Method and apparatus for glucose control and insulin dosing for diabetics

• US 20050272640A1
• Filed: 05/12/2005
• Published: 12/08/2005
• Est. Priority Date: 05/13/2004
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Doyle, Francis J. III, Jovanovic, Lois
• Granted Patent: US 7,651,845 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61M 2005/1405 Patient controlled analgesia [PCA]
• CPC Class Codes: A61M 2005/14296 Pharmacokinetic models
• CPC Class Codes: A61M 2205/3523 using telemetric means
• CPC Class Codes: A61M 2205/3592 using telemetric means, e.g. radio or optical transmission
• CPC Class Codes: A61M 2230/201 Glucose concentration
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• 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 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• 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 computer implemented method and associated apparatus for the combined control of insulin bolus dosing and basal delivery for the goal of achieving normal glycemic response to meals, exercise, stressors, and other perturbations to blood glucose levels. A run-to-run algorithm is used to monitor blood glucose levels and adjust insulin delivery as conditions are varied.

Claims

1. A run-to-run control method of deriving the optimal dosage of insulin to provide both the basal insulin requirement and the meal-related insulin dosing of an individual, comprising:

estimating insulin sensitivity of an individual;

observing a postprandial glucose response to at least one meal; and

estimating a preprandial dosage of insulin for a subsequent day'"'"'s corresponding meal based on the insulin sensitivity of said individual and observed postprandial glucose response to the meal and preprandial dose of insulin for a current day;

wherein dosage amount for a subsequent day is higher than, lower than, or the same as, dosage amount for a current day.

2. A method as recited in claim 1, wherein said insulin dosage comprises an insulin analog.

3. A method as recited in claim 1, wherein said dosage further comprises timing of said dosage of insulin.

4. A method as recited in claim 1, wherein maximum glucose levels following each meal are maintained within the normal glycemic range.

5. A method as recited in claim 1, wherein a subsequent day'"'"'s preprandial insulin dosages are corrected based on one or more meal-related postprandial glucose measurements from a previous day.

6. A method as recited in claim 5, wherein said dosage corrections incorporate at least one of the variables of time of day, carbohydrate content of a meal, preprandial glucose concentration and time since last meal bolus.

7. A method as recited in claim 1, further comprising:

repeating said estimating step on a daily basis until glucose levels converge to a predetermined target range.

8. A method as recited in claim 1, further comprising:

(a) measuring blood glucose level during a current day;

(b) estimating insulin dosage for said subsequent day as a function of said measured blood glucose level during said current day;

(c) administering said insulin dosage based on said estimate; and

repeating steps (a) through (c).

9. A method as recited in claim 1, wherein a day comprises a twenty-four hour period during which meals are ingested at variable times during the period.

10. A method as recited in claim 9, wherein more than three meals are ingested during the day.

11. A method as recited in claim 9, wherein fewer than three meals are ingested during the day.

12. A method as recited in claim 3, wherein said timing and amount of said insulin dosages provide an insulin dosing profile that is optimized over time.

13. A method as recited in claim 1, wherein said observation step comprises at least one measurement of blood glucose levels from a sensor taken from the group of sensors consisting essentially of an implanted glucose sensor, an optical glucose sensor and a pin prick glucose sensor.

14. A method as recited in claim 13, wherein said parameter indicative of insulin sensitivity of said individual is selected from the group consisting essentially of an exercise level and a degree of stress.

15. A method as recited in claim 14, wherein said exercise level parameter has mild, moderate or strenuous exercise levels.

16. A method as recited in claim 14, wherein said degree of stress parameter has mild, moderate or severe stress levels.

17. A method as recited in claim 1, wherein said estimating step is a function of said blood glucose level measurement, meal size and timing.

18. A method as recited in claim 1, wherein said estimating step is a function of said blood glucose level measurement, meal size, carbohydrate content, timing, and meal duration.

19. A method as recited in claim 18, wherein said parameter indicative of insulin sensitivity of said individual is selected from the group of stresses consisting essentially of physical stress, psychological stress or hormonal stress.

20. A method as recited in claim 1, wherein the preprandial dosage of insulin for a subsequent day'"'"'s meal is iteratively updated over time.

21. A method as recited in claim 20, wherein said dosage comprises insulin amount and timing of delivery.

22. A method of controlling blood glucose levels in a diabetic individual, comprising:

(a) measuring blood glucose level associated with a first time period;

(b) as a function of said blood glucose level, estimating insulin bolus dosage amount associated with a second time period subsequent to said first time period;

(c) administering said insulin bolus based on said estimate; and

(d) repeating steps (a) through (c);

(e) wherein dosage amount for said second time period is higher than, lower than, or the same as, dosage for said first time period.

23. A method as recited in claim 22, wherein said first time period comprises a day during which at least one meal is eaten.

24. A method as recited in claim 23, wherein said second time period comprises a subsequent day during which at least one meal is eaten.

25. A method as recited in claim 22, wherein said first and second time periods comprise periods of one day.

26. A method as recited in claim 22:

wherein said first time period comprises a twenty-four hour period during which at least one meal is eaten; and

wherein said second time period comprises a twenty-four hour period during which at least one meal is eaten.

27. A method as recited in claim 22, wherein said dosage further comprises timing of said dosage of insulin.

28. A method as recited in claim 22, wherein a meal is skipped during first time period, the second time period or both the first and second time periods.

29. A method as recited in claim 22, wherein said estimating step determines amount and timing for meal-related bolus dosing during said second time period.

30. A method as recited in claim 22, wherein insulin bolus dosing is optimized over time.

31. A method as recited in claim 22, wherein said estimating step is a function of said blood glucose level measurement and at least one parameter indicative of the insulin sensitivity of said individual.

32. A method as recited in claim 31, wherein said parameter indicative of insulin sensitivity of said individual is selected from the group consisting essentially of exercise level, physical stress, psychological stress and hormonal stress.

33. A method as recited in claim 22, wherein said estimating step is a function of said blood glucose level measurement, meal size and timing.

34. A method as recited in claim 22, wherein said estimating step is a function of said blood glucose level measurement, meal size, meal carbohydrate content, pre-prandial glucose concentration, time since last bolus, time of day, and at least one parameter indicative of insulin sensitivity of said individual.

35. A method as recited in claim 34, wherein said parameter indicative of physical state of said individual is selected from the group consisting essentially of exercise level and degree of stress.

36. A method as recited in claim 22, wherein maximum glucose levels following each meal are maintained in the normal glycemic range.

37. A method as recited in claim 22, wherein said the preprandial dosage of insulin for a subsequent day'"'"'s meal is iteratively updated over time.

38. A method as recited in claim 37, wherein said dosage comprises amount and timing.

39. An apparatus for run-to-run control of meal-related insulin dosing of an individual, comprising:

a programmable computing device; and

programming executable by said computer device for carrying out the operations of;

estimating a preprandial dosage of insulin for a subsequent day'"'"'s corresponding meal based on observed response for a current day;

wherein dosage amount for a subsequent day is higher than, lower than, or the same as, dosage for a current day.

40. An apparatus as recited in claim 39, wherein said dosage further comprises amount and timing of insulin administration.

41. An apparatus as recited in claim 39, wherein maximum glucose levels following each meal are maintained in the normal glycemic range.

42. An apparatus as recited in claim 39, wherein preprandial insulin dosages of a subsequent day are corrected based on glucose measurements of one or more previous days.

43. An apparatus as recited in claim 39, wherein said programming further carries out the operations of:

repeating said estimating step on a daily basis until glucose levels converge to a predetermined range.

44. An apparatus as recited in claim 39, wherein said programming further carries out the operations of:

(a) measuring blood glucose level during a current day;

(b) estimating insulin dosage for said subsequent day as a function of measured blood glucose level during said current day;

(c) administering said insulin based on said estimate; and

(d) repeating operations (a) through (c).

45. An apparatus as recited in claim 39, wherein a day comprises a twenty-four hour period during which breakfast, lunch and dinner meals are eaten.

46. An apparatus as recited in claim 39, wherein insulin dosing is optimized over time.

47. An apparatus as recited in claim 39, wherein said estimating step is a function of said blood glucose level measurement and at least one parameter indicative of the insulin sensitivity of said individual.

48. An apparatus as recited in claim 47, wherein said parameter indicative of the insulin sensitivity of said individual is selected from the group consisting essentially of a degree of physical, psychological or hormonal stress.

49. An apparatus as recited in claim 39, wherein said estimating step is a function of said blood glucose level measurement and meal size and timing.

50. An apparatus as recited in claim 39, wherein said estimating step is a function of said blood glucose level measurement, meal size and timing, and at least one parameter indicative of the insulin sensitivity of said individual.

51. An apparatus as recited in claim 50, wherein said parameter indicative of insulin sensitivity of said individual is selected from the group consisting essentially of exercise level and degree of stress.

52. An apparatus as recited in claim 39, wherein said the preprandial dosage of insulin for a subsequent day'"'"'s meal is iteratively updated over time.

53. An apparatus as recited in claim 52, wherein said dosage comprises amount and timing.

54. An apparatus for iterative control of blood glucose levels in a diabetic individual, comprising:

a programmable computing device; and

programming executable by said computing device for carrying out the operations of;

(i) measuring blood glucose level associated with a first time period;

(ii) as a function of said blood glucose level, estimating insulin bolus dosage associated with a second time period subsequent to said first time period;

(iii) administering said insulin bolus based on said estimate; and

(iv) repeating operations (i) through (iii);

wherein dosage amount for said second time period is higher than, lower than, or the same as, dosage for said first time period.

55. An apparatus as recited in claim 54, wherein said first time period comprises a day during which at least one meal is eaten.

56. An apparatus as recited in claim 54, wherein said second time period comprises a subsequent day during which at least one meal is eaten.

57. An apparatus as recited in claim 54, wherein said first and second time periods comprise periods of one day.

58. An apparatus as recited in claim 54:

wherein said first time period comprises a twenty-four hour period during which breakfast, lunch and dinner meals are eaten; and

wherein said second time period comprises a twenty-four hour period during which breakfast, lunch and dinner are eaten.

59. An apparatus as recited in claim 54, wherein said estimating operation determines amount and timing for meal-related bolus dosing during said second time period.

60. An apparatus as recited in claim 54, wherein insulin bolus dosing is optimized over time.

61. An apparatus as recited in claim 54, wherein said estimating operation is a function of said blood glucose level measurement and at least one parameter indicative of the insulin sensitivity of said individual.

62. An apparatus as recited in claim 61, wherein said parameter indicative of the insulin sensitivity of said individual is selected from the group consisting essentially of exercise level and degree of stress.

63. An apparatus as recited in claim 54, wherein said estimating operation is a function of said blood glucose level measurement and meal size and timing.

64. An apparatus as recited in claim 54, wherein said estimating operation is a function of said blood glucose level measurement, meal size and timing, and at least one parameter indicative of insulin sensitivity of said individual.

65. An apparatus as recited in claim 64, wherein said parameter indicative of insulin sensitivity of said individual is selected from the group consisting essentially of an exercise level and a degree of stress.

66. An apparatus as recited in claim 54, wherein maximum glucose levels following each meal are maintained within a normal glycemic range.

67. An apparatus as recited in claim 54, wherein said the preprandial dosage of insulin for a subsequent day'"'"'s meal is iteratively updated over time.

68. An apparatus as recited in claim 67, wherein said dosage comprises amount and timing.

69. An apparatus as recited in claim 54, further comprising:

means for administering a quantity of insulin or insulin analog to the body of an individual.

70. An apparatus as recited in claim 69, wherein said means for administering insulin comprises an insulin pump.

71. An apparatus as recited in claim 69, wherein said means for administering insulin comprises an insulin inhaler.

72. An apparatus as recited in claim 54, wherein said programming operations further comprise estimating a basal insulin dosage.