in accordance with the obtained dynamic final target glucose value;

for the current sampling point, operating the insulin infusion device to deliver insulin from the insulin reservoir in accordance with the adjusted closed-loop insulin infusion rate; and

repeating, for subsequent sampling points, the steps of calculating a dynamic glucose setpoint value, adding the calculated dynamic glucose setpoint value to the target glucose setpoint value, adjusting the closed-loop insulin infusion rate, and operating the insulin infusion device, wherein the method decreases the calculated dynamic glucose setpoint value over time such that the obtained dynamic final target glucose value approaches the target glucose setpoint value.

7. The closed-loop insulin infusion system of claim 6, wherein adjusting the closed-loop insulin infusion rate over time is performed in accordance with a proportional-integral-derivative insulin feedback (PID-IFB) control algorithm that calculates the closed-loop insulin infusion rate based on a proportional component, an integral component, and a derivative component, and further based on states of an insulin pharmacokinetic model corresponding to subcutaneous, plasma, and effective site compartments.

8. The closed-loop insulin infusion system of claim 6, wherein each of cd₁, cd₂, and cn₁ is based on two time constants of the discretized second order transfer function model.

9. The closed-loop insulin infusion system of claim 6, wherein:

DynSP(n−

1) is equal to zero for an initial calculation of the dynamic glucose setpoint value;

DynSP(n−

2) is equal to zero for the initial calculation of the dynamic glucose setpoint value; and

DeltaGlu(n−

1) is equal to zero for the initial calculation of the dynamic glucose setpoint value.

10. The closed-loop insulin infusion system of claim 6, wherein the fixed final target glucose value is equal to the target glucose setpoint value.