Calculation of Insulin Sensitivity Factors used to determine correction doses of insulin at varying levels of glycemia in human patients.

Abstract

This invention discloses a method of calculating insulin sensitivity factors for use in calculating insulin doses dynamically as a function of current blood glucose level based on a temporally-weighted average of the patient's total daily insulin dose, the pharmacodynamic and/or pharmacokinetic profile of the insulin used, and the patient's typical ratio of basal insulin to bolus insulin. When average total daily insulin and the other relevant variables are inserted into the equation, the result is a mathematical function that can be used to estimate the effects of each unit of insulin delivered on a patient's blood glucose level. This mathematical equation is valid over a wide range of diabetic conditions and could be widely used throughout the world at very little cost (and at considerable improvement) to the current technology in use for these purposes.

Claims

1. A method of calculating an estimated sensitivity to a required dose of insulin to correct hyperglycemia, comprising: a formula as follows: $\mathrm{ISF}=\frac{1800}{\mathrm{BBR}.Math.\mathrm{TDD}.Math.\log \left(\frac{\mathrm{BG}}{\mathrm{TTPF}}\right)}$ where, ISF=Insulin Sensitivity Factor (sometimes also referred to as a Correction Factor). BBR=Basal/Bolus Ratio Factor, a number in the range of 0.1 to 1.9 which will vary based on the ratio of bolus insulin to basal insulin that the patient requires. TDD=A temporally-weighted average of the patient's normal daily insulin use, expressed in units of insulin per day BG=The patient's current blood glucose concentration (measured/expressed in milligrams per deciliter). TTPF=Time-to-peak factor, a number that varies inversely with the time in minutes it takes for a particular insulin to reach peak concentration in the bloodstream

2. The method of claim 1 where a user of the invention incorporates the formula into an item of existing software, where the item of existing software is used to determine insulin doses to be administered to the patient by an automated insulin delivery system comprised of a glucose monitor, an insulin pump, and an interoperable automated glycemic controller, whether integrated into the pump system or implemented as a separate device.

3. The method of claim 1, where a user of the invention incorporates the formula into an item of new software, where the item of new software is used to control insulin delivery in an automated insulin delivery system where the item of new software determines a dosage of insulin to be administered to a patient.

4. The method of claim 1, where a user of the invention incorporates the formula into both a new software system and an existing software system, where both the new software system and the existing software system determine a dosage of insulin to be administered to the patient.

5. The method of claim 1, where the formula provides an accurate estimation of the sensitivity of the patient to a given insulin dose.

6. The method of claim 5, where the insulin sensitivity estimate is dynamic in nature, as one or more of the various components of the equation change.

7. The method of claim 6, where the method can be used in monitoring systems for hospitalized patients to better predict hypoglycemia.

8. The method of claim 7, where the method can be used in a stand-alone system that monitors glucose levels continuously or intermittently.

9. The method of claim 7, where the method can be used in existing glucose monitors and insulin pumps to improve their predictions, performance, and dosing accuracy.

10. The method of claim 1, where the numerator of the function has a range of 1,200 to 2,000.

11. The method of claim 1, where the numerator of the function has a range of 2,000 to 2,800.

12. The method of claim 1, where the numerator of the function has a range of 1,600 to 2,000

13. The method of claim 1, additionally comprising a second step of taking the ISF (Insulin Sensitivity Factor) and using it to compute a correct dosage of insulin.

14. The method of claim 13, where a user of the invention incorporates the formula into an item of existing software, where the item of existing software is used to determine insulin doses to be administered to the patient by an automated insulin delivery system comprised of a glucose monitor, an insulin pump, and an interoperable automated glycemic controller, whether integrated into the pump system or implemented as a separate device.

15. The method of claim 13, where a user of the invention incorporates the formula into an item of new software, where the item of new software is used to control insulin delivery in an automated insulin delivery system where the item of new software determines a dosage of insulin to be administered to a patient.

16. The method of claim 13, where a user of the invention incorporates the formula into both a new software system and an existing software system, where both the new software system and the existing software system determine a dosage of insulin to be administered to the patient.

17. The method of claim 13, where the formula provides an accurate estimation of the sensitivity of the patient to a given insulin dose, where the insulin sensitivity estimate is dynamic in nature, as one or more of the various components of the equation change.

18. The method of claim 17, where the method can be used in monitoring systems for hospitalized patients to better predict hypoglycemia, where the method can be used in a stand-alone system that monitors glucose levels continuously or intermittently.

19. The method of claim 13, where the method can be used in existing glucose monitors and insulin pumps to improve their predictions, performance, and dosing accuracy.

20. The method of claim 13, where the numerator of the function has a range of 1,200 to 2,000.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0034] One preferred form of the invention will now be described with reference to the accompanying drawings.

[0035] FIG. 1 is a formula, according to the preferred form of the invention.

DETAILED DESCRIPTION OF THE FIGURES

[0036] Many aspects of the invention can be better understood with references made to the drawings below. The components in the drawings are not necessarily drawn to scale. Instead, emphasis is placed upon clearly illustrating the components of the present invention. Moreover, like reference numerals designate corresponding parts through the several views in the drawings. Before explaining at least one embodiment of the invention, it is to be understood that the embodiments of the invention are not limited in their application to the details of construction and to the arrangement of the components set forth in the following description or illustrated in the drawings. The embodiments of the invention are capable of being practiced and carried out in various ways. In addition the phraseology and terminology employed herein are for the purpose of description and should not be regarded as limiting.

[0037] FIG. 1 is a mathematical formula calculating an insulin sensitivity factor to be used for determining correction doses of rapid-acting insulin, according to a preferred form of the invention. This initial determination is part of a treatment regimen for diabetic patients.

[0038] Definition Terms:

[0039] ISF=Insulin Sensitivity Factor (sometimes also called a Correction Factor)

[0040] BG —Glucose concentration in blood plasma (measured in milligrams per deciliter)

[0041] TDD=an average, which may be a weighted average, of the patient's total daily dose of insulin, expressed in units per day.

[0042] BBR=an adjustment factor, related to the ratio of basal insulin needs to bolus insulin needs for an individual patient.

[0043] TTPF=an adjustment factor which varies inversely with the time a particular formulation of insulin takes to reach peak concentration in a patient's bloodstream.

[0044] To use this method of calculating an insulin sensitivity factor to be used for determining correction doses of rapid-acting insulin, a temporally weighted average of the patient's total daily dose (TDD) of insulin is inserted into the denominator of the function at the spot labelled “TDD.” A basal/bolus ratio (BBR) adjustment factor related to the ratio of basal to bolus insulin typically required by the patient, and configurable by the patient or their healthcare provider is inserted into the denominator of the function at the spot labelled “BBR.” This adjustment factor will vary within the range of 0.1 to 1.9, with a patient whose total daily insulin usage is equally split between basal and bolus insulin having a “BBR” of approximately 1.0. A time-to-peak factor (TTPF) that varies inversely with the time in minutes it takes the particular insulin type and formulation used by the patient to reach its maximum concentration in the bloodstream is inserted at the spot labelled “TTPF.” The time-to-peak factor is estimated to be approximately 50 for standard insulin aspart preparations (Novologl Novorapid and equivalent generics), 55 for standard insulin lispro (Humalog, Admelog, equivalent generics), 65 for adjuvenated insulin aspart (Fiasp), and approximately 75 for adjuvenated insulin lispro (Lyumjev). A blood glucose concentration obtained from a glucometer or other approved method of determining blood glucose is then inserted into the function at the spot labelled BG. The calculation is then performed by dividing BG by TTPF, adding 1, taking the natural logarithm of the result, multiplying that intermediate result by the product of TDD and BBR to yield a final denominator for the equation and dividing 1800 by that final denominator to produce an estimated insulin sensitivity factor (ISF).

[0045] Unique Features of the Invention: Current dose calculations for insulin use a static number as an estimate of insulin sensitivity, independent of glycemia or the pharmacokinetic profile of the insulin in use. The method described provides a way to replace that static number used in dosage calculations with a mathematical function capable of computing insulin sensitivity dynamically across a wide glycemic range and range of rapid-acting and ultra-rapid-acting analog insulins, allowing for more accurate dosing of insulin in patients with insulin-requiring diabetes, resulting in significantly more accurate dosing during times where blood glucose is elevated (hyperglycemia).

[0046] In one embodiment of the invention, the invention provides a method of calculating an estimated sensitivity to a required dose of insulin to correct hyperglycemia, comprising: a formula as follows:

[00001]$\mathrm{ISF}=\frac{1800}{\mathrm{BBR}.Math.\mathrm{TDD}.Math.\log \left(\frac{\mathrm{BG}}{\mathrm{TTPF}}+1\right)}$ [0047] where, [0048] ISF=Insulin Sensitivity Factor (sometimes also referred to as a Correction Factor). [0049] BBR=Basal/Bolus Ratio Factor, a number in the range of 0.1 to 1.9 which will vary based on the ratio of bolus insulin to basal insulin that the patient requires. [0050] TDD=A temporally-weighted average of the patient's normal daily insulin use, expressed in units of insulin per day [0051] BG=The patient's current blood glucose concentration (measured/expressed in milligrams per deciliter). [0052] TTPF=Time-to-peak factor, a number that varies inversely with the time in minutes it takes for a particular insulin to reach peak concentration in the bloodstream

[0053] In this embodiment, a user of the invention can incorporate the formula into an item of existing software, where the item of existing software is used to determine insulin doses to be administered to the patient by an automated insulin delivery system comprised of a glucose monitor, an insulin pump, and an interoperable automated glycemic controller, whether integrated into the pump system or implemented as a separate device. Aternatively, the user can incorporate the formula into an item of new software, where the item of new software is used to control insulin delivery in an automated insulin delivery system where the item of new software determines a dosage of insulin to be administered to a patient. Finally, it is contemplated that a user could incorporate the formula into both a new software system and an existing software system, where both the new software system and the existing software system determine a dosage of insulin to be administered to the patient.

[0054] In this embodiment, the formula provides an accurate estimation of the sensitivity of the patient to a given insulin dose and the insulin sensitivity estimate is dynamic in nature, as one or more of the various components of the equation change. The method can be used in monitoring systems for hospitalized patients to better predict hypoglycemia or in a stand-alone system that monitors glucose levels continuously or intermittently. The method can be used in existing glucose monitors and insulin pumps to improve their predictions, performance, and dosing accuracy and contemplates a numerator where the numerator of the function has a range of 1,200 to 2,000, 2,000 to 2,800, or 1,600 to 2,000.

[0055] It is also contemlated that a user could take a second step of taking the ISF (Insulin Sensitivity Factor) and using it to compute a correct dosage of insulin.

[0056] It should be understood that while the preferred embodiments of the invention are described in some detail herein, the present disclosure is made by way of example only and that variations and changes thereto are possible without departing from the subject matter coming within the scope of the following claims, and a reasonable equivalency thereof, which claims I regard as my invention.

[0057] All of the material in this patent document is subject to copyright protection under the copyright laws of the United States and other countries. The copyright owner has no objection to the facsimile reproduction by anyone of the patent document or the patent disclosure, as it appears in official governmental records but, otherwise, all other copyright rights whatsoever are reserved.