Note: Descriptions are shown in the official language in which they were submitted.
CA 02519249 2010-12-08
METHOD AND SYSTEM FOR DETERMINING INSULIN DOSING SCHEDULES
AND CARBOHYDRATE-TO-INSULIN RATIOS IN DIABETIC PATIENTS
FIELD OF THE INVENTION
The invention relates generally to the field of digital aids to assist in the
treatment of
diabetic patients who use insulin pumps or multiple dosing insulin regimens
and provides a
method for determining insulin dosing schedules in diabetic patients.
BACKGROUND OF THE INVENTION
Diabetes Mellitus has been treated for many years by insulin injection. Three
recent
advances are changing diabetes care: The Insulin Pump, new insulin formulas
for Multiple
Dose Injection, and Inhaled Insulin. These are discussed below:
THE INSULIN PUMP: The invention of the insulin pump revolutionized diabetes
care. It is
a battery-powered device about the size of a pager. It contains a cartridge of
insulin and
pumps the insulin through a flexible tube into the patient via an "infusion
set", which is a
small plastic needle or "canula" fitted with an adhesive patch. The invention
of the pump
makes it possible to adopt a typical insulin regimen as follows: Basal Insulin
is injected
slowly and continuously at a rate that can be programmed to change multiple
times during
the day (about 4 or 5 changes per day is common). Between the changes, the
Basal Insulin
Rate of infusion is constant. The constant periods are called "intervals".
Additionally,
boluses of insulin can be injected on command by the patient. There are two
main types of
boluses:
Meal Boluses are infused just before a meal in an amount, proportional to the
glycemic
effect of the meal. This is generally proportional to the number of grams of
carbohydrate
in the meal. The proportionality constant is a personalized number called the
Carbohydrate-to-Insulin Ratio, CIR. It is used as follows:
Meal Insulin Bolus = (grams of carbohydrates in the meal)/CIR (1)
This calculation is generally performed by the patient, but there are pump
models that
can store the patient's CIR in memory and require only the grams of
carbohydrate in the
meal as the input.
Correction Boluses are infused immediately after a Blood Glucose test has been
performed; the amount of the correction bolus is proportional to the error in
the
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blood glucose concentration from the patient's personalized Target Blood
Glucose.
The proportionality constant is a personalized number called the Correction
Factor,
CF. It is used as follows:
Corrective Insulin Bolus = (Blood Glucose concentration - Target)/CF (2)
There are two types of Corrective Bolus, each with a different Target:
Time-Boundary Corrective Insulin Boluses are administered in a fasting state
at the
end of a time interval.
After-Meal Corrective Boluses are administered from one to five hours after a
meal,
most often within the time interval.
Recently, pump manufacturers have been incorporating digital features in their
pumps
that make treatment easier. Some pumps can store the values of CF and Target
and
require only the Blood Glucose Concentration (BG) as input. Among these new
digital features is the "Insulin-On-Board" feature. This feature
mathematically
models the amount of insulin still in the body at a given time after a bolus
and
recommends reductions to the boluses accordingly. This feature makes After-
Meal
Corrective Boluses more safe and practical.
MULTIPLE DOSE INJECTION (MDI): Advances are being made in developing
different types of insulin. Some are very long acting and non-peaking. The
long-
acting insulin can be injected as infrequently as once per day in a regimen
very
similar to a pump patient's basal insulin regimen. Injections of rapid-acting
types of
insulin can be given as meal and correction boluses. The two types together
act as a
system. These insulins are available in portable "pens" (named for their
resemblance
to writing implements). The pens have been mated with BG meters in "kits" in
which the devices communicate so that the combined memory is stored in one of
the
two devices in the "kit".
INHALED INSULIN: Inhaled insulin delivery systems are under development for
short-acting insulin. It is expected that the inhalers will be combined with
BG meters
into "kits" like the ones used for MDI, then the present invention will be
able to
handle inhaled insulin in the same manner. This development is expected in the
future.
The nature of diabetes care is very quantitative. Ironically, the
proliferation of
numbers makes the use of lengthy algorithms on pocket calculators too time-
consuming and therefore prohibitively expensive. The majority of
endocrinologists,
therefore, use experience-based subjective methods. In the interest of
providing
greater subjective feel for the case at hand, endocrinologists often use the
numbers to
simply help them discern trends; then treat the trends. For instance, they
commonly
view the blood glucose (BG) scatter c harts and printouts t o discern trends b
y such
subjective means as the visual density of dots on the BG scatter chart and the
relative
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location of the areas of highest density. They translate these trends into
insulin dose
changes using their experience.
Experienced-based and subjective methods are often not uniform from one
practitioner to
the next. Additionally, there is a shortage of endocrinologists and other
diabetes
specialists. Accordingly, the management of diabetes is done in a disorganized
manner
by clinicians of widely varying degrees of expertise. The result is that
control of diabetes
in most patients, while satisfactory, is not optimal. As a result of sub-
optimal BG
control, the course of diabetes can include complications involving all body
systems.
These complications are associated with premature mortality and are associated
with a
cost, which amounts to 19% of the health dollars to care for 6% of the
population.
BRIEF SUMMARY OF THE INVENTION
In one aspect, the present invention provided a method for periodically
adjusting a
diabetic patient's insulin dosing schedule the method comprising the steps
wherein
insulin doses are determined as a function of Basal Insulin, Meal Insulin and
Corrective
Insulin, wherein Basal Insulin includes round-the-clock insulin doses, Meal
Insulin
includes one or more discrete doses of insulin taken in conjunction with meals
which are
either prescribed by dose-amount or in accordance with the formula {Meal
Insulin Dose}
= {amount of Carbohydrates in a meal}/CIR, where CIR is the ratio of
Carbohydrate-to-
Insulin, and Corrective Insulin includes one or more insulin doses taken in
response to a
blood glucose reading, referred to as BG, in accordance with the following
formula:
{Corrective Insulin Dose} = {BG - TargetBG}/CF, where CF is a Correction
Factor, and
TargetBG is the desired blood glucose concentration for the patient, wherein
said CF,
TargetBG, CIR or Meal Insulin Doses, and the rate of delivery of Basal
Insulin, referred
to as Basal Rate, follow schedules through a day in which their values may
change in one
or more scheduled time intervals during the day, wherein said insulin dosing
schedule is
adjusted by means of adjusting the schedules of CF, TargetBG, CIR or Meal
Doses, and
Basal Rate, wherein said adjustments are made as follows: Old Data comprised
of values
from a previous day or plurality of days of values of CF, CIR, Meal Insulin
Doses, Basal
Rates, TargetBG, Total Daily Insulin, BG's and amounts of Carbohydrates, are
used to
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determine an output of adjusted parameters comprised of schedules for CF, CIR
or Meal
Insulin doses, and Basal Rates, incorporating adjusted values for said
parameters for at
least one time interval during the day, wherein an amount of adjustment of the
sum of
Basal Insulin plus Meal Insulin during a given time interval, referred to as
Prescription
Insulin, is determined as a variable fraction, referred to as Krxlnsl, of the
Corrective
Insulin for the given time interval, and wherein either a change for adjusting
Basal
Insulin or a change for adjusting Meal Insulin is estimated, referred to as
Preliminary
Estimation, and then the other component is determined by deducting said
Preliminary
Estimation from the change for Prescription Insulin, wherein the Preliminary
Estimation
of the change for Meal Insulin for the given time interval is the change for
total day's
Meal Insulin multiplied times the ratio of the Old Meal Insulin determined
from Old Data
from a previous given time interval to a total day's Old Meal Insulin
determined from
Old Data from a previous day, and wherein a preliminary estimation of the
change for
Total Day's Meal Insulin is input by a user or estimated by a Basal-over-Total
Feedback
Factor (BoTFbk) multiplied times the change for Total Day's Prescription
Insulin, and
wherein adjustments to a patient's insulin dosing schedule are either employed
in an
insulin delivery device to adjust the insulin doses delivered by the device,
or are
outputted to a memory or display for use in adjusting the patient's insulin
dosing
schedule.
In another aspect, the present invention provided a method for adjusting a
diabetic
patient's insulin dosing parameters within an insulin delivery device or
within a
practitioner's computer, the method comprising the steps wherein the diabetic
patient
receives insulin doses as a function of Basal Insulin, Meal Insulin and
Corrective Insulin,
wherein Basal Insulin includes insulin doses administered round-the-clock and
which
may be administered in a long-acting form or a short-acting form from the
delivery
device in which the rate of administration of Basal Insulin, referred to as
Basal Rate, may
be scheduled, wherein Meal Insulin includes one or more discrete doses of
insulin taken
in conjunction with meals either pre-prescribed or in accordance with the
formula {Meal
Insulin Dose} = {amount of Carbohydrates in a meal}/CIR, where CIR is the
ratio of
Carbohydrate-to-Insulin, wherein Corrective Insulin includes one or more doses
of
insulin taken in response to a blood glucose reading, referred to as BG, in
accordance
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with the following formula: {Corrective Insulin Dose} = {BG - TargetBG}/CF,
where
CF is a Correction Factor, and TargetBG is the desired blood glucose
concentration for
the patient, and wherein the patient's day is divided into one or more time
intervals,
wherein data, referred to as Old Data, is comprised of values from a previous
day or
plurality of days of values of CF, CIR, Basal Rates, Meal Insulin Doses,
TargetBG, Total
Daily Insulin, BG's and amounts of Carbohydrates, are used as input for
determining an
output of adjusted parameters comprised of schedules for CF, Basal Rate, Meal
Insulin
and CIR, incorporating a value of each parameter for each time interval during
the day,
wherein the method comprises adjusting the parameters, wherein the adjustment
for Meal
Insulin for a given time interval is estimated by the following formula:
{adjustment for
Meal Insulin for the given time interval} _ {total daily Corrective Insulin
for previous
day * Krxlnsl} * {Meal Insulin for a previous given time interval} / {total
daily Meal
Insulin for a previous day) * { 1-BoTFbk}, where KRxInsl is a variable
fraction from
zero through one that determines the size of all the adjustments and is set
for a balance
between speed of convergence and patient safety, and wherein BoTFbk is a
feedback
factor whose purpose is to bring the patient's ratio of Basal Insulin/Total
Insulin to a
target value, and wherein the adjustment for Basal Rate is given by the
formula:
{adjustment for Basal Rate in the given time interval} _ { {total previous
Corrective
Insulin value * Krxlnsl} - {adjustment for Meal Insulin for the interval}} /
{time
duration of the interval}, and wherein the adjusted CIR in a given time
interval is
calculated as the amount of Carbohydrates in a previous given interval divided
by the
adjusted Meal Insulin and wherein the adjustments are employed in the insulin
delivery
device to adjust the insulin doses delivered by the device or are outputted to
a display or
memory.
The present invention overcomes the aforementioned disadvantages of current
care, by
providing a method to analyze and prescribe changes to the daily insulin-
dosing schedule
of diabetic patients using insulin pumps, multiple-dose subcutaneous
injection, or inhaled
insulin. The method divides the patient's day into selected time intervals in
which
adjustable schedules are provided for Basal Insulin dosage rates and
Carbohydrate-to-
insulin Ratio(s) (to determine Meal Insulin doses). The time boundaries and
Basal Rate
changes are usually set by the Practictioner to coincide with the patient's
meals. The
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patients are usually encouraged to test their Blood Glucose (BG) at the time
boundaries
just before they eat. The invention uses two systems of insulin nomenclature:
CONVENTIONAL INSULIN NOMENCLATURE:
Total Daily Insulin = Prescription Insulin + Corrective Insulin (3)
where: Prescription Insulin = Basal Insulin + Meal Insulin (4)
The invention incorporates the concept of utilizing the Corrective Insulin
over a selected
time interval as an "error" in the patient's Prescription Insulin (Basal
Insulin + Meal
Insulin) for the whole day as well as for each time interval. Methods are
included for
estimating the change to one of the two components of Prescription Insulin,
then
determining the change to the other component by subtracting from the error.
Therefore,
there are two basic algorithmic forms, which are called "Floats":
The Meallns Float:
The change in Basal Insulin is estimated first; then the invention calculates
the change in
Meal Insulin to be the error in Prescription Insulin minus the change in Basal
Insulin.
Some of the ways for estimating the change in Basal Insulin are:
Borrowing Basal Rate from another interval;
Estimating Basal Rate from another algorithm (e.g. a Basal Float);
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Estimating change in Basal Insulin from the carb-free latter part of a time
interval using the Time-Boundary Corrective Insulin (at the end of the
interval) as the error indicator. The float is done on the first part of the
interval, using the After-Meal Corective Insulin as the error
or
The Basal Float:
The change in Meal Insulin is estimated first; then the invention calculates
the change
in Basal Insulin to be the error in Prescription Insulin minus the change in
Meal
Insulin. Some of the ways for estimating the change in Meal Insulin are:
Borrowing Meal Insulin or CIR from another interval;
Estimating the change in Meal Insulin for an interval as a share of the Change
in Total Day's Meal Insulin in the same proportion as (Carbs for the
interval)/(Total Day's Carbs);
Estimating the change in Meal Insulin for an interval as a share of the Change
in Total Day's Meal Insulin in the same proportion as (Meal Insulin for the
interval)/(Total Day's Meal Insulin).
ENHANCED INSULIN NOMENCLATURE:
Also, to provide another way of accounting for After-Meal Insulin, the
invention
identifies "Enhanced Variables" as a system of insulin nomenclature that lumps
the
After-Meal Corrective Insulin with the Meal Insulin as follows:
Total Daily Insulin=Enhanced Prescription Insulin+Time-Boundary Corrective
Insulin
(5)
where
Enhanced Prescription Insulin = Basal Insulin + Enhanced Meal Insulin (6)
and:
Enhanced Meal Insulin = Meal Insulin + After-Meal Corrective Insulin (7)
The Floats are very similar:
The Mealhns Float:
The change in Basal Insulin is estimated first; then the invention calculates
the change
in Enhanced Meal Insulin to be the error in Enhanced Prescription Insulin
minus the
change in Basal Insulin. Some of the ways for estimating Basal Insulin are:
Borrowing Basal Rate from another interval
Estimating Basal Rate from another algorithm (e.g. a Basal Float)
or
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The Basal Float:
The change in Enhanced Meal Insulin is estimated first; then the invention
calculates
the change in Basal Insulin to be the error in Enhanced Prescription Insulin
minus the
change in Enhanced Meal Insulin. Some of the ways for estimating Enhanced Meal
Insulin are:
Borrowing Enhanced Meal Insulin or CIR from another interval;
Estimating the change in Enhanced Meal Insulin for an interval as a share of
the Change in Total Day's Enhanced Meal Insulin in the same proportion as
(Carbs for the interval)/(Total Day's Carbs);
Estimating the change in Enhanced Meal Insulin for an interval as a share of
the Change Total Day's Enhanced Meal Insulin in the same proportion as
(Enhanced Meal Insulin for the interval)/(Total Day's Enhanced Meal
Insulin);
IN GENERAL:
It may not be desirable to apply all of the error term to effect a change.
Methods are
included for applying a limited amount of the error in order to avoid
overshoots.
The above selection of "Float" algorithms have been developed in two main
versions:
Daily Update Version: The Float algorithms above are embodied in a program
that
uses the previous day's data to make calculations for the present day. In this
version,
the full amounts of the error terms are not applied, but instead a
predetermined
fraction of the error terms are applied. If the error was valid, a reduced
amount of it
will show-up the next day. This next day's reduced error will be reduced by
the same
fraction and so on until the error disappears asymptotically. This version is
especially well-suited for installation in insulin pumps, inhaled insulin
kits, MDI
injection kits, PDA's and other portable devices.
Multiple Days' Data Version: The Float algorithms above are embodied in a
program
that uses the recent calendar period (e.g. last few weeks) for the data
source. The data
are therefore averages. The full amounts of the error terms are not
necessarily
applied, but instead the fraction or amount of error to be applied is input by
the
practitioner. These versions are suitable for installation in the
practitioner's computer.
A sub-version of this version determines the error fractions automatically. It
is
suitable for the patients' computer, or a website, for use with patients who
have
insulin pumps, or kits for Multiple Daily Injection or Inhaled Insulin.
The various aspects of the present disclosure may be more clearly understood
and
appreciated from a review of the following detailed descriptionof the
disclosed
embodiments and by reference to the appended figures.
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BRIEF DESCRIPTION OF THE FIGURES
Figure 1 illustrates an exemplary embodiment of the Input Form for the
Multiple
Days' Data Version for Insulin Pumps (Type D). The inner panel is the SubForm.
It
has two p ages, which can b e reached b y sc rolling. The first o f t here is
shown. It
contains single-valued data (not scheduled data).
Figure 2 illustrates an exemplary embodiment of the Input Form for the
Multiple
Days' Data Version for Insulin Pumps (Type D). The inner panel is the SubForm.
It
1o has two pages, which can be reached by scrolling. The second of these is
shown. It
contains daily schedule data.
Figure 3 an exemplary embodiment o the source of the multiplier FinsAuto,
which
automates dRxlnsAuto in the automated Multiple Days' Data Version (Automatic
Digital Advisor) by comparing the standard deviation of the patient's BGs to
the
mean standard deviation from the database. If the patient's number is high,
the
multiplier (which is always < 1) is reduced. The automated change in Enhanced
Prescription Insulin is FinsAuto times the Time-Boundary Corrective Insulin
times
another factor.
DETAILED DESCRIPTION OF THE INVENTION
1. TAFLE OF CONTENTS
The invention is a set of algorithms used to determine the various insulin-
dosing rates,
and Carbohydrate-to-Insulin Ratio(s) that comprise the daily insulin-dosing
schedule
for a patient. The "Float Algorithms" apply to all exemplary embodiments
described
herein. The description, as shown in the table of contents below, is broken
down first
by "Embodiment" (pump or MDI) and then by "Version" (Daily Update or Multiple
Day's Data) and finally by "Algorithm" (Basal Float1, Meal Insulin Float 1,
etc).
1. TABLE OF CONTENTS
2. SUFFIXES and TIME INDICES
3. GLOSSARY
4. GENERIC DERIVATIONS
4.1 MAKING CHANGES IN THE CARBOHDRATE-TO-INSULIN RATIO, CIR
4.2 SOME IMPORTANT EQUATIONS
4.2.1 CONVENTIONAL INSULIN NOMENCLATURE
4.2.2 ENHANCED INSULIN NOMENCLATURE:
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4.2.3 GENERAL
4.3 THE TWO-LEVEL BASAL SYSTEM, and the Kf CALCULATOR
4.3.1 STATISTICAL CORRELATION
4.3.2 AVERAGING
5. TYPES OF INSULIN DELIVERY SYSTEMS
6. DESCRIPTION BY, VERSION, EMBODIMENT, ALGORITHM
6.1 VERSIONS USING DAILY UPDATE
6.1.1 PRELIMINAR Y DERIVATIONS
6.1.1.1 TIME INTERVALS AND CORRECTIVE INSULIN
6.1.1.2 Krxlnsl: GOVERNS THE SIZE OF INSULIN CHANGES
6.1.2 FOR PUMPS (TYPE E)
6.1.2.1 BASAL-TO-TOTAL RATIO
6.1.2.2 BASAL FLOAT 1, (deMeallns is proportional to eMeallns or Carbs)
6.1.2.3 BASAL FLOAT 2, deMeallns value from outside the interval }
6.1.2.4 MEAL INSULIN FLOAT 1
6.1.2.5 OVERVIEW OF 6.1.1.2 and 6.1.1.3
6.1.2.6 MEAL FLOAT 2 (uses AMCorIns(i) as error)
6.1.3 FOR MULTIPLE DOSE INJECTION (MDI) AND INHALED INSULIN.-
6.1.3.1 BASAL FLOAT 1. (not used with MDI or Inhaled Insulin)
6.1.3.2 BASAL FLOAT 2, (The value of dMeallns is from outside the interval)
6.1.3.3 MEAL INSULIN FLOAT 1
6.1.3.4 OVERVIEW OF 6.1.3
6.1.3.5 MEAL INSULIN FLOAT 2, (uses AMCorIns(i) as an error term)
6.1.4 SKIPPED BG'S
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6.1.5 A MODIFIED BOLUS CALCULATOR
6.1.6 CHANGING THE PATIENT'S SCHEDULE
6.2 VERSIONS USING MULTIPLE-DAYS' DATA
6.2.1 MULTIPLE DAYS' DATA (DIGITAL AD VISOR) FOR PRACTITIONERS
6.2.1.1 FOR PUMPS
6.2.1.1.1 PUMP TYPED and E
6.2.1.1.1.1 Basal Float 1, (deMeallns is proportional to eMeallns or Carbs)
6.2.1.1.1.2 Basal Float 2, (not used with Multiple Days' Data)
6.2.1.1.1.3 Meal Insulin Float 1
6.2.1.1.1.4 Overview of 6.2.1.1.1.1 and 6.2.1.1.1.3 Multiple Days' Data
Type D pumps
6.2.1.1.1.5 Meal Insulin Float 2 (uses AMCorIns as the error)
6.2.1.1.2 PUMP TYPE C
6.2.1.1.3 PUMP TYPE B
6.2.1.1.4 PUMP TYPE A
6.2.1.2 SUBCUTANEOUS MULTIPLE DOSE and INHALED INSULIN
6.2.1.2.1 BASAL FLOAT 1
6.2.1.2.2 MEAL INSULIN FLOAT 1
6.2.1.2.3 MEAL INSULIN FLOAT 2 (uses AMCorlns(i) as an error)
6.2.1.3 LIMITED DOMAIN OF deRxlnsl and the SAFETY-NET FORMULA
for MULTIPLE DAYS' DATA VERSIONS
6.2.1.3.1 LIMITED DOMAIN OF deRxlnsl
6.2.1.3.2 SAFETY-NET FORMULA
6.2.1.3.2.1 For Basal Float 1
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6.2.1.3.2.2 For Meal Insulin Float 1
6.2.1.3.2.3 For Meal Insulin Float 2 (uses AMCorIns(i) as error )
6.2.2 A UTOMA TIC MULTIPLE DAYS' DATA (DIGITAL AD VISOR)
6.2.2.1 AUTOMATION OF deRxlnsl
6.2.2.2 AUTOMATION OF deMeallns
6.2.2.3 AUTOMATIC ROUNDING OF CIR FOR PUMP TYPE A
6.3 NON-FLOAT ALGORITHM
7 TIME INTERVALS
7.1 FINDING THE DAY'S LAST ENTRY
2. SUFFIXES and TIME INDICES:
In the present invention, the 24 hour day is divisible into multiple time
intervals. The
boundaries of time intervals are numbered in the manner of: timeO, time 1,
time2, etc.
These time boundaries w ill be referred to g enerically as t ime(i), w here
"i" denotes
"time index".
The Time Intervals, dt(i), are found by subtracting the consecutive time
boundaries.
dt(i) = time(i+l) - time(i) (8)
Each time interval is numbered the same as its upstream time boundary as shown
above.
Special mention should be made of the interval surrounding midnight.
dtO = 24 + timel - Tmax (9)
where Tmax is the last time boundary in the day, usually Bedtime. The method
of
finding Tmax is set forth in a later section.
The time boundaries are generally defined by the changes in the Basal Rate (in
pumps) or by average mealtimes. Practitioners often set up the patient's
schedule so
that the Basal Rate changes, mealtimes, BG tests, Corrective Insulin Boluses,
and
Meal Insulin Boluses all occur at these time boundaries. While not mandatory,
this
practice is preferred for use with the invention. The Basal Rates are numbered
the
same as time intervals, thus BR1 goes between timel and time2.
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The other parameters (besides Basal Rate) are identified with the exact time
boundaries, though in practical use, the patients cannot be expected to follow
such a
strict schedule. Therefore, there is a need for another set of time periods
(called
"bins" to distinguish them from intervals), each of which envelops a time
boundary.
The parameters that are said to occur "at a time boundary" actually occur in a
bin and
are given the same index number as the time boundary enveloped by the bin. The
tests and boluses can be sorted into these "Time-Boundary bins". In the case
of the
Multiple Days' Data Versions, this is most often handled by the downloading
software of the Blood Glucose Meters and Insulin Pumps, in which a schedule of
bins
can be set up. In the case of the Daily Update Versions, the midpoints of the
primary
time intervals may be used to define the boundaries of these bins.
Note that Time-Boundary Corrective Insulin measures the insulin error in the
previous interval, thus when calculating parameters for the ith interval, the
insulin
error is "TBCorIns(d,i+1)".
Parameters that do not follow the schedules of time intervals lack the time
interval
index integer. In the Multiple Days' Versions, these parameters lack any index
at, all.
In the Daily Update Versions, all parameters are given a day's index, "d", "d-
l", etc
in the manner of BF(d,i) or TDD(d).
Figure 1 and Figure 2 show the two pages of an exemplary Input Form for
Version
6.2.1.1.1, the Multiple Days' Data Version for Pump D. Figure 1 shows un-
indexed
parameters that have a single value for the Interaction. Figure 2 shows the
time
intervals containing time-interval-indexed parameters.
The parameters that pertain to a unique date and time are denoted with the
functional
form: "parameter(t)". A few of these appear in the derivations herein for
explanatory purposes, but none are used in the present invention.
3. GLOSSARY:
Average Glycemic Index (AGI): For average carbohydrates, the ratio of the
grams of
glucose entering the blood within two hours divided by the total grams of
sugar in the
carbohydrate. There are published studies for this figure. It ranges between
60%
and 90%.
s
AIM Formulas : An acronym for "Accurate Insulin Management" (See Ref 1, which
is incorporated by reference as if fully set forth herein). A set of
statistically derived
formulas used to estimate three parameters for the patient. There are three
formulas.
In each, a constant (beginning with "K") was determined statistically:
BasalAIM = Kb * TDDavg (10)
CFaim = Kef / TDDavg (11)
CIRaim = Kcir * BodyWeight(lbs) / TDDavg (12)
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The values of these constants change from time to time as new research is
done.
The latest values (See Ref 1) are: Kb = 0.48, Kcf--1700, Kcir=2.8
After-Meal Corrective Insulin: Corrective boluses taken after meals (post-
prandially)
in the previous day in the ith interval. (Daily Update Version)
AMCorIns(d-l,i): "After-Meal Corrective Insulin ": Corrective boluses taken
after
meals (post-prandially) in the previous day in the ith interval. (Daily Update
Version)
AMCorIns(i): "After-Meal Corrective Insulin for the ith time interval" The
average
of corrective boluses taken after meals (post-prandially) in the ith time
interval.
(Multiple Past Days Version)
Basal Rate: The rate in (insulin units / hour) at which Basal Insulin is
administered.
Basal Rate Float: CIR or Meal Insulin is determined by the practitioner or by
an
estimation formula and BR is determined by subtracting the change in Meal
Insulin
(Enhanced or conventional) from the total desired change, dRxInsl (Enhanced or
conventional).
Basal(d): "Basal Insulin." Basal insulin for the current day, calculated from
the basal
rates by the invention. (Daily Update Version)
Basal(d,i): Basal Insulin for the current day and time interval (Daily Update
Version)
Basal(i): Basal for the time interval (Multiple Days' Version)
Basal: "Basal Insulin." 1. General definition: Insulin that is administered
continuously by pump or insulin that is injected manually and stays in the
body for a
long time due to its special chemical make-up. 2. Computer variable: The
current total
of Basal Insulin administered during the day as calculated from the basal
rates.
SUM( Basal(i)) over the day calculated by the invention. (Multiple Days'
Version)
BasalTot: "Basal Insulin Total." Current Basal Insulin dose programmed into
the
pump at the time of the interaction with the Practitioner. Calculated by the
pump. It
should equal Basal. (Multiple Day's Version)
BG(i): Average of blood glucose tests over many days at approximately the same
time boundary, time(i), during the day, calculated by the glucose meter's
downloading
software. (Multiple Day's Version)
BGmean: Overall average of blood glucose tests since last interaction or in
the
calendar period being analyzed, obtained from the BG meter's downloading
software.
(Multiple Day's Version)
BGpd: "BG's per day." The average number of B G tests per day in the calendar
period being analyzed. (Multiple Day's Version)
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BGsd(i): "BG standard deviation for the ith time interval" obtained from the
BG
meter's downloading software. (Multiple Day's Version)
BGsd: "BG standard deviation," over the calendar period being studied.
Obtained
from the BG meter's downloading software. (Multiple Day's Version)
BG, Blood Glucose Concentration: These tests are self-administered several
times
during the day, usually on the time boundaries. At the present state of the
art, they are
determined by placing a drop of blood on a test strip in a blood glucose
meter. The
meter stores the values and times in its memory. At each practitioner/patient
interaction, the values are generally downloaded from the Blood Glucose
Meter's
memory by software that graphs the data points and calculates several values
including the overall average denoted BGmean, and the time boundary averages,
denoted BG(i). Some models of BG meter are able to link to insulin pumps
providing
a combined and integrated download of data.
Bin: A time period enveloping a Time Boundary of the primary Time Interval
system. Any BG test or bolus occurring within the Bin is treated as though it
occurred on the Time Boundary.
Bolus: (from the Latin, ball) Insulin infused in a short elapsed time as
ordered by the
patient, as distinguished from Basal Insulin, which is infused slowly,
continuously
and automatically either by a pre-programmed pump or by injection of a slow-
acting
insulin.
Bolus Time Period(i): Boluses are identified with Time Boundaries, but there
is
variability in the timing of them. To resolve this, a system of Bolus Time
Periods is
used. It has boundaries alternating in staggered fashion between the
boundaries of the
regular Basal Intervals such that any BG or Bolus falling in the Bolus Time
period is
automatically considered as occurring exactly on the regular Basal Time
Boundary.
Boli(i): "Bolus Insulin": The average sum of Meal Insulin + Corrective Insulin
for a
time interval, so called because it is administered in boluses rather than
continuously. (Multiple Past Days' Version)
BoT : "Basal over Total", Basal / TDD .
BoT(d): "Basal over Total" Basal/TDD for the day.
BoTFbk: `Basal over Total, Feedback". A parameter in the Daily Update
Versions.
This factor, multiplied times the day's proposed insulin change, will yield
the amount
of change to Basal.
BoTTgt: "Basal over Total, Target." The desired value of Basal/TDD (Daily
Update
Version)
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BoTTgtRec: "Basal over Total, Target Recommended" Recommended value of
BoTTgt (Daily Update Version)
BR(d,i): "Basal Rate" for the ith time interval." Current setting for the rate
at which
Basal Insulin is delivered. The rate is programmable in the pump so that it
can
change several times during the day. (Daily Update Version)
BR(i): "Basal Rate" for the time interval." Current setting for the rate at
which Basal
Insulin is delivered. The rate is programmable in the pump so that it can
change
several times during the day. (Multiple Days' Version)
BRavg: "Basal Rate Average", Basal/24
BRavgRec: "Basal Rate Average Recommended"
BRf. "Basal Rate, Fasting". The BR that would sustain a patient's blood
glucose in
the target range if no meals are consumed within 12 hours previous and if the
measurement is not being made in the Late-Sleep Interval (to avoid the
complications
of the Pre-Dawn effect).
BRkey: The key Basal Rate. Other Basal Rates are pegged to it.
BRlateSlp: "Basal Rate in Late-Sleep time interval".
BRrec(i): "Basal Rate, Recommended for the ith time interval." Calculated by
the
present invention. (Multiple Past Days Version)
BRreliable: A set of basal rate data chosen for reliability, high frequency of
associated BG tests, etc. Used with the Kf calculator
BRrx(i): "Basal Rate, Prescription for the ith time interval." The value the
Practitioner gives to the patient, after reviewing the case. (Multiple Past
Days
Version)
BRsimilar: A set of basal rate data chosen for similarity or closeness to the
fasting
basal rate. Used with the Kf calculator
Carbohydrate-to-Insulin Ratio ( see CIR): A personalized conversion constant;
current value.
Carb-Counting: The technique of determining meal insulin by first counting the
grams of carbohydrate in the meal about to be consumed and then dividing by
CIR.
Carbm: "Carbohydrate grams modified"; Used in bolus calculators that
incorporate
exercise.
Carbs: "Grams of Carbohydrate"
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CarbSh(i): "Carb Share." When used with all but pump type A, actual grams of
carbohydrate or 15 gm "exchanges" are used. When used with pump type A, with
no
memory for Meallns(i), this parameter is the Practitioner's or Patients's
estimate of
the relative magnitude of carbohydrates consumed in each time interval. For
pump
type A any units are acceptable, because the parameter is only used as a
percent of the
total, CarbShTot. Example units: grams of carbohydrate (preferred), percent of
the
total, units of meal insulin (if CIR constant). (Multiple Days' Version)
to CarbShTot: "Carb ShareTotal"; calculated as CarbShTot = suin(CarbSh(i))
CF: "Correction Factor." A personalized factor used to calculate Correction
Boluses.
See CorBol(t) and AIM
Change to: as in "Change to Pescription Insulin", "Change to Basal Insulin",
"Change to Enhanced Meal Insulin". This phrase denotes a proposed change in
the
named quantity, from the 1 ast measured v alue t o the r ecommended v alue. F
or the
Daily Update version, this is the change from one day to the next. For
theMultiple
Days' Data Version this is the change from the average over the past calendar
period
to the recommended value. Digital variables denoting changes are p receeded b
y a
lower-case "d" as in calculus.
CIR(d,i): " Carbohydrate-to-Insulin Ratio" The CIR for a time interval dt(i)
in the
current day. (Daily Update Version)
CIR(i): "Carbohydrate-to-Insulin Ratio" The CIR for a time interval dt(i).
(Multiple
Past Days Version)
CIR: "Carbohydrate-to-Insulin Ratio". A personalized conversion constant;
current
value.
CIR = (weight of carbohydrates consumed) / (insulin required to metabolize the
carbohydrates) (13)
See MealBol(t), and AIM. Calculation of this parameter is one of the chief
goals of
PumpMaster. (Multiple Past Days Version)
CIRrec(i):"Carbohydrate-to-Insulin Ratio, recommended for a time interval"
(Multiple Past Days' Version)
CIRrec:"Carbohydrate-to-Insulin Ratio, recommended" (Multiple Past Days
Version)
CorBol(t): "Corrective Bolus at a unique date and time." The patient
periodically
tests his/her Blood Glucose concentration. If it is too high, the patient
calculates a
bolus of insulin by the formula:
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CorBol(t) _ (BG(t) - Target) / CF (14)
Where Target is the desired BG level and CF is a personalized Correction
Factor.
Corlns(i): "Corrective Insulin." The sum of CorBol(t) at all times within the
interval,
including "After-Meal" and "Time-Boundary" times. (Multiple Past Days'
Version)
Corlns(d,i) "Corrective Insulin." The sum of CorBol(t) at all times within the
interval
including "After-Meal" and "Time-Boundary" times during the current day.
(Daily
Update Version)
CorTot(d): "Corrective Insulin Total." The sum of corrective insulin at all
times
within the current day. (Daily Update Version)
CorTot: "Corrective Insulin Total." The average of the sum of corrective
insulin at
all times within day. (Multiple Past Day's Version)
dBasalAuto: The automated version of dBasal. (Automatic Multiple Days'
Version)
dBaslToAIM: The change in Basal necessary to achieve the BasalAlM value
deMeallns(d,i): "Change in Enhanced Meal Insulin" for the time interval for
the
current day. (Daily Update Version)
deMeallns(i): "Change in Enhanced Meal Insulin" for the time interval.
(Multiple
Past Days Version)
deMealhis: "Change in Total Enhanced Meal Insulin." For the whole day.
(Multiple
Past Days' Version)
deMeallnsAuto: The automated version of dEmeallns. (Automatic Multiple Days'
Version)
deRxlnsAuto: "Change in Enhanced Prescription Insulin, Automatic"; estimated
automatically. (Automatic Multiple Days' Version)
deRxlnsl(d,i): "change in Enhanced Prescription Insulin in a time interval of
the
current day" (Daily Update Version)
deRxlnsl(i): "change in Enhanced Prescription Insulin in a time interval"
(Multiple
Past Days Version)
deRxlnsl: "change in Total Day's Enhanced Prescription Insulin" (Multiple Past
Days
Version)
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deRxlnslld(i): "change in Enhanced Prescription Insulin, large domain in the
interval"
The "Safety-Net" formula. One of two formulas for deRxInsl(i). (Multiple Days'
Version)
deRxlnslsd(i): "change in Total Enhanced Prescription Insulin, small domain";
One
of two formulas for
deRxlnsl(i) for "Safety-Net" purposes. (Multiple Days' Version)
dt(i): "difference in time"; The length of the "ith" time interval
Early-Sleep Time Interval: The time interval starting with Bedtime and ending
with
the Mid-Sleep time boundary. Most diabetic patients are encouraged not to
snack at
bedtime and to take a mid-sleep BG at about 3:00 AM. If this advice is
followed,
then the Early Sleep Time Interval gives a good indication of the true
"inactive basal
rate", BRf, that underlies many other time intervals.
eMealhis(d,i): "Enhanced Meal Insulin for the time interval." The sum of the
Meal
Boluses plus the After-Meal Corrective Boluses during time interval dt(i) for
the
current day. (Daily Update Version)
eMeallns(i): "Enhanced Meal Insulin for the time interval." A multiple-day
average
of the sum of After-Meal Insulin plus T ime-Boundary Corrective Insulin in a
time
interval. (Multiple Past Days Version)
eMeallnsRec(d,i): " Enhanced Meal Insulin Recommended for the current day and
time interval". (Daily Update Version)
eMeallnsRec(i): "Enhanced Meal Insulin for the time interval, recommended".
Calculated by the invention. (Multiple Past Days Version)
eMeallnsTot(d): "Enhanced Meal Insulin Total for the current day" T he sum o f
eMeallns(i) during the current day. (Daily Update Version)
eMeallnsTot: "Enhanced Meal Insulin Total." The sum of Meallns(i) plus the sum
of After-Meal Corrective Insulin during the whole day averaged over several
days.
(Multiple Days' Version)
Enhanced: A word used to describe a certain modified variable system, in which
After-Meal Corrective Insulin is incorporated as part of Meal Insulin.
eRxlnsl: "Total Day's Enhanced Prescription Insulin." A subset of TDD, defined
as:
The sum of Enhanced Meal Insulin + Basal Insulin during the day. It is usually
"Prescription" by the practitioner. The invention proposes methods of
calculating it
automatically.
ExerCarbs: "Exercise Carbs." The equivalent of exercise in grams of
carbohydrate.
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FlnsAuto: A multiplier that limits dRxlnsAuto. (Automatic Multiple Days'
Version)
Fixed-Meal: Another simpler technique of determining meal insulin other than
carb-
counting. It involves eating meals of fixed menu preceded by fixed amounts of
insulin.
Float: An algorithm in which the change to one of the two main parameters,
Emeallns or BR is estimated or determined by the practitioner, and the change
to the
other parameter is determined by subtracting the estimated insulin change from
the
total desired change in insulin. The "floated" parameter is the one that is
determined
by subtraction.
Glycemiclndex: T he ratio o f calories available from c arbohydrates within 2
hours
after consumption to total calories in the carbs. It is different for
different types of
carbs.
Interaction: "Patient/practitioner Interaction." An inclusive term, including
person-
to-person interactions, and telecommunication-based interactions in which the
patient's parameters are re-adjusted.
Interval: The day is divided into time intervals for the purpose of enabling a
patient's
insulin dosing to be varied throughout the day and analyzed on a time-
dependent
basis. The intervals usually are bounded at the times of the Basal Rate
changes.
Kb: A statistically-derived constant used in the formula for estimated Basal.
The
latest publication of the "AIM" formulas give the latest value of Kb=0.48 (Ref
1). It
is used in the formula:
Basal = Kb * TDDavg (15)
Kcf: A statistically-derived constant used in the formula for estimated CF.
The latest
publication of the "AIM" formulas (Ref 1) give the latest value of Kcir=1700 .
It is
used in the formula:
CF = Kcf / TDDavg (16)
Kcir: A statistically-derived constant used in the formula for estimated CIR.
The
latest publication of the "AIM" formulas (Ref 1) give the latest value of
Kcir=2.8 . It
is used in the formula:
CIR = Kcir*BodyWeight / TDDavg (17)
KcirW: A constant used in the formula for estimated CIR. The latest
publication
(Ref 1) give the latest value of Kcir=500. It is used in the formula:
CIR = KcirW / TDDavg (18)
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Kcycle: A constant representing the fraction by which CorTot is intended to be
reduced in a specified number of days (Ncycle). (Daily Update Version)
Keyb: as in "Key Basal Rate", An identifier for an interval that is considered
to have
dependable data and whose BR is also used in other intervals.
Keyc: as in "Key CIR", An identifier for-an interval that is considered to
have
dependable data and whose CIR is also used in other intervals.
Kf = "K fasting"; A constant <1. The ratio of fasting basal rate to a chosen
"reliable" basal rate
Kf = BRf / BRreliable (19)
Knnauto: "K meals,auto"; a positive constant < =1 whose purpose is determining
deMeallns. (Automatic Multiple Days' Version)
Kfbk: "K Feedback", A constant in the formula for BoTFbk that adjusts the
speed of
convergence (days) of the Basal-to-Total Ratio to a target value. (Daily
Update
Version)
Krxlnsl: a positive constant < =1 whose purpose is limiting dRxlnsl. (Daily
Update
Version)
KrxInslMax: The maximum allowable value of deRxlnsl/TBCorTot (Multiple Days'
Version)
Late-Sleep Time Interval: (same as Pre-Dawn Time Inteval) The time interval
starting with the Mid Sleep time boundary and ending with the Breakfast time
boundary. This time interval is characterized by the "Pre-Dawn Effect", which
is a
need for somewhat more insulin that would be normally expected. It is believed
that
this effect is linked to a release of growth hormone. This time interval is
the most
dependably carb-free of all the intervals. It would be the best candidate for
the
"inactive fasting basal rate" were it not for the Pre-Dawn Effect.
Meal Insulin: Insulin taken in a "bolus" concurrently or just before
consumption of
carbohydrates.
Meal Insulin Float: BR is determined by the practitioner or by an estimation
formula,
and Meal Insulin (enhanced or conventional) is determined by subtracting the
change
in Basal from the total desired change, dRxlnsl (Enhanced or conventional).
Then
change in CIR is determined from the change in Meal Insulin (enhanced or
conventional). Use of this type of Float allows the Basal Rates to be kept
more
uniform. This is a benefit if a patient skips a meal.
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MealBol(t): "Meal Bolus at a unique date and time." When eating, a patient
calculates the grams of carbohydrates being consumed and calculates an insulin
bolus
by the following formula:
MealBol(t) = ( gm of carbohydrate) / CIR (20)
where CIR is the personalized Carbohydrate-to-Insulin Ratio
Meallns(d,i) = Meal insulin within a time interval (Daily Update Version)
Meallns(i) = Meal insulin within a time interval (Multiple Past Day's Version)
MeallnsTot = The total of meal insulin in a day
NBGs(i): "number of BG's in the time interval" over the calendar period being
analyzed. (Multiple Day's Version)
NBGs: "number of BG's." Total number of BG tests in the BG meter since last
download or in the calendar period being analyzed. (Multiple Day's Version)
Ncycle: the number of days until a fraction Kcycle of the insulin error is
removed.
(Daily Update Version)
NDbg: "number of days of blood glucose." Number of days of BG tests in the
calendar period being analyzed. (Multiple Day's Version)
Peg: (verb) To set a parameter (CIR or BR) in one interval equal to a constant
times
the same parameter in another interval. The parameter is said to be "pegged"
to the
key interval. Normally the constant is equal to the ratio of the parameters on
day of
adjustment by the Practitioner, so that the same ratio is maintained in the
future.
Pen: A pocket-portable insulin delivery device, named for its resemblance to a
writing implement.
PmPctBGsd: The database "population" mean of the quantity (BGsd/BGmean), used
in the automation of
deRxlnsl. (Automatic Multiple Days' Version)
Practitioner: The physician or nurse who analyzes a diabetic patient's
parameters and
prescribes insulin dose regimen.
Pre-Dawn Time Interval: (same as Late-Sleep Time Interval)
PsdPctBGsd: The database "population" standard deviation of the quantity
(BGsd/BGmean), used in the automation of deRxlnsl. (Automatic Multiple Days'
Version)
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Reliable data set: A special use of the word to indicate an interval or set of
data that
has good statistics on a certain parameter, i.e. high frequency of BG testing,
low
Standard Deviation.
Rxlnsl: "Total Day's Prescription Insulin." A subset of TDD, defined as: The
sum of
Meal Insulin + Basal Insulin during the day. It is prescribed by the
practitioner,
unlike Corrective Insulin.
Similar data set: A special use of the word indicating that the data set is
likely to have
a parameter of a value close to one being sought statistically.
Swtch: "Switching parameter"; A two valued parameter whose purpose is to
evaluate deRxlnsl relative to some domain limits and shift between the two
"domain"
equations for deRxlnsl(i). (Multiple Days' Version)
Target: General: A number used in a feedback algorithm representing the
desired
result.
TargetAM: "Target Blood Glucose After Meals". Corrective insulin is calculated
according to how high a patient's BG is above the TargetAM. See CorBol
TargetTB: "Target Blood Glucose Before Meals". Corrective insulin is
calculated
according to how high a patient's BG is above the TargetTB. See CorBol
Target Basal-to-Total Ratio: The desired value of daily Basal Insulin divided
by
Total Daily Insulin. Used in a feedback algorithm.
TBCorlns(d-l,i+l). "Time-Boundary Corrective Insulin." The patient is usually
instructed to test his or her BG at the time boundaries. This parameter is the
previous
day's total of Corrective Insulin taken on or near the time boundary,
time(i+l). (Daily
Update Version)
TBCorIns(i+l): "Time-Boundary Corrective Insulin in the (i+l)th time
interval." The
patient is usually instructed to test his or her BG at the time boundaries.
This
parameter is the average over several days of the total of Corrective Insulin
taken on
or near a time boundary, time(i+l). (Multiple Past Days Version)
TBCorTot(d): "Time-Boundary Corrective Insulin Total for the current day".
(Daily
Update Version)
TBCorTot: "Time-Boundary Corrective Insulin Total": The sum of TBCorIns(i)
over
the whole day. (Multiple Past Days Version)
TDD(d-1): "Total Daily Dose" of insulin. The total amount of insulin a patient
received during the previous day. (Daily Update Version)
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TDDavg: "Total Daily Dose of Insulin, average." The average of TDD for several
days. (Multiple Past Days Version)
Time(i): The "ith" time boundary
Time-Boundary Corrective Insulin: Corrective Insulin Boluses taken at or near
a
boundary of a time interval. Typically a BG test is taken at the time boundary
(just
before eating if the next interval is a meal interval) and the corrective
bolus is
calculated from this BG test.
TimeLabel(i): A short text phrase labeling each time boundary. PumpMaster
offers
several standard entries: Mid-Sleep, Pre-Breakfast, Pre-Lunch, Pre-Supper,
Bedtime,
Snack, and Basal Rate Change.
Tmax: The last time boundary of a patient's day. Usually bedtime.
4. GENERIC DERIVATIONS:
4.1 MAKING CHANGES IN THE CARBOHDRATE-TO-INSULIN RATIO, CIR:
We can re-arrange the definition of CIR in two different ways, one for current
conditions and one as a recommendation, assuming that the carbohydrates do not
change:
Carbs = CIR * Meal Insulin
(21)
CIRrec = Carbs / Recommended Meal Insulin
(22)
If Meal Insulin or Carbs are not known, then differential methods can be
employed:
CIRrec = CIR + dCIR
(23)
We need the derivative of CIR with respect to Meal Insulin to use in the
formulas
below (the derivative is in parentheses):
dCIR= (dCIR/dMeal Insulin) * dMeal Insulin
(24)
And
dMeal Insulin = dCIR / (dCIR/dMeal Insulin)
(25)
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The following derivation leads to the formula for calculating dCIR, the change
in
CIR, that will produce a change d(Meal Insulin) in Meal Insulin. There are
several
ways to calculate or estimate the derivative. To obtain them, start with the
definition
of CIR:
CIR = Carbs / (Meal Insulin)
(26)
Differentiate using calculus:
(dCIR/dMeal Insulin) Carbs / (Meal Insulin)2
(27)
Substitute equation (21) into equation (27) to obtain:
(dCIR/dMeal Insulin) _ - CIR / (Meal Insulin)
(28)
This is an estimate of the derivative that depends on CIR. It is possible to
eliminate
CIR from the equation by substituting a correlation from a statistical study.
For
example, the AIM correlation, (Ref 1) is used below. It says:
CIR = Kcir BodyWt / TDDavg
(29)
where Kcir is a statistically-determined constant.
Substitute this into equation (28) for CIR to obtain the following generic
equation:
(dCIR/dMeal Insulin) (Kcir * BodyWt / TDDavg) /(Meal Insulin)
(30)
If Meal Insulin is unavailable, it can be calculated as:
Meal Insulin = TDDavg - Basal - Corrective Insulin
(31)
Leading to:
(dCIRJdMeal Insulin) _ - (Kcir * BodyWt / TDDavg) I (TDDavg - Basal -
Corrective Insulin)
(32)
The AIM statistical studies show that Basal is slightly less than half of
TDDavg.
Corrective Insulin is usually small, so we can say that Meal Insulin is
approximately
half of TDDavg. This leads from equation (30) to the equation:
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(dCIR/dMeal Insulin) (Kcir * BodyWt * 2 / TDDavg2 )
(33)
and finally:
dCIR (Kcir * BodyWt * 2 / TDDavg2 * dMeal Insulin
(34)
Another correlation (Ref 2) estimates CIR= Kcirw/TDD. By similar steps this
leads
to:
dCIR = - (Kcirw * 2 / TDDavg2) * dMeal Insulin
(35)
The change in Meal Insulin, dMeallns, may be obtained as follows:
dMealIns = MeallnsNew - MealInsOld
(36)
dMealIns = Carbs * (1/ClRnew - 1/CIRold )
(37)
or it may be input by the Practitioner.
4.2 SOME IMPORTANT EQUATIONS:
4.2.1 CONVENTIONAL INSULIN NOMENCLATURE
The earlier section showing the different types of insulin is re-written below
using the
variable names.
Recall the definitions: RxInsl: Prescription Insulin,
TBCorTot: Total Day's Time-Boundary Corrective Insulin,
AMCorTot: Total Day's After-Meal Corrective Insulin
CorTot: Totol Day's Corrective Insulin
TDD = RxInsl + CorTot
(38)
Where RxInsl = Basal + Meallns
(39)
For small changes:
dRxlnsl = dBasal + dMealIns
(40)
Within a time interval, similar equations holds true:
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Rxlnsl(i) = Basal(i) + Meallns(i)
(41)
dRxlnsl(i) = dBasal(i) + dMeallns(i)
(42)
The present invention incorporates the following concept: The Total Day's
Corrective Insulin, CorTot represents an "error" in the patient's Prescription
Insulin;
the goal is CorTot=O. The practitioner (or an automatic algorithm) decides how
much
of CorTot to eliminate. This amount is called dRxlnsl mimicking the words
"Change
in Total Prescription Insulin". By making this change, the program can
indirectly
cause CorTot to be reduced in the days ahead. dRxlnsl may be determined
differently, depending on the Version:
Daily Update Version: Krxlnsl is a pre-determined constant <=1. It is used to
set
dRxlnsl in the manner shown below:
dMeallns + dBasal = dRxlnsl = Krxlnsl * CorTot (43)
Similarly, in the time interval:
dMeallns(i) + dBasal(i) = dRxlnsl(i) = Krxlnsl Corlns(i+l)
(44)
At the present time Krxlnsl = 0.16 for the Daily Update algorithms, but the
value of
Krxlnsl is subject to adjustment for optimum safety and performance.
Multiple Days' Data Version: In the Manual Sub-Version, dRxlnsl is input by
the
Practitioner for each Patient/Practitioner Interaction. Any value is allowed
up to a
maximum of KrxlnslMax*CorTot, where KrxlnslMax is a fractional constant:
dMeallns + dBasal = dRxInsl <= KrxlnslMax * CorTot
(45)
Each time interval gets its share of the "fix" in proportion to its share of
the total error
dMeallns(i) + dBasal(i) = dRxlnsl(i) = dRxlnsl * (Corlns(i+l) /CorTot)
(46)
At the present time, KrxlnslMax = 0.5 but is subject to adjustment for optimum
safety
and performance.
In the automatic Sub-version, an automatic method determines dRxlnsl
(explained in
the section entitled"Automatic Multiple Days' Data (Digital Advisor)".
The left-hand-side of equation (44) or (46) is implemented for the interval in
one of
two ways. These are given the name "floats":
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The Meallns Float: dBasal(i) is estimated first; then the invention calculates
dMeallns(i) = dRxInsl(i) - dBasal(i). Some of the ways for
estimating dBasal(I) are:
Borrowing new Basal Rate from another interval;
Estimating Basal Rate from another algorithm (e.g. a Basal
Float);
Estimating dBasal(i) from the carb-free latter part of a time
interval using TBCorlns(i) as the error indicator. The float
is done on the first part of the interval, using AMCorlns(i)
as the error.
(47
)
or
The Basal Float: dMeallns(i) is estimated first; then the invention calculates
dBasal(i) = dRxlnsl(i) - dMeallns(i). Some of the ways for
estimating dMeallns(i) are:
Borrowing Meallns(i) or CIR(i) from another interval;
Estimating dMeallns(i) as a share of day's total d Meallns
in the same proportion as CarbSh(i)/CarbShTot;
Estimating dMeallns(i) as a share of day's total dMeallns
in the same proportion as Meallns(i)/MeallnsTot
(48
4.2.2 ENHANCED INSULIN NOMENCLATURE:
The types of insulin-delivery systems that incorporate Insulin-on-board
calculations
make. it safer for the patient t o use After-Meal Corrective Insulin dosing,
(variable
name: AMCorIns) It is called "corrective" because it uses the correction
formula,
equation (14). However, since it is part of the insulin needed to cope with a
specific
meal of carbs, it is more convenient to lump it together with Meal Insulin by
defining
new variables:
Enhanced Meal Insulin: eMeallns = Meallns + AMCorIns
Enhanced Prescription Insulin: eRxlnsl = Basal + eMealIns
This is explained better as follows:
TDD = eRxlnsl + TBCorlns
(49)
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where eRxlnsl=Basal + eMeallns
(50)
and eMeallns = Meallns + AMCorIns
(51)
The two quantities in eMealIns are added together at the start of these
calculations and
treated as a single variable.
For small changes:
deRxlnsl = dBasal + deMeallns
(52)
Within a time interval, similar equations holds true:
eRxlnsl(i) = Basal(i) + eMeallns(i)
(53)
deRxlnsl(i) = dBasal(i) + deMeallns(i)
(54)
The present invention incorporates the following concept: The Total Time-
Boundary
Corrective Insulin, TBCorTot represents an "error" in the patient's Enhanced
Prescription Insulin; the goal is TBCorTot=O. The practitioner (or an
automatic
algorithm) decides how much of TBCorTot to eliminate. This amount is called
deRxlnsl mimicking the words "Change in Total Enhanced Prescription Insulin".
By
making this change, the program can indirectly cause TBCorTot to be reduced in
the
days ahead. deRxlnsl may be determined differently, depending on the Version:
Daily Update Version: Krxlnsl is a pre-determined constant <=1. It is used to
set
deRxlnsl in the manner shown below:
deMeallns + dBasal = deRxlnsl= Krxlnsl a= TBCorTot
(55)
Similarly, in the time interval:
deMeallns(i) + dBasal(i) = deRxlnsl(i) = Krxlnsl * TBCorlns(i+1)
(56)
At the present time Krxlnsl = 0.16 for the Daily Update algorithms, but the
value of
Krxlnsl is subject to adjustment for optimum safety and performance.
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Multiple Days' Data Version: In the Manual Sub-Version, deRxlnsl is input by
the
Practitioner for e ach Patient/Practitioner Interaction. Any value is allowed
up to a
maximum of KrxlnslMax*TBCorTot, where KrxlnslMax is a fractional constant <=l.
deMealins + dBasal = deRxlnsl <= KrxinslMax * TBCorTot
(57)
Each time interval gets its share of the "fix" in proportion to its error :
deMealins(i) + dBasal(i) = deRxlnsl(i) = deRxinsl * (TBCorIns(i+l) /TBCorTot)
(58)
At the present time KrxlnslMax = 0.5 but is subject to adjustment for optimum
safety
and performance. In the automatic Sub-version, an automatic method determines
deRxlnsl (explained "Automatic Digital Assistant).
The left-hand-side of equation (56) or (58) is implemented for the interval in
one of
two ways. These are given the name "floats":
The Mealins Float: dBasal(i) is estimated first; then the invention calculates
deMeallns(i) = deRxlnsl(i) - dBasal(i). Some of the ways for
estimating dBasal(i) are:
Borrowing Basal(i) from another interval
Estimating Basal(i) from another algorithm
(e.g. a Basal Float)
(59)
or
The Basal Float: deMeallns is estimated first; then the invention calculates
dBasal(i) = deRxlnsl(i) - deMeallns(i) Some of the ways for
estimating deMealins are:
Borrowing eMeallns(i) or CIR(i) from another interval
Estimating deMeallns(i) as a share of day's total deMeallns
in the same proportion as CarbSh(i)/CarbShTot.
(60
)
Estimating deMeallns(i) as a share of day's total
deMealins in the same proportion as
eMeallns(i)/eMeallnsTot
4.2.3 GENERAL
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For a given Version, the different time intervals may have different types of
float.
The Basal float has the advantage that it can be used for all time intervals
in the day,
enabling easy changes to the patient's daily routine.
The Meal Insulin Float has the advantage that Basal Rate schedule can be kept
simple,
and changes in eating habits can be handled by CIR which addresses the changes
only
if the person consumes carbs and takes a meal bolus. However, since the Meal
Insulin Float can only affect the time intervals with meals in them, the Basal
Float
equations must still be used for the non-meal intervals.
4.3 THE TWO-LEVEL BASAL SYSTEM, and the Kf CALCULATOR
Some Practitioners prefer a "Two Level Basal" schedule, that assigns a single
Basal
Rate, BRf, (for BR fasting) around the clock except for the Late-Sleep time
interval,
just before waking. The Late-Sleep interval is different because of the "Pre-
Dawn
Phenomenon", which is the requirement for somewhat more insulin during the
second
half of the sleep period. This results in the two-levels of Basal Rate: BRf
and
BRlateSlp. Finding BRf becomes an important task.
A non-meal interval would be best for determining BRf. Typically, the non-meal
intervals are the Early-Sleep and Late-Sleep intervals. However, neither of
these is a
perfect candidate:
The E arly-Sleep interval, i f t ruly m eal-free, would give the b est v alue
o f BRf, but
often patients "cheat" by taking a bedtime snack. Also, the patient must
interrupt his
or her sleep in order to take the necessary mid-sleep BG test, so the data is
often not
available.
The Late-Sleep or pre-dawn interval is the most readily available and most
often
meal-free, but this interval is unsuitable because of the "dawn phenomenon".
Neither
of these is a perfect candidate for BRf.
The present invention incorporates two generalized methods that are designed
to
provide several ways to calculate BRf. Some nomenclature should be explained:
BRf
is intended to be used in most intervals excluding a few which are called
"excluded
intervals". One interval or category of BR's with good statistical reliability
may be
nominated as a "reliable" interval (with basal rate BRreliable). Another
interval or
data set may be nominated as a "similar" interval because its basal rate,
BRsimilar, is
similar to BRf. The present invention uses two generic methods to obtain BRf.
4.3.1 Statistical Correlation:
BRf may be obtained by a familiar least squares formula that statistically
correlates
paired values of "reliable" and "similar" data over the recent calendar period
with-a
correlation constant, Kf, estimated to fit the formula BRsimilar = Kf *
BRreliable.
Kf = SUM[ (BRsimilar) * (BRreliable) SUM[ BRreliable2
(61)
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Once calculated, the correlation constant, Kf, is used to convert the values
of the
"reliable" basal rates into values of BRf until the next Practitioner
interaction:
BRf = BRreliable * Kf
(62)
4.3.2 Averaging:
BRf may be obtained by averaging certain sets of BRsimilar data from the same
day
or the previous day (in the case of the Daily Update Version), or from the
recent
calendar period (in the case of the Multiple Days' Data Version). The
smoothing
effect of the averaging process helps to produce good values.
Some particular applications of these two methods are described below:
The the Early-Sleep BR's of nights in which there was no bedtime snack are
used
as BRsimilar. Paired with these are values of Late Sleep BR immediately
following, in the early morning of the next calendar day, which are used as
BRreliable. The formula for subsequent use is: BRf = Kf * BRlateSlp
(63)
The average of BR's except BR1ateSlp may be nominated as the similar data set,
paired with BRlateSlp as the reliable data set. The resulting formula appears
the
same, as equation (63) though the Kf is different.
The average of all BR's except BR1ateSlp may be used directly as BRf.
The average of all BR's i.e. (Basal/24) may be used directly as BRf.
The average of all BR's i.e. (Basal/24) may be nominated as the similar data
set,
paired with BR1ateSlp as the reliable data set. Once again the resulting
formula is
the same as equation (63).
The Early-Sleep BR's of nights in which there was no bedtime snack are used as
BRsimilar. Paired with these are "reliable" values of Basal/24. The formula
for
subsequent use is: BRf = Kf * Basal/24
(64)
The average of BR's except BR1ateSlp may be nominated as the similar data set,
paired with the average of all BG's, i.e. Basal/24 as the reliable data set.
The
resulting formula is the same as (64) but Kf is different.
The average of the Basal Float 1 results for all the other intervals (except L
ate-
Sleep interval) may be nominated as the similar data set, paired with
BRlateSlp as
the reliable data set. Once again the resulting formula looks the same as
equation
(63)
The average of the Basal Float 2 results for all the other intervals (except L
ate-
Sleep interval) may be nominated as the similar data set, paired with
BRlateSlp as
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the reliable data set. Once again the resulting formula looks the same as
equation
(63)
The average of the Meal Insulin Float 2 results for all the other intervals
(except
Late-Sleep interval) may be nominated as the similar data set, paired with
BRlateSlp as the reliable data set. Once again the resulting formula looks the
same
as equation (63),
Additional applications of this type are mentioned throughout the text that
follows.
General discussion of Kf:
The Kf Calculator is particularly well-suited for the Multiple Days' Data
Versions so
that it will be performed external to the insulin-delivery device. It is
designed to be
operated by the Practitioner at the time of a patient/practitioner
interaction. This is
because it depends upon digital memory of a sufficient number of nights to
obtain
enough data points to calculate an accurate value for Kf.
5. TYPES OF INSULIN DELIVERY SYSTEMS:
The following is a list of insulin delivery systems showing the Versions of
the present
invention applicable to each:
Type A pumps: Have memory for TDD for several days. They have memory of the
programmed Basal schedule, Basal(i). They have no memory for CF, CIR, CIR(i),
BG(i), MealBol(t), Meallns(i), TBCorIns, AMCorlns, CorBol(t), or Corlns(i).
Therefore, average combined boluses for the day must be obtained by
subtracting
Basal from TDDavg. Example: Medtronic MiniMed Paradigm 511.
Version 6.2.1.1.4: which uses Multiple Days' Accumulated Data. Program
is external to pump.
Type B pumps: In addition to the Type A memories, these have BG(i), actual
carbs
for CarbSh(i); CIR(i), CF, and Combined Boluses, Boli(i). Examples: Medtronic
MiniMed Paradigm 512 and 712.
Version 6.2.1.1.3: which uses Multiple Days' Data. Program external to pump.
Type C pumps: In addition to other Type B memories, these have memories for
Meallns(i) and Corlns(i). Example: Deltec Cozmo.
Version 6.2.1.1.2: which uses Multiple Day's Data. Program external to
pump.
Type D pumps: In addition to Type C memories, these pumps have, as a minimum,
memories for AMCorIns(i) and TBCorlns(i).
Versions 6.2.1.1.1: which uses Multiple Days' Data. Program external to
PUMP.
Type E pumps: Have all the parameters of the Type D pumps as a minimum and
have
the program installed internally.
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Versions 6.1.2: which uses automatic Daily Update. Program internal to
pump.
Version 6.2.1.1.1: which uses Multiple Days' Accumulated Data. Program
external to pump.
Subcutaneous or Inhaled Insulin Delivery in which the insulin delivery device
and the
BG meter clip together into a kit or otherwise communicate with each other so
that
data is recorded digitally.
Versions 6.1.3: which uses automatic Daily Update. Program internal to the
lo kit.
Version 6.2.1.2: which uses Multiple Days' Accumulated Data. Program
external
to the kit.
For the purpose of ease of presentation, these are re-organized in the Table
of
Contents. The different types of algorithm are shown as well:
6. DESCRIPTION BY, VERSION, EMBODIMENT, ALGORITHM:
6.1. VERSIONS USING DAILY UPDATE:
6.1.1 PRELIMINARY DERIVATIONS:
6.1.1.1 TIME INTERVALS AND CORRECTIVE INSULIN
The index "d" denotes the present day.
The index "i" denotes the "ith" time boundary or time interval (following the
time
boundary).
The Time-Boundary Corrective Insulin, TBCorIns(d,i) is the sum of corrective
boluses occurring at the beginning of the ith interval. Each bolus. needs to
be
identified as a Time-Boundary bolus, and it needs to be identified with the
ith interval.
This may be accomplished by a suitable combination of the following methods:
identified with the ith interval if it falls between the midpoint of the
previous
interval and the midpoint of the ith interval.
identified as a Time-Boundary Corrective bolus if it comes before the Meal
Bolus with the same index number.
one or both of these identifications input by the patient at bolus-time, using
the
controls on the insulin-delivery device.
The After-Meal Corrective insulin A MCorlns(d,i) i s the sum o f corrective b
oluses,
identified by a suitable combination of the following methods:
identified with the ith interval if it falls within the ith interval.
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identified as an After-Meal Corrective bolus by the fact of coming after the
Meal Bolus for the meal that marks the start of the interval.
one or both of these identifications input by the patient at bolus-time, using
the
controls on the insulin-delivery device.
6.1.1.2 Krxlnsl: GOVERNS THE SIZE OF INSULIN CHANGES
Suppose the operation of the invention is analyzed starting at an arbitrary
starting
time, when TBCorTot = TBCorTotStart. This represents an error to the
invention.
The purpose is to decrease each day's "error", TBCorTot, by a fractional
amount
Krxlnsl*TBCorTot, where Krxlnsl<=1. This means that, starting with a "starting
error", TBCorTotStart, the error should decrease in a geometric sequence. A
fter a
number of days, Ncycle,
The remaining error, TBCorTot(Ncycle) = TBCorTotStart*[1-Krxlnsl]N,ycle
(65)
This remaining error approaches near-zero as Ncycle increases. Thep hrase "
near-
zero" can be defined by setting a reasonably small number for a Percent
Remaining
Error.
Percent Remaining Error = [1-KrxInsl]NC'
(66)
For a suitable combination of Percent Remaining Error and Ncycle, the equation
can
be solved for I xxInsl. This is done by the invention as follows:
Krxlnsl = 1 - (Percent Remaining Error )("rreY"e)
(67)
The Percent Remaining Error is set by the inventors but is subject to change.
(A
typical value is 10%). The choice of Ncycle is left to the practitioner. (A
typical
value is 14 days). This example leads to an exemplary value of Krxlnsl=0.16 .
In
plain language, "A choice of 0.16 for Krxlnsl eliminates 90% of the error in
two
weeks." It is used in the Daily Update algorithms as follows:
deRxlnsl = Krxlnsl * TBCorTot
(68)
or
dRxlnsl = Krxlnsl * TBCorTot
(69)
In the interval:
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deRxlnsl(i) = KrxInsl * TBCorIns(i+1)
(70)
or
dRxlnsl(i) = Krxlnsl * TBCorlns(i+1)
(71)
6.1.2 FOR PUMPS (TYPE E)
6.1.2.1 BASAL-TO-TOTAL RATIO:
The Basal(d)/TDD(d) ratio is called BoT(d) for "Basal over TDD". It is
calculated
every day. It has been determined by medical studies that certain ratios of
Basal(d)/TDD(d) lead to better management of diabetes. a target for
Basal(d)/TDD(d)
ratio can be set into the program by the patient or practitioner. It is called
BoTTgt for
"Basal over TDD, Target".
The invention contains a feedback factor to bring BoT(d) to BoTTgt. The
feedback
factor incorporates a constant Kfbk to regulate the speed of convergence:
BoTFbk(d) = BoT(d) + Kfbk` ( BoTTgt - BoT(d) )*sign(deRxlnsl)
(72)
Where the resulting value is not allowed to be less than zero or greater than
one.
This factor, multiplied times the day's proposed total insulin change will
yield the
amount o f c hange to Basal. The "sign" function ensures that the magnitude of
the
change is correct for the "direction" of the change. The constant Kfbk is
adjusted to
achieve the optimum speed of convergence to BoTTgt. The feedback factor is
applied
as follows:
dBasal = BoTFbk(d) * deRxlnsl
(73)
deMeallns = (1-BoTFbk(d)) * deRxlnsl
(74)
The invention provides a recommendation for BoTTgt, named BoTTgtRec, which is
calculated as follows:
BoTTgtRec = 1 - 4*CarbShTot*(Average Glycemic Index)/(a statistical
correlation
for caloric intake as a function of height, weight, and other easily known
patient
parameters)
This formula changes carbs to calories by use of the conversion factor 4, then
multiplies b y glycemic index t o obtain the i mmediately-available calories
from the
carbs, then divides by the patient's caloric intake as estimated by body
conformation.
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This gives the requirement for Meallns/TDD. Basal to Total ratio is one minus
this
quantity.
The present versions of the invention generally do not use this concept for
both
dBasal and deMeallns in the same time interval, but instead use one of them
and
determine the other parameter by subtraction from the total, deRxlnsl in the
manner
described in the definition of "Float".
6.1.2.1 BASAL FLOAT 1, (deMeallns is proportional to eMeallns or Carbs)
This algorithm estimates Meal Insulin using the feedback factor, BoTFbk(d).
The
Enhanced insulin nomenclature system is used. The total change in Enhanced
Meal
Insulin is taken from equations (72) and (76):
deMeallns(d) = Krxlnsl * (1 - BoTFbk(d-1)) * TBCorTot(d-1)
(75)
The portion of this quantity, which is assigned to the interval is
proportional to the
interval's share of Enhanced Meal Insulin from the day before. This concept is
applied in the following equation:
deMeallns(d,i) = Krxlnsl *(1- BoTFbk(d-1)) * TBCorTot(d-1)* eMeallns(d-
l, i)/eMeallnsTot(d-1)
(76)
eMeallns(d,i) = eMealIns(d-l,i) + Krxlnsl *(1- BoTFbk(d-1)) * TBCorTot(d-
1)'' eMealIns(d- l ,i)/eMeallnsTot(d-1)
(77)
Using equation (22) gives:
CIR(d,i) = CarbSh(d-l,i) / [eMealIns(d-l,i) + Krxlnsl *(1- BoTFbk(d-1)) *
TBCorTot(d-1)*eMealIns(d-1,i) / eMeallnsTot(d-1)]
(78)
As in the definition of a Basal Float, statement (60):
BR(d,i) = BR(d-l,i) + (deRxlnsl(d,i) - deMeallns(d,i))/dt(i)
(79)
Using equation (70) gives:
BR(d,i) = BR(d-l,i) + Krxlnsl * [ TBCorIns(d-l,i+1) - (1-BoTFbk(d-
1))*TBCorTot(d-1)*eMeallns(d-l,i) / eMeallnsTot(d-l) ] / dt(i)
(80)
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This algorithm can b e used i n a 11 t ime intervals " across the b oard". If
u sed i n a 11
intervals, this algorithm has the effect of maintaining the original
prescribed "shape"
of the CIR or Meallns schedule; that is, each eMeallns(d,i) is multiplied by
the same
factor, so that they rise or fall in unison.
6.1.2.2 BASAL FLOAT 2, (deMeallns value from outside the interval )
This algorithm is used in intervals where the Meallns or CIR value is borrowed
from
outside the interval (pegged to another interval.) This method is useful in
non-meal
time intervals, because meal insulin data in these intervals is not dependable
enough
for calculations. All the CuR's go up or down in proportion to the "Key CIR".
The
CIR schedule maintains the same "shape" and each CIR preserves the same ratio
to
the key CIR that it had on the first day, d=1. The key CIR may be chosen from
several sources, usually from a time interval that h as meals and uses a M eat
Float
algorithm. The number of the key CIR interval is keyc. The Enhanced insulin
nomenclature system is used.
CIR(d,i) = [CIR(d-1, keyc) / CIR(1, keyc) ]* CIR(l, i)
(81)
Equation (37) is adapted as shown below. The Enhanced nomenclature system is
used, but note that the desired change is the same in both systems:
deMeallns(d,i)= dMealIns(d,i) = CarbSh(d-1,i)*[1/CIR(d,i)- 1/CIR(d-l,i)]
(82)
BR(d,i) = BR(d-1,i) + dBR(d,i)
(83)
The "Float" equation can be obtained from statement (60) as follows:
BR(d,i) = BR(d-1,i) + (deRxlnsl(d,i) - deMeallns(d,i))/dt(i)
(84)
Then equation (56) is applied as follows:
BR(d,i) = BR(d-l,i) + [ Krxlnsl*TBCorIns(d-l,i+l) - deMeallns(d,i) ] / dt(i)
(85)
BR(d,i) = BR(d-l,i) +[ Krxlnsl * TBCorlns(d-l,i+l) - CarbSh(d-l,i)*[l/CIR(d,i)-
1/CIR(d-1,i)]] / dt(i)
(86)
6.1.2.3 MEAL INSULIN FLOAT 1
This algorithm pegs BR to a "Key" basal rate, i.e. all the basal rates go up
or down in
proportion to the key basal rate. The Basal schedule maintains the same
"shape" and
each Basal Rate preserves the same ratio to the key basal rate that it had on
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day, d=1. The key basal rate may be chosen from several sources, usually from
a time
interval that has no meals and uses a Basal Float algorithm. The key interval
number
is keyb. The Enhanced insulin nomenclature system is used.
BR(d,i) _ [BR(d-1, keyb) / BR(1, keyb) ]* BR(l, i)
(87)
The key basal rate can also be obtained from a calculation that uses the
overall result
of a Basal Float 1 algorithm, i.e. Basal(d-1) plus the correction. The formula
uses
d=1 like the one above.
BR(d,i) _ [Basal(d-1) + BoTFbk(d-1)*Krxlnsl*TBCorTot(d-1)] / Basal(t)
BR(l,i)
(88)
The key basal rate may also be obtained from:
From a sum of basal rates over all the intervals.
Basal(d) = SUM( BR(d,i) * dt(i)
)
(89)
BR(d,i) _ [(Basal(d)/Basal(t)] * BR(l,i)
(90)
Whatever the source of BR(d,i), the change in Basal Rate is:
dBR(d,i) = BR(d,i) - BR(d-1,i)
(91)
As in the definition of a Meal Insulin Float, statement (59):
deMeallns(d,i) = Krxlnsl * TBCorIns(d-l,i+l) - dBR(d,i) *dt(i)
(92)
deMeallns(d,i)=Krxlnsl*TBCorlns(d-1,i+1)-( BR(d,i) - BR(d-l,i) )*dt(i) (93)
eMeallns(d,i) = eMeallns(d-1,i) + Krxlnsl * TBCorIns(d-l,i+l) - (BR(d,i) -
BR(d-
1,i)) * dt(i)
(94)
Paraphrasing equation (22) gives:
CIR(d,i) = CarbSh(d-1, i) / eMeallns(d, i) (95)
CIR(d,i) = CarbSh(d-1,i) / [ eMeallns(d-l,i) + Krxlnsl * TBCorlns(d-1,i+1) -
(BR(d,i) - BR(d-1,i)) * dt(i) ] (96)
6.1.2.4 OVERVIEW OF 6.1.1.2 and 6.1.1.3
The Basal Float 2 algorithm is used in conjunction with the Meal Insulin 1
float as
follows:
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The practitioner's latest prescription is input for the first day, d=l. This
data is the
starting point for the automatic daily update sequence. The non-meal intervals
are
provided with Basal Float 2 algorithms, pegging their CIR's to a "Keyc"
interval.
One of the non-meal-containing intervals is nominated as the "Keyb" Basal Rate
(usually the Late-Sleep interval or the average Basal/24). The Basal rates in
the meal-
containing intervals are pegged to the Key Basal Rate to maintain their
original ratios
to the key basal rate. The meal-containing intervals are provided with Meal
Insulin
Float algorithms.
6.1.2.5 MEAL FLOAT 2 (uses AMCorIns(i) as error)
This algorithm makes use of after-meal BG testing. These tests and associated
After-
Meal Corrective Boluses divide the interval into two parts. The algorithm uses
AMCorlns(d-l,i) as an "error" indicator for the first part of the interval,
where the
float is calculated. The value of dBasal(d-l,i) is obtained from the carb-free
second
part of the interval, which uses TBCorlns(d-l,i+l) as an error term for
dBasal(d-l,i)
The "Enhanced" insulin terminology is not used.
Define: Timeb(d-1,i)= The time of the after-meal bolus after the ith time
boundary.
dtb(d-1,i) = Time(i+1) - Timeb(d-l,i) (97)
dta(d-l,i) = Timeb(d-l,i) - Time(i) (98)
In the second part of the interval:
BR(d,i) = BR(d-l,i) + Krxlnsl TBCorlns(d-l,i+l) /dtb(d-l,i) (99)
Having obtained Basal Rate from the second part of the interval (or another
source),
the following statement can be said of the first part of the interval:
dBR(d,i) = BR(d,i) - BR(d-1,i)
(100)
Meallns(d,i) = Meallns(d-i,i) + Krxlnsl *AMCorlns(d-l,i) - dBR(d,i) * dta(d-
l,i)
(101)
CIR(d,i) = CarbSh(d-l,i) / Meallns(d,i)
(102)
6.1.3 FOR MULTIPLE DOSE INJECTION (MDI) AND INHALED INSULIN.-
The Basal insulin is administered in the form of long-acting insulin as
infrequently as
once per day. Corrective Insulin and Meal Insulin are administered as needed
in the
form of injected or inhaled short-acting insulin. This algorithm is suitable
for "kits"
in which the BG Meter and the insulin delivery device clip together or are
otherwise
linked, in order to maintain a combined digital history and a place for the
program to
reside.
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6.1.3.1 BASAL FLOAT 1. (not used with MDI or Inhaled Insulin)
6.1.3.2 BASAL FLOAT 2, ( The value of dMeallns is from outside the interval )
This algorithm is used in intervals where the Meallns or CIR value is borrowed
from
outside the interval (pegged to another interval.) This method is useful in
non-meal
time intervals, because meal insulin data in these intervals is not dependable
enough
for calculations. All the CIR's rates go up or down in proportion to the "Key
CIR".
The CIR schedule maintains the same "shape" and each CIR preserves the same
ratio
to the key CIR that it had on the day of the most recent interaction with the
Practitioner, d=1. The key CIR may be chosen from several sources, usually
from a
time interval that has meals and uses a Meal Float algorithm. The number of
the key
CIR interval is keyc. The Enhanced insulin nomenclature system is used.
CIR(d,i) = [CIR(d-1, keyc) / CIR(1, keyc) ]* CIR(l, i)
(103)
Equation (37) is adapted as shown below. The Enhanced nomenclature system is
used, but note that the desired change is the same in both systems:
deMeallns(d,i)= dMeallns(d,i) = CarbSh(d-l,i)*[1/CIR(d,i)- 1/CIR(d-l,i)]
(104)
BR(d,i) = Basal(d-1)/24 + dBR(i)
(105)
from equation (54) it can be seen that:
BR(d,i) = Basal(d-1)/24 + (deRxlnsl(d,i) - deMeallns(d,i))/dt(i)
(106)
BR(d,i) = Basal(d-1)/24 + [ Krxlnsl*TBCorlns(d-1,i+1) - deMeallns(d,i) ] /
dt(i)
(107)
A non-meal interval using this algorithm (or some other suitable source) is
used as the
"reliable" data set. The resulting basal rate by equation (117) is used to
determine the
whole day's Basal.
Basal(d) = 24 * (some conversion factor) * BR(d-1,reliable)
(108)
A recommended practice is the use of the Late-Sleep interval as the "reliable"
interval. The following equation is given without explanation, as it will be
covered by
another section.
Basal(d) = 24 * Kf * BR(d-1,LateSleep)
(109)
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6J.3.3 MEAL INSULIN FLOAT 1
The Enhanced insulin nomenclature system is used. This algorithm is used
primarily
for meal-containing intervals. The whole day's Basal(d) can be from a key
interval's
Basal Float calculation as in equation (119).
dBasal(d,i) = (Basal(d) - Basal(d-1)) * dt(i) / 24
(110)
Whatever the source of Basal data, the Meal Insulin Float continues as
follows:
The present invention calculates a schedule of new CIR(d,i) values, using the
equation
below, which is similar to equation (103):
CIR(d,i) = CarbSh(d-l,i) / [ eMeallns(d-l,i) + Krxlnsl * TBCorlns(d-1,i+1) -
(Basal(d) - Basal(d-1)) * dt(i) / 24 ]
(111)
6.1.3.4 OVERVIEW OF 6.1.3
The day's schedule is programmed as follows: An interval ( usually a non-meal
interval) is nominated as the "reliable" interval and is provided with a Basal
Float 2
algorithm, with its CIR pegged to a meal interval. The BR from this "reliable"
interval is used to determine the round-the-clock BR and the total daily Basal
dose,
which equals a constant (e.g. Kf or a constant of that type) times BRreliable
times 24.
The meal-containing intervals are provided with Meal Insulin Float algorithms
and
use the same single-valued round-the-clock BR. The non-meal intervals other
than
the "reliable" interval contain no calculations; their CIR's are pegged to a
meal
interval and their BR's are the same as all the others.
6.1.3.5 MEAL INSULIN FLOAT 2, (uses AMCorIns(i) as an error term
This algorithm makes use of after-meal BG testing. These tests and associated
bolus
divide the interval into two parts. The algorithm uses AMCorIns(d-l,i) as an
"error"
indicator for the first part of the interval, where the float is done.
Define: Timeb(d-l,i)= The time of the after-meal bolus after the ith time
boundary.
dtb(d-l,i) = Time(i+1) - Timeb(d-l,i)
(112)
dta(d-1,i) = Timeb(d-1,i) - Time(i)
(113)
The Basal Rates are the same in all intervals; only Basal(d) is needed. It may
be
obtained from one of several sources.
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The carb-free second part of the interval uses TBCorIns(d-1,i+1) as an error
term for dBasal(d,i) The "Enhanced" insulin terminology is not used. In the
second part of the interval:
BR(d,i) = BR(d-l,i) + Krxlnsl * TBCorlns(d-l,i+l) /dtb(d-l,i)
(114)
This result, obtained from a single "key" interval yields Basal(d):
Basal(d) = [BR(d, key) / BR(1, key) ]* Basal(1)
(115)
The full schedule of results from the second part of the interval, equation
(116)
may be converted to a full day's basal as follows:
Basal(d) = SUM over i [ BR(d,i) * dt(i) ] (117)
A Basal Float 1 algorithm like version 6.1.2.1 in a "reliable" interval may be
used to provide a round-the-clock basal rate.
A Basal Float 1 algorithm used in an overall manner, to obtain the day's total
basal:
Basal(d) _ [Basal(d-1) + BoTFbk(d-1)*Krxlnsl*TBCorTot(d-1)]
(118)
Whatever the source for Basal(d), the following statement can be said of the
first part
of the interval:
Meallns(d,i) = Meallns(d-1,i) + Krxlnsl *AMCorlns(d-l,i) - (Basal(d) - Basal(d-
1) *
dta(i)/24
(119)
If the source is the second part of the interval, then this becomes:
Meallns(d,i) = Meallns(d-1,i) + Krxlnsl *AMCorlns(d-1,i) - BoTFbk(d-1)
* Krxlnsl*TBCorTot(d-1)* dta(i)/24
(120)
CIR(d,i) = CarbSh(d-l,i) / Meallns(d,i)
(121)
6.1.4 SKIPPED BG'S
Versions 1 and all sub-versions keep track of a special "virtual interval"
consisting of
the combined Early-Sleep and Late-Sleep intervals. This is for use in the
event that
the patient skips the Mid-Sleep BG test. A Basal Float calculation is kept
current over
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this combined interval and is used to provide the basal rate for both
component
invervals if the BG test between them is skipped. This technique is used for
often-
skipped BG's like the Mid-Sleep BG just described. This technique can be used
for
any number of adjacent time intervals with skipped BG's on the boundaries.
However, for seldom-skipped BG's it is more expedient to merely substitute
BG=Target so that a zero value is calculated for Corlns(i). This causes no
change and
allows the previous value to remain. For this reason, the BG(d,i) parameters
have
default values of TargetAM or TargetTB until input is made.
6.1. S A MODIFIED BOL US CALCULATOR
Many pump models provide a bolus calculator programmed inside. It performs the
calculations in equations (20) and (14). The present invention treats exercise
as a
special adaptation of the Bolus calculator. There are input boxes for exercise
in units
of carbs, defining a new variable, ExerCarbs. The arithmetic difference
between them
is used as a variable Carbm shown below:
Carbm = Carbs - ExerCarbs (122)
This may also be used for exercise alone without carbs. The modified Bolus
Calculator also can calculate Correction Boluses. They must be designated
"Time-
Boundary" or "After-Meal" by the patient to flag the memory record and to
select the
correct one of the two targets: T argetAM and T argetTB. T he modified b
oluses
(meal and correction) are summed. If the result is positive, the pump infuses
the
calculated insulin amount as an ordinary bolus. If the result is negative, the
pump
suspends the Basal pumping for an amount of time calculated as follows:
TimeOut = - NegativeBolus(t) / BR(d,i) (133)
Or it may reduce the basal for a time:
TimeReduced = - NegativeBolus(t) / (BR(d,i) - BRreduced) (134)
6.1.6 CHANGING THE PATIENT'S SCHEDULE
Section 1.1 above has described a normal 9 to 5 day. However, patients have
many
different schedules. T o allow for t his, the interval type i s i dentified
for e ach time
interval by a parameter IntrvlType, which can have the following values:
M for "Meal Interval"
Kb for "keyb interval", typically the Late-Sleep interval, or other Non-Meal
Interval in which food is never consumed.
Kc for "keyc interval" the source of pegged CIR's
S for "snack interval" in which food is occasionally consumed.
R for "reliable"
The adjustments to this feature are made by the Practitioner (not the patient
unless it
is with Practitioner guidance). The practitioner makes sure there is always a
value of
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IntrvlType for each time interval. He or she can change this if desired. There
is no
restriction on the others. The present invention processes this data as
follows:
If IntrvlType=Kb, go to Algorithm 6.1.2.3, Basal Float 2
This results in a calculation of BR(d,keyb).
If IntrvlType=Kc, go to Algorithm 6.1.2.4, Meal Insulin Float 4
This results in a calculation of BR(d,keyb).
If IntrvlType=R, go to Algorithm 6.1.2.3, Basal Float 2
This results in a calculation of BRsimilar.
If IntrvlType = S go to Algorithm 6.1.2.3, Basal Float 2
If IntrvlType = M THEN:
IF a Time-Boundary BG is missing, go to Algorithm 6.1.4
IF an After-Meal Corrective Dose is present, go to Algorithm 6.1.2.6 Meal,
Insulin
Float 2
ELSE go to Algorithm 6.1.2.4, Meal Insulin Float 1
6.2 VERSIONS USING MULTIPLE-DAYS' DATA:
Instead o f re-adjusting the patient's parameters with the previous day's
data, these
Versions use the average accumulated data over the calendar period prior to
the
patient/practitioner interaction. The data for each time interval during the
day is
averaged separately over all the days. The day index, "d", is dropped and
instead, the
new parameters are distinguished from the current parameters as follows:
Current
parameters have no suffix. Calculated and recommended parameters have a suffix
"rec". Prescribed parameters have suffix "rx". The "rx" parameters are input
by the
practitioner after considering the recommendations of the "rec" parameters.
Parameters marked "Parameter(i)" are for the "ith" interval. Parameters with
nothing
in parentheses are non-scheduled parameters for which there is only one value
for
each p atient/practitioner interaction. Thus "BRrec(i)" refers to the
Recommended
Basal Rate for the "ith" interval e.g. BRrecl, BRrec2 . . etc, and BRrx(i)
refers to
the Prescribed Basal Rates.
6.2.1 MULTIPLE DAYS' DATA (DIGITAL AD VISOR) FOR PRACTITIONERS
Krxlnsl is replaced by deRxlnsl/TBCorTot so (135)
deRxlnsl(i) = deRxlnsl/TBCorTot * TBCorIns(i+1) (136)
Interactive Input Forms:
An exemplary form of the present invention is a two-table Access Database.
There is
a "one-to-many" relationship between the "patients' table", Tp and the
"interactions
table", Ti. There is a digital interactive Input Form (described in more
detail in
section 6.2.1.1.1.
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The practitioner obtains some of the patients data by the exam or interview
process.
Other data is obtained by downloading the data from the pump and BG meter,
either
directly into the invention, or by using the manufacturer's software to make
printed
copies, which are then transcribed into the invention's interactive digital
input form
manually. The manufacturer's downloading software normally provides a schedule
of
Bins (time periods enveloping the primary Time Boundaries) and calculates
averages
pertaining to each time boundary for several parameters including BG(i),
AMCorlns(i), TBCorlns(i) and Meallns(i). (Recall as an example, that
Meallns(i)
represents the average of total Meal Insulin boluses within the ith Bin.)
6.2.1.1 FOR PUMPS
6.2.1.1.1 PUMP TYPED and E
The formulas for pumps Types D and E are the simplest, so they will be
discussed
first.
Interactive Input Forms:
The main Input Form is the outer panel in Figure 1. It collects the patient's
permanent demographic data for table Tp. A SubFonn (inner panel) collects the
data
from the patient/practitioner interaction for table Ti. The Sub Form has two
pages
that can be reached by the scroll bar. The first page (Figure 1) addresses un-
indexed
parameters which have a single value for each patient/practitioner
interaction. The
second page (Figure 2) addresses the standard modal day's schedule, containing
the
parameters with time-interval indexes like those referred-to herein in the
manner of
"parameter(i)"
6.2.1.1.1.1 Basal Float 1, (deMeallns is proportional to eMeallns or Carbs)
This algorithm is similar to Basal Float algorithm 6.1.2.2 for Daily Update
Version.
The Enhanced insulin nomenclature system is used.
Transpose equation (52) to show that dBasal is determined by the other two
parameters:
dBasal = deRxlnsl - deMeallns (137)
dBasal(i) = deRxlnsl(i) - deMeallns(i) (138)
deMeallns(i) is estimated by saying that the distribution of deMeallns among
the
intervals is proportional to the distribution of eMeallns, i.e.:
deMeallns(i) = deMeallns * eMeallns(i)/eMeallnsTot (139)
eMeallnsRec(i) = eMeallns(i) + deMeallns *eMealIns(i)/eMeallnsTot (140)
By equation (22):
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CIRrec(i) = CarbSh(i)/eMeallnsRec(i)
(141)
CIRrec(i) = CarbSh(i)/[ eMeallns(i) + deMeallns *eMeallns(i)/eMealInsTot]
(142)
Note that both eMeallnsRec(i) and CIRrec(i) are merely the original value
times an
across-the-board factor. In the manner of statement (60), Basal is "Floated"
by
subtracting deMeallns(i) from deRxlnsl(i):
BRrec(i) = BR(i) + [ deRxlnsl(i) - deMeallns(i)] / dt(i) (143)
Substituting equations (133) and (136) into this gives:
BRrec(i) = BR(i) + [ deRxlnsl/TBCorTot * TBCorlns(i+l)
- deMeallns* eMeallns(i)/eMeallnsTot] / dt(i) (144)
Also calculated is the value of. BRaveRec = (Basal + deRxlnsl - deMeallns) /
24
(145)
The practitioner uses this version of the invention as follows:
When all the patient's data has been input from downloads or otherwise, The
Basal
Float is almost ready to calculate the main goals (a schedule of recommended
basal
rates, BRrec(i) and a schedule of recommended ClRrec(i)). The practitioner
needs to
input at least two of the three quantities in equation (134). The present
invention will
do the rest. So, the practitioner looks over the data obtained so far,
particularly
TBCorTot. Then he or she makes a judgment as to "How much of TBCorTot do I
want to add to Prescription Insulin as a change?" Then he or she inputs
deRxlnsl,
which must be within the built-in input limits (see section: Limited Domain).
Basal(i)
will be "floated", so the other quantity needed from the practitioner is
deMeallns.
Before inputting he must ask himself, "When I prescribe this change, deRxlnsl,
how
much of it do I want to assign to Enhanced Meal Insulin?" He can make this
judgement by comparing the ratio of Basal / TDDavg (known as BoT in the
present
embodiment) to the optimum value from the AIM statistical studies (48% from
latest
publication). For instance, if Basal is too high he can use greater than half
of
deRxlnsl as deMeallns. This will raise deMeallns relative to deRxlnsl, thus
lowering
Basal. There may be other considerations of a medical nature that may
influence the
practitioner's decision. The choice of deMeallns may have input limits. The
outputs
are BRrec(i), B RavgRec, and CIRrec(i) as calculated by the equations above.
The
practitioner considers these recommended values and inputs the "rx" values
based
upon his judgment.
6.2.1.1.1.2 Basal Float 2, (not used with Multiple Days' Data)
6.2.1.1.1.3 Meal Insulin Float 1
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This Version is similar to the Version 6.1.2.4, Meal Insulin Float. For input,
it
requires the Prescribed Basal Rates, BRrx(i), which are input by the
Practitioner. The
Practitioner may desire "advice" before inputting BRrx(i). The values of
BRrec(i)
and BRaveRec from the result of Version 6.2.1.1.1.1, Basal Float 1, above, are
good
advice, so they are provided on the same computer screen Input Form. The value
of
BRf from the Kf calculator is also good advice. The Enhanced insulin
nomenclature
system is used.
Transpose equations (52) and (54) to show that deMeallns is determined by the
other
two parameters:
deMeallns = deRxInsl - dBasal (146)
deMeallns(i) = deRxlnsl(i) - dBasal(i) (147)
BRrx(i) = input by practitioner (148)
The "Float" is very similar to equation (100); it is set up as follows:
Equation (132) is used to modify equation (100) with the result below:
deMeallns(i) = (deRxInsl/TBCorTot)* TBCorIns(i+l) - (BRrx(i) - BR(i) )*dt(i)
(149)
eMeallnsRec(i) = eMeallns(i) + deRxInsl/TBCorTot TBCorIns(i+l) - (BRrx(i)-
BR(i) ) *dt(i) (150)
Using equation (22) gives:
CIRrec(i) = CarbSh(i) / eMeallnsRec(i)
(151)
ClRrec(i) = CarbSh(i) / [eMeallns(i) + deRxlnsl/TBCorTot * TBCorIns(i+l) -
(BRrx(i) - BR(i)) *dt(i)] (152)
The Practitioner considers this schedule of CIRrec(i) and then inputs:
CIRrx(i) = input by the Practitioner (153)
6.2.1.1.1.4 Overview of 6.2.1.1.1.1 and 6.2.1.1.1.3 Multiple Days' Data, Pump
Type
D
Recommendations are provided for Basal Float and Meal Insulin Float on the
same
Input Form (see Figure 2), so that the practitioner can consider Basal Float
recommendations, BRrec(i), BRaveRec, and BRf when filling in the prescribed
BRrx(i) schedule. The Meal Insulin Float uses these "BRrx(i)" values as input.
Then
it calculates CIRrec(i) as output for the meal-containing intervals. Then the
Practitioner fills in the blanks for CIRrx(i). Backtracking the discussion a
little: The
practitioner's choice of BRrx(i) is very influential. Discussion:
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The practitioner can use all of the BRrec(i) values as BRrx(i) if desired.
This
has the e ffect o f changing the entire meal insulin (or CIR) schedule by the
same factor across the board.
or
A simple basal schedule can be used to give the patient more meal-skipping
flexibility, as mentioned earlier. For instance:
The practitioner can use the BR's for non-meal intervals "as is". This
probably will include the "Early-Sleep" and "Late-Sleep" intervals.
The Practitioner can use a single carefully judged Fasting Basal Rate, BRf,
to underlie the meal intervals. Determining this basal rate is one of the
Practitioner's major tasks. The BRf Calculator may be used at the
Practitioner's discretion.
6.2.1.1.1.5 Meal Insulin Float 2 (uses AMCorlns as the error)
This algorithm makes use of after-meal BG testing. These tests divide the
interval
into two parts. The algorithm uses AMCorIns(i) as an "error" indicator for the
first
part of the interval, where the float is done. The value of dBasal(i) is
obtained from
the carb-free second part of the interval, which uses TBCorlns(i+l) as an
error term
for dBasal(i). The "Enhanced" insulin terminology is NOT used.
Define: Timeb(i)= The time of the after-meal bolus after the ith time
boundary.
dta(i) = Timeb(i) - Time(i) (154)
dtb(i) = Time(i+1) - Timeb(i) (155)
In the second part of the interval:
BRrec(i) = BR(i) + Krxlnsl * TBCorlns(i+1) /dtb(i) (156)
dBR(I) = BRrec(i) - BR(i) (157)
Having obtained Basal Rate from the second part of the interval (or other
source), the
following statement can be said of the first part of the interval:
MeallnsRec(i) = Meallns(i) + Krxlnsl *AMCorIns(i) - dBR(i) * dta(i) (158)
If the second part of the interval was used, this becomes:
MeallnsRec(i) = Meallns(i) + Krxlnsl *AMCorlns(i)
- dta(i) * Krxlnsl * TBCorIns(i+l)/ dtb(i) (159)
CIRrec(i) = CarbSh(i) / MeallnsRec(d,i) (160)
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If desired, the factor Krxlnsl may be obtained from dRxlnsl input by the
practitioner
as described earlier:
Krxlnsl = dRxlnsl / (AMCorTot+TBCorTot) (161)
Alternatively, Krxlnsl may be replaced by two "K-factors", one for each part
of the
time interval: KrxInsAM and KrxInsTB:.
First, Basal Rate is determined from the second part of the interval:
to BRrec(i) = BR(i) + KrxInsTB * TBCorhns(i+l) /dtb(i) (162)
Then Meal Insulin is determined from the first part of the interval:
MeallnsRec(i) = Meallns(i) + KrxInsAM *AMCorlns(i) - dta(i) * KrxInsTB*
TBCorIns(i+l)/ dtb(I) (163)
CIRrec(i) = CarbSh(i) / MeallnsRec(d,i) (164)
This alternative method may shift the Basal/TDD ratio and may be useful if
such a
result is intended.
6.2.1.1.2 PUMP TYPE C
Pumps of these types are intermediate between Types A and D. The algorithms of
6.2.1.1.1.1 and 6.2.1.1.1.3 and their overview are applicable to Type B pumps,
except
that:
TBCorIns(i) is not available, so it must be calculated by the formula:
TBCorlns(i) = AVG over calendar period of ( (BG(t) - TargetTB)/CF) (165)
AMCorlns(i) is not available so Meal Float 2 cannot be used.
6.2.1.1.3 PUMP TYPE B
Pumps of these types are intermediate between Types A and C. The algorithms o
f
6.2.1.1.1.1, 6.2.1.1.1.3, and their Overview are applicable to Type B pumps,
except
that in addition to the limitations of Pump Type C:
Meallns(i) is not available, so dMeallns(i) is estimated by:
dMeallns(i) = dMeallns * CarbSh(i)/CarbShTot (166)
6.2.1.1.4 PUMP TYPE A
Type A pumps are the simplest, but have complicated formulas for the reason
that the
values for the absent parameters must be calculated using estimation formulas.
These
estimation formulas add complexity. In addition to the limitations of Type B
pumps,
the Type A pumps are limited as follows:
Because of the lack of data, the only appropriate algorithm for Type A pumps
is
"Basal Float 1, similar to Version 6.2.1.1.1.1.
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There are no memories for BG(i), so values for TBCorlns(i) and AMCorlns(i)
must be calculated from BG data downloaded from the BG meter. This data may
contain anomalous or unused BG test results and is not as dependable as the BG
data from the pump's memory.
There are no memories for CarbSh(i), so the practitioner must estimate. The
only
use of the data is in the ratio CarbSh(i)/CarbShTot, so the units do not
matter; the
practitioner may use grams, exchanges, percent of total, units of insulin, or
any
other units proportional to Meal Insulin.
The lack of good data makes CIR hard to calculate. A single CIR is calculated
for use round-the-clock. The differential formula (34) is used:
dCIRcalcA = [ - (Kcir * Wt *2 / TDDavg2 ] * deMeallns (167)
A slight complication is that Type A pumps have no memory for CIR, so the
patient must keep track of it. To make this easier for the patient, only
integer (or
half integer values for CIR < 8) are prescribed. Therefore, a two-step manual
input is used:
dCIRcalcA is calculated by the invention and appears on the screen. The
practitioner rounds it to the preferred rounded quantity and puts the value
back
into the reverse equation as dCIR. Then the invention calculates:
deMeallnsCalcA dCIR / (Kcir * Wt * 2 / TDDavg2) (168)
Then the practitioner inputs this value into the box for deMealIns. Not
surprisingly, the resulting value of dCIIRalcA is integer-valued. The
recommended value, CIRrecA, is automatically calculated as follows:
CIRrecA = dCIRcalcA + CIR (169)
6.2.1.2 SUBCUTANEOUS MULTIPLE DOSE and INHALED INSULIN
Manual injection patients usually use two types of insulin:
Long-acting insulin for "basal" injections as infrequently as once per day
Short-acting insulin for meal and correction boluses.
The insulin delivery devices include "pens" and inhalers.
There are "kits' currently being developed that consist of a B G meter that,
clips o r
links to an insulin-delivery device (an insulin injection "pen" or an insulin
inhaler) in
such a way that the data is shared. The BG test results are used to calculate
a
corrective insulin dose automatically, and the insulin delivery device is
automatically
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set f o r use. Also, carbs can be entered manually so that Meal Insulin
Boluses are
similarly calculated and pre-set. Digital memory is available in either the
meter or
the insulin delivery device so that the combined BG and insulin history can be
downloaded by the Practitioner.
There are several types of insulin available. The input form contains input
boxes for
the brand names or generic names of the two types of insulin prescribed.
The formulas deal with basal amounts in each time interval, rather than basal
rates.
The long time-response of the long-acting insulin makes Basal Rate schedule
adjustments impractical.
6.2.1.2.1 BASAL FLOAT 1
The partnership of Basal Float 1 and Meal Insulin Float 1 may be employed in a
similar manner to pumps Types D and E. Similarities and differences: As in
pumps
the Practitioner inputs deRxlnsl and deMeallns. The input boxes for BR(i) are
replaced by a single box for Basal, a single BR is calculated (one twenty-
fourth of
Basal) . The values of BRrec(i) are shown individually as in pumps. As in
pumps, a
value is calculated for BRaveRec using equation (141). All the BRrx(i) are
replaced
by a single box for BRrx, and Basalrx is calculated (24 times BRrx). After
reviewing
the recommendations for Basal and Basal Rate, the Practitioner inputs BRrx
6.2.1.2.2 MEAL INSULIN FLOAT 1
The Meal Insulin Float 1 is similar to that used with Type D pumps. The
Enhanced
insulin nomenclature system is used.
The v alue o f BasalRx from the previous s ection (or s ome other source) is
used as
input by the Meal Insulin Float 1 algorithm.
dBasal(i) = (Basalrx - Basal) * dt(i) / 24 (170)
The present invention then calculates a schedule of recommended CIRrec(i)
values,
using a Meal Insulin Float. The formula is adapted from equation (103) by
applying
equation (132):
CIRrec(i) = CarbSh(i) eMeallns(i) + (deRxInsl * TBCorlns(i+l)/TBCorTot -
(BaslRx -Basal)*dt(i)/24 ] (171)
6.2.1.2.3 MEAL INSULIN FLOAT 2 (uses AMCorlns(i) as an error)
This algorithm makes use of after-meal BG testing. These tests and associated
boluses divide the interval into two parts.
Define: Timeb(i)= The time of the after-meal bolus after the ith time
boundary.
dtb(i) = Time(i+l) - Timeb(i) (172)
dta(i) = Timeb(i) - Time(i) (173)
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The algorithm uses AMCorIns(i) as an "error" indicator for the first part of
the
interval, where the float is calculated. A figure for BasalRx is needed. The
Practitioner places it in an input box after reviewing the invention's
calculated
recommendations, which may be one or more of the following:
BasalRec may be obtained from the carb-free second part of the interval, which
uses TBCorhls(i+l) as an error term for dBasal(i) The "Enhanced" insulin
terminology is not used. In the second part of the interval:
BRrec(i) = BR(i) + Krxlnsl * TBCorlns(i+l) /dtb(i) (174)
or
This result from a "reliable" interval may be converted to a full day's basal
as
follows: BasalRec = BRreliable*Kf * 24 (176)
or
BasalRec may be obtained from the sum of the results above:
BasalRec = SUM over i (BRrec(i) * dt(i)) (176)
or
BasalRec may be obtained from a Basal Float 1 calculation in a "reliable"
interval.
This result is converted in the same manner as equation (171)
or
Another source of BasalRec is the total recommended Basal from a Basal Float 1
algorithm, converted in the same manner as equation (172)
Whatever the source for BasalRec, the Practitioner inputs BasalRx. The
following
statement can be said of the first part of the interval:
MeallnsRec(i) = Meallns(i) + Krxlnsl *AMCorIns(i) - Basal * dta(i)/24 (177)
CIRrec(i) = CarbSh(i) / MeallnsRec(i) (178)
The factor K rxlnsl may be obtained from dRxlnsl input by the practitioner as
described earlier:
Krxlnsl = dRxlnsl / (AMCorTot +TBCorTot) (179)
Alternatively, if the method of equation (170) is used, Krxlnsl may be
replaced by
two "K-factors", one for each part of the time interval: KrxlnsAM and
KrxInsTB:
First, Basal Rate is determined from the second part of the interval:
BRrec(i) = BR(i) + KrxInsTB * TBCorIns(i+l) Idtb(i) (180)
Then Meal Insulin is determined from the first part of the interval:
MeallnsRec(i) = Meallns(i) + Krx1nsAM *AMCorIns(i)
- dta(i) * KrxInsTB * TBCorlns(i+l) /dtb(i) (181)
CIRrec(i) = CarbSh(i) / MeallnsRec(d,i) (182)
This alternative method may shift the Basal/TDD ratio and may be useful if
such a
result is intended.
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6.2.1.3 LIMITED DOMAIN OF deRxlnsl and the SAFETY-NET FORMULA for
MULTIPLE DAYS' DATA VERSIONS
6.2.1.3.1 LIMITED DOMAIN OF deRxlnsl
The Float formulas using Multiple Days' Data for whole intervals work only
within
certain limits in which the changes called for are less than TBCorTot and in
the same
direction (same sign).
Both these conditions are contained in the requirement that
TBCorTot / deRxlnsl > 1 (183)
If the parameters go beyond this limit then nonsensical results occur. To
prevent this
from happening and to provide a further margin of safety, there are input
limits placed
upon the parameters to prevent the Practitioner from inputting numbers out of
the
acceptable range. The input limit is in the form of the parameter KrxlnslMax.
The
limit is in the form:
TBCorTot / deRxlnsl >= 1 / KrxlnslMax (184)
If KrxlnslMax <= 1, then the nonsensical results are avoided. The value of 0.5
i s
currently in use.
6.2.1.3.2 SAFETY-NET FORMULA:
6.2.1.3.2.1 For Basal Float 1
As mentioned above, the Float formulas using Multiple Days' Data work only
within
certain limits. The first line of defense is the input limits mentioned above.
However,
there MAY BE ways to circumvent the input limits, on purpose or accidentally.
To
protect against this possibility, there is a second line of defense, the
safety net
formulas. E ach o f t he Float formulas actually uses two formulas for
deRxlnsl(i),
each over a different domain of deRxlnsl.
Small Domain: This is the "acceptable" domain, using the formulas discussed so
far.
If TBCorTot/deRxlnsl>1, then the formula below is used. It produces accurate
results over its limited domain in which the changes called for are less than
or equal to
the Total Enhanced Corrective Insulin and in the same direction. It apportions
to each
time interval a small amount of the deRxlnsl proportional to the time
interval's share
of the TBCorTot. Most patient/practitioner interactions are in the small
domain. The
"small domain" formula has been discussed earlier. It is re-written below. The
suffix
"sd" is added to the name the name to show what it is:
deRxlnslsd(i) = deRxlnsl*TBCorlns(i+l)/TBCorTot (185)
Large Domain: The formula introduced below is a backup to the input limits
placed
upon deRxlnsl. If the desired change to deRxlnsl is not in the small domain,
i.e. if
TBCorTot/deRxlnsl<1, then the formula below is used. It produces a less
accurate
but safe result when the changes called for are larger than TBCorTot or in the
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direction opposite to TBCorTot. The right-hand side starts with the full
corrective
insulin for the time interval. T hen the "overshoot" of deRxlnsl over TBCorTot
is
apportioned among the time intervals, but the apportioning fraction includes
Basal as
well as Enhanced Corrective Insulin, making it a less sensitive fraction, but
less exact.
In its role as a backup to the input limits, the large domain formulas are
designed
never to be used. The Safety-Net formula for Type D pumps, Basal Float 1
Algorithm 6.2.1.1.1.1, is as follows:
deRxlnslld(i) = TBCorIns(i+1) + (deRxlnsl - TBCorTot) *(TBCorIns(i+l) +
Basal(i))/(TBCorTot + Basal) (186)
The transition between these two formulas is accomplished by a logical
variable
called Swtch, which has a value of zero (0) in the small domain and one (1) in
the
large domain.
IF (TBCorTot /deRxlnsl>=1) THEN Swtch=0 ELSE Swtch=l (187)
The invention accomplishes this as follows:
Swtch = IF(TBCorTot /deRxlnsl >=1,0,1) (188)
Swtch helps to put the two equations together into a single equation, which is
switched from (236) to (238) as needed. This is shown below:
deRxlnsl(i)= swtch * deRxlnslld(i) + (1-swtch)*deRxlnslsd(i) (189)
After substituting the large and small domain formulas into this, it reduces
to the
following equation, which requires fewer computer fields:
deR.xlnsl(i) = swtch*TBCorlns(i+1) + (deRxlnsl -
Swtch*TBCorTot)*(TBCorIns(i+l) + Swtch*Basal(i)) / (TBCorTot+Swtch*Basal)
(190)
This equation in turn is substituted into one of the Float equations, e.g.
equation (140)
to yield the result below, which produces a schedule of recommended basal
rates.
BRrec(i) _ [ Basal(i) + Swtch*TBCorlns(i+l) + (deRxlnsl-
Swtch*TBCorTot)*(TBCorIns(i+l)+Swtch*Basal(i))/(TBCorTot+Swtch*Basal) -
dMeallns*CarbSh(i)/CarbShTot ] /dt(i) (191)
For Pump Types A, TBCorInsA(i) is substituted for TBCorIns(i) and TBCorTotA
for
TBCorTot in the above equation.
6.2.1.3.2.2 For Meal Insulin Float 1
The same definitions of the two domains for deRxlnsl are used in the Meal
Insulin
Float formulas, Algorithm 6.2.1.1.1.3 Leading to:
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eMeallnsRec(i) = eMeallns(i) + Swtch*TBCorIns(i+1) + ( deRxlnsl -
Swtch*TBCorTot )
*[ TBCorlns(i+1)+ Swtch*eMeallns(i) ] / [ TBCorTot + Swtch*eMeallnsTot ]
- (BRrx(i) - BR(i) )*dt(i) (192)
This is converted to CIRrec(i) by an adaptation of equation (22):
CIRrec(i) = CarbSh(i) / eMeallnsRec(i) (193)
CIRrec(i) = CarbSh(i) eMealIns(i) + swtch* TBCorTot + (deRxlnsl -
swtch*TBCorTot)*(TBCorlns(i+l )+
swtch*eMealIns(i))/(TBCorTot+swtch*eMeallnsTot) - dt(i)*(BRrx(i)
- BR(i)) ] (194)
Where Swtch is the same "switching parameter" introduced earlier by equation
(183)
to shift the formula between two different domains.
6.2.1.3.2.3 For Meal Insulin Float 2 (uses AMCorIns(i) as error )
Small Domain:
Over the whole interval:
dRxlnslsd(i) _ [dRxlnsl / (AMCorTot +TBCorTot)] * (AMCorlns(i) +
TBCorlns(i)) (195)
This can be thought of as an equation in two parts:
For the last part of the interval:
dRxlllslsdb(i) _ [dRxlnsl / (AMCorTot +TBCorTot)] * TBCorlns(i)
3o dBasalb(i) (196)
Note that this is all Basal Insulin.
For the first part of the interval:
dRxlnslsda(i) _ [dRxlnsl / (AMCorTot +TBCorTot)] * AMCorIns(i) (197)
Large Domain:
For the last part of the interval:
dRxlnslldb(i) = TBCorlns(i) +(dRxlnsl - AMCorTot -TBCorTot)*
( TBCorlns(i)+ BR(i)*dtb(i))/(AMCorTot +TBCorTot + Basal) (198)
For the first part of the interval:
dRxlnsllda(i) = AMCorIns(i) +(dRxlnsl - AMCorTot -TBCorTot)*
(AMCorlns(i) + BR(i)*dta(i))/(AMCorTot +TBCorTot + Basal) (199)
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The sum of the two corrective insulin totals must be used in the switch
parameter.
Swtchm = IF((AMCorTot + TBCorTot) /dRxlnsl >=1,0,1) (200)
6.2.2 A UTOMA TIC MULTIPLE DAYS' DATA (DIGITAL AD VISOR)
The descriptions so far in Version 2 describe the "manual" version of the
Multiple
Past Days' algorithm. The automatic features described below are to remove the
pauses for human judgement and input.
6.2.2.1 AUTOMATION OF deRxlnsl:
To automate the parameter deRxhisl, the present invention makes use of the
fact that
it is more difficult to control the diabetes of a patient whose BG tests, have
a high
percent standard deviation, (BGsd/BGmean) compared to the database norm. The
present invention uses a simple ramp function for this as shown below:
Some new parameters:
FlnsAuto is a multiplier for use in the formula for deRxlnsAuto as follows:
deRxlnsAuto=FlnsAuto * KrxlnslMax*TBCorTot (201)
where
KrrxlnslMax is a positive constant <=1, introduced earlier. It is subject to
change
by the programmers if necessary. The present value is 0.5.
Two definitions:
PmPctBGsd: Database "population" mean of the quantity (BGsd/BGmean) .
PsdPctBGsd: Database "population" standard deviation of the quantity
(BGsd/BGmean), i.e. the database standard deviation of the personal standard
deviations.
In the present invention, FlnsAuto is a ramp function as follows:
IF BGsd/BGmean < PmPctBGsd + PsdPctBGsd then FlnsAuto = 1
IF PmPctBGsd + PsdPctBGsd <= BGsd/Bgmean < =PmPctBGsd + 2 PsdPctBGsd,
THEN FlnsAuto 1 - (BGsd/Bgmean - PmPctBGsd - PsdPctBGsd) /
PsdPctBGsd ]
IF BGsd/BGmean > PmPctBGsd + 2 PsdPctBGsd then FlnsAuto = 0 (202)
This function describes a flat region followed by a ramp down to zero
as shown in Figure 3.
6.2.2.2 AUTOMATION OF deMeallns:
The present invention makes use of the parameter dBslToTgt, which is a general
advisory parameter that shows what change in Basal is necessary to achieve
BoTTgt.
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dBslToTgt = TDD * BoTTgt - Basal (203)
Two steps are employed to automate dMeallns:
The first equation below assigns to the change an absolute value equal to the
minimum absolute value of deRxlnsl or dBaslToTgt. The reason is to avoid
overshooting either BoTTgt or deRxlnsl. The second equation uses the result
from
the first, together with equation (57), to calculate a max value for
deMeallnsAuto;
then it limits deMeallnsAuto to Kmauto times its max value if it is positive
(in the
direction of adding insulin). The parameter Kmauto is subject to adjustment by
the
programmers.
dBasalAuto = IF[ABS(dBaslToTgt/deRxlnsl) <1, ABS(dBaslToTgt),
ABS(deRxlnsl)] *sgn(dBaslToTgt) (204)
deMeallnsAuto=IF[(deRxlnsl>dBasalAuto,Kmauto*(deRxlnsl-dB asalAuto),
(deRxlnsl-dBasalAuto)] (205)
where Kmauto is a positive constant < =1, presently set at 1.
The value of BoTTgt may be obtained from the AIM study's value for Kb or from
BoTTgtRec from Section 6.1.2.1 Basal-to-Total Ratio
6.2.2.3 AUTOMATIC ROUNDING OF CIR FOR PUMP TYPE A:
In the manual mode for Type A, a two-step process is required to obtain a half-
integer
value for C IR in the range below 8. The automatic feature accomplishes this
by
multiplying the floating point number dCIRcalcA by two, then rounding off to a
whole number, and then dividing by two. The result is input into the reverse
equation
to correct the dMealIns for the change.
6.3 NON-FLOAT ALGORITHM
This algorithm uses the BoTFbk(d) factor to determine both Basal Rate and CuR.
This type of algorithm is shown below in a Daily Update Version:
eMeallns(d,i) = eMeallns(d-l,i) + Krxlnsl*(1-BoTFbk(d-1))*
TBCorlns(d-l,i+l) (206)
CIR(d,i) = CIR(d-1,i) - KrxInsl*(1-BoTFbk(d-1)) * eCorlns(d-1,i+1) * CIR(d-
l,i)/eMeallns(d-l,i) (207)
BR(d,i) = BR(d-l,i) + Krxlnsl*BoTFbk(d-1)*TBCorlns(d-l,i+l) (208)
This method has the advantage of being very accurate, but has the disadvantage
of
assigning large changes in meal insulin to time intervals that have little to
no c arb
consumption. For this reason, the version is suitable only for the intervals
containing
the main meals.
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7. TIME INTERVALS:
Theoretically, there should be no limit on the number of time intervals in the
day.
However, for reasons of screen space, there is a limit on the number of time
intervals
that may be used. Also, for an individual patient, fewer than the screen's
maximum
may be used. The invention needs to find the last one. The last time boundary
of the
day (before midnight) is called Tmax. It is found by a routine that picks out
the time
boundary with the highest 2 4-hour clock t ime. This routine is incorporated
into a
single formula of nested IF statements shown below. (note: In MS Access the NZ
function makes nulls and zeros act the same):
Tmax=
IIf(NZ([Time 1 ])>NZ([Time2]), [Time 1 ],IIf(NZ([Time2])>NZ([Time3]),
[Time2],IIf(N
Z([Time3 ])>NZ([Time4]), [Time3],IIf(NZ([Time4])>NZ([Time5]),
[Time4],IIf(NZ([Ti
me5])>NZ([Time6]),[Time5],IIf(NZ([Time6])>NZ([Time7]),[Time6],[Time7]))))))
(209)
The Time Intervals, dt(i), are found by subtracting the consecutive time
boundaries.
dt(i) = time(i+l) - time(i) copy of
(4)
Special mention should be made of the interval surrounding midnight.
dt0 = 24 + timel - Tmax copy of
(5)
7.1 FINDING THE DAY'S LAST ENTRY
Since people rarely go to bed exactly at midnight, it often occurs that some
parameters normally associated with bedtime affect the early morning time
interval.
For instance, Meal Insulin taken at bedtime affects the Corrective Insulin of
the mid-
sleep time boundary. The formula below will find the last entry of the day:
[MeallnsLast] = IIF([Time2]=[Tmax],
[Meallns2],0)+IIF([Time3]=[Tmax],[Meallns3],0)
+IIF([Time4]=[Tmax],[Meallns4],0) + IIF([Time5]=[Tmax],[Meallns5],0) +
IIF([Time6]=[Tmax],[MealIns6],0) + IIF([Time7]=[Tmax],[Meallns7],0) (210)
The recommended values for the last time interval in the day need to be re-
located on
the screen. The following is an example using Recommended Basal Rate, BR:
BRrec(i) = IIF([Time(i)] = [Tmax], [BRrecLast], [BRrec(i) regular formula])
(211)
Other alternative embodiments will become apparent to those skilled in the art
to
which an exemplary embodiment pertains without departing from its scope and
spirit.
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REFERENCES:
1. Paul C Davidson, Harry R Hebblewhite, Bruce W Bode, Pat L Richardson, R
Dennis Steed:
N Spencer Welch, and Joseph Johnson; "Statistical Estimates for CSII
Parameters:
Carbohydrate-to-Insulin Ratio (CIR, 2.8 Rule); Correction Factor (CF, 1700
Rule); and
Basal Insulin"; Diabetes Technology Meeting Poster, 10/31/2002. (Will be
published in
Diabetes Technology and Therapeutics April 2003.
2. John Walsh, Ruth Roberts, Varma Chandrasekhar, and Timothy Bailey; USING
INSULIN, 2003
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ADDENDUM A
SQL listing for Multiple Day's Data Version for Insulin Pumps (Type Q. This
Version of the Invention is embodied in a Microsoft Access database for use by
the
Practitioner as he/she interacts with a patient.
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *
*
SELECT TI.Tp PatientID, TP.SSN, TP.Name, TP.Endo, TP.DOB, TP.Sex,
TP.OnsetDMdate, TP.PumpStartDate, TP.PhoneNos, TP.Email,
TLlntractionID, TI.IntrDate,
TI.Hgt, TI.Wt, TI.HbAlc, TI.Creatinine, TI.Microalb,
TI.BGmean, TI.BGsd, TI.BGsd, TI.NBGs,
TI.TDDa, TI.TDDb, TI.TDDc, TI.TDDd, TI.TDDe, TI.TDDf,
(NZ([TDDa])+NZ([TDDb])+NZ([TDDc])+NZ([TDDd])+NZ([TDDe])+NZ([TDDf]))
/(-IsNumeric([TDDa])-IsNumeric([TDDb])-IsNumeric([TDDc])-lsNumeric([TDDd])-
IsNumeric([TDDe])-IsNumeric([TDDf])) AS TDDavg,
[Basal]/[TDDavg] AS BasalOvrTDD,
0.48*[TDDavg] AS BasalAIM,
[BasalAIM] -[Basal] AS dBslToAIM,
TLBasalrx,
TI.TargetBG, TI.TargetBGrx,
TI.CF, 1708/[TDDavg] AS CFaim, TI.CFrx,
TI.CIR, 2.81*[wt]/[TDDavg] AS CIRaim,
IIf([sex]="m",(([Hgt]-60) '6+106)* 13/8,(([Hgt]-60)*5+100)** 13/8) AS
[Carbspd(Hgt)],
1-[CarbShTot]*0.8/[Carbspd(Hgt)] AS BoTTgtRec,
[CarbShTot]/[eMeallnsTot] AS [CIR(carb)], TI.MeallnsTotARx,
[CarbShTot]/[MeallnsTotARx] AS [CIR(MeallnslRx)],
TI.TypelnsShort, TI.TypelnsLong,
TI.Diet, TI.PumpType, TI.iComment,
TI.TimeLabl2, TI.TimeLabl3, TI.TimeLabl4, TI.TimeLabl5, TI.TimeLabl6,
TI.TimeLabl7, TI.TimeLabl8,
0 AS Timel, TI.Time2, TI.Time3, TI.Tiine4, TI.Time5, TI.Time6, TI.Time7,
TI.Time8,
IIf(NZ([Time2])>NZ([Time3]), [Time2],IIf(NZ([Time3])>NZ([Time4]),
[Time3],IIf(N
Z([Time4])>NZ([Time5]), [Time4],IIf(NZ([Time5 ])>NZ([Time6]), [Time5
],IIf(NZ([Ti
me6])>NZ([Time7] ), [Time6],IIf(NZ([Time7])>NZ([Time8] ), [Time7],
[Time8]))))))
AS Tmax,
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TI.CarbSh2, TI.CarbSh3, TI.CarbSh4, TI.CarbSh5, TI.CarbSh6, TI.CarbSh7,
TI.CarbSh8,
NZ([CarbSh2])+NZ([CarbSh3])+NZ([CarbSh4])+NZ([CarbSh5])+NZ([CarbSh6])+N
Z([CarbSh7])+NZ([CarbSh8]) AS CarbShTot,
IIf([Time2]=[Tmax], [CarbSh2],0)+Ilf([Time3 ]=[Tmax], [CarbSh3],
0)+IIf([Time4]=[T
max], [Carbsh4], 0)+IIf([Time5 ]=[Tmax], [CarbSh5 ],0)+IIf([Time6]=[Tmax],
[CarbSh6
],0)+IIf([Time7]=[Tmax], [CarbSh7],0)+NZ([CarbSh8]) AS CarbShLast,
TI.Meallns2, TI.MealIns3, TI.MealIns4, TI.Meallns5, TI.Meallns6, TI.Meallns7,
TI.Meallns8,
TI.AMCorIns2, TI.AMCorIns3, TI.AMCorIns4, TI.AMCorIns5, TI.AMCorlns6,
TI.AMCorIns7,
TI.AMCorlns8,
TI.TBCorIns2, TI.TBCorIns3, TI.TBCorIns4, TI.TBCorIns5, TI.TBCorlns6,
TI.TBCorIns7, TI.TBCorIns8,
NZ([TBCorIns2])+NZ([TBCorIns3])+NZ([TBCorins4])+NZ([TBCorInsS])+NZ([TB
Corhis6])+NZ([TBCorIns7])+NZ([TBCorIns8]) AS TBCorTot,
[Meallns2]+[AMCorlns2] AS eMeallns2
[MealIns3]+[AMCorlns3] AS eMeallns3
[Meallns4]+[AMCorlns4] AS eMeallns4
[Meallns5]+[AMCorIns5] AS eMeallns5
[Meallns6]+[AMCorlns6] AS eMeallns6
[Meallns7]+[AMCorlns7] AS eMeallns7
[Meallns8]+[AMCorlns8] AS eMeallns8
NZ([eMeallns2])+NZ([eMealIns3])+NZ([eMeallns4])+NZ([eMeallns5])+NZ([eMeal
Ins6])+NZ([eMeallns7])+NZ([eMeallns8]) AS eMeallnsTot,
IIf([Time2]=[Tmax],NZ([eMeallns2]),0)+IIf([Time3]=[Tmax],NZ([eMealIns3]),0)+II
f([Time4]=[Tmax],NZ([eMeallns4]),0)+IIf([Times]=[Tmax],NZ([eMeallns5]),0)+IIf(
[Time6]=[Tmax],NZ([eMealIns6]),0)+IIf([Time7]=[Tmax],NZ([eMealIns7]),0)+NZ([
eMeallns8]) AS eMeallnsLast,
[Time2]+24-[tmax] AS dtO,
IIf(NZ([Time2])>O,[time2]-[timel],O) AS dtl,
IIf(NZ([Time3])>O,[time3]-[time2],O) AS dt2,
IIf(NZ([Time4])>O,[time4]-[time3],O) AS dt3,
IIf(NZ([Time5])>O,[time5]-[time4],O) AS dt4,
IIf(NZ([Time6])>O,[time6]-[time5],O) AS dt5,
Ilf(NZ([Time7])>O, [time7]-[time6],O) AS dt6,
IIf(NZ([Time8])>O,[time8]-[time7],O) AS dt7,
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TI.BR1, TI.BR2, TLBR3, TI.BR4, TI.BR5, TI.BR6, TI.BR7, TI.BR8,
[BR1]*[dtO] AS BaslO,
[BR2]*[dt2] AS Basl2,
[BR3]*[dt3] AS Basl3,
[BR4]*[dt4] AS Basl4,
[BR5]*[dt5] AS Basl5,
[BR6]*[dt6] AS Bas16,
[BR7]*[dt7] AS Basl7,
NZ([Bas17])+NZ([Basl6])+NZ([Basl5])+NZ([Basl4])+NZ([Basl3])+NZ([Basl2])+NZ
([BaslO]) AS Basal,
TI.BG2, TI.BG3, TI.BG4, TI.BGS, TI.BG6, TI.BG7, TI.BG8,
TI.CIR1, TI.CIR2, TI.CIR3, TI.CIR4, TI.CIR5, TI.CIR6, TI.CIR7, TI.CIR8,
IIf([Time2]=[Tmax],[CIR2],0)+IIf([Time3]=[Tmax],[CIR3],0)+IIf([Time4]=
[Tmax],[
CIR4],O)+IIf([Time5]=[Tmax],[CIR5],0)+IIf([Time6]=[Tmax],[CIR6],0)+IIf([Time7]
=[Tmax],[CIR7],O)+NZ([CIR8]) AS CIRLast,
TI.deRxInsl,
TI.deMeallns,
[deRxlnsl]-[deMealIns] AS dBasal,
[CarbShTot]/([eMealhlsTot]+[deMeallns]) AS CIRrecC,
TLCIRrx,
Ilf(O<=[deRxlnsl]/[CorTot]<=1,0,1) AS swtch,
([Basl0]+[swtch] * [TBCorlns2]+([deRxInsl]-
[swtch] *[TBCorTot])*([TBCorlns2]+[swtch] * [BaslO])
/([TBCorTot]+[swtch] * [BaslTot])-[deMeallns] *
[eMeallnsLast]/[eMeallnsTot])/[dt0]
AS BRrecAO,
[BRrecAO] AS BRrecAl,
([Basl2]+[swtch] * [TBCorlns3]+([deRxlnsl]-
[swtch] * [TBCorTot])* ([TBCorlns3 ]+[swtch] * [Basl2])
/([TBCorTot]+[swtch]*[BaslTot])-
[deMeallns]*NZ([eMeallns2])/[eMeallnsTot])/[dt2] AS BRrecA2,
([B asl3 ]+[ swtch] * [TB C orlns 4]+([ deRxlns l] -
[swtch] * [TBCorTot])*([TBCorlns4]+[swtch] * [Basa3])
/([TBCorTot]+[swtch]*[BaslTot])-
[deMeallns]*NZ([eMeallns3])/[eMealhisTot])/[dt3] AS BRrecA3,
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([Basl4]+[swtch] *[TBCorlns5]+([deRxInsl]-
[swtch] * [TBCorTot])*([TBCorIns5]+[swtch] * [Basl4])
/([TBCorTot]+[swtch] * [BaslTot])-
[deMeallns]*NZ([eMeallns4])/[eMeallnsTot])/[dt4] AS BRrecA4,
([Basl5]+[swtch] * [TBCorlns6]+([deRxlnsl]-
[swtch] * [TBCorTot])*([TBCorlns6]+[swtch] * [Basl5])
/([TBCorTot]+[swtch] * [BaslTot])-
[deMeallns]*NZ([eMeallns5])/[eMeallnsTot])/[dt5] AS BRrecA5,
([Basl6]+[swtch] * [TBCorlns7]+([deRxhisl]-
[swtch] *[TBCorTot])*([TBCorlns7]+[swtch]* [Basl6])
/([TBCorTot]+[swtch] * [BaslTot])-
[deMeallns]*NZ([eMealIns6])/[eMeallnsTot])/[dt6] AS BRrecA6,
([Basl7]+[swtch] *[TBCorlns8]+([deRxlnsl]-
[swtch] * [TBCorTot])*([TBCorlns8]+[swtch] * [Basl7])
/([TBCorTot]+[swtch] *[BaslTot])-
[deMeallns]*NZ([eMealIns7])/[eMeallnsTot])/[dt7] AS BRrecA7,
TI.BRrx1, TI.BRrx2, TI.BRrx3, TI.BRrx4, TI.BRrx5, TI.BRrx6, TI.BRrx7,
TI.BRrx8,
0 AS TimeRxl,
TI.TiineRx2, TI.TimeRx3, TI.TimeRx4, TI.TimeRx5, TI.TiineRx6, TI.TimeRx7,
TI.TimeRx8,
IIf(NZ([TimeRx2])>NZ([TimeRx3]), [Timelbx2],IIf(1\TZ([TimeRx3 ])>NZ([TimeRx4]
)
, [TimeRx3 ],IIf(NZ([TimeRx4])>NZ([TimeRx5]), [TimeRx4],IIf(NZ([TimeRx5])>NZ
([TimeRx6]),[TimeRx5],IIf(NZ([TimeRx6])>NZ([TimeRx7]), [TimeRx6],IIf(NZ([Ti
meRx7])>NZ([TimeRx8]),[TimeRx7],[TimeRx8])))))) AS TRxmax,
IIf(NZ([TimeRx2])>0, [TimeRx2]+24-[Trxmax],0) AS dTrxO,
IIf(NZ([TimeRx2])>0,[TimeRx2]-[TimeRx1],0) AS dTrx1,
IIf(NZ([TimeRx3])>0,[TimeRx3]-[TimeRx2],0) AS dTrx2,
IIf(NZ([TimeRx4])>0,[TimeRx4]-[TimeRx3],0) AS dTrx3,
IIf(NZ([TimeRx5])>0,[TimeRx5]-[TimeRx4],0) AS dTrx4,
IIf(NZ([TimeRx6])>0,[TimeRx6]-[TimeRx5],0) AS dTrx5,
IIf(NZ([TimeRx7])>0,[TimeRx7]-[TimeRx6],0) AS dTrx6,
IIf(NZ([TimeRx8])>0,[TimeRx8]-[TimeRx7],0) AS dTrx7,
[CarbShLast]/([eMeallnsLast]+[deRxlnsl] * [TBCorlns2]/[TBCorTot]-([BRrx 1 ]-
[BR1])*[dt0]) AS CIRrec0,
[CarbSh2]/([eMeallns2]+[deRxlnsl] * [TBCorlns3 ]/[TBCorTot]-([BRrx2] -
[BR2])*[dt2]) AS CIRrec2,
[CarbSh3]/([eMeallns3 ]+[deRxlnsl] * [TBCorlns4]/[TBCorTot]-([BRrx3]-
[BR3])*[dt3]) AS CIRrec3,
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[CarbSh4]/([eMeallns4]+[deRxlnsl]* [TBCorlns5]/[TBCorTot]-([BRrx4]-
[BR4])*[dt4]) AS CIRrec4,
[Carb Sh5 ]/([eMeallns5]+[deRxlnsl] * [TBCorlns6]/[TBCorTot]-([BRrx 5]-
[BR5])*[dt5]) AS CIRrec5,
[CarbSh6]/([eMeallns6]+[deRxlnsl]*[TBCorlns7]/[TBCorTot]-([BRrx6]-
[BR6])*[dt6]) AS CIRrec6,
[CarbSh7]/([eMealln.s7]+[deRxlnsl]*[TBCorIns8]/[TBCorTot]-([BRrx7]-
[BR7])*[dt7]) AS CIRrec7,
TI.eMeallnsRx1, TI.eMeallnsRx2, TI.eMealInsRx3, TI.eMeallnsRx4,
TI.eMeallnsRx5, TI.eMeallnsRx6, TI.eMeallnsRx7,
TI.CIRrxl, TI.CIRrx2, TI.CIRrx3, TLCIRrx4, TI.CIRrx5, TLCIRrx6, TI.CIRrx7,
TI.CIRrx8, TI.InptFormType
FROM TP INNER JOIN TI ON TP.PatientlD = TI.Tp PatientlD
ORDER BY TI.IntrDate DESC;
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