Method and system to derive multiple glycemic patterns from glucose measurements during time of the day

1. A system for management of diabetes of a subject, the system comprising:

at least one glucose monitor that is configured to measure a glucose concentration based on an enzymatic reaction with physiological fluid in a biosensor that provides an electrical signal representative of the glucose concentration; and

a controller in communication with the at least one glucose monitor, the controller being configured to receive or transmit glucose data representative of glucose levels measured by the glucose monitor over a predetermined time period and to determine whether the glucose data includes or does not include:

(a) an overall trend of the glucose data, the overall trend having:

(1) a minimum number of glucose measurements;

(2) a minimum number of glucose measurements that have values in an above a target range, below a target range, or in-range category in a time slot; and

(3) a percentage of glucose measurements in the timeslot being greater than a minimum threshold;

(b) a minor trend of the glucose data, the minor trend having a minimum number of glucose measurements within a specified number of days that have values above a target range, below a target range, or in-range category in the time slot and all of the glucose measurements in the minimum number must be within a specified number of hours of each other; and

(c) a significant trend of the glucose data, the significant trend having:

(1) a minimum number of glucose measurements;

(2) a chi-squared test confidence level greater than a threshold; and

the controller, upon determination of the glucose data including both of the overall trend and minor trend but not the significant trend, annunciating to the subject such determination and using both of the determined overall trend and minor trend to calculate an amount of a drug to be delivered to the subject; and

a drug delivery device in communication with the controller, the drug delivery device being configured to deliver the calculated amount of the drug to the subject.

2. The system of claim 1 , in which the minimum number of glucose measurements comprises about 14 measurements; the minimum number of glucose measurements in one of the in-range, above a target range or below a target range comprises about two for measurements below a target range, about three measurements above a target range, 4 measurements that are within the target range; and the minimum threshold comprises about 50% of the measurements being above a target range, 5% of the measurements being below the target range, 70% being within the target range.

3. The system of claim 1 , in which the minimum number of glucose measurements of a minor trend comprises about two for measurements below a target range, about three measurements above a target range, about seven measurements that are within the target range and the specified number of hours comprises about 3 hours.

4. The system of claim 1 , in which the significant trend is statistically and significantly different than the trends observed in other timeslots and a chi-squared test is used to determine if a particular time slot of the time slots is statistically significantly different than other time slots; the statistical test being based on a percentage of hypoglycemic incidence per the time slot interval and a predicted percentage of hypoglycemic incidence per the time slot interval, and the controller is configured to annunciate that a significant trend has been detected in the particular time slot.

5. The system of claim 4 , in which the chi-squared test utilizes a confidence level ranging from about 90% to about 99%.

6. The system of claim 4 , in which the controller is configured to:

calculate a chi-squared χ 2 using the following equation:

χ

2

=

∑

i

=

1

n

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(

L

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L

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pre

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2

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L

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2

L

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where χ 2 =chi-squared, i represents a particular time slot interval, n is a total number of time slot intervals, L i is a number of substantially hypoglycemic glucose concentration measurements that occur during time slot interval i, L i,pre is a predicted number of substantially hypoglycemic glucose concentration measurements that will occur during time slot interval i, and L i,pre ′ is a predicted number of non-hypoglycemic glucose concentration measurements that will occur interval time i;

compare the calculated χ 2 to a χ 2 value in a table based on a number of degrees of freedom for each of the time slot intervals i;

determine that at least one of the time slot intervals are statistically significantly different if the calculated χ 2 is greater than the χ 2 value of the table; and

calculating L i,pre and L i,pre ′ using estimation equations comprises:

L

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i

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and

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L

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N

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N

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where N i represents the total number of glucose concentration measurements performed during time interval i.

7. The system of claim 6 , in which the controller is further configured to:

identify one of the time slot intervals as being statistically significantly different with a Z test.

8. The system of claim 7 , in which the controller is further configured to:

calculate Z i using a Z test, the Z test comprising:

Z

i

=

(

L

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L

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SE

i

where Z i represents a Z test at a particular time slot interval i and SE i represents a standard error for a particular time slot interval i;

compare a calculated Z i to a Z value in a table; and

identify that one of the time slot intervals is statistically significantly different if the calculated Z i is greater than the Z test; and

annunciate the one of the time slot intervals.

9. The system of claim 8 , wherein the Z test includes a threshold of about one to about two.

10. The system of claim 9 , in which the controller is configured to:

calculate SE i , using a standard error equation comprising:

SE

i

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1

N

i

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L

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pre

*

(

N

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L

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)

11. A method of managing diabetes risks of a subject, the method comprising:

determining at least one of certain trends in a time of a day for glucose measurements with at least one glucose monitor and a controller in communication with the at least one glucose monitor, the controller including a microprocessor and configured to receive or transmit glucose data representative of glucose levels measured by the glucose monitor, and the determining comprising:

performing a plurality of glucose measurements over a predetermined time period with the glucose monitor;

identifying, with the microprocessor, from the plurality of glucose measurements whether the glucose data includes or does not include:

(a) an overall trend of the glucose data, the overall trend having:

(1) a minimum number of glucose measurements;

(2) a minimum number of glucose measurements that have values in the above a target range, below a target range, or in-range category in the time slot; and

(3) a percentage of glucose measurements in the timeslot being greater than a minimum threshold;

(b) a significant trend in which such significant trend is statistically and significantly different than the trends observed in other timeslots and a chi-squared test is used to determine if a particular time slot of the time slots is statistically significantly different than other time slots; the statistical test being based on a percentage of hypoglycemic incidence per the time slot interval and a predicted percentage of hypoglycemic incidence per the time slot interval; and

(c) a minor trend of the glucose data, the minor trend having a minimum number of glucose measurements within a specified number of days that have values above a target range, below a target range, or in-range category in the time slot and all of the glucose measurements in the minimum number must be within a specified number of hours of each other

in the event the identifying step indicates the glucose data includes both of the overall trend and the minor trend but not the significant trend:

using at least one of the overall trend or the minor trend to calculate an amount of a drug to be delivered to the subject by a drug delivery device in communication with the controller, wherein the amount of the drug is calculated to manage diabetes risks of the subject; and

delivering, by the drug delivery device, the calculated amount of the drug to the subject.

12. The method of claim 11 , wherein a chi-squared test is used to determine if any of the time slots is statistically significantly different from other time slots.

13. The method of claim 12 , wherein the chi-squared test comprises a confidence level of about 90%.

14. The method of claim 13 , wherein the number of glucose measurements is greater than about 14.

15. The method of claim 13 , further comprising:

calculating a chi-squared χ 2 using the following:

χ

2

=

∑

i

=

1

n

⁢

(

L

i

-

L

i

,

pre

)

2

L

i

,

pre

+

∑

i

=

1

n

⁢

(

L

i

′

-

L

i

,

pre

′

)

2

L

i

,

pre

′

where χ 2 =chi-squared, i represents a particular time slot interval, n is a total number of time slot intervals, L i is a number of substantially hypoglycemic glucose concentration measurements that occur during time slot interval i, L i,pre is a predicted number of substantially hypoglycemic glucose concentration measurements that will occur during time slot interval i, and L i,pre ′ is a predicted number of non-hypoglycemic glucose concentration measurements that will occur interval time i;

comparing a calculated χ 2 to a χ 2 value in a table based on a number of degrees of freedom for each of the time slot intervals i; and

determining that at least one of the time slot intervals are statistically significantly different if the calculated χ 2 is greater than the χ 2 value on the table.

16. The method of claim 15 , further comprising:

calculating L i,pre and L i,pre ′ using estimation equations comprising:

L

i

,

pre

=

∑

i

=

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L

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and

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N

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*

N

i

where N i represents the total number of glucose concentration measurements performed during time interval i.

17. The method of claim 13 , further comprising: identifying one of the time slot intervals as being statistically significantly different using a Z test.

18. The method of claim 17 , in which the Z test comprises:

Z

i

=

(

L

i

-

L

i

,

pre

)

SE

i

where Z i represents a Z test at a particular time slot interval i and SE i represents a standard error for a particular time slot interval i; and the method further comprising:

comparing a calculated Z i to a Z value in a table; and

identifying that one of the time slot intervals is statistically significantly different if the calculated Z i is greater than the Z test.

19. The method of claim 18 , wherein the Z test includes a threshold of about one and

calculating SE i , using a standard error equation comprising:

SE

i

=

1

N

i

*

L

i

,

pre

*

(

N

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-

L

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)

.