Systems, devices, and methods for alleviating glucotoxicity and restoring pancreatic beta-cell function in advanced diabetes mellitus

11723,592

16/817161

March 12, 2020

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.

Hygieia, Inc. (Livonia, MI, US)

Hygieia, Inc. (Livonia, MI, US)

1. 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 if there have been an excessive number of hypoglycemic events over a predefined period of time, and to vary at least one of the one or more components in the patient's present insulin dosage regimen in response to a determination that there have been an excessive number of hypoglycemic events over the predefined period of time; 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 the patient's insulin dosage regimen in accordance with said determination of whether to adjust said insulin dosage regimen by increasing, decreasing, or pausing the patient's dosage regimen to dampen or prevent unstable oscillations, wherein said adjustment weighs both A1C percentage and the number of hypoglycemic events within the predefined period of time in order to achieve an improved glycemic composite index, and the restoration of beta-cell function which reduces exogenous insulin reliance; 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.

2. 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 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.

3. 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.

4. The system of claim 3 , wherein the data corresponding at least to the patient's blood-glucose-level measurements determined at a plurality of times are associated with an identifier indicative of when the measurement was input into the memory.

5. The system of claim 4 wherein the one or more components in the patient's present insulin dosage regimen comprise a long-acting insulin dosage component, and wherein the processor is programmed to determine from the identifier indicative of when a measurement was input into the memory at least whether the measurement is a morning or bed-time blood-glucose-level measurement, to determine whether the patient's morning and bed-time blood-glucose-level measurements fall within a predefined range, and to determine by how much to vary the patient's long-acting insulin dosage component only when the patient's morning and bed-time blood-glucose-level measurements are determined to fall outside of said desired glycemic range.

6. The system of claim 5 , wherein, in connection with the determination of by how much to vary at least one of the one or more components in the patient's present insulin dosage regimen, the at least one processor is programmed to factor in an insulin sensitivity correction factor that defines both the percentage by which any of the one or more components of the insulin dosage regimen may be varied and the direction in which any fractional variations in any of the one or more components are rounded to the nearest whole number.

7. The system of claim 6 , wherein the at least one memory further stores data corresponding to a patient's present weight, and wherein the insulin sensitivity correction factor is in part determined from the patient's present weight.

8. The system of claim 6 , wherein the determination of by how much to vary the long-acting insulin dosage component of a patient's present insulin dosage regimen is a function of the present long-acting insulin dosage, the insulin sensitivity correction factor, and the patient's blood-glucose-level measurements.

9. The system of claim 3 , wherein the processor is programmed to determine 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.

10. The system of claim 3 , wherein the processor is programmed to determine from the data inputs corresponding at least to the patient's blood-glucose-level measurements determined at a plurality of times if the patient's blood-glucose level measurements fall within or outside said desired glycemic range, and to vary 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 desired glycemic range.

11. The system of claim 10 , wherein the processor is further programmed to determine from the data inputs corresponding at least to the patient's blood glucose-level measurements determined at a plurality of times whether the patient's blood glucose-level measurements determined at a plurality of times represent a normal or abnormal distribution.

12. The system of claim 10 , wherein the determination of whether the patient's blood-glucose-level measurements determined at a plurality of times represent a normal or abnormal distribution comprises determining whether the third moment of the distribution of the patient's blood-glucose-level measurements determined at a plurality of times fall within said desired glycemic range.

13. The system of claim 3 , 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 and plasma glucose correction factor, and wherein the processor is programmed to determine whether and by how much to vary the patient's carbohydrate ratio and plasma glucose correction factor.

14. The system of claim 13 , wherein, in connection with the determination of by how much to vary at least one of the one or more components in the patient's present insulin dosage regimen, the at least one processor is programmed to factor in an insulin sensitivity correction factor that defines both the percentage by which any one or more components of the insulin dosage regimen may be varied and the direction in which any fractional variations in the one or more components are rounded to the nearest whole number.

15. The system of claim 14 , wherein the determination of by how much to vary the present plasma glucose correction factor component of a patient's insulin dosage regimen is a function of a predefined value divided by the mean of the total daily dosage of insulin administered to the patient, the patient's present plasma glucose correction factor, and the insulin sensitivity correction factor.

16. The system of claim 15 , wherein a value representing twice the patient's daily dosage of long-acting insulin in the present insulin dosage regimen is substituted for the mean of the total daily dosage of insulin administered to the patient as an approximation thereof.

17. The system of claim 15 , wherein the plasma glucose correction factor component of the patient's insulin dosage regimen is quantized to predefined steps of mg/dl.

18. The system of claim 14 , wherein the determination of by how much to vary the present carbohydrate ratio component of a patient's insulin dosage regimen is a function of a predefined value divided by the mean of the total daily dosage of insulin administered to the patient, the patient's present carbohydrate ratio, and the insulin sensitivity correction factor.

19. The system of claim 18 , wherein a value representing twice the patient's daily dosage of long-acting insulin in the present insulin dosage regimen is substituted for the mean of the total daily dosage of insulin administered to the patient as an approximation thereof.

20. The system of claim 18 , wherein the at least one processor is programmed to determine a correction factor that allows variations to the carbohydrate ratio component of a patient's insulin dosage regimen to be altered in order to compensate for a patient's individual response to insulin at different times of the day.

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