PREDICTIVE CONTROL BASED SYSTEM AND METHOD FOR CONTROL OF INSULIN DELIVERY IN DIABETES USING GLUCOSE SENSING

• US 20100262117A1
• Filed: 10/31/2008
• Published: 10/14/2010
• Est. Priority Date: 11/02/2007
• Status: Abandoned Application

• Current Assignee: University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Raimondo, Davide Martino, Magni, Lalo, Dalla Man, Chiara, De Nicolao, Giuseppe, Cobelli, Claudio
• Application Number:
  US12/740,275
• Publication Number:
  US 20100262117A1
• Time in Patent Office: Days
• US Class Current: 604/504
• 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: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2230/201 Glucose concentration
• 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 50/50 for simulation or modelling of medical disorders

Abstract

A system and method for providing optimal insulin injections to a subject, using a controller, a continuous glucose monitor, and an insulin delivery unit is disclosed. The controller possesses a discrete-time, linear model predictive control law, means for sending information to the insulin delivery unit, and means for receiving information from the CGM. The control law implemented is derived from a discrete-time model of glucose insulin dynamics and an aggressiveness parameter. The result is that using only glucose measurements obtained from sensor readings and, prior values of external insulin infusion and meal and exercise announcement the optimal insulin injection necessary to safely regulate blood glucose can be calculated.

Claims

1. A system for providing optimal insulin injections to a subject to be used with a continuous glucose monitor (CGM) and an insulin delivery unit, said system comprising:

a controller, wherein said controller comprises;

a discrete-time, linear model predictive control law,

means for sending information to said insulin delivery unit, and

means for receiving information from said CGM.

2. The system of claim 1, wherein said control law is derived from a discrete-time model of glucose insulin dynamics and an aggressiveness parameter.

3. The system of claim 2, wherein said control law is derived from said discrete-time model of glucose insulin dynamics by linearizing a model about an equilibrium point that is associated with the average basal values of a population model.

4. The system of claim 3, wherein said control law may be expressed as

u=κ

^MPC(x).

5. The system of claim 2, wherein said aggressiveness parameter is determined from data that is individualized to said subject.

6. The system of claim 5, wherein said aggressiveness parameter is determined according to suitable features of the subject, wherein said features comprise one or more of the following input parameters:

clinical parameters including but not limited to body weight, average total daily utilization insulin, and carbohydrate ratio and

parameters obtained from insulin and glucose data collected during a screening visit.

7. The system of claim 6, wherein said aggressiveness parameter is given by the equation

8. The system of claim 7, wherein one or more of said regression coefficients are selected according to whether the subject is a member of one or more of a set of predefined classes.

9. The system of claim 8, wherein said set of predefined classes includes one or more of the following:

child, adolescent, and adult.

10. The system of claim 2, wherein said aggressiveness parameter is determined off-line.

11. The system of claim 2, wherein said aggressiveness parameter represents how aggressively the controller should adjust its insulin output to achieve a desired glucose level in a subject.

12. The system of claim 2, wherein said discrete-time model of glucose insulin dynamics describes deviations from the subject'"'"'s fasting glucose concentration and basal insulin rate.

13. The system of claim 12, wherein said discrete-time model of glucose insulin dynamics is represented by the following state space equations:

δ

x(k+1)=A_Dδ

x(k)+B_Duδ

u(k)+B_Ddd(k)

δ

y(k)=C_Dδ

x(k)

where δ

x(k)=x(kT_s)−

x, δ

u(k)=u(kT_s)−

ū and

δ

y(k)=y(kT_s)−

y.

14. The system of claim 2, wherein, for a given stage corresponding to a discrete time period, using said control law, a first insulin rate is determined by solving a finite horizon optimal control problem so that a cost function is minimized.

15. The system of claim 14, wherein, for a given stage corresponding to a discrete time period, said first insulin rate is determined by considering a set of parameters, said set of parameters comprising one or more of the following:

a state vector,

target glucose concentration, and

future glucose disturbances.

16. The system of claim 15, wherein said state vector is expressed as:

17. The system of claim 15, wherein said vector of target glucose concentrations is expressed as:

18. The system of claim 15, wherein said future glucose disturbances are expressed as:

19. The system of claim 15, wherein said future glucose disturbances represent meal announcements.

20. The system of claim 15, wherein said cost function is expressed as:

21. The system of claim 15, wherein said first insulin rate is determined by considering a set of additional operational parameters, said set of additional operational parameters comprising one or more of the following:

upper limit on the allowable glucose level in the subject,

lower limit on the allowable glucose level in the subject,

prediction horizon for achieving target glucose level, and

control horizon for future optimal insulin injections.

22. The system of claim 21, wherein said additional operational parameters have associated weight factors which indicate their relative importance.

23. The system of claim 21, wherein said prediction horizon is between about two and about four hours.

24. The system of claim 21, wherein said control horizon is between about two and about four hours.

25. The system of claim 15, wherein a second insulin rate is determined by applying discretization and safety filters to said first insulin rate.

26. The system of claim 25, wherein said safety filters include one or more of the following:

ensure that the rate of insulin applied does not exceed a certain limit within a certain time period,

ensure that the rate of insulin applied does not exceed a certain limit within a certain time period after a meal, and

ensure that basal rate does not exceed a certain percentage of the subject specified basal rate per hour.

27. The system of claim 25, wherein said safety filters include a safety filter to ensure that no more than about 3 units of bolus insulin are applied within a one hour period.

28. The system of claim 25, wherein said safety filters include a safety filter to ensure that no more than about 10 units of bolus insulin per hour (not counting basal insulin) are applied within about 2 hours of a meal.

29. The system of claim 25, wherein said safety filters include a safety filter to ensure that the basal rate does not exceed about 150% of the subject'"'"'s specified basal rate per hour.

30. The system of claim 25, wherein the controller sends information to the insulin delivery unit based upon the second insulin rate, said information indicating a current optimal insulin injection.

31. The system of claim 1, wherein said control law is derived from a continuous-time model of glucose insulin dynamics and an aggressiveness parameter.

32. The system of claim 1, wherein the controller receives information from said CGM at regular time intervals.

33. The system of claim 32, wherein said time intervals are approximately one minute apart.

34. The system of claim 32, wherein the duration of said time intervals may be varied.

35. The system of claim 1, wherein the controller sends information to said insulin delivery unit at regular time intervals.

36. The system of claim 35, wherein said time intervals are approximately fifteen minutes apart.

37. The system of claim 35, wherein the duration of said regular time intervals may be varied.

38. The system of claim 1, wherein the controller receives information from the CGM through a wireless connection.

39. The system of claim 1, wherein the controller receives information from the CGM through a wired connection.

40. The system of claim 1, wherein the controller communicates with the insulin delivery unit through a wireless connection.

41. The system of claim 1, wherein the controller communicates with the insulin delivery unit through a wired connection.

42. The system of claim 1, wherein the system is fully within the body of the subject.

43. The system of claim 1, wherein the system is partially within the body of the subject.

44. The system of claim 1, wherein the controller is within or attached to said CGM.

45. The system of claim 1, wherein the controller is within or attached to said insulin delivery unit.

46. The system of claim 1, wherein said insulin delivery unit delivers insulin to the subject upon receiving a command from the controller.

47. The system of claim 1, wherein said insulin delivery unit is comprised of an insulin pump.

48. The system of claim 47, wherein said insulin pump is the Omnipod from Insulet corporation.

49. The system of claim 47, wherein said insulin pump is the Deltec Cozmo from Smiths Medical.

50. The system of claim 1, wherein said insulin delivery unit comprises an insulin reservoir.

51. The system of claim 1, wherein said insulin delivery unit comprises a cannula for subcutaneous insertion.

52. The system of claim 1, wherein said CGS is the Navigator from Abbott Diabetes Care.

53. The system of claim 1, wherein said CGS is the Dexcom from Dexcom, Inc.

54. The system of claim 1, wherein said CGS is the Guardian/Paradigm from Medtronic.

55. The system of claim 1, wherein said subject is a human being.

56. A system for providing optimal insulin injections to a subject, said system comprising:

a continuous glucose monitor (CGM),

an insulin delivery unit, and

a controller, wherein said controller comprises;

a discrete-time, linear model predictive control law,

means for sending information to said insulin delivery unit, and

means for receiving information from said CGM.

57. A system for providing optimal insulin injections to a subject to be used with a continuous glucose monitor (CGM), said system comprising:

an insulin delivery unit, and

a controller, wherein said controller comprises;

a discrete-time, linear model predictive control law,

means for sending information to said insulin delivery unit, and

means for receiving information from said CGM.

58. A system for providing optimal insulin injections to a subject to be used with an insulin delivery unit, said system comprising:

a continuous glucose monitor (CGM), and

a controller, wherein said controller comprises;

a discrete-time, linear model predictive control law,

means for sending information to said insulin delivery unit, and

means for receiving information from said CGM.

59. A computer method for providing optimal insulin injections to a subject to be used with a continuous glucose monitor (CGM) and an insulin delivery unit, said method comprising:

providing a discrete time linear model predictive control law,

sending information to an insulin delivery unit, and

receiving information from the CGM.

60. The method of claim 59, wherein said control law is derived from a discrete-time model of glucose insulin dynamics and an aggressiveness parameter.

61. The method of claim 60, wherein said control law is derived from said discrete-time model of glucose insulin dynamics by linearizing a model about an equilibrium point that is associated with the average basal values of a population model.

62. The method of claim 61, wherein said control law may be expressed as

u=κ

^MPC(X).

63. The method of claim 60, wherein said aggressiveness parameter is determined from data that is individualized to said subject.

64. The method of claim 63, wherein said aggressiveness parameter is determined according to suitable features of the subject, wherein said features comprise one or more of the following input parameters:

clinical parameters including but not limited to body weight, average total daily utilization insulin, and carbohydrate ratio, and parameters obtained from insulin and glucose data collected during a screening visit.

65. The system of claim 64, wherein said aggressiveness parameter is given by the equation

66. The method of claim 65, wherein one or more of said regression coefficients are selected according to whether the subject is a member of one or more of a set of predefined classes.

67. The method of claim 66, wherein said set of predefined classes includes one or more of the following:

child, adolescent, and adult.

68. The method of claim 60, wherein said aggressiveness parameter is determined off-line.

69. The method of claim 60, wherein said aggressiveness parameter represents how aggressively the controller should adjust its insulin output to achieve a desired glucose level in a subject.

70. The method of claim 60, wherein said discrete-time model of glucose insulin dynamics describes deviations from the subject'"'"'s fasting glucose concentration and basal insulin rate.

71. The method of claim 70, wherein said discrete-time model of glucose insulin dynamics is represented by the following state space equations:

δ

x(k+1)=A_Dδ

x(k)+B_Duδ

u(k)+B_Ddd(k)

δ

y(k)=C_Dδ

x(k)

where δ

x(k)=x(kT_s)−

x, δ

u(k)=u(kT_s)−

ū and

δ

y(k)=y(kT_s)−

y.

72. The method of claim 60, wherein said method further comprising determining a first insulin rate by solving a finite horizon optimal control problem so that a cost function is minimized.

73. The method of claim 72, further comprising determining said first insulin rate by considering a set of parameters, said set of parameters comprising one or more of the following:

a state vector,

target glucose concentration, and

future glucose disturbances.

74. The method of claim 73, wherein said state vector is expressed as:

75. The method of claim 73, wherein said vector of target glucose concentrations is expressed as:

76. The method of claim 73, wherein said future glucose disturbances are expressed as:

77. The method of claim 73, wherein said future glucose disturbances represent meal announcements.

78. The method of claim 73, wherein said cost function is expressed as:

79. The method of claim 73, further comprising determining said first insulin rate by considering a set of additional operational parameters, said set of additional operational parameters comprising one or more of the following:

upper limit on the allowable glucose level in the subject,

lower limit on the allowable glucose level in the subject,

prediction horizon for achieving target glucose level, and

control horizon for future optimal insulin injections.

80. The method of claim 79, wherein said additional operational parameters have associated weight factors which indicate their relative importance.

81. The method of claim 79, wherein said prediction horizon is between about two and about four hours.

82. The method of claim 79, wherein said control horizon is between about two and about four hours.

83. The method of claim 73, further comprising determining a second insulin rate by applying discretization and safety filters to said first insulin rate.

84. The method of claim 83, wherein said safety filters include one or more of the following:

ensuring that the rate of insulin applied does not exceed a certain limit within a certain time period,

ensuring that the rate of insulin applied does not exceed a certain limit within a certain time period after a meal, and

ensuring that basal rate does not exceed a certain percentage of the subject specified basal rate per hour.

85. The method of claim 83, wherein said safety filters include a safety filter ensuring that no more than about 3 units of bolus insulin are applied within a one hour period.

86. The method of claim 83, wherein said safety filters include a safety filter ensuring that no more than about 10 units of bolus insulin per hour (not counting basal insulin) are applied within about 2 hours of a meal.

87. The method of claim 83, wherein said safety filters include a safety filter ensuring that the basal rate does not exceed about 150% of the subject'"'"'s specified basal rate per hour.

88. The method of claim 83, further comprising sending information to the insulin delivery unit based upon the second insulin rate, said information indicating a current optimal insulin injection.

89. The method of claim 59, wherein said control law is derived from a continuous-time model of glucose insulin dynamics and an aggressiveness parameter.

90. The method of claim 59, further comprising sending information from said CGM at regular time intervals.

91. The method of claim 90, wherein said time intervals are approximately one minute apart.

92. The method of claim 90, wherein the duration of said time intervals may be varied.

93. The method of claim 59, further comprising sending information to said insulin delivery unit at regular time intervals.

94. The method of claim 93, wherein said time intervals are approximately fifteen minutes apart.

95. The method of claim 93, wherein the duration of said regular time intervals may be varied.

96. The method of claim 59, further comprising receiving information from the CGM through a wireless connection.

97. The method of claim 59, further comprising receiving information from the CGM through a wired connection.

98. The method of claim 59, further comprising communicating with the insulin delivery unit through a wireless connection.

99. The method of claim 59, further comprising communicating with the insulin delivery unit through a wired connection.

100. The method of claim 59, wherein the method steps are performed within the body of the subject.

101. The method of claim 59, wherein the method steps are partially performed within the body of the subject.

102. The method of claim 59, wherein said controlling occurs within said CGM or in external communication with said CGM.

103. The method of claim 59, wherein said controlling occurs within said insulin delivery unit or in external communication with said insulin delivery unit.

104. The method of claim 59, wherein said insulin delivery unit delivers insulin to said subject upon receiving a command.

105. The method of claim 59, wherein said insulin delivery unit comprises an insulin pump.

106. The method of claim 105, wherein said insulin pump is the Omnipod from Insulet corporation.

107. The method of claim 105, wherein said insulin pump is the Deltec Cozmo from Smiths Medical.

108. The method of claim 59, wherein said insulin delivery unit comprises an insulin reservoir.

109. The method of claim 59, wherein said insulin delivery unit comprises a cannula for subcutaneous insertion.

110. The method of claim 59, wherein said CGS is the Navigator from Abbott Diabetes Care.

111. The method of claim 59, wherein said CGS is the Dexcom from Dexcom, Inc.

112. The method of claim 59, wherein said CGS is the Guardian/Paradigm from Medtronic.

113. The method of claim 59, wherein said subject is a human being.

114. A computer method for providing optimal insulin injections to a subject, said method comprising:

performing continuous glucose monitor monitoring,

performing insulin delivery,

providing a discrete time linear model predictive control law,

sending information to an insulin delivery unit, and

receiving information from a CGM.

115. A computer system for providing optimal insulin injections to a subject to be used with a continuous glucose monitor (CGM) said system comprising:

performing insulin delivery,

providing a discrete time linear model predictive control law,

sending information to an insulin delivery unit, and

receiving information from a CGM.

116. A method for providing optimal insulin injections to a subject to be used with an insulin delivery unit, said system comprising:

performing continuous glucose monitor monitoring,

providing a discrete time linear model predictive control law,

sending information to an insulin delivery unit, and

receiving information from a CGM.

117. A computer readable medium for use with a processor, to be used with a continuous glucose monitor (CGM) and an insulin delivery unit, having computer executable instructions for performing a method for computing an optimal adapting insulin injection, wherein said method comprises:

providing a discrete time linear model predictive control law

sending information to an insulin delivery unit, and

receiving information from the CGM.

118. The computer readable medium of claim 117, wherein said control law is derived from a discrete-time model of glucose insulin dynamics and an aggressiveness parameter.

119. The computer readable medium of claim 118, wherein said control law is derived from said discrete-time model of glucose insulin dynamics by linearizing a model about an equilibrium point that is associated with the average basal values of a population model.

120. The computer readable medium of claim 118, wherein said computer readable medium further contains instructions for determining a first insulin rate by solving a finite horizon optimal control problem so that a cost function is minimized.

121. The computer readable medium of claim 120, wherein said computer readable medium further contains instructions for determining said first insulin rate by considering a set of parameters, said set of parameters comprising one or more of the following:

a state vector,

target glucose concentration, and

future glucose disturbances.