Clinical variable determination

A computer implemented method of determining a clinical variables utilizing an insulin pump that includes initiating blood glucose measurements, initiating ingestion of carbohydrates and receiving input data based on the blood glucose measurements and the ingestion of carbohydrates and utilizing the data to calculate clinical variables. The invention may include presenting instructions to a patient to take various actions and to input various data. The clinical variables determined may be stored in memory and then used to calculate insulin doses and to send a signal to an insulin pump to infuse the insulin dose calculated.

FIELD OF THE INVENTION

The invention relates to determining clinical variables that are utilized in the operation of an insulin pump. Such clinical variables may include insulin sensitivity factor and the carbohydrate factor, also known as the insulin to carbohydrate ratio. The invention also relates to systems and methods for automating the determination of these clinical variables.

BACKGROUND OF THE INVENTION

The control of insulin pump therapy benefits greatly from knowing certain clinical variables including the insulin sensitivity factor and the carbohydrate factor, also known as carb factor or the insulin to carbohydrate ratio. Typically, these factors are determined by a manual method of administering insulin or carbohydrates and observing the effect of this administration on blood glucose level.

Calculation of insulin sensitivity factor is based on all of the units of insulin that a person takes in one day. Insulin sensitivity factor is also sometimes referred to as correction factor or correction bolus and is based on the drop in blood glucose level caused by one unit of insulin in units of milligrams per deciliter (mg/dL). Patients who are using insulin find that there are times when they need to make insulin adjustments in order to maintain blood glucose within target levels. In some cases, patients need to add more insulin at meal times to correct for high blood glucose. At other times, it may be necessary to correct a high blood glucose that is not associated with a meal. To utilize the insulin sensitivity factor to apply a corrective dose of insulin, it is necessary to know how many milligrams per deciliter one unit of insulin lowers the blood glucose. This value may vary with the individual patient and may also vary throughout the day or during times of illness. Generally, the goal is to apply a correction bolus that returns the blood glucose level to within thirty milligrams per deciliter of the target blood glucose level within three hours after the dose is given.

One method of calculating the insulin sensitivity factor is to take a three-day average of the total amount of insulin taken per day. This may be done by adding the basal daily total units of insulin taken in a given day to the bolus daily total units of insulin taken in that day to arrive at a total insulin value for that day. The insulin sensitivity factor is then determined by dividing a constant by the total daily insulin intake. Depending upon the type of insulin used, the constant varies. For some types of insulin the constant is considered to be 1,800; for other types of insulin the constant is considered to be 1,700; for yet other types of insulin, the constant is considered to be 1,500. In general, the 1500 sensitivity constant, sometimes referred to as the “1500 rule”, is used to estimate the blood glucose level drop, in milligrams per deciliter, for every unit of regular insulin taken. The 1800 sensitivity constant, sometimes referred to as the “1800 rule”, is used to estimate the blood glucose level drop, in milligrams per deciliter, for every unit of rapid-acting insulin taken. For example, if a patient has utilized thirty units total insulin daily and a correction constant of 1500 is used, 1500 divided by thirty equals fifty. This means that one unit of insulin would typically lower blood glucose for that patient by approximately 50 milligrams per deciliter (mg/dL).

The insulin sensitivity factor or correction factor is then used to calculate an insulin correction bolus dose. The correction bolus dose is calculated by subtracting from the current blood glucose level the target blood glucose and then dividing that difference by the insulin sensitivity factor. For example, if a patient has a current blood glucose of 200 milligrams per deciliter, and a target blood glucose of 100 milligrams per deciliter, 200 less 100 equals 100. 100 divided by the correction factor of 50 indicates that 2.0 units of insulin should be given for a correction dose.

The carbohydrate factor, also known as insulin to carbohydrate ratio or insulin to carb ratio, helps determine how much insulin should be taken to provide for proper metabolism of carbohydrates that would be eaten at a meal or in a snack. Carb ratios are calculated on a variable basis. For example, some patients might take 1.5 units of insulin for every carbohydrate choice, while others might take 1 unit of insulin for every 10 grams of carbohydrate that is expected to be eaten. Insulin-to-carb ratios vary from person to person and insulin to-carb-ratio may change over the course of treatment for some patients. Insulin to carb ratio may even vary depending upon the time of day.

Carb factors are commonly calculated using the “500 rule” (which is also sometimes known as the “450 rule” when using regular, non-fast acting insulin). Once the carb factor is known, the number of grams of carbohydrates in food that is to be eaten can be divided by the carb factor to determine how many units of bolus insulin is needed to cover metabolism of the carbohydrates that are to be eaten. This option provides patients flexibility in their food choices because the number of carbohydrates being ingested can be compensated for with a matching dose of insulin. According to the 500 or the 450 rule, an estimate of the number of grams of carbohydrates metabolized per unit of fast-acting insulin is determined. A constant of 450 is used for calculation with regular insulin. For example, when utilizing rapid-acting insulin, the constant of 500 is divided by the total daily dose of insulin to determine the grams of carbohydrates that are covered by one unit of rapid-acting insulin. The total daily insulin, sometimes abbreviated TDD, includes all fast-acting insulin taken before meals plus all long acting insulin used in a day. Correction doses of rapid-acting insulin taken to correct high blood glucose readings during the day should also be factored into the daily dosage.

The 500 rule is most accurate for those whose bodies make no insulin of their own and who receive 50 to 60 percent of their total daily dosage as basal insulin. For patients utilizing an insulin pump, the determined values used are then manually entered into the insulin pump where they are used to control insulin dosage. Examples of such pumps and various features that can be associated with such pumps include those disclosed in U.S. patent application Ser. No. 13/557,163, U.S. patent application Ser. No. 12/714,299, U.S. patent application Ser. No. 12/538,018, U.S. Provisional Patent Application No. 61/655,883, U.S. Provisional Patent Application No. 61/656,967 and U.S. Pat. No. 8,287,495, each of which is incorporated herein by reference.

However, none of the above estimation techniques for insulin sensitivity factor or carbohydrate factor is as accurate as would be ideal. Further, many patients are well-known to be non-compliant with medication regimens, particularly when the regimen becomes more complex or burdensome. Accordingly, there is still room for improvement in these areas.

SUMMARY OF THE INVENTION

The present invention relates to automating or partially automating the determination of values for insulin sensitivity factor, carbohydrate factor and insulin action time in the context of “smart” insulin pumps; particularly in some embodiments, a smart insulin pump having a larger display. According to the invention, the pump or another electronic device queries and instructs the patient through the process of determining clinical variables such as, for example, the insulin sensitivity factor or the carbohydrate factor (also known as the carb ratio). Further, the invention contemplates the incorporation of continuous glucose monitoring (CGM) into the determination of the insulin sensitivity factor or the carbohydrate factor by taking advantage of the tracking and trending strengths of CGM.

According to one embodiment of the invention, the controller of the insulin pump provides directions for what the patient should do, including either prompting the patient to take blood glucose measurements (e.g., by obtaining a blood sample via a finger stick and testing the blood glucose level directly with a blood glucose meter as is commonly done) or taking advantage of the monitoring estimates of a patient's blood glucose level through a continuous glucose monitoring system. A CGM system provides a substantially continuous estimated blood glucose level through a transcutaneous sensor that measures analytes, such as glucose, in the patient's interstitial fluid rather than their blood. Examples of CGMs include the Seven®, Seven® PLUS, and G4™ Platinum monitoring systems sold by Dexcom®, Inc. of San Diego, Calif. CGM systems typically consist of a transcutaneously-placed sensor, a transmitter, and a monitor (either a stand-alone monitor or one built into an insulin pump). Such systems and definitions of related terms are described in greater detail in, e.g.: U.S. Pat. Nos. 8,311,749; 7,711,402; and 7,497,827; each of which is hereby incorporated by reference in its entirety. A CGM system enables a patient or caregiver to insert a single sensor probe under the skin for multiple days, such as for a week. Thus, the patient is only required to perform a single moderately invasive action with a single entry point in the subdermal layer on, e.g., a weekly basis. The system estimates the level of blood glucose periodically and sends that information to a monitor that is carried by the patient. Because the CGM estimates blood glucose levels from analyzing interstitial plasma or fluid, rather than from analyzing blood as is done with blood glucose meters, however, CGMs generally are not as well-suited for accurate blood glucose monitoring. Accordingly, CGMs are most often used for identifying trends in blood glucose levels over time and for providing estimates thereof. Typically, after a monitoring period, during which the patient or caregiver can monitor estimated blood glucose levels in real-time, the sensor is removed and information stored in the continuous glucose monitoring system may be, e.g., downloaded into a computer for analysis.

According to one example embodiment, the invention asks the user to ingest a certain amount of carbohydrates and prompts them to take blood glucose measurements before and at a certain time after the ingestion of carbohydrates. The prompts may be directed to the patient who takes the measurement and inputs it. The prompts may be initiated based on input from a CGM system.

As mentioned, the CGM system is particularly useful for trending and tracking of estimated blood glucose levels while being less useful for identifying precise numerical values for actual blood glucose levels. Thus, the CGM can be incorporated to identify when blood glucose is rising, falling or is flat for a period of time. According to the invention, these factors can be used to identify when to prompt a patient to take a blood glucose measurement and to input the findings of the measurement into the infusion pump controller to gather data to determine insulin sensitivity factor or carb factor.

Based on this information, the carb ratio may then be determined automatically by the controller. The carbohydrate ratio can then be automatically set into the pump for use in further applications of insulin based on ingestion of carbohydrates.

According to another embodiment, the invention includes determining insulin action time. After a bolus of insulin is infused, blood glucose level will decrease. This reduction is observable with CGM. Accordingly this method is well suited to be performed along with the insulin sensitivity factor determination discussed herein. After a bolus of insulin is infused the time for a selected reduction in blood glucose level to be achieved is recorded. This determines the insulin action time.

A method of determining insulin action time, according to an embodiment of the invention, includes infusing a bolus of insulin; waiting a minimum period of time; receiving an input from the CGM that the blood glucose level has reached a level or stable state and identifying the insulin action time by noting the time between infusion of insulin and the achieving of the level or stable state. Alternately, the fall in blood glucose level according to the CGM can be extrapolated to an inflection point from when the blood glucose level decline is most rapid. Alternately, the fall in blood glucose level according to the CGM can be extrapolated from a time when substantially all of the blood glucose decrease has occurred. For example, extrapolation can be based on a point wherein approximately seventy five percent of the blood glucose decrease has occurred. The time between infusion of the insulin and the inflection point can be taken as the insulin action time. The fall in blood glucose level can also be extrapolated from a time when significantly all of the blood glucose decrease has occurred, such as, for example, after 75% of the decrease has occurred.

DETAILED DESCRIPTION

Provided herein are systems, devices and methods for accurately determining clinical variables in an infusion pump and particularly in an insulin infusion pump. Examples of such pumps and various features that can be associated with such pumps include those disclosed in U.S. patent application Ser. No. 13/557,163, U.S. patent application Ser. No. 12/714,299, U.S. patent application Ser. No. 12/538,018, U.S. Provisional Patent Application No. 61/655,883, U.S. Provisional Patent Application No. 61/656,967 and U.S. Pat. No. 8,287,495, each of which is incorporated herein by reference.

Some embodiments may include advances in the internal components, the control circuitry, and improvements in a user interface of the systems and devices. The advances may allow for a safer and more accurate delivery of medicament to a patient than is currently attainable today from other devices, systems, and methods. Although embodiments described herein may be discussed in the context of the controlled delivery of insulin, delivery of other medicaments as well as other applications are also contemplated. Device and method embodiments discussed herein may be used for pain medication, chemotherapy, iron chelation, immunoglobulin treatment, dextrose or saline IV delivery, or any other suitable indication or application. Non-medical applications are also contemplated.

FIGS. 1A-1Ddepict an embodiment of a portable infusion pump system110including an infusion cartridge112and pump device114. Infusion cartridge112can be a reversibly removable and interchangeable element that may be inserted into different pump devices. Referring toFIG. 1A, a front view of the pump device114is depicted and includes a user friendly user interface116on a front surface118of the pump device114. The user interface116includes a touch sensitive screen120that may be configured to display a variety of screens used for displaying data, facilitating data entry by a patient, providing visual tutorials, as well as other interface features that may be useful to a patient operating the pump device114.FIG. 1Bis a rear view of the pump device114and illustrates the detachable installment of the infusion cartridge112in a slot122of the pump device114which is configured to accept the cartridge112.

FIG. 1Cis a schematic view of an open housing124of the pump device114depicting components that may be included in embodiments of the pump device114. The cartridge112may include a fluid interface configured to receive a fluid such as collapsible reservoir126. The collapsible reservoir126may be formed from a flexible material or membrane128that is disposed about an interior volume of the reservoir126. The cartridge112also includes a substantially rigid container130sealed around the flexible material of the collapsible reservoir126. A disposable delivery mechanism132is disposed within the disposable cartridge112and may have a fill port134with a re-sealable septum136sealed over the fill port134, a reservoir inlet port138in fluid communication with an interior volume140of the collapsible reservoir126, a fluid dispense port142in fluid communication with a bore144of the delivery mechanism132, a vent inlet port146and a vent outlet port148, both in fluid communication with the bore144. The collapsible reservoir126may have a bag-like structure with flexible walls that can collapse and expand depending upon the amount of material in the volume of the reservoir. The interior volume of the reservoir may be in fluid isolation from the remaining interior volume of the rigid container130.

The cartridge112may be releasably and operatively secured to a housing124of the pump device114. The housing124may be configured to house a drive mechanism150including a motor152and gear box154disposed in the housing124and detachably coupled to a spool member156of the delivery mechanism132. At least one pressure sensor158may be disposed in a volume160between an outside surface162of the flexible material or membrane128of the collapsible reservoir126and an inside surface164of the substantially rigid shell or case130. The graphic user interface116may be operatively coupled to a controller168, which may include at least one processor170, a memory device172and connective circuitry or other data conduits that couple the data generating or data managing components of the device. A power storage cell in the form of a battery174that may be rechargeable may also be disposed within the housing124. Data generating or managing components of the device may include the processor(s)170, the memory device172, sensors158, including any pressure or temperature sensors, the GUI166and the like.

The pressure inside the infusion cartridge112, and particularly the vented volume160of the infusion cartridge112, may be measured by a pressure sensor158disposed in the infusion cartridge112or in the pump device114in a volume, such as pocket186as shown inFIG. 1D.

Pocket186is an interior volume disposed within the pump device114and in fluid communication with an interior volume of the fluid cartridge112. The pocket186is in sealed relationship with the interior volume160of the cartridge. As such, a pressure sensor158disposed within the volume of the pocket186will read the pressure of the volume160in the cartridge, but can remain with the pump device114after disposal of the disposable cartridge112. This configuration lowers the cost of the cartridge while providing for pressure measurement within the cartridge112. In some embodiments, data from the pressure sensor158may be used to provide a measurement of how much insulin or other medicament is being delivered by the first pump device114. Alternatively, the pressure sensor158can be disposed within the cartridge directly in the vented volume160.

The pump device114can also include a thermistor or other temperature sensor188including an optical or infrared sensor that measures the temperature of the insulin or other medicament within the reservoir126upon coupling the infusion cartridge112with the pump device114. Taking the temperature of the air may be important in measuring how much insulin or other medicament is in the fluid reservoir. In some embodiments, the thermistor or other temperature sensor188is positioned in the pocket186such that it can measure the temperature of the air in the pocket186as shown inFIG. 1D. As noted above, the pocket186may also include a pressure sensor158coupled to the controller168for measuring pressure within the pocket186and volume160. Because the air in the pocket186is in fluid communication with the residual air within the chamber160, the temperature and pressure of the air in the infusion cartridge112surrounding the fluid reservoir126may be equal or approximately equal to the temperature and pressure of the air in contact with the temperature sensor188and pressure sensor158. In turn, the temperature sensor188may provide a relatively accurate measurement of the temperature of the insulin or other medicament within the reservoir126.

Referring toFIGS. 2-7, an embodiment of the delivery mechanism132is depicted in a fluid delivery cycle sequence wherein fluid from the interior volume of the reservoir126is drawn into the bore220of the delivery mechanism132and dispensed from the dispense outlet port142.

Referring again toFIG. 2, a portion of the fluid reservoir cartridge112including a delivery mechanism132is shown in section as well as a portion of a drive mechanism150of an infusion pump. The disposable fluid cartridge112includes the delivery mechanism132which has a delivery mechanism body236and a bore220disposed in the delivery mechanism body236. The bore220, which may have a substantially round transverse cross section, includes a distal end238, a proximal end240disposed towards the drive mechanism150of the infusion pump114, an interior volume242, a reservoir inlet port138, a fluid dispense port142, a vent inlet port146and a vent outlet port148. The spool156, which may also have a substantially round transverse cross section, is slidingly disposed within the bore220and forms a collapsible first volume244and a vent second volume246between the bore220and an outside surface266of the spool156.

The collapsible first volume244of the delivery mechanism132may be positionable to overlap the reservoir inlet port138independent of an overlap of the fluid dispense port142. The collapsible first volume244may be formed between a first seal248around the spool156, a second seal250around the spool, an outer surface of the spool body between the first and second seal250and an interior surface252of the bore220between the first and second seal248and250. The first and second seals248and250are axially moveable relative to each other so as to increase a volume of the collapsible volume244when the first and second seals248and250are moved away from each other and decrease the collapsible volume244when the seals248and250are moved closer together.

The second seal250is disposed on a main section254of the spool156of the delivery mechanism132and moves in conjunction with movement of the rest of the spool. A proximal end196of the spool156is coupled to a ball portion194of a drive shaft190of the drive mechanism150of the pump device114. The drive mechanism150includes a rack and pinion192mechanism actuated by an electric motor152through a gear box154. As such, the second seal250moves or translates axially in step with axial translation of the spool156and drive shaft190. The first seal248, however, is disposed on a distal section258of the spool156which is axially displaceable with respect to the main section254of the spool156. The distal section of the spool156is coupled to the main section of the spool by an axial extension260that is mechanically captured by a cavity261in the main section254of the spool156. This configuration allows a predetermined amount of relative free axial movement between the distal section258of the spool and the nominal main section254of the spool156.

For some embodiments, a volume of a “bucket” of fluid dispensed by a complete and full dispense cycle of the spool156may be approximately equal to the cross section area of the bore220multiplied by the length of displacement of the captured axial extension of the spool156for the distal section258. The complete bucket of fluid may also be dispensed in smaller sub-volumes in increments as small as a resolution of the drive mechanism150allows. For some embodiments, a dispense volume or bucket defined by the complete collapsible volume244of the delivery mechanism132may be divided into about 10 to about 100 sub-volumes to be delivered or dispensed. In some cases, the maximum axial displacement between the distal section and main section of the spool may be about 0.01 inch to about 0.04 inch, more specifically, about 0.018 inch, to about 0.022 inch.

In use, once the reservoir cartridge112of the infusion pump system110has been installed or otherwise snapped into place in the slot122of the pump device114, the interior volume140of the collapsible reservoir126may then be filled with a desired fluid121for dispensing. In order to fill the reservoir126, the spool156may be translated by the drive mechanism150to a hard stop position226as shown inFIG. 2. In the hard stop position226the first seal248is disposed proximally of a relief port310, the relief port310being disposed in fluid communication between a distal end238of the bore220and the reservoir volume140. In the hard stop position, the first seal248is also disposed distally of the reservoir inlet port138. In the hard stop position, a distal end316of the spool156is contacting the distal end238of the bore220or a shoulder portion312of the distal end238of the bore220to prevent any further distal displacement of the spool156.

A reservoir fill port134is disposed on a top portion of the bore220substantially opposite the bore220of the reservoir inlet port138. With the spool156and seals248,250,262and264thereof so positioned, a patient may then obtain an amount of a desired fluid to be dispensed. In some cases, if the desired fluid to be dispensed is insulin or other suitable medicament, the patient127typically stores the insulin in a refrigerated glass container. The insulin is then accessed with a hypodermic needle222of a syringe device and drawn into an interior volume of the syringe (not shown). The tip of the hypodermic needle222of the syringe may then be pushed through a septum membrane136that seals the reservoir fill port134as shown and fluid is manually dispensed from the interior volume of the syringe, through the hypodermic needle222, through a bubble trap volume314in the bore220of the delivery mechanism132and into the interior volume140of the collapsible reservoir126of the cartridge112as shown by the arrow318inFIG. 2.

As discussed above with regard to other embodiments of the delivery mechanism132, the vented volume160of the cartridge112disposed between an outside surface162of the flexible membrane128of the collapsible reservoir126and an inside surface164of the rigid shell130may include or be in operative communication with a pressure sensor158. The pressure sensor158may be used to monitor the pressure within the vented volume160during the filling of the collapsible reservoir126. The controller168of the pump system114may be programmed with information regarding the fixed volume of the rigid shell130of the cartridge112and configured to calculate the volume of fluid loaded into the collapsible reservoir126based on the pressure rise within the rigid shell130upon filling of the collapsible reservoir126. The data regarding the volume of fluid loaded into the collapsible reservoir126may be stored and used to calculate and display data later in the use cycle such as fluid remaining in the collapsible reservoir126and the like.

Once the collapsible reservoir126contains a desired amount of a fluid121to be dispensed, a dispense cycle may be initiated by driving the spool156with the drive mechanism150based on commands from a controller168of the pump device to a position with the collapsible first volume244in communication with the reservoir inlet port138. The hard stop position depicted inFIG. 2is such a position. If the spool156has been driven to this hard stop position226in a distal direction from previous proximal position, the friction generated between the first seal248of the spool156and the inside surface252of the bore220will have collapsed the collapsible volume244of the delivery mechanism132with the first seal248and second seal250in a least axially separated state. In this state, the collapsible volume244has a minimum volume. Such a state of the delivery mechanism132is shown inFIG. 2. Once in this pre-fill position, the spool156may then be driven so as to axially separate the first and second seals248and250(and the main section254of the spool156and distal section258of the spool156) of the collapsible first volume244and draw fluid into the first volume244through the reservoir inlet port138from the reservoir126as shown by the arrow320inFIG. 3. As the fluid121is drawn into the collapsible volume244, the pressure within the vented volume160decreases. As previously discussed, this drop in pressure may be used in accordance with the ideal gas law to determine the amount of material taken from the collapsible reservoir126. An unexpected reading based on the magnitude of the translation of the main section254of the spool156may also be used to detect a failure of a portion of the delivery mechanism132in some cases.

The collapsible volume244of the delivery mechanism132may be completely filled by proximally retracting the main section254and second seal250of the spool156relative to the first seal248and distal section258of the spool156as shown by arrow322on spool156inFIG. 4. Once filled, the spool156may then be driven in a proximal direction as shown inFIG. 5wherein there are two seals248and250disposed in the bore220between the reservoir inlet port138and relief port310and the dispense port142. As shown by arrow323and arrow324inFIG. 5, both the main section254and distal section258of the spool156are proximally retracted together. The captured axial extension of the distal section258by the main section254pulls the distal section along without axial displacement between the main section254and distal section258of the spool156. The dispense port may be in fluid communication with a subcutaneous portion of a patient's body. The delivery mechanism132always includes at least one seal248or250disposed in the bore220between the reservoir volume140and material121disposed therein and the dispense port142in order to prevent a free flow condition wherein the material121in the reservoir126is in uninterrupted communication with the patient's body.

Once filled, the spool156and filled collapsible volume244may be proximally displaced with the drive mechanism150to a position with the collapsible first volume244in communication with the fluid dispense port142of the bore220as shown inFIG. 6. Once the spool156is positioned as depicted inFIG. 6, the main section of the spool156may then be axially driven in a distal direction by the drive mechanism150with the distal section258of the spool remaining stationary or substantially stationary. This axial distal movement of the main section254as indicated by arrow326on the spool156depicted inFIG. 7, serves to at least partially collapse the collapsible first volume244. Collapsing the first volume244of the delivery mechanism132dispenses fluid from the collapsible first volume244through the fluid dispense port142as shown by the arrow328inFIG. 7. Once all fluid from the collapsible first volume244is dispensed in this manner, additional cycles as described above can be completed to provide additional insulin to the patient. Further details on the operation and configuration of such an infusion pump can be found in U.S. Pat. No. 8,287,495 which is hereby incorporated by reference herein in its entirety.

According to an embodiment of the invention, the method400includes initiating a first blood glucose measurement402, receiving input data related to first blood glucose measurement404, presenting instructions to a patient to ingest a quantity of carbohydrates406, receiving an input from the patient indicating the quantity of carbohydrates ingested408, receiving input from the patient of a first time that the carbohydrates were ingested410, waiting a predetermined period of time412, initiating a second blood glucose measurement414, receiving input data related to the second blood glucose measurement416, calculating a change in blood glucose between the first blood glucose measurement and the second blood glucose measurement418, calculating a carbohydrate factor by dividing the change in blood glucose by the quantity of carbohydrates ingested420, saving the carbohydrate factor in memory422, receiving input from the patient as to quantity of carbohydrates to be ingested at a meal424, utilizing the carbohydrate factor in memory to calculate an insulin dose to be infused prior to the meal426and sending a signal to an infusion device controller to infuse the insulin dose428.

FIG. 12depicts a graph of blood glucose versus time that relates to calculation of a carbohydrate factor as described herein. Up until time tc, the patient's blood glucose is stable at a first level. At time tc, the carbohydrates ingested by the user begin raising the user's blood glucose level until it is done increasing and/or levels off at a second, higher level at time ts. The change in blood glucose between the time levels, ΔBG, can be used along with the known amount of carbohydrates consumed to determine the individual's carbohydrate factor.

Alternately, the taking of blood glucose level measurements can be based on waiting a minimum amount of time and alerting the patient to take a second blood glucose level measurement at a time when data from the CGM indicates that the rate of change of blood glucose level has decreased to below a preselected threshold.

According to another embodiment of the invention, the invention may further include presenting instructions to the patient to initiate the first blood glucose measurement and receiving the input data related to the first blood glucose measurement from the patient430. The instructions may be presented visually or verbally (such as by voice emulation software). For example, instructions may be presented via interface116.

According to another embodiment of the invention, the invention may include receiving the input data related to the first blood glucose measurement from a continuous glucose monitoring system434such as those described above and in documents incorporated by reference herein.

According to another embodiment of the invention, the invention may include presenting instructions to the patient at the second time to take a second blood glucose measurement436and receiving input data from the patient related to the second blood glucose measurement438.

According to another embodiment of the invention, the method may include receiving the input data related to the second blood glucose measurement from a continuous glucose monitoring system440.

According to another embodiment of the invention, the invention may include receiving the input data from a continuous glucose monitoring system that identifies a peak of a postprandial rise in blood glucose and instructing the patient to take a blood glucose measurement at that time442.

According to another embodiment of the invention, the method may include receiving the input data from a continuous glucose monitoring system that identifies when blood glucose level has flattened or stabilized after a postprandial rise in blood glucose and instructing the patient to take a blood glucose measurement at that time444.

According to another embodiment of the invention, the invention includes a computer implemented method of determining an insulin sensitivity factor utilizing an insulin pump445. The computer may include an onboard controller or processor incorporated into an ambulatory infusion device as well as a remote device that is in communication with the onboard controller or processor.

The method may include initiating a first blood glucose measurement446, receiving input data related to the first blood glucose measurement448, initiating an infusion of a known pre-selected quantity of insulin450, recording a time of the infusion of the known quantity of insulin452, waiting a predetermined length of time454, initiating a second blood glucose measurement456, receiving input data related to the second blood glucose measurement458, calculating a change in blood glucose between the first blood glucose measurement and the second blood glucose measurement460, calculating an insulin sensitivity factor by dividing the change in blood glucose by the quantity of insulin infused462, saving the insulin sensitivity factor in memory464, receiving input identifying current blood glucose level and target blood glucose level466, utilizing the insulin sensitivity factor in memory to calculate an insulin dose to be infused468and sending a signal to an insulin pump to infuse the insulin dose calculated470.

FIG. 11depicts a graph of blood glucose versus time that relates to calculation of an insulin sensitivity factor as described herein. The user takes a known quantity of insulin. Up until time ti, the patient's blood glucose is stable at a first level. At time ti, the insulin begins dropping the user's blood glucose level until it is done decreasing and/or levels off at a second, lower level at time ts. The change in blood glucose between the time levels, ΔBG, can be used along with the known amount of insulin ingested to determine the individual's insulin sensitivity factor.

An embodiment of the invention may further include initiating the first blood glucose measurement by presenting instructions, for example, to the patient to perform the measurement472.

According to another embodiment of the invention, the invention may include initiating the second blood glucose measurement based on input from a continuous glucose monitoring system that identifies when blood glucose levels have flattened or stabilized after the infusion of insulin and instructing, for example, the patient to take a blood glucose measurement at that time474.

Alternately, the taking of blood glucose level measurements can be based on waiting a minimum amount of time and alerting the patient to take a second blood glucose level measurement at a time when data from the CGM indicates that the rate of change of blood glucose level has decreased to below a preselected threshold. According to another embodiment of the invention, the invention may include initiating the first blood glucose measurement based on input from a continuous glucose monitoring system that identifies that the blood glucose level is flat or stable and instructing, for example, the patient to take a blood glucose measurement at that time476.

According to another embodiment of the invention, the invention may include initiating the second blood glucose measurement by presenting instructions, for example, to the patient to perform the measurement478.

According to another embodiment of the invention, the invention includes an ambulatory infusion device including a controller programmed with an algorithm to cause the insulin pump to execute a method as discussed above.

According to another embodiment, the invention includes determining the insulin action time. After a bolus of insulin is infused, blood glucose level will decrease. This reduction is observable with CGM. Accordingly this method is well suited to be performed along with the insulin sensitivity factor determination discussed herein. After a bolus of insulin is infused the time for a selected reduction in blood glucose level to be achieved is recorded. This determines the insulin action time.

Referring toFIG. 10, a method of determining insulin action time, according to an embodiment of the invention includes infusing a bolus of insulin482; waiting a minimum period of time484; receiving an input from the CGM that the blood glucose level has reached a level or stable state; identifying the insulin action time by noting the time between infusion of insulin and the achieving of the level or stable state486. Alternately, the fall in blood glucose level according to the CGM can be extrapolated to an inflection point when the blood glucose level decline is most rapid488. The time between infusion of the insulin and the inflection can be taken as the insulin action time490.

FIG. 13depicts a graph of blood glucose versus time that relates to calculation of an insulin sensitivity factor as described herein. Up until time ti, the patient's blood glucose is stable at a first level. At time ti, the user takes a known quantity of insulin. In response to the insulin, the user's blood glucose level drops until it is done decreasing and/or levels off at a second, lower level at time ts. The time that the blood glucose level takes to go from the first level to the second level between tiand ts, Δt, can be used to determine the insulin action time.

The present invention may be embodied in other specific forms without departing from the spirit of the essential attributes thereof; therefore, the illustrated embodiments should be considered in all respects as illustrative and not restrictive, reference being made to the appended claims rather than to the foregoing description to indicate the scope of the invention.