Determination of glucose sensitivity and a method to manipulate blood glucose concentration

• US 20040197846A1
• Filed: 12/23/2003
• Published: 10/07/2004
• Est. Priority Date: 01/18/2001
• Status: Abandoned Application

• Current Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Original Assignee: Sensys Medical, Inc. (Sensys Medical Limited)
• Inventors: Hockersmith, Linda, Monfre, Stephen L., Hazen, Kevin H., Blank, Thomas B.
• Application Number:
  US10/746,352
• Publication Number:
  US 20040197846A1
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The invention provides a method of determining an individual'"'"'s glucose metabolism sensitivity based upon the shape of a glucose profile in response to a stimulus, such as a caloric challenge. The sensitivity of an individual may be used to project a glucose response profile or to achieve a targeted response in the individual'"'"'s blood glucose concentrations in response to a stimulus, such as medication, exercise, or caloric intake. An actual glucose response to a stimulus is determined using parameters that measure the shape of a glucose profile resulting from the stimulus. The glucose response provides rapid feedback of an individual'"'"'s diabetic state.

Claims

1. A method of determining glucose sensitivity, comprising the steps of:

providing at least a portion of a glucose profile, said profile comprising a plurality of blood glucose concentrations for an individual which report after said individual receives a stimulus;

evaluating a shape of said profile based on one or more parameters of said shape; and

determining glucose sensitivity of said individual based on evaluation of said shape.

2. The method of claim 1, wherein said stimulus comprises a caloric challenge.

3. The method of claim 2, wherein said caloric challenge comprises a glucose challenge.

4. The method of claim 1, wherein said plurality of blood glucose concentrations comprise a time series.

5. The method of claim 1, wherein said plurality of blood glucose concentrations are actual values.

6. The method of claim 1, wherein said blood glucose concentrations are relative values.

7. The method of claim 2, wherein said parameters comprise any of:

a rate of increase in glucose concentration after said caloric challenge;

a peak monitored glucose concentration;

a first time period, wherein said glucose profile is above a threshold level;

a rate of decrease of said glucose concentration after said peak glucose concentration;

an area under the curve of said glucose profile; and

an area under the curve of said glucose profile over a second period of time.

8. The method of claim 7, wherein said evaluating step comprises:

establishing a value for any of said parameters based upon a scale defined by values indicative of either a normal condition or one of a plurality of abnormal conditions.

9. The method of claim 7, wherein said evaluation step comprises:

determining a weight for at least one of said parameters.

10. The method of claim 9, wherein said step of determining a weight comprises the steps of:

assigning each parameter a value on either a linear or non-linear scale, according to value of said parameter, wherein said assigned value is adjusted by said weight.

11. The method of claim 10, wherein minimum and maximum of said scale correspond to predetermined threshold values for a normal condition and a diabetic condition, respectively.

12. The method of claim 10, wherein ranges of values represented by said scale are established according to standard diagnostic criteria.

13. The method of claim 10, wherein missing parameters are assigned a weight of zero.

14. The method of claim 10, wherein missing data are supplied from historical data.

15. The method of claim 10, further comprising the step of:

calculating one or more glucose sensitivity factors based on actual or relative values of said parameters and said weights.

16. The method of claim 15, wherein said step of calculating said glucose sensitivity factor comprises the step of:

calculating a weighted average of said weighted parameters according to;

$\mathrm{SF}=\frac{\left(P_1<br><br>W_1+P_2<br><br>W_2+P_3<br><br>W_3+P_4<br><br>W_4+P_5<br><br>W_5+P_6<br><br>W_6\right)}{\left(W_1+W_2+W_3+W_4+W_5+W_6\right)},$

 

wherein SF=said glucose sensitivity factor.

17. The method of claim 15, wherein said step of calculating glucose sensitivity factors comprises the step of:

calculating a weighted average of said weighted parameters according to;

${\mathrm{SF}}_2=\frac{\left(P_7<br><br>W_7+P_8<br><br>W_8\right)}{\left(W_7+W_8\right)},$

 

wherein SF₂=said glucose sensitivity factor.

18. The method of claim 15, wherein said step of calculating glucose sensitivity factors comprises the step of:

calculating a weighted average of said weighted parameters according to;

${\mathrm{SF}}_3=\frac{\left(P_1<br><br>W_1+P_2<br><br>W_2+P_3<br><br>W_3+\mathrm{\dots <br><br>}+P_n<br><br>W_n\right)}{\left(W_1+W_2+W_3+\mathrm{\dots <br><br>}+W_n\right)},$

 

wherein SF₃=said glucose sensitivity factor.

19. The method of claim 15, wherein said step of calculating glucose sensitivity factors comprises the steps of:

calculating a weighted average of a first set of selected weighted parameters according to;

${\mathrm{SF}}_4=\frac{\left(P_1<br><br>W_1+P_6<br><br>W_6\right)}{\left(W_1+W_6\right)},$

 

wherein SF₄=a first glucose sensitivity factor; and

calculating a weighted average of a second set of selected weighted parameters according to;

$S<br><br>\text{\hspace{1em}<br><br>}<br><br>F_5=\frac{\left(P_2<br><br>W_2+P_3<br><br>W_3+P_4<br><br>W_4+P_5<br><br>W_5\right)}{\left(W_2+W_3+W_4+W_5\right)},$

 

wherein SF₅=a second glucose sensitivity factor.

20. The method of claim 1, further comprising the step of:

advising said subject of glucose sensitivity.

21. The method of claim 1, wherein said glucose concentrations are obtained using any of:

a noninvasive blood glucose analyzer;

a minimally invasive blood glucose analyzer;

an invasive blood glucose analyzer;

a semi-continuous glucose analyzer; and

a continuous glucose analyzer.

22. The method of claim 1, wherein a processing device so programmed executes said steps.

23. The method of claim 1, wherein said plurality of blood glucose concentrations comprise blood glucose concentrations from before and after a glucose or meal challenge.

24. The method of claim 1, further comprising the step of:

projecting a glucose response that results from any of;

a medication;

a caloric intake; and

a physical activity.

25. The method of claim 24, wherein said medication comprises insulin.

26. The method of claim 25, further comprising the step of:

adjusting dosage of said medication; and

adjusting an intake time of said medication.

27. The method of claim 24, wherein said caloric intake comprises any of:

liquid food;

solid food;

solid and liquid food;

a carbohydrate rich drink;

a carbohydrate rich meal; and

a mixture of carbohydrate, fat, and protein.

28. The method of claim 24, wherein said physical activity is characterized by at least one of:

duration of exercise; and

intensity of exercise.

29. The method of claim 24, wherein said parameters include any of:

fasting glucose concentration;

rate of increase of glucose concentration following said glucose challenge;

peak monitored glucose concentration;

duration glucose remains elevated;

rate of decrease of glucose concentration following said peak concentration;

minimum glucose concentration following said peak concentration;

area under the curve for the glucose profile; and

area under the curve during a subset in time of the glucose profile.

30. The method of claim 29, wherein said step of projecting said glucose response comprises calculation of said projected response according to:

31. A method of projecting a glucose concentration response, comprising the steps of:

providing a glucose sensitivity, wherein said glucose sensitivity is determined from the shape of a glucose concentration profile of an individual;

providing a stimulus, wherein said stimulus comprises any of;

a medication;

a caloric intake;

a physical activity; and

using said glucose sensitivity for said individual to project said glucose concentration response that results from said stimulus.

32. The method of claim 31, wherein said glucose concentration response is a glucose response profile that comprises glucose concentration as a function of time.

33. The method of claim 31, further comprising any of the steps of:

adjusting dosage of said medication; and

adjusting time of said medication intake.

34. The method of claim 33, wherein said medication comprises insulin.

35. The method of claim 31, wherein said caloric intake comprises any of:

solid food;

liquid food;

solid and liquid food;

a carbohydrate rich drink;

a carbohydrate rich meal; and

a mixture of carbohydrate, fat, and protein.

36. The method of claim 31, wherein said step of providing a stimulus comprises any of:

adjusting duration of said exercise; and

adjusting intensity of said exercise.

37. The method of claim 31, wherein said step of using said glucose sensitivity comprises calculation of said projected response according to:

38. The method of claim 31, further comprising the step of:

generating a glucose concentration profile through the intake of at least one of carbohydrates and insulin.

39. The method of claim 38, wherein said glucose concentration profile comprises any of:

a physiologically normal glucose profile; and

a set of glucose concentrations, wherein the minimum and maximum of said set of glucose concentrations fall between 70 and 140 mg/dL.

40. The method of claim 38, wherein said glucose concentration profile comprises:

a specified glucose profile, wherein shape specifications are used to specify said specified glucose profile.

41. The method of claim 31, further comprising the step of:

using exogenous insulin to assist shifts between blood glucose concentrations.

42. The method of claim 31, further comprising the step of:

generating a calibration model for use in noninvasive methods of blood glucose determination employing spectroscopic instrumentation based on idealized anti-correlated glycemic profiles.

43. A method of determining a glucose response, comprising the steps of:

providing a stimulus, wherein said stimulus comprises at least one of;

a medication;

a caloric intake; and

a physical activity;

providing at least a portion of a glucose profile, said profile comprising a plurality of blood glucose concentrations for an individual which result after said individual receives said stimulus;

evaluating a shape of said profile based on one or more parameters of said shape; and

determining said glucose response based on evaluation of said shape.

44. The method of claim 43, wherein said medication comprises any of

insulin;

and

an analog of insulin.

45. The method of claim 43, wherein said caloric intake comprises any of:

solid food;

liquid food;

solid and liquid food; and

a mixture of carbohydrate, fat, and protein.

46. The method of claim 43, wherein said physical activity comprises:

a duration of exercise; and

an intensity of exercise.

47. The method of claim 43, wherein said plurality of blood glucose concentrations comprise a time series.

48. The method of claim 43, wherein said parameters comprise any of:

an initial fasting glucose concentration;

a rate of increase in glucose concentration after said caloric challenge;

a peak monitored glucose concentration;

a first time period, wherein said glucose profile is above a threshold level;

a glucose concentration after elapse of a predetermined time interval;

a rate of decrease of said glucose concentration after said peak glucose concentration;

an area under the curve of said glucose profile; and

an area under the curve of said glucose profile over a second period of time.

49. The method of claim 43, wherein said evaluation step comprises:

establishing a value for any of said parameters based upon a scale defined by values indicative of any of;

a normal condition; and

one of a plurality of abnormal conditions.

50. The method of claim 43, further comprising the step of:

determining a weight for at least one of said parameters in said evaluation step.

51. The method of claim 50, wherein said weight corresponding to each of said parameters is individually determined.

52. The method of claim 43, further comprising a step of:

evaluating said step of providing a stimulus, wherein the stimulus is evaluated as either too large or too small as compared to a normal glucose profile in terms of said glucose response.

53. The method of claim 52, wherein said evaluation step comprises the step of:

calculating a weighted average of said weighted parameters according to;

$R<br><br>\text{\hspace{1em}<br><br>}<br><br>F=\frac{\left(P_1<br><br>W_1+P_2<br><br>W_2+P_3<br><br>W_3+\mathrm{\dots <br><br>}+P_n<br><br>W_n\right)}{\left(W_1+W_2+W_3+\mathrm{\dots <br><br>}+W_n\right)},$

 

wherein RF=said response factor.

54. The method of claim 53, further comprising a step of:

informing said individual of results of said evaluation step, wherein said individual is provided with information for disease management.

55. The method of claim 53, wherein said disease is diabetes mellitus.

56. A method for shifting blood glucose concentration in an individual from a starting value to a target value, said method comprising the steps of:

providing a first stimulus to said individual;

calculating a required amount of said stimulus to produce said shift according to a formula, said formula comprising;

$R_2=R_1*\frac{I_2}{I_1}$

 

where R₂ is a projected response;

ingesting said stimulus by said individual; and

observing an actual shift in blood glucose concentration caused by said stimulus.

57. The method of claim 56, wherein said stimulus is any of:

a caloric intake; and

a medicine.

58. The method of claim 56, wherein said caloric intake is any of:

a liquid food;

a solid food;

a liquid and solid food;

a carbohydrate rich fluid;

a carbohydrate rich solid; and

a mixture of carbohydrate, protein, and fat.

59. The method of claim 56, wherein said medicine is any of:

a regular insulin; and

an insulin analog.

60. The method of claim 56, wherein said blood glucose shift comprises a glucose excursion.

61. The method of claim 60, wherein said glucose excursion is any of:

flat; and

specified by one or more shape parameters.

62. The method of claim 61, wherein said shape parameters comprises at least one of:

initial fasting glucose concentration;

rate of increase of glucose concentration following said glucose challenge;

peak monitored glucose concentration;

duration glucose remains elevated;

rate of decrease of glucose concentration following said peak concentration;

minimum glucose concentration following said peak concentration;

area under the curve for the glucose profile; and

area under the curve during a subset in time of the glucose profile.

63. The method of claim 60, further comprising the step of:

calculating a second required amount of stimulus according to said formula, wherein said second required amount comprises an amount of stimulus to be ingested by said individual to effect said target glucose excursion; and

ingesting said second required amount of carbohydrate by said individual.

64. The method of claim 63, wherein said stimulus is any of:

a second caloric intake; and

a second medicine.

65. The method of claim 63, wherein said second caloric intake is any of:

a liquid food;

a solid food;

a liquid and solid food;

a carbohydrate rich fluid;

a carbohydrate rich solid; and

a mixture of carbohydrate, protein, and fat.

66. The method of claim 63, wherein said second medicine is any of:

a regular insulin; and

an insulin analog.

67. The method of claim 63, wherein said blood glucose shift comprises multiple glucose excursions.

68. The method of claim 67, wherein said multiple excursions are any of:

anti-correlated; and

specified in terms of at least one shape parameter.

69. The method of claim 63, further comprising the step of:

producing idealized, anti-correlated glycemic profiles, wherein calibration models are generated for use in non-invasive methods of blood glucose determination employing spectroscopic instrumentation

70. The method of claim 63, further comprising the step of:

generating a calibration model for use in noninvasive methods of blood glucose determination employing spectroscopic instrumentation based on idealized inversely correlated glycemic profiles produced using said formula