Method and system for determining insulin dosing schedules and carbohydrate-to-insulin ratios in diabetic patients

Abstract

Method for digitally determining the daily insulin regimen for a diabetic patient. The invention divides the patient's day into adjustable time intervals containing basal insulin dosage rates and Carbohydrate-to-Insulin Ratio(s) (for determining meal insulin doses). The invention identifies the Corrective Insulin doses over a time interval as an “error” in the Prescription Insulin (Basal Insulin+Meal Insulin). Methods involve first estimating the change to one of these two components of Prescription Insulin, and then determining the change to the other by subtracting from the error. One method estimates Change in Meal Insulin distributed among intervals proportional to old Meal Insulin. Another method lumps After-Meal Corrective Insulin together with Meal Insulin. Another method splits the interval at the After-Meal Corrective Dose and determines Basal from Time-Boundary Corrective Dose. Data may be obtained from the previous day, and a small fraction of error applied, leading to asymptotic reduction of error. Data may be obtained from recent history, and a larger fraction of error applied by doctor or automatic method.

1 - 129 . (canceled) 
     
     
         130 . A computer-implemented method of dynamically adjusting an insulin dosing scheme of a subject in an insulin pen, comprising:
 obtaining, by at least one computing device and comprising at least one hardware processor, data from the insulin pen comprising a previous insulin dosing scheme of the subject and blood glucose data of the subject relating to the previous insulin dosing scheme; and   determining, by the at least one computing device, an adjusted insulin dosing scheme for the subject based on the data and the previous insulin dosing scheme, the adjusted insulin dosing scheme comprising:
 (a) combining, by the at least one computing device, a base insulin dosage scheme administered over a given previous time interval, whereby long-acting characteristics of the dosage cause the effect of a constant Basal Insulin with an additional insulin dosage administered in relation to a meal taken during the previous given time interval (Meal Insulin) to determine a previous total insulin prescribed for the previous given time interval (Prescription Insulin); 
 (b) determining, by the at least one computing device, an error in a previous total insulin prescribed by determining a difference between previous blood glucose data and a blood glucose target, dividing the difference by a Correction Factor (CF), applying a configurable fraction (KrxIns) of the divided difference to determine the error, and applying a portion of said error to Meal Insulin and a portion of the error to Basal Insulin, by:
 determining, by the at least one computing device, a preliminary desired change to Basil Insulin as an independent variable and then determining a change to Meal Insulin as a dependent variable, wherein the change to Meal Insulin is calculated as the error in the previous total insulin prescribed less the preliminary desired change to Basal Insulin; and 
 
 (c) determining, by the at least one computing device, a change to a Carbohydrate-to-Insulin Ratio (CIR) to be used in adjusting the insulin dosing scheme to arrive at an adjusted insulin dosing scheme either by:
 (i) multiplying, by the at least one computing device, the change to Meal Insulin by a rate of change of the Carbohydrate-to-Insulin Ratio (CIR) with respect to Meal Insulin, which is determined as a calculus derivative of a population-based correlation, or 
 (ii) determining, by the at least one computing device, a change for the Carbohydrate-to-Insulin Ratio (CIR) for a 24 hour period based on a combination of a total Meal Insulin for the 24 hour period plus the error in the previous total insulin prescribed for the 24 hour period minus a change for Basal Insulin for the 24 hour period, and dividing a total amount of carbohydrates for the 24 hour period by the combination; and 
 
   causing, by the at least one computing device, the adjusted insulin dosing scheme determined for the subject to be shown in a display of an insulin device for an implementation of the adjusted insulin dosing scheme; and   linking the adjusted insulin dosing scheme to the insulin pen to cause a change in the dose setting of the pen of at least a portion of the adjusted insulin dosing scheme.   
     
     
         131 . The computer-implemented method of  claim 130 , wherein the adjusted insulin scheme is comprised of one or more adjusted values for a daily schedule of Basal Doses, one or more values of Correction Factor (CF) and a daily schedule of Carbohydrate-to-Insulin Ratios, or a daily schedule of Meal Insulin doses. 
     
     
         132 . The computer-implemented method of  claim 130 , further comprising rendering, by the at least one computing device, the adjusted insulin dosing scheme in a video screen, generating, by the at least one computing device, a printed report, generating, by the at least one computing device, a digital file, or communicating, by the at least one computing device, the adjusted insulin dosing scheme to an operating program of the insulin pen. 
     
     
         133 . An insulin pen configured to dynamically adjust an insulin dosing scheme of a subject, comprising:
 an insulin cartridge containing insulin;   a disposable needle configured to provide the insulin from the insulin cartridge into the subject;   a battery;   at least one computing device comprising at least one hardware processor; and   program instructions executable in the at least one computing device that, when executed, cause the at least one computing device to determine an insulin dosing scheme by which insulin is introduced into the subject by:
 accessing data comprising a previous insulin dosing scheme of the subject and blood glucose data of the subject relating to the previous insulin dosing scheme; and 
 determining an adjusted insulin dosing scheme for the subject based on the data, the adjusted insulin dosing scheme comprising: 
 using multiple daily insulin doses comprised of: a Rapid-Acting insulin for use in conjunction with meals, and a Long-Acting insulin, which can be administered as infrequently as once per day, as Basal Insulin, enabling the calculation of an hourly Basal rate of release administered during the day, equal to the daily total of Long-Acting insulin divided by 24.
 (a) calculating a total daily basal insulin dosage of Long-Acting insulin administered over the day containing a previous given time interval, and calculating Basal Insulin released during a previous time interval as the duration of the time interval times the daily amount of Basal Insulin divided by 24, and combining the calculated Basal Insulin amounts with an additional insulin dosage of rapid-acting insulin administered in relation to a meal taken during the previous time interval (Meal Insulin) to determine a previous total insulin prescribed for the previous time interval (Prescription Insulin), 
 (b) determining an error in the previous total insulin prescribed by determining a difference between previous blood glucose data tested at the end of the previous time interval and a blood glucose target, dividing the difference by a Correction Factor (CF), 
 applying a fraction of the divided difference to determine the error, and applying a portion of the error to Meal Insulin and a portion of the error to Basal Insulin, by: 
 determining a preliminary desired change to Basal Insulin as an independent variable and then determining a change to Meal Insulin as a dependent variable, wherein the change to Meal Insulin is calculated as the error in the previous total insulin prescribed less the preliminary desired change to Basal Insulin; and 
 (c) determining a change to a Carbohydrate-to-Insulin Ratio (CIR) to be used in adjusting meal insulin in an adjusted insulin dosing scheme either by:
 (i) multiplying a desired change for Meal Insulin by a rate of change of the Carbohydrate-to-Insulin Ratio (CIR) with respect to Meal Insulin, which is determined as a calculus derivative of a population-based correlation, or 
 (ii) determining a change for the Carbohydrate-to-Insulin Ratio (CIR) for the given time interval based on a combination of a total Meal Insulin for the previous time interval plus the error in for the previous given time interval minus a change for Basal Insulin for the given time interval, and dividing a total amount of carbohydrates for the previous given time interval by the combination; and 
 
 (d) providing, via the needle of the insulin pen, at least a portion of the insulin to the subject in accordance with the adjusted insulin dosing scheme determined for the subject. 
 
   
     
     
         134 . The insulin Pen of  claim 133 , wherein the preliminary estimate of the change to the Basal insulin for a time interval is determined by the steps of:
 (a) using a previously configured sequence of time intervals during the day, and designating one of the intervals not normally containing a meal as a source of the data for adjusting Basal (referred-to herein as the Fasting Interval); and   (b) determining an error in the previous basal insulin of the Fasting Interval as Kreliability*KrxIns*(Fasting BG−TargetBG)/(Correction Factor (CF)).   
     
     
         135 . The insulin pen of  claim 133 , wherein the adjusted insulin scheme is comprised of one or more adjusted values for a daily schedule of Basal Doses, one or more values of a daily schedule of Correction Factors (CF), and either a daily schedule of Carbohydrate-to-Insulin Ratios, or a daily schedule of Meal Insulin doses. 
     
     
         136 . The insulin pen of  claim 133 , further comprising program instructions that, when executed, cause the at least one computing device to render the adjusted insulin dosing scheme in a screen of an electronic display, the screen display showing the doses of both types of insulin, but the executable instructions of the pen allowing injection of only the doses for the type of insulin within the cartridge. 
     
     
         137 . The computer-implemented method of  claim 130 , wherein the change to Carbohydrate-to-Insulin Ratio of step(c)(i) is determined as the rate of change of CIR with respect to a total insulin dose for a 24 hour period times the rate of change of the total insulin dose for the 24 hour period with respect to Meal Insulin for the 24 hour period times the desired change to Meal Insulin for the period under consideration. 
     
     
         138 . The insulin pen of  claim 133 , wherein the change to Carbohydrate-to-Insulin Ratio of step(c)(i) is determined as the rate of change of CIR with respect to a total insulin dose for a 24 hour period times the rate of change of the total insulin dose for the 24 hour period with respect to Meal Insulin for the 24 hour period times the desired change to Meal Insulin for a period under consideration. 
     
     
         139 . A system, comprising:
 at least one insulin device comprising a display, an insulin pen and means for linking data from the insulin pen with a kit device;   the kit device containing a computing device comprising at least one hardware processor, linked to the pen and linked to a central computing device by a cellular system or the Internet;   a Blood Glucose Meter capable of linking to the kit device to the cellular network or the Internet; and   an application executable in the at least one computing device that, when executed, causes the at least one computing device to:
 access data comprising a previous insulin dosing scheme of a subject and blood glucose data of the subject relating to the previous dosing scheme; and 
 determine an adjusted insulin dosing scheme for the subject based on an analysis of the data performed by the at least one computing device, the adjusted insulin dosing scheme comprising:
 (a) using multiple daily injections comprised of: a Rapid-Acting Insulin for use with meals and correction doses, and a Long-Acting Insulin for use as Basal insulin, wherein the Long-Acting Insulin is an extended-release formulation that can be administered as infrequently as once per day, from a separate linked pen, 
 (b) using data records of a previous insulin dosing scheme to combine a basal insulin dosage released over a previous given time interval (Basal Insulin) with an additional insulin dosage administered in relation to a meal taken during the previous given time interval (Meal Insulin) to determine a previous total insulin prescribed for the given time interval (Prescription Insulin), 
 (c) determining an error in the previous total insulin prescribed for the previous given time interval by determining a difference between previous blood glucose data tested at the end of the previous time interval and a blood glucose target, dividing the difference by a Correction Factor (CF), applying a fraction of the divided difference to determine the error, and applying a portion of the error to Meal Insulin and a portion of the error to Basal Insulin, by:
 determining a preliminary desired change to Basal Insulin as an independent variable and then determining a change to Meal Insulin as a dependent variable, wherein the change to Meal Insulin is calculated as the error in the previous total insulin prescribed less the preliminary desired change to Basal Insulin; and 
 
 (d) determining a change for a Carbohydrate-to-Insulin Ratio (CIR) to be used in implementing the adjusted insulin dosing scheme in a given time interval either by:
 (i) multiplying the change for Meal Insulin by a rate of change of the Carbohydrate-to-Insulin Ratio (CIR) with respect to Meal Insulin, which is determined as a calculus derivative of a population-based correlation, or 
 (ii) determining a change for the Carbohydrate-to-Insulin Ratio (CIR) for the given time interval, based on a combination of a total Meal Insulin for the given time interval plus the error in the previous total insulin prescribed for the previous time interval minus a change for Basal Insulin for the given time interval, and dividing a total amount of carbohydrates for the given time interval by the combination; and 
 
 (e) causing, by the at least one computing device, the adjusted insulin dosing scheme determined for the subject to be shown in the display of the pen for an implementation of the adjusted insulin dosing scheme; and 
 (f) setting the dose in the pen for administration of, at least a portion of, the insulin to the subject in accordance with the adjusted insulin dosing scheme determined for the subject. 
 
   
     
     
         140 . The system of  claim 139 , wherein the preliminary estimate of the change for the Basal Insulin for a time interval is determined by the steps of:
 (a) using a previously configured sequence of time intervals during the day, and designating one of the intervals not normally containing a meal (Reliable Fasting Interval) to serve as the source of the data for adjusting Basal Insulin;   (b) determining an error in the previous prescribed insulin in the Reliable Fasting Interval by determining a difference between previous blood glucose data tested at the end of the previous time interval and a blood glucose target, dividing the difference by a Correction Factor (CF), applying a fraction of the divided difference to determine the error;   (c) determining a preliminary change for the Basal Insulin in the Fasting Interval as a portion equaling the full amount of the error in the Fasting Interval, while allocating none of the error to meal insulin in the Fasting Interval;   (d) determining a change to the total day's Basal Insulin dose as the change for the Basal Insulin in the Fasting Interval times 24 divided by the duration of the fasting interval, and determining the change for a whole-day Basal Insulin Rate as the total day's Basal Insulin dose divided by 24; and   (e) determining the preliminary estimate of the change for the Basal Insulin for the interval under consideration as the preliminary estimate of the change for Basal Insulin for the Fasting Interval times the duration of the interval under consideration divided by the duration of the Fasting Interval, wherein this method is mathematically equivalent to using the whole-day Basal Insulin Rate times the duration of the interval under consideration.   
     
     
         141 . The system of  claim 140 , wherein the reliable Fasting Interval is the later portion of the patient's sleep time, and an optional adjustment factor (Kf) can be applied to correct for a dawn effect. 
     
     
         142 . The system of  claim 139 , wherein the insulin pen is linked to the kit device by a Smart Phone, and the Smart Phone is linked by a cellular network or the Internet to a central computing device, and a Blood Glucose Meter is linked to the smart phone and/or by the cellular network or the Internet to the computing device. 
     
     
         143 . The system of  claim 139 , wherein the adjusted insulin scheme is comprised of one or more adjusted values for a daily schedule of Basal Doses, a daily schedule of one or more values of Correction Factor (CF), and either a daily schedule of Meal Insulin doses, or a daily schedule of one or more values of Carbohydrate-to-Insulin Ratio (CIR). 
     
     
         144 . The system of  claim 139 , wherein an adjustment to the insulin dose is linked to the insulin pen causing the insulin pen to set a mechanism for providing at least the portion of the insulin to the subject in accordance with the adjusted insulin dosing scheme and further comprising causing the insulin pen to inject, when manually actuated, the set dose of insulin from an insulin cartridge into the subject through a needle. 
     
     
         145 . The system of  claim 139 , wherein the application, when executed, further causes the at least one computing device to render the adjusted insulin dosing scheme in a video screen, generate a printed report, generate a digital file, communicate the adjusted insulin dosing scheme to an operating program of the insulin pen, and render the adjusted insulin doses on a display of the pen. 
     
     
         146 . The system of  claim 139 , wherein the change to Carbohydrate-to-Insulin Ratio of  claim 139  step(d)(i) is determined as the rate of change of CIR with respect to a total insulin dose for a 24 hour period times the rate of change of the total insulin dose for the 24 hour period with respect to Meal Insulin for the 24 hour period times the desired change for meal insulin for the time period under consideration. 
     
     
         147 . The computer-implemented method of  claim 130 , wherein the previous insulin dosing scheme is comprised of one or more values for a daily schedule of Basal Doses, a daily schedule of Correction Factors (CF), and either a daily schedule of Meal Insulin doses, or one or more values of Carbohydrate-to-Insulin Ratio, (CIR). 
     
     
         148 . The insulin pen of  claim 133 , wherein the previous insulin dosing scheme is comprised of one or more values for a daily schedule of Basal Doses, a daily schedule of Correction Factor (CF), and either: a schedule of one or more Carbohydrate-to-Insulin Ratios, a daily schedule of Meal Insulin doses, or one or more val. 
     
     
         149 . The system of  claim 139 , wherein the previous insulin dosing scheme is comprised of one or more values for a daily schedule of Basal doses, a daily schedule of Carbohydrate-to-Insulin Ratios, a daily schedule of Meal Insulin doses, and one or more values of Correction Factor (CF). 
     
     
         150 . The system of  claim 139 , wherein the data pertaining to the previous given time interval also refers to a clock-time interval over multiple previous days using the same insulin scheme and the data is aggregated over the multiple days by calculations involving the mean, median, minimum, maximum or other aggregation method. 
     
     
         151 . The computer-implemented method of  claim 130 , wherein the computing device is implemented in a blood glucose (BG) meter or kit device, the blood glucose data is from a BG meter, and wherein the display of an insulin device comprises part of the insulin pen or part of an auxiliary device in the kit. 
     
     
         152 . The computer-implemented method of  claim 130 , wherein the given previous time period is a period of 24 hours and the base insulin dosage scheme is administered in the form of one or more discrete doses.