System Coordinator and Modular Architecture for Open-Loop and Closed-Loop Control of Diabetes

• US 20120078067A1
• Filed: 05/28/2010
• Published: 03/29/2012
• Est. Priority Date: 05/29/2009
• Status: Active Grant

• Current Assignee: University of Virginia
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Kovatchev, Boris P., Patek, Stephen D., Breton, Marc D.
• Granted Patent: US 10,420,489 B2
• Time in Patent Office: Days
• US Class Current: 600/301
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 20/30 relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising
• CPC Class Codes: G16H 20/60 relating to nutrition control, e.g. diets
• 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

Abstract

A structure, method, and computer program product for a diabetes control system provides, but is not limited thereto, the following: open-loop or closed-loop control of diabetes that adapts to individual physiologic characteristics and to the behavioral profile of each person. An exemplary aspect to this adaptation is biosystem (patient or subject) observation and modular control. Consequently, established is the fundamental architecture and the principal components for a modular system, which may include algorithmic observers of patients'"'"' behavior and metabolic state, as well as interacting control modules responsible for basal rate, insulin boluses, and hypoglycemia prevention.

Claims

1. A structure for a diabetes control system comprising:

modules for processing and storing data;

conduits between modules; and

signals produced in the event that certain modules are not inserted within the structure.

2. The structure of claim 1, further comprising different implementations of modules that can be inserted and/or interchanged.

3. The structure of claim 1, wherein the modules for processing and storing data include one or more of the following:

one or more data acquisition modules;

one or more observer modules;

one or more routing modules;

one or more control modules; and

one or more safety modules.

4. The structure of claim 3, wherein the one or more data acquisition modules receive one or more of the following types of information:

continuous glucose monitoring data;

insulin pump data;

exercise data; and

meal data.

5. The structure of claim 4, wherein the exercise data includes heart rate information, motion sensor information, and other indicators of physical activity.

6. The structure of claim 4, wherein the meal data includes acknowledgements of meals as they arrive.

7. The structure of claim 3, wherein the one or more data acquisition modules output one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

8. The structure of claim 3, wherein the one or more observer modules receive one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

9. The structure of claim 3, wherein the one or more observer modules process one or more of the following:

metabolic measurements;

metabolic disturbances; and

metabolic treatments.

10. The structure of claim 9, wherein the metabolic measurements include one or more of the following:

continuous glucose measurements; and

insulin measurements.

11. The structure of claim 9, wherein the metabolic disturbances include one or more of the following:

meals; and

exercise.

12. The structure of claim 9, wherein the metabolic treatments include one or more of the following:

insulin injections;

other pharmaceuticals (hormones) associated with the management of diabetes;

treatments for hypoglycemia; and

glucagon injections.

13. The structure of claim 12, wherein other pharmaceuticals include hormones.

14. The structure of claim 12, wherein treatments for hypoglycemia include administering rescue carbohydrates and/or glucagon injections.

15. The structure of claim 3, wherein the one or more observer modules construct and update an internal representation or estimate of a metabolic state of an individual.

16. The structure of claim 3, wherein the one or more observer modules transmit metabolic state information to the one or more control modules.

17. The structure of claim 3, wherein the one or more observer modules keep an internal representation of a behavioral pattern of an individual.

18. The structure of claim 3, wherein the one or more observer modules assess risks of undesirable events.

19. The structure of claim 3, wherein the one or more observer modules include a short term observer module.

20. The structure of claim 19, wherein the short term observer module contains information relating to:

metabolic state;

meal excursion;

or

metabolic state and meal excursion.

21. The structure of claim 19, wherein the short term observer module observes X times per hour, where X is 0<

X<

7200.

22. The structure of claim 19, wherein the short term observer module outputs one of the following:

a vector of estimates of key metabolic states of an individual;

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

or

both the vector of estimates of key metabolic states and the sample or history of processed glucose samples.

23. The structure of claim 22, wherein the vector of estimates includes plasma glucose and plasma insulin.

24. The structure of claim 3, wherein the one or more observer modules include a long term observer module.

25. The structure of claim 24, wherein the long term observer module contains information relating to behavioral profiles.

26. The structure of claim 25, wherein the behavioral profiles are daily behavioral profiles.

27. The structure of claim 24, wherein the long term observer module assesses behavioral profiles X times per month, where X is 0<

X<

60.

28. The structure of claim 24, wherein the long term observer module outputs one or more of the following types of information:

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

29. The structure of claim 28, wherein the daily profile of the individual'"'"'s meal behavior as a function of the time of day includes probabilities of eating at various times throughout the day and/or probabilities of taking various meals defined by carbohydrate, protein, and fat content.

30. The structure of claim 28, wherein the daily profile of the individual'"'"'s exercise behavior as a function of the time of day includes probabilities of various levels of physical activity throughout the day.

31. The structure of claim 28, wherein the daily profile of the individual'"'"'s utilization of insulin as a function of the time of day includes a trend analysis for meal and correction boluses and/or a trend analysis for basal rate profiles.

32. The structure of claim 28, wherein the daily profile of an individual'"'"'s meal behavior defines a probabilistic description of the individual'"'"'s eating behavior within given meal regimes throughout a day.

33. The structure of claim 28, further comprising using behavioral data to define a patient'"'"'s breakfast regime and then assessing the probability of taking breakfast at any specific point of time within that regime.

34. The structure of claim 3, wherein the one or more routing modules include a system coordinator.

35. The structure of claim 34, wherein the system coordinator coordinates the distribution of input signals to control one or more modules and allocates different segments of diabetes management to different control modules.

36. The structure of claim 34, wherein the system coordinator receives one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

estimated glucose excursion due to meals.

37. The structure of claim 34, wherein the system coordinator outputs one or more of the following types of information:

a most recent actual insulin pump command;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

estimated glucose excursion due to meals; and

an estimate of blood glucose concentration offset by the estimated contribution of meals.

38. The structure of claim 3, wherein the one or more control modules perform:

daily profile control;

compensation control to target; and

/or

meal control.

39. The structure of claim 38, wherein daily profile control includes determining a basal rate baseline setting throughout the day.

40. The structure of claim 38, wherein compensation control to target includes small adjustments to the basal rate baseline to correct hyperglycemia and reduce the likelihood of hypoglycemia.

41. The structure of claim 38, wherein meal control includes a schedule of meal insulin following acknowledgement of a particular meal.

42. The structure of claim 3, wherein the one or more control modules include:

a first control module to calculate and suggest a basal insulin delivery;

a second control module to calculate and suggest compensation of the basal delivery in case of non-meal-related deviations; and

a third control module to calculate and suggest meal insulin boluses.

43. The structure of claim 42, wherein the first control module receives one or more of the following types of information:

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

44. The structure of claim 42, wherein the first control module outputs a reference insulin infused at a specific time.

45. The structure of claim 42, wherein the second control module receives one or more of the following types of information:

an estimate of blood glucose concentration offset by the estimated contribution of meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

exercise process data at the specific time;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

46. The structure of claim 42, wherein the second control module outputs a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

47. The structure of claim 42, wherein the third control module receives one or more of the following types of information:

meal data at the specific time;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals; and

a daily profile of an individual'"'"'s meal behavior as a function of the time of day.

48. The structure of claim 42, wherein the third control module outputs one or more of the following types of information:

a recommended insulin infusion at a specific time for accommodating meals; and

estimated glucose excursion due to meals.

49. The structure of claim 42, wherein the second control module compensates a basal delivery up or down.

50. The structure of claim 42, wherein the third control module further calculates and suggests pre-meal priming boluses.

51. The structure of claim 42, wherein:

the first control module operates approximately daily;

the second control modules operates approximately every fifteen to thirty minutes; and

the third control module operates approximately every several hours.

52. The structure of claim 3, wherein the one or more safety modules include a system supervision module.

53. The structure of claim 52, wherein the system supervision module receives one or more of the following types of information:

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

reference insulin infused at a specific time;

a recommended insulin infusion at a specific time for accommodating meals; and

a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

54. The structure of claim 52, wherein the system supervision module outputs one or more of the following types of information:

insulin allowed at a specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

total insulin infusion allowed by the safety supervision module at the specific time.

55. The structure of claim 52, wherein the safety supervision module:

receives information from the one or more observer modules and one or more control modules;

determines whether there is an increased risk of hypoglycemia or hyperglycemia;

if it is determined that there is an increased risk of hypoglycemia, automatically reducing or discontinuing a suggested infusion; and

if it is determined that there is an increased risk of hyperglycemia, automatically notifying the user of the risk.

56. The structure of claim 55, wherein the increased risk of hypoglycemia is an increased risk of upcoming hypoglycemia or an increased risk of prolonged hypoglycemia.

57. The structure of claim 55, wherein the suggested infusion is an insulin infusion or a glucagon infusion.

58. The structure of claim 55, further comprising a display device for displaying real-time information to an individual.

59. The structure of claim 58, wherein the individual is a subject or a doctor.

60. The structure of claim 58, wherein the real-time information includes one or more of the following:

a warning of hypoglycemia;

a warning of hyperglycemia;

a suggestion to reduce insulin delivery; and

a suggestion to reject or reduce pre-meal or correction boluses.

61. The structure of claim 3, further comprising an insulin injector for injecting insulin based on the output of the one or more safety modules.

62. A computer program product comprising a computer useable medium having a computer program logic for enabling at least one processor in a computer system for a diabetes control system, said computer program logic comprising:

modules for processing and storing data;

conduits between modules; and

producing signals in the event that certain modules are not inserted within the system.

63. The computer program product of claim 62, further comprising different implementations of modules that can be inserted and/or interchanged.

64. The computer program product of claim 62, wherein the modules for processing and storing data include one or more of the following:

one or more data acquisition modules;

one or more observer modules;

one or more routing modules;

one or more control modules; and

one or more safety modules.

65. The computer program product of claim 64, wherein the one or more data acquisition modules receive one or more of the following types of information:

continuous glucose monitoring data;

insulin pump data;

exercise data; and

meal data.

66. The computer program product of claim 65, wherein the exercise data includes heart rate information, motion sensor information, and other indicators of physical activity.

67. The computer program product of claim 65, wherein the meal data includes acknowledgements of meals as they arrive.

68. The computer program product of claim 64, wherein the one or more data acquisition modules output one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

69. The computer program product of claim 64, wherein the one or more observer modules receive one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

70. The computer program product of claim 64, wherein the one or more observer modules process one or more of the following:

metabolic measurements;

metabolic disturbances; and

metabolic treatments.

71. The computer program product of claim 70, wherein the metabolic measurements include one or more of the following:

continuous glucose measurements; and

insulin measurements.

72. The computer program product of claim 70, wherein the metabolic disturbances include one or more of the following:

meals; and

exercise.

73. The computer program product of claim 70, wherein the metabolic treatments include one or more of the following:

insulin injections;

other pharmaceuticals (hormones) associated with the management of diabetes;

treatments for hypoglycemia; and

glucagon injections.

74. The computer program product of claim 73, wherein other pharmaceuticals include hormones.

75. The computer program product of claim 73, wherein treatments for hypoglycemia include administering rescue carbohydrates and/or glucagon injections.

76. The computer program product of claim 64, wherein the one or more observer modules construct and update an internal representation or estimate of a metabolic state of an individual.

77. The computer program product of claim 64, wherein the one or more observer modules transmit metabolic state information to the one or more control modules.

78. The computer program product of claim 64, wherein the one or more observer modules keep an internal representation of a behavioral pattern of an individual.

79. The computer program product of claim 64, wherein the one or more observer modules assess risks of undesirable events.

80. The computer program product of claim 64, wherein the one or more observer modules include a short term observer module.

81. The computer program product of claim 80, wherein the short term observer module contains information relating to:

metabolic state;

meal excursion;

or

metabolic state and meal excursion.

82. The computer program product of claim 80, wherein the short term observer module observes X times per hour, where X is 0<

X<

7200.

83. The computer program product of claim 80, wherein the short term observer module outputs one of the following:

a vector of estimates of key metabolic states of an individual;

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

or

both the vector of estimates of key metabolic states and the sample or history of processed glucose samples.

84. The computer program product of claim 83, wherein the vector of estimates includes plasma glucose and plasma insulin.

85. The computer program product of claim 64, wherein the one or more observer modules include a long term observer module.

86. The computer program product of claim 85, wherein the long term observer module contains information relating to behavioral profiles.

87. The computer program product of claim 86, wherein the behavioral profiles are daily behavioral profiles.

88. The computer program product of claim 85, wherein the long term observer module assesses behavioral profiles X times per month, where X is 0<

X<

60.

89. The computer program product of claim 85, wherein the long term observer module outputs one or more of the following types of information:

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

90. The computer program product of claim 89, wherein the daily profile of the individual'"'"'s meal behavior as a function of the time of day includes probabilities of eating at various times throughout the day and/or probabilities of taking various meals defined by carbohydrate, protein, and fat content.

91. The computer program product of claim 89, wherein the daily profile of the individual'"'"'s exercise behavior as a function of the time of day includes probabilities of various levels of physical activity throughout the day.

92. The computer program product of claim 89, wherein the daily profile of the individual'"'"'s utilization of insulin as a function of the time of day includes a trend analysis for meal and correction boluses and/or a trend analysis for basal rate profiles.

93. The computer program product of claim 89, wherein the daily profile of an individual'"'"'s meal behavior defines a probabilistic description of the individual'"'"'s eating behavior within given meal regimes throughout a day.

94. The computer program product of claim 89, further comprising using behavioral data to define a patient'"'"'s breakfast regime and then assessing the probability of taking breakfast at any specific point of time within that regime.

95. The computer program product of claim 64, wherein the one or more routing modules include a system coordinator.

96. The computer program product of claim 95, wherein the system coordinator coordinates the distribution of input signals to control one or more modules and allocates different segments of diabetes management to different control modules.

97. The computer program product of claim 95, wherein the system coordinator receives one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

estimated glucose excursion due to meals.

98. The computer program product of claim 95, wherein the system coordinator outputs one or more of the following types of information:

a most recent actual insulin pump command;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

estimated glucose excursion due to meals; and

an estimate of blood glucose concentration offset by the estimated contribution of meals.

99. The computer program product of claim 64, wherein the one or more control modules perform:

daily profile control;

compensation control to target; and

/or

meal control.

100. The computer program product of claim 99, wherein daily profile control includes determining a basal rate baseline setting throughout the day.

101. The computer program product of claim 99, wherein compensation control to target includes small adjustments to the basal rate baseline to correct hyperglycemia and reduce the likelihood of hypoglycemia.

102. The computer program product of claim 99, wherein meal control includes a schedule of meal insulin following acknowledgement of a particular meal.

103. The computer program product of claim 64, wherein the one or more control modules include:

a first control module to calculate and suggest a basal insulin delivery;

a second control module to calculate and suggest compensation of the basal delivery in case of non-meal-related deviations; and

a third control module to calculate and suggest meal insulin boluses.

104. The computer program product of claim 103, wherein the first control module receives one or more of the following types of information:

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

105. The computer program product of claim 103, wherein the first control module outputs a reference insulin infused at a specific time.

106. The computer program product of claim 103, wherein the second control module receives one or more of the following types of information:

an estimate of blood glucose concentration offset by the estimated contribution of meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

exercise process data at the specific time;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

107. The computer program product of claim 103, wherein the second control module outputs a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

108. The computer program product of claim 103, wherein the third control module receives one or more of the following types of information:

meal data at the specific time;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals; and

a daily profile of an individual'"'"'s meal behavior as a function of the time of day.

109. The computer program product of claim 103, wherein the third control module outputs one or more of the following types of information:

a recommended insulin infusion at a specific time for accommodating meals; and

estimated glucose excursion due to meals.

110. The computer program product of claim 103, wherein the second control module compensates a basal delivery up or down.

111. The computer program product of claim 103, wherein the third control module further calculates and suggests pre-meal priming boluses.

112. The computer program product of claim 103, wherein:

the first control module operates approximately daily;

the second control modules operates approximately every fifteen to thirty minutes; and

the third control module operates approximately every several hours.

113. The computer program product of claim 64, wherein the one or more safety modules include a system supervision module.

114. The computer program product of claim 113, wherein the system supervision module receives one or more of the following types of information:

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

reference insulin infused at a specific time;

a recommended insulin infusion at a specific time for accommodating meals; and

a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

115. The computer program product of claim 113, wherein the system supervision module outputs one or more of the following types of information:

insulin allowed at a specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

total insulin infusion allowed by the safety supervision module at the specific time.

116. The computer program product of claim 113, wherein the safety supervision module:

receives information from the one or more observer modules and one or more control modules;

determines whether there is an increased risk of hypoglycemia or hyperglycemia;

if it is determined that there is an increased risk of hypoglycemia, automatically reducing or discontinuing a suggested infusion; and

if it is determined that there is an increased risk of hyperglycemia, automatically notifying the user of the risk.

117. The computer program product of claim 116, wherein the increased risk of hypoglycemia is an increased risk of upcoming hypoglycemia or an increased risk of prolonged hypoglycemia.

118. The computer program product of claim 116, wherein the suggested infusion is an insulin infusion or a glucagon infusion.

119. The computer program product of claim 116, further comprising a display device for displaying real-time information to an individual.

120. The computer program product of claim 119, wherein the individual is a subject or a doctor.

121. The computer program product of claim 119, wherein the real-time information includes one or more of the following:

a warning of hypoglycemia;

a warning of hyperglycemia;

a suggestion to reduce insulin delivery; and

a suggestion to reject or reduce pre-meal or correction boluses.

122. The computer program product of claim 64, further comprising an insulin injector for injecting insulin based on the output of the one or more safety modules.

123. A method for enabling a diabetes control system, the method comprising:

providing modules for processing and storing data;

providing conduits between modules; and

producing signals in the event that certain modules are not inserted within the system.

124. The method of claim 123, further comprising different implementations of modules that can be inserted and/or interchanged.

125. The method of claim 123, wherein the modules for processing and storing data include one or more of the following:

one or more data acquisition modules;

one or more observer modules;

one or more routing modules;

one or more control modules; and

one or more safety modules.

126. The method of claim 125, wherein the one or more data acquisition modules receive one or more of the following types of information:

continuous glucose monitoring data;

insulin pump data;

exercise data; and

meal data.

127. The method of claim 126, wherein the exercise data includes heart rate information, motion sensor information, and other indicators of physical activity.

128. The method of claim 126, wherein the meal data includes acknowledgements of meals as they arrive.

129. The method of claim 125, wherein the one or more data acquisition modules output one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

130. The method of claim 125, wherein the one or more observer modules receive one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time; and

meal data at the specific time.

131. The method of claim 125, wherein the one or more observer modules process one or more of the following:

metabolic measurements;

metabolic disturbances; and

metabolic treatments.

132. The method of claim 131, wherein the metabolic measurements include one or more of the following:

continuous glucose measurements; and

insulin measurements.

133. The method of claim 131, wherein the metabolic disturbances include one or more of the following:

meals; and

exercise.

134. The method of claim 131, wherein the metabolic treatments include one or more of the following:

insulin injections;

other pharmaceuticals (hormones) associated with the management of diabetes;

treatments for hypoglycemia; and

glucagon injections.

135. The method of claim 134, wherein other pharmaceuticals include hormones.

136. The method of claim 134, wherein treatments for hypoglycemia include administering rescue carbohydrates and/or glucagon injections.

137. The method of claim 125, wherein the one or more observer modules construct and update an internal representation or estimate of a metabolic state of an individual.

138. The method of claim 125, wherein the one or more observer modules transmit metabolic state information to the one or more control modules.

139. The method of claim 125, wherein the one or more observer modules keep an internal representation of a behavioral pattern of an individual.

140. The method of claim 125, wherein the one or more observer modules assess risks of undesirable events.

141. The method of claim 125, wherein the one or more observer modules include a short term observer module.

142. The method of claim 141, wherein the short term observer module contains information relating to:

metabolic state;

meal excursion;

or

metabolic state and meal excursion.

143. The method of claim 141, wherein the short term observer module observes X times per hour, where X is 0<

X<

7200.

144. The method of claim 141, wherein the short term observer module outputs one of the following:

a vector of estimates of key metabolic states of an individual;

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

or

both the vector of estimates of key metabolic states and the sample or history of processed glucose samples.

145. The method of claim 144, wherein the vector of estimates includes plasma glucose and plasma insulin.

146. The method of claim 125, wherein the one or more observer modules include a long term observer module.

147. The method of claim 146, wherein the long term observer module contains information relating to behavioral profiles.

148. The method of claim 147, wherein the behavioral profiles are daily behavioral profiles.

149. The method of claim 146, wherein the long term observer module assesses behavioral profiles X times per month, where X is 0<

X<

60.

150. The method of claim 146, wherein the long term observer module outputs one or more of the following types of information:

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

151. The method of claim 150, wherein the daily profile of the individual'"'"'s meal behavior as a function of the time of day includes probabilities of eating at various times throughout the day and/or probabilities of taking various meals defined by carbohydrate, protein, and fat content.

152. The method of claim 150, wherein the daily profile of the individual'"'"'s exercise behavior as a function of the time of day includes probabilities of various levels of physical activity throughout the day.

153. The method of claim 150, wherein the daily profile of the individual'"'"'s utilization of insulin as a function of the time of day includes a trend analysis for meal and correction boluses and/or a trend analysis for basal rate profiles.

154. The method of claim 150, wherein the daily profile of an individual'"'"'s meal behavior defines a probabilistic description of the individual'"'"'s eating behavior within given meal regimes throughout a day.

155. The method of claim 150, further comprising using behavioral data to define a patient'"'"'s breakfast regime and then assessing the probability of taking breakfast at any specific point of time within that regime.

156. The method of claim 125, wherein the one or more routing modules include a system coordinator.

157. The method of claim 156, wherein the system coordinator coordinates the distribution of input signals to control one or more modules and allocates different segments of diabetes management to different control modules.

158. The method of claim 156, wherein the system coordinator receives one or more of the following types of information:

a single, processed glucose sample at a specific time, or a history of glucose samples up to a specific time, or a statistic computed from glucose samples up to a specific time;

a most recent actual insulin pump command, or a history of recent insulin pump commands up to a specific time, or a statistic computed from recent commands;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

estimated glucose excursion due to meals.

159. The method of claim 156, wherein the system coordinator outputs one or more of the following types of information:

a most recent actual insulin pump command;

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day;

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

estimated glucose excursion due to meals; and

an estimate of blood glucose concentration offset by the estimated contribution of meals.

160. The method of claim 125, wherein the one or more control modules perform:

daily profile control;

compensation control to target; and

/or

meal control.

161. The method of claim 160, wherein daily profile control includes determining a basal rate baseline setting throughout the day.

162. The method of claim 160, wherein compensation control to target includes small adjustments to the basal rate baseline to correct hyperglycemia and reduce the likelihood of hypoglycemia.

163. The method of claim 160, wherein meal control includes a schedule of meal insulin following acknowledgement of a particular meal.

164. The method of claim 125, wherein the one or more control modules include:

a first control module to calculate and suggest a basal insulin delivery;

a second control module to calculate and suggest compensation of the basal delivery in case of non-meal-related deviations; and

a third control module to calculate and suggest meal insulin boluses.

165. The method of claim 164, wherein the first control module receives one or more of the following types of information:

a vector of estimates of key metabolic states of an individual;

a daily profile of an individual'"'"'s meal behavior as a function of the time of day;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

166. The method of claim 164, wherein the first control module outputs a reference insulin infused at a specific time.

167. The method of claim 164, wherein the second control module receives one or more of the following types of information:

an estimate of blood glucose concentration offset by the estimated contribution of meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances;

exercise process data at the specific time;

a daily profile of the individual'"'"'s exercise behavior as a function of the time of day; and

a daily profile of the individual'"'"'s utilization of insulin as a function of the time of day.

168. The method of claim 164, wherein the second control module outputs a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

169. The method of claim 164, wherein the third control module receives one or more of the following types of information:

meal data at the specific time;

insulin allowed at the specific time by the one or more safety modules as part of a response to meals; and

a daily profile of an individual'"'"'s meal behavior as a function of the time of day.

170. The method of claim 164, wherein the third control module outputs one or more of the following types of information:

a recommended insulin infusion at a specific time for accommodating meals; and

estimated glucose excursion due to meals.

171. The method of claim 164, wherein the second control module compensates a basal delivery up or down.

172. The method of claim 164, wherein the third control module further calculates and suggests pre-meal priming boluses.

173. The method of claim 164, wherein:

the first control module operates approximately daily;

the second control modules operates approximately every fifteen to thirty minutes; and

the third control module operates approximately every several hours.

174. The method of claim 125, wherein the one or more safety modules include a system supervision module.

175. The method of claim 174, wherein the system supervision module receives one or more of the following types of information:

exercise process data at the specific time;

meal data at the specific time;

a vector of estimates of key metabolic states of an individual;

reference insulin infused at a specific time;

a recommended insulin infusion at a specific time for accommodating meals; and

a recommended residual insulin infusion at a specific time to compensate for non-meal-related disturbances.

176. The method of claim 174, wherein the system supervision module outputs one or more of the following types of information:

insulin allowed at a specific time by the one or more safety modules as part of a response to meals;

insulin allowed at the specific time by the one or more safety modules as part of a response to non-meal disturbances; and

total insulin infusion allowed by the safety supervision module at the specific time.

177. The method of claim 174, wherein the safety supervision module:

receives information from the one or more observer modules and one or more control modules;

determines whether there is an increased risk of hypoglycemia or hyperglycemia;

if it is determined that there is an increased risk of hypoglycemia, automatically reducing or discontinuing a suggested infusion; and

if it is determined that there is an increased risk of hyperglycemia, automatically notifying the user of the risk.

178. The method of claim 177, wherein the increased risk of hypoglycemia is an increased risk of upcoming hypoglycemia or an increased risk of prolonged hypoglycemia.

179. The method of claim 177, wherein the suggested infusion is an insulin infusion or a glucagon infusion.

180. The method of claim 177, further comprising a display device for displaying real-time information to an individual.

181. The method of claim 180, wherein the individual is a subject or a doctor.

182. The method of claim 180, wherein the real-time information includes one or more of the following:

a warning of hypoglycemia;

a warning of hyperglycemia;

a suggestion to reduce insulin delivery; and

a suggestion to reject or reduce pre-meal or correction boluses.

183. The method of claim 125, further comprising an insulin injector for injecting insulin based on the output of the one or more safety modules.