SYSTEMS, DEVICES, AND METHODS FOR ALLEVIATING GLUCOTOXICITY AND RESTORING PANCREATIC BETA-CELL FUNCTION IN ADVANCED DIABETES MELLITUS

• US 20140343530A1
• Filed: 08/05/2014
• Published: 11/20/2014
• Est. Priority Date: 04/04/2008
• Status: Active Grant

• Current Assignee: Hygieia, Inc.
• Original Assignee: Hygieia, Inc.
• Inventors: Bashan, Eran, Hodish, Israel
• Granted Patent: US 10,624,577 B2
• Time in Patent Office: Days
• US Class Current: 604/504
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• 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 5/4842 Monitoring progression or stage of a disease
• 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 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 20/17 delivered via infusion or injection

Abstract

Systems, methods and/or devices for treating diabetes mellitus by alleviating glucotoxicity and restoring pancreatic beta-cell function, comprising at least a first memory for storing data inputs corresponding at least to one or more components in a patient'"'"'s present insulin dosage regimen, and data inputs corresponding at least to the patient'"'"'s blood-glucose-level measurements determined at a plurality of times, and a processor operatively connected to the at least first memory. The processor is programmed at least to determine from the data inputs corresponding to the patient'"'"'s blood-glucose-level measurements determined at a plurality of times whether and by how much to vary at least one of the components of the patient'"'"'s present insulin dosage regimen. Also disclosed are systems, methods, and/or devices for alleviating glucotoxicity and restoring pancreatic beta-cell function, comprising establishing the patient'"'"'s current glycemic state relative to a desired glycemic range and determining from at least one of a plurality of the data corresponding to the patient'"'"'s blood glucose-level measurements whether and by how much to adjust at least one of the components in the patient'"'"'s present insulin dosage regimen.

Claims

1-11. -11. (canceled)

12. A method for treating diabetes mellitus by alleviating glucotoxicity and/or restoring pancreatic beta-cell function in a patient, the method comprising:

storing one or more components of the patient'"'"'s insulin dosage regimen;

drawing blood samples from the patient at a plurality of times;

ascertaining the patient'"'"'s blood glucose-level measurements in said blood samples;

tagging each of said blood glucose-level measurements with an identifier reflective of when said measurement was obtained;

establishing the patient'"'"'s current glycemic state relative to a desired glycemic range;

determining from the patient'"'"'s blood glucose-level measurements whether and by how much to adjust at least one component of the one or more components of the patient'"'"'s present insulin dosage regimen to stay within said desired glycemic range and administer the lowest insulin dosage;

adjusting said at least one component in accordance with said determination in a manner that dampens or prevents unstable oscillations; and

performing said steps of the method until the insulin dosage regimen required to stay within the desired glycemic range is lowered to a predetermined level.

13. The method of claim 12 wherein said unstable oscillations are dampened or prevented by ensuring that said adjustment is limited to an intermittent value.

14. The method of claim 12 wherein said unstable oscillations are dampened or prevented by ensuring that the current increase in the patient'"'"'s insulin dosage regimen is less than the previous decrease in the patient'"'"'s insulin dosage regimen.

15. The method of claim 12 wherein said unstable oscillations are dampened or prevented by ensuring that the current decrease in the patient'"'"'s insulin dosage regimen is less than the previous increase in the patient'"'"'s insulin dosage regimen.

16. The method of claim 12 wherein said unstable oscillations are dampened or prevented by inserting ‘

off intervals’

between different directions of dosage adjustments.

17. The method of claim 12 wherein said determination of whether and by how much to adjust at least one component of the patient'"'"'s present insulin dosage regimen is made by calculating the total daily amount of insulin.

18. The method of claim 12 wherein said determination of whether and by how much to adjust at least one component of the patient'"'"'s present insulin dosage regimen is made by calculating the amount by which any component of the dosage is greater than the same component for the previous dosage.

19. The method of claim 12 wherein said determination of whether and by how much to adjust at least one component of the patient'"'"'s present insulin dosage regimen is made by majority voting rule.

20. The method of claim 12 wherein said determination of whether and by how much to adjust at least one component of the patient'"'"'s present insulin dosage regimen is subject to a consecutive dosage increment rule to establish an off period if a more than a desired number of increments has occurred.

21. The method of claim 21, wherein said consecutive dosage increment rule prevents two consecutive increments from occurring and creates an off period after each dosage increment.

22. The method of claim 21, wherein said consecutive dosage increment rule allows more than two consecutive increments but no more than eight consecutive increments.

23-35. -35. (canceled)

36. An apparatus for alleviating glucotoxicity and/or restoring pancreatic beta-cell function in a patient over time, comprising:

at least a first computer-readable memory for storing one or more components in a patient'"'"'s present insulin dosage regimen and the patient'"'"'s blood-glucose-level measurements determined at a plurality of times within a predefined period of time;

at least one data input for obtaining data corresponding to the patient'"'"'s blood glucose-level measurements determined at the plurality of times;

a timer for monitoring the predetermined time period, the timer being incremented based on at least one of the passage of a predetermined increment of time and the receipt of at least one of the plurality of blood glucose-level measurements;

at least one processor operatively connected to the at least first computer-readable memory, the processor programmed at least to;

tag the plurality of blood glucose-level measurements with an identifier reflective of when the measurement was obtained;

calculate, after obtaining one of the plurality of blood glucose-level measurements but before obtaining a subsequent blood glucose-level measurement, any deviation of the obtained blood glucose-level measurement from a desired glycemic range;

adjust at least one of the one or more components in the patient'"'"'s insulin dosage regimen in response to a determination that the most recently obtained blood glucose-level measurement was not within a desired glycemic range;

wherein the timer is reinitiated after the determination that that the most recently obtained blood glucose-level measurement was not within a desired glycemic range over the predefined period of time;

determine, at the end of the predefined period of time, from a plurality of the data corresponding to the patient'"'"'s blood glucose-level measurements, the variation of at least one of the one or more components in the patient'"'"'s insulin dosage regimen that is necessary in order to maintain the patient'"'"'s blood glucose-level measurements within a predefined range;

reinitiate said timer after said adjustment and said determination; and

repeatedly tag said measurements, calculate said deviation, adjust said at least one component, and determine said variation until the insulin dosage regimen required to stay within the desired glycemic range is lowered to a predetermined level.

37. The apparatus of claim 36, further comprising a data entry device enabling a user to modify the identifier associated with each blood-glucose-level measurement data-input.

38. The apparatus of claim 36, wherein the at least one processor further determines on a predefined schedule whether and by how much to vary at least one of the one or more components in the patient'"'"'s present insulin dosage regimen.

39. The apparatus of claim 36, wherein the at least one processor further determines, at the end of the predetermined period of time, from the plurality of the data corresponding to the patient'"'"'s blood-glucose-level measurements, if the patient'"'"'s blood-glucose level measurements fall within or outside of said predefined range, and varying at least one of the one or more components in the patient'"'"'s present insulin dosage regimen only if the patient'"'"'s blood-glucose level measurements fall outside of said predefined range.

40. The apparatus of claim 36, wherein the at least one processor further determines from the patient'"'"'s blood-glucose-level measurements whether the patient'"'"'s blood-glucose-level measurements represent a normal distribution.

41. The apparatus of claim 40, wherein the determination of whether the patient'"'"'s blood-glucose-level measurements represent a normal distribution comprises determining whether the third moment of the distribution of the patient'"'"'s blood-glucose-level measurements fall within said predefined range.

42. The apparatus of claim 36, wherein the one or more components in the patient'"'"'s present insulin dosage regimen comprise a long-acting insulin dosage component.

43. The apparatus of claim 36, wherein the one or more components in the patient'"'"'s present insulin dosage regimen comprise a short-acting insulin dosage component defined by a carbohydrate ratio or a fixed meal dose, and plasma glucose correction factor.

44. A system for alleviating glucotoxicity and/or restoring pancreatic beta-cell function in a patient, the system comprising:

at least one memory for storing data corresponding at least to one or more components of a patient'"'"'s present insulin dosage regimen, and data corresponding at least to the patient'"'"'s blood-glucose-level measurements measured at a plurality of times during a predetermined time period; and

at least one processor operatively connected to the at least one memory, the at least one processor configured to;

initiate a timer to monitor the predetermined time period;

increment the timer based on at least one of the passage of a predetermined increment of time and the receipt of at least one of the plurality of blood glucose-level measurements;

tag the plurality of blood glucose-level measurements with an identifier reflective of when the measurement was obtained;

calculate, after obtaining one of the plurality of blood glucose-level measurements but before obtaining a subsequent blood glucose-level measurement, any deviation of the obtained blood glucose-level measurement from a desired glycemic range;

adjust at least one of the one or more components in the patient'"'"'s insulin dosage regimen in response to the determination that the most recently obtained blood glucose-level measurement was not within a desired glycemic range;

wherein the timer is reinitiated after the determination that was not within a desired glycemic range; and

determine, at the end of the predetermined time period, from a plurality of the data corresponding to the patient'"'"'s blood glucose-level measurements whether and by how much to vary at least one of the one or more components in the patient'"'"'s present insulin dosage regimen in order to maintain the patient'"'"'s blood glucose-level measurements within a predefined range;

wherein the timer is reinitiated after the determination of whether and by how much to vary at least one of the one or more components in the patient'"'"'s present insulin dosage regimen; and

repeatedly increment said timer, tag said measurements, calculate said deviation, adjust said at least one component, and determine said variation until the insulin dosage regimen required to stay within the desired glycemic range is lowered to a predetermined level.

45-74. -74. (canceled)