Insulin regimen for delivering insulin during fasting periods

Abstract

A method of insulin management implemented by an insulin delivery system including an insulin delivery device (130) is provided, the method including detecting (201) an initiation activity associated with preparation for use of an insulin delivery device (130) in the form of an automatic insulin delivery device wearable on a user's body during a fasting period within an overall time period, and initiating (202) automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements received periodically during the fasting period.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 63 / 332,001, entitled “INSULIN MANAGEMENT FOR DELIVERING INSULIN DURING A FASTING PERIOD,” filed April 18, 2022, the entire contents of which are incorporated herein by reference.

[0002] This disclosure relates to insulin management. In particular, this disclosure relates to insulin management for delivering insulin during fasting periods. This disclosure also relates to the coordination of such insulin management with other therapeutic modalities. This disclosure also relates to glucagon management using management systems, devices, and methods comparable to those described for insulin. [Background technology]

[0003] Currently, a number of diabetes management methods are used in the form of different insulin therapies. One insulin therapy is continuous subcutaneous insulin therapy provided by a continuous use insulin pump. Known insulin pumps provide continuous subcutaneous insulin infusion (CSII) by attaching a reservoir of insulin inside the pump to the user's body for delivery via a cannula for subcutaneous insertion. Insulin pumps may have a controller built into the pump body or may have a separate controller that controls the delivery of insulin. Automatic insulin delivery (AID) is provided by using a pump in conjunction with blood glucose monitoring from a device worn on the body that periodically measures blood glucose readings.

[0004] Known insulin pumps are worn continuously throughout the day and night, so that the insulin pump delivers a single type of rapid-acting insulin as a combination of basal insulin and bolus insulin. Basal insulin is the background insulin required for a person to maintain a target blood glucose level, not counting insulin administered or determined to counteract blood glucose rises caused by ingested food. When provided by CSII, such rapid-acting basal insulin, i.e. background insulin, is conventionally provided at a pre-set and / or default basal rate and delivered to the user in a pre-set and / or default basal pattern. For example, 2 units per hour are delivered at a continuous rate or in a series of pre-defined doses that are not calculated or adjusted based on real-time blood glucose levels. In pumps, the basal rate may vary over time, but is generally stable and accounts for about 50% of the total insulin requirement of a type 1 diabetes patient. In contrast to CSII basal insulin and / or background insulin, CSII prandial bolus insulin doses are infused by the pump to cover ingested food or to correct high blood glucose levels. Known insulin pumps require accurate estimation of numerous user-specific variables that must be used to ensure safe and effective insulin delivery over a 24-hour cycle. However, accurate estimations can be difficult to determine and may require adjustments over time. Continuously used insulin pumps are costly and inconvenient for patients because they must be worn continuously on the body day and night.

[0005] Another common method of diabetes management is provided by conventional insulin therapy or multiple daily injections (MDI) to provide flexible insulin therapy. Various regimes are known, which may include bolus insulin (or prandial insulin) provided by injecting a meal-proportional amount of fast-acting insulin before each meal, and basal insulin provided by injecting long-acting insulin once or twice a day. Insulin pen solutions to provide MDI are used by the majority of patients and generally offer patients lower costs and greater flexibility compared to CSII. However, the use of insulin pens suffers from the need to be awake to use them, along with syringes and inhalable solutions. This results in reduced rest time and / or poor glycemic control, especially during the night when patients want to rest undisturbed and wake up at a healthy target blood glucose range.

[0006] Typically, diabetic patients use a single solution for diabetes management therapy, at least in part, due to the complexity of coordinating different therapies and / or the associated risks. Some risks include unrecognized insulin stacking and misinformed insulin delivery. Each available diabetes management method has a unique set of behavioral requirements, costs, and potential clinical outcomes. No solution meets the favorable behavioral, cost, and clinical outcome requirements for all diabetic patients. Patients typically follow their physician's recommendations for a particular method and adapt their lifestyle to that solution.

[0007] The foregoing discussion of the background of the invention is intended only to facilitate an understanding of the invention. It should be understood that this discussion is not an admission that any of the materials referred to were part of the common general knowledge in the art at the priority date of this application. Summary of the Invention

[0008] Aspects of the invention are defined in the appended claims. Various aspects of the disclosure are defined in the following paragraphs, and one or more combinations of any feature may be combined with different aspects. According to one aspect of the disclosure, there is provided an insulin management method implemented by an insulin delivery system including an insulin delivery device, the method comprising: detecting an initiation activity associated with preparation for use of an insulin delivery device in the form of an automatic insulin delivery device wearable on a user's body for the duration of a fasting period within an overall period; and initiating automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements periodically received during the fasting period. The insulin delivery system may be integrated within the insulin delivery device with a controller that performs the method steps. Alternatively, the insulin delivery system may include one or more computing systems that perform one or more method steps remotely.

[0009] The method may include detecting a termination activity associated with the end of use of the insulin delivery device and terminating the automatic delivery of an insulin correction bolus dose. The initiation activity may have a primary function other than initiating the automatic delivery of insulin from the insulin delivery device, thereby simultaneously reusing as an instruction to initiate the automatic delivery of insulin from the insulin delivery device. The initiation activity may include one or more of the following: the arrival of a preset time of day; the removal of the insulin delivery device from a charger; and the attachment of a disposable insulin supply unit to the insulin delivery device. The initiation activity may include one or more of the following: attachment of the insulin delivery device to a user; the removal of an applicator of the insulin delivery device from the insulin delivery device; and a verbal instruction or selection by the user indicating a desire to initiate the automatic delivery of insulin. The initiation activity may include at least one or more of: proximity or pairing of a controller of the insulin delivery device to a user computing device on which a user application associated with the insulin delivery device is installed; proximity or pairing of a controller of the insulin delivery device to a smart insulin pen; proximity or pairing of a controller of the insulin delivery device to a blood glucose monitor; receipt of a blood glucose monitor measurement; a fill level of an insulin reservoir of the disposable insulin supply unit indicating an insulin reservoir sufficiently filled to initiate automatic delivery of insulin; and movement of a plunger of an insulin reservoir of the disposable insulin supply unit indicating filling of the insulin reservoir. The method may include receiving from the paired user computing device total daily basal dose information received from a non-fasting insulin management modality for a defined period of time prior to the fasting period for use in determining a correction bolus dose. Initiating the automatic delivery of insulin may include priming the delivery device so that it is ready to deliver insulin.

[0010] The insulin delivery device may refrain from administering basal insulin at a preset or default rate or in a preset or default pattern. The method may deliver insulin in the form of a correction bolus dose in response to the received blood glucose measurement, the correction bolus dose being compensated by a determined insulin onboard. The method may deliver at least a first correction bolus dose compensated by a determined insulin onboard set equal to an assumed insulin onboard determined based on an assumed external dose calculated to correct the user's initial blood glucose value to the target blood glucose value. The method may include calculating the correction bolus dose by comparing the evaluated blood glucose measurement to the target blood glucose value to obtain a difference, adjusting the difference by a user insulin sensitivity factor to obtain a resulting dose, and compensating the resulting dose by the determined insulin onboard.

[0011] The determined insulin onboard may include the expected insulin onboard and the known delivered insulin from the delivery device. The correction bolus dose may be based on the user's insulin sensitivity factor derived from the total daily basal dose information used during the defined period before the fasting period. The total daily basal dose information is the average total number of basal dose units administered during the entire period.

[0012] The correction bolus dose may be calculated based on at least one of a fixed target blood glucose value for all users and a fixed insulin action time for all users. The method may limit the correction bolus dose to a defined maximum dose per correction bolus dose such that the correction bolus dose is a fraction of the total correction bolus dose.

[0013] The evaluated blood glucose measurements may be evaluated using a variety of different methods that may be used individually or in combination. The evaluated blood glucose measurements may be evaluated at least in part by smoothing the received blood glucose measurements with a low pass filter to reduce the effects of noise and / or rapid perturbations to obtain a blood glucose value. The evaluated blood glucose measurements may be evaluated at least in part by retaining received blood glucose measurements that are less than a rolling average of a predetermined number of previous received blood glucose measurements and retaining the rolling average for the remaining received blood glucose measurements. The evaluated blood glucose measurements may be evaluated at least in part by projecting forward a downward trend of the received blood glucose measurements and adding the downward trend to the blood glucose measurements used for dose calculation. The downward trend may be determined based at least in part on a maximum negative slope between any received blood glucose measurement and a reference blood glucose measurement within a predetermined time frame. The evaluated blood glucose measurements may be evaluated at least in part by fitting the received blood glucose measurements within a predetermined time frame to a trend having a median slope (or other average slope) selected from a plurality of regression fitting slopes for different rolling subsets of the received blood glucose measurements within the predetermined time frame. The evaluated blood glucose measurements may be evaluated at least in part by filtering the received blood glucose measurements, the filtering including, for increasing received blood glucose measurements, imposing progressively increasing limits on how much each subsequent received blood glucose measurement may increase compared to the previous received blood glucose measurement, and, for decreasing received blood glucose measurements, amplifying how much each subsequent received blood glucose measurement may decrease compared to the previous received blood glucose measurement.

[0014] The method may include dividing the correction dose into delivery portions having a maximum delivery rate for a maximum amount of insulin delivered over a given period of time. The method may include determining an initial user insulin sensitivity factor for the fasting period based on received total daily basal dose information. The method may include adjusting the initial user insulin sensitivity factor by a sensitivity safety factor configured to bias the calculation of periodic correction bolus doses toward smaller insulin doses. Adjusting the target blood glucose value by the target safety factor may be based at least in part on the difference between the received blood glucose measurements and the target blood glucose value. Adjusting the calculated correction bolus dose by the overall safety factor may be configured to limit the calculated bolus dose to a maximum delivery rate of insulin delivered over the period between deliveries of the correction bolus doses. The target blood glucose value may be time-varying to decrease over time during the fasting period, and the rate of decrease of the target blood glucose value over time is determined based on an assumption that the blood glucose level is decreasing due to existing externally administered insulin administered prior to the fasting period. The user insulin sensitivity factor may be initially set to a predetermined value and adjusted over time based at least in part on the difference between the received blood glucose measurements and the expected blood glucose value. Evaluating the blood glucose measurements may include filtering for increasing blood glucose values ​​and may not include filtering for decreasing blood glucose values. Evaluating the blood glucose measurements may include adjusting for long-term downward trends over a period of several hours during the fasting period. Delivering at least a portion of the correction dose may include delivering an initial zero dose.

[0015] The method may include delivering insulin in the form of a correction bolus dose of insulin in response to the received blood glucose measurements from an insulin delivery device during fasting periods of the entire period. The insulin delivery device refrains from administering basal insulin at a preset or default rate or pattern, and insulin is received by the user during non-fasting periods of the entire period from a non-fasting insulin management modality, the non-fasting insulin management modality providing at least one of a basal dose of insulin and a bolus dose of insulin. A single non-fasting period and a single fasting period may be provided during the entire period, the single fasting period being a major sleep portion of the user's normal daily routine.

[0016] The method may include providing the user with an adjustment between a non-fasting insulin control regimen and a delivery device. The adjustment may include providing the user with one or more recommendations regarding the non-fasting insulin control regimen and / or the delivery device. The adjustment may include providing the user with a prediction regarding a hypothetical use of the non-fasting insulin control regimen and / or the delivery device. The one or more predictions include one or more of a prediction of the user's waking blood glucose level if the user utilizes the delivery device for a recommended time frame overnight; a prediction of the user's waking blood glucose level if the user adjusts the daily basal insulin dose to a different value from the current value; and a prediction of the user's waking blood glucose level if the user does not utilize the delivery device overnight.

[0017] The adjusting may include adjusting a fasting ending procedure for the user, which includes receiving information regarding a fasting ending meal requiring a meal bolus; splitting the fasting ending meal bolus into a first portion equal to the remaining insulin in the delivery device at the end of the fasting period and a second portion to be delivered to the user utilizing a non-fasting insulin management modality in a non-fasting period immediately following the fasting period; and providing instructions to the user for delivering the second portion of the fasting ending meal bolus dose from the non-fasting insulin management modality.

[0018] According to one aspect of the disclosure, an insulin management system for an insulin delivery device in the form of an automatic insulin delivery device wearable on a user's body for the duration of a fasting period within an overall period is provided, the system comprising an initiation component configured to detect an initiation activity associated with preparation for use of the insulin delivery device, and a delivery component configured to initiate automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements received periodically during the fasting period. The system may include an end detection component configured to detect an end activity associated with termination of use of the insulin delivery device. The initiation activity may have a primary function other than initiating automatic delivery of insulin from the insulin delivery device, thereby simultaneously being reused as an indication to initiate automatic delivery of insulin from the insulin delivery device.

[0019] The initiation component may be configured to detect one or more of the following as the initiating activity: the arrival of a preset time of day; the removal of the insulin delivery device from the charger; and the attachment of a disposable insulin supply unit to the insulin delivery device. The initiation component may be configured to detect one or more of the following as the initiating activity: the attachment of the insulin delivery device to a user; the removal of an applicator of the insulin delivery device from the insulin delivery device; and a verbal instruction or selection by the user indicating a desire to initiate automatic insulin delivery. The initiation component may be configured to detect one or more of the following as the initiating activity: the proximity or pairing of a controller of the insulin delivery device to a user computing device having a user application associated with the insulin delivery device installed; the proximity or pairing of a controller of the insulin delivery device to a smart insulin pen; the proximity or pairing of a controller of the insulin delivery device to a blood glucose monitor; the receipt of a blood glucose monitor measurement; a fill level of an insulin reservoir of the disposable insulin supply unit indicating a sufficiently filled insulin reservoir to initiate automatic insulin delivery; and a movement of a plunger of an insulin reservoir of the disposable insulin supply unit indicating filling of the insulin reservoir. The wake-up component may be configured to detect receipt from a paired user computing device of total daily basal dose information received from a non-fasting insulin management modality for a defined period prior to a fasting period for use in determining a correction bolus dose.

[0020] The delivery component may be configured to prime the delivery device so that it is ready to deliver insulin. The delivery component may include a processor and a memory configured to provide non-transitory computer readable program instructions to the processor to perform the functions of the component.

[0021] The system may further include a mobile user computing device comprising a processor and a memory configured to provide non-transitory computer readable program instructions to the processor to perform the functions of the following components: a basal insulin input component configured to request a value from the user of total daily basal dose information used for a defined period of time prior to the fasting period; and a controller pairing component configured to pair the mobile user computing device to a controller of the delivery device.

[0022] According to one aspect of the disclosure, an automatic insulin delivery device is provided that is wearable on a user's body for the duration of a fasting period, the delivery device comprising: a durable portion including a delivery component configured to control delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements (the delivery component comprises an activation component configured to detect an initiation activity associated with preparation for use of the insulin delivery device; and a delivery component configured to initiate automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements received periodically during the fasting period), and a disposable portion including a reservoir configured to contain insulin and configured to automatically deliver the correction bolus dose to the user. The reservoir may be configured to be fillable from a non-fasting insulin injection device used during a non-fasting period preceding the fasting period.

[0023] According to one aspect of the disclosure, a computer-implemented method is provided for managing delivery of insulin during fasting periods from a delivery device in the form of a wearable automatic insulin delivery device worn during the fasting period, the computer-implemented method being executed by a computing application provided on a mobile user computing device, the computer-implemented method including requesting a value from a user of total daily basal dose information used for a defined period prior to the fasting period; pairing the mobile user computing device with a controller of the delivery device, the controller detecting an initiation activity associated with preparing to use the insulin delivery device, thereby initiating automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements periodically received during the fasting period; and transmitting and receiving information to and from the controller of the delivery device during the fasting period. The value from the user of total daily basal dose information may include a normal number of units of basal insulin received from a non-fasting form of insulin therapy.

[0024] The method may include pairing the mobile user computing device to a blood glucose monitor to enable transfer of blood glucose measurements to a delivery device via the mobile user computing device. The method may include providing the user with a display of a session history of information regarding the fasting period. The method may include providing the user with user training in the use of the delivery device. The method may include coordinating a fasting-ending procedure for the user including splitting a fasting-ending meal bolus into a first portion equal to remaining insulin in the delivery device at the end of the fasting period and a second portion delivered to the user utilizing a delivery method other than the delivery device during a non-fasting period immediately following the fasting period.

[0025] According to one aspect of the disclosure, there is provided a method of insulin management using an insulin delivery device in the form of an automatic insulin delivery device wearable on a user's body for the duration of a fasting period within an overall period, the method including performing an initiation activity associated with preparing the insulin delivery device for use; and receiving an automatic delivery of insulin in the form of a correction bolus dose in response to received blood glucose measurements received periodically during the fasting period. The method may provide at least one of an insulin sensitivity factor and total daily basal dose information to the insulin delivery device for use by the user for a defined period prior to the fasting period.

[0026] The method may include performing a termination activity associated with ending use of the insulin delivery device. Performing the initiation activity may include one or more of: removing the insulin delivery device from a charger; and attaching a disposable insulin supply unit to the insulin delivery device. Performing the initiation activity includes one or more of: attaching the insulin delivery device to a user; removing an applicator of the insulin delivery device from the insulin delivery device; and a verbal instruction or selection by the user indicating a desire to begin automatic delivery of insulin. Performing the initiation activity includes at least one of: pairing a controller of the insulin delivery device to a user computing device having a user application associated with the insulin delivery device installed; pairing a controller of the insulin delivery device with a smart insulin pen; filling an insulin reservoir of the disposable insulin supply unit; and causing a movement of a plunger of the insulin reservoir indicating filling of the insulin reservoir.

[0027] Features and elements of one aspect of the present disclosure may be included in other aspects of the present disclosure to form different embodiments of systems, devices, methods, and computer program products.

[0028] Embodiments of the present invention are now described, by way of example only, with reference to the accompanying drawings, in which features or elements of the described embodiments may be used in other embodiments within the scope of the present disclosure. [Brief description of the drawings]

[0029] [Figure 1A] FIG. 1 is a schematic diagram illustrating an exemplary embodiment of an overall treatment configuration in which the present disclosure may be implemented. [Figure 1B] 1 is a flow chart of an exemplary embodiment of an insulin management method according to one aspect of the present disclosure. [Figure 1C] 1 illustrates the overall period during which two different modes of insulin management may be used in a non-overlapping manner, according to some exemplary embodiments. [Figure 2A] 1 is a flow chart of an exemplary embodiment of a method for controlling insulin delivery according to aspects of the present disclosure. [Figure 2B] 1 is a flow chart of an exemplary embodiment of a method for controlling insulin delivery according to aspects of the present disclosure. [Figure 2C] 1 is a flow chart of an exemplary embodiment of a method for controlling insulin delivery according to aspects of the present disclosure. [Figure 3A] 1 is a graph illustrating an exemplary method of processing blood glucose measurements according to an aspect of the present disclosure. [Figure 3B] 1 is a graph illustrating an exemplary method of processing blood glucose measurements according to an aspect of the present disclosure. [Figure 3C] 1 is a graph illustrating an exemplary method of processing blood glucose measurements according to an aspect of the present disclosure. [Figure 3D] 1 is a graph illustrating an exemplary method of processing blood glucose measurements according to an aspect of the present disclosure. [Figure 4] FIG. 1 is a block diagram of an exemplary embodiment of a system for controlling insulin delivery according to one aspect of the present disclosure. [Figure 5A] 1 is a flow chart of an exemplary embodiment of a method of using a delivery device to control the delivery of insulin, according to aspects of the present disclosure. [Figure 5B]1 is a flow chart of an exemplary embodiment of a method of using a delivery device to control the delivery of insulin, according to aspects of the present disclosure. [Figure 5C] 1 is a flow chart of an exemplary embodiment of a method of using a delivery device to control the delivery of insulin, according to aspects of the present disclosure. [Figure 6A] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6B] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6C] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6D] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6E] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6F] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6G] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6H] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6I] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6J] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6K] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6L] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 6M] 1A-1C are a series of schematic diagrams illustrating an exemplary embodiment of a delivery device according to an aspect of the present disclosure. [Figure 7A]1 is a flow chart of an exemplary embodiment of a method provided by a computer application for interacting with a delivery device to control the delivery of insulin according to an aspect of the present disclosure. [Figure 7B] 1 is a flow chart of an exemplary embodiment of a method provided by a computer application for interacting with a delivery device to control the delivery of insulin according to an aspect of the present disclosure. [Figure 7C] 1 is a swim lane flowchart illustrating an exemplary use case for controlling insulin delivery during fasting periods and / or coordinating insulin management of such fasting periods with another therapeutic modality utilized during non-fasting periods, according to some exemplary aspects of the present disclosure. [Figure 8] FIG. 1 is a block diagram of an exemplary embodiment of a system for providing a computer application for interacting with a delivery device to control the delivery of insulin, according to one aspect of the present disclosure. [Figure 9] FIG. 1 illustrates an example of a computing device capable of implementing various aspects of the present disclosure. [Figure 10A] 1 is a graph illustrating an exemplary patient storyline during a method of controlling insulin delivery according to one aspect of the present disclosure. [Figure 10B] 1 is a graph illustrating an exemplary patient storyline during a method of controlling insulin delivery according to one aspect of the present disclosure. [Figure 10C] 1 is a graph illustrating an exemplary patient storyline during a method of controlling insulin delivery according to one aspect of the present disclosure. [Figure 10D] 1 is a graph illustrating an exemplary patient storyline during a method of controlling insulin delivery according to one aspect of the present disclosure. [Figure 10E] 1 is a graph illustrating an exemplary patient storyline during a method of controlling insulin delivery according to one aspect of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] The present disclosure describes a drug management method, system, and delivery device for delivering drugs (e.g., insulin and / or glucagon) from a wearable automated drug delivery device. The drug delivery device may be used during fasting periods, e.g., less than about 12 hours, and the wearable automated drug delivery device is configured and intended to be utilized only during fasting periods. When the automated drug delivery device is configured to deliver insulin, the device may be considered an automatic insulin delivery device, i.e., an AID device. Several embodiments are described below in the context of insulin delivery. However, the disclosure is not so limited and also contemplates similar or identical embodiments configured to deliver any other drug that affects blood glucose levels, e.g., glucagon, to increase blood glucose concentrations when blood glucose levels fall below a predetermined level, e.g., during sleep, or during exercise or otherwise energetically demanding physical activity. In such an embodiment for delivering glucagon, the fasting period may be a period of exercise or activity.

[0031] By definition, diabetic patients are unable to adequately regulate blood glucose levels due to a virtually complete lack of endogenous insulin secretion (type 1 diabetic patients) or insufficient endogenous insulin secretion (type 2 diabetic patients). Thus, diabetic patients essentially require insulin management procedures at all times to maintain blood glucose levels within a desired target range. Thus, managing automated insulin delivery only during daily fasting periods, e.g., while sleeping, presents several unique challenges.

[0032] First, the user must integrate a supplemental method of insulin administration outside of fasting periods (e.g., multiple insulin injections each day to cover basal and meal bolus requirements), but tracking insulin administration between multiple insulin delivery modes can be cumbersome for the user. Second, because there are two transitions each day between the supplemental non-fasting mode of insulin delivery and the automatic fasting mode of insulin delivery, it may be desirable to engage and disengage the automatic fasting mode at appropriate times (e.g., engage at the start of the fasting period and disengage at the end of the fasting period), but natural variations in the timing and duration of these fasting or sleep periods make it difficult to determine the appropriate times for engagement and disengagement from day to day. Third, since automatic insulin dosing only during fasting periods generally occurs while the user is sleeping and fasting, it is very important to prevent overdelivery of insulin and resulting hypoglycemic events during fasting periods, which requires accurate calculation of the insulin already in the user's system at the start of the fasting period, but users are not always very good at accurately estimating or calculating the actual insulin on board (IOB), especially as the time since the last manual insulin injection increases and the insulin already in the body is gradually metabolized by the body.

[0033] Furthermore, the majority of diabetes (type 1 and type 2) patients continue to rely on multiple daily injection (MDI) therapy for diabetes management. Unfortunately, while there are many valid reasons why patients may choose MDI therapy, nighttime control remains a missing component (compared to automated insulin delivery (AID)). Until now, nighttime-only AID use has not been practical or even achievable because setting up a conventional insulin pump therapy (especially with an AID) is a very complicated process that requires significant ramp-up time. Furthermore, continuous subcutaneous insulin infusion (CSII) is designed to inject basal and / or background insulin at a predefined rate, not for use with exogenous basal insulin. For example, conventional AIDs include delivery of basal and / or background insulin at predefined, pre-set, and / or default rates that are not calculated or adjusted in real-time (or substantially in real-time) based on real-time (or substantially in real-time) blood glucose levels. Such basal, baseline, and / or background insulin infusions are inconsistent with daily basal pen doses and are not practical for a twice-daily transition. Additionally, the transition from an AID to a pen and back often leaves some active insulin in the body during the switch, which current systems cannot handle.

[0034] Aspects of the present disclosure, as described below, address each of these potential problems, among any number of other potential problems, including through methods, devices, and systems for integrating supplemental methods of insulin administration outside of fasting periods; methods, devices, and systems for controlling insulin administration during fasting periods using events indicating the start and / or end of fasting periods; and / or methods, devices, and systems for automatic calculation and delivery of correction doses of insulin during fasting periods, thereby providing simplified, safe, and effective management of time in range (TIR) ​​during prolonged fasting periods. While embodiments described herein may be directed to one or more of the problems discussed above, the present disclosure contemplates utilizing and / or incorporating any one or more features from any one or more of the embodiments, together with any one or more features from any other one or more of the embodiments described herein.

[0035] The methods described herein solve the transition complexity problem for episodic use, among other issues, by providing a simplified system that allows for easy transition between two different diabetes management modalities. In one implementation, the systems and methods described herein allow seamless, intermittent, episodic use of MDI for basal insulin during the daytime cycle and AID during the nighttime cycle, thereby allowing the user to benefit from lower costs, greater flexibility, and improved clinical outcomes. For example, diabetes management therapy with daily basal and daytime bolusing is achieved by MDI therapy, while overnight glycemic control is achieved by a short-term worn insulin pump. The short-term worn insulin pump provides AID control during fasting, allowing the user to sleep soundly and wake up in the target glycemic range without having to wake up for correction boluses.

[0036] Embodiments of insulin management methods, systems, and delivery devices are described for delivering insulin during fasting periods from a wearable automatic insulin delivery (AID) device designed and intended to be worn only during fasting periods. A delivery algorithm is provided for automatic calculation and delivery of correction doses. This provides simplified, safe, and effective management of time in range (TIR) ​​during fasting periods, for example, less than about 12 hours. The fasting period can be the intended fasting period. The fasting period can be overnight or any period, requiring only correction boluses in an additive sense to any existing basal and meal bolus therapy, which can still be "on board" throughout the fasting period. The fasting period can be the period during the daily cycle when the user is asleep. For most users, the fasting period can be an overnight period between 6 and 12 hours, during which the user typically lies in a resting position and does not eat during this time.

[0037] The described insulin management embodiment is based on the user receiving insulin from the non-fasting insulin management modality during the non-fasting period of the total period. The non-fasting period may be the time when the user is awake in the daily cycle. However, the non-fasting period may also include short periods of sleep, such as daytime naps. The fasting period and the non-fasting period together may form a total period, such as a 24-hour period, or other regular total period for users with non-daily cycles (e.g., shift workers). The non-fasting insulin management modality provides a basal dose of insulin and a bolus dose of insulin. The total period may be 24 hours, as this is the normal daily routine for the user. However, the total period may be adjusted for users who require a different schedule, such as shift work. The non-fasting insulin management modality and the fasting period insulin delivery device are intended to be used supplementarily, without overlapping use. For example, typically, no doses are given from the non-fasting insulin management modality during the wearing of the fasting period insulin delivery device. However, the doses applied by the two therapies may remain in the body as insulin on-board during the other therapy.

[0038] An embodiment of the insulin management method uses a fasting insulin delivery device in the form of an automatic insulin delivery device wearable on the user's body for the duration of the fasting period to deliver insulin from the fasting insulin delivery device during the fasting period of the entire period. The fasting insulin delivery device gradually delivers fast-acting insulin over the fasting period to correct high blood glucose measurements during the fasting period, these are called correction bolus doses. In response to the received blood glucose measurements, the fasting insulin delivery device delivers correction bolus doses when compared to the target blood glucose value. The fasting insulin delivery device refrains from administering a background basal dose, since a basal dose is assumed to be taken during the non-fasting portion from the non-fasting insulin management modality. In the non-fasting insulin management modality in the form of an injection, the basal dose can be provided by a long-acting insulin taken once or twice a day.

[0039] The wearable AID device may be in the form of a pump that is worn only during fasting, for example, a pump that is worn only at night. Examples of suitable pumps are provided in PCT Patent Application No. PCT / IB2021 / 060206 (International Publication No. WO 2022 / 097057), the contents of which are incorporated herein by reference. A fasting-worn pump delivers fast-acting insulin in small correction doses. Since there are no meals to cover during the fasting period, small correction doses can be safely administered gradually to keep the user within the target range. Various safeguards are provided in the delivery algorithm to ensure that there is no over-correction. Unlike a continuously worn pump, a basal dose is not administered by a fasting-worn pump, so the basal dose cannot be turned off to accommodate over-correction.

[0040] The described embodiment of the delivery algorithm is designed to perform only small correction boluses while the user is fasting for a limited period of time. No meal bolus or basal rate delivery is provided. The calculation of the delivery algorithm may be simplified and based on the maximum amount of insulin in the pump's reservoir that can be delivered at the maximum dose per calculation period. This is informed by the user's periodic blood glucose measurements to allow safe and effective delivery of correction boluses of insulin without the need for information about basal rates, carbohydrate ratios, or insulin action time. Correction boluses correct for changes in blood glucose levels that are not corrected by basal or bolus insulin doses administered during non-fasting periods (e.g., during the day) and vary based on daily activity, food intake, and overall health.

[0041] In the following description, various embodiments of methods, systems, and devices are described with reference to the drawings. Individual features of each described embodiment may be used in other embodiments. Where a method is described in a flowchart and features are described by steps of the flowchart, the following may apply: One or more of the described individual features of the method may be achieved by a single step. Individual features described as a single method step may be performed by multiple steps. Some of the described individual features may be duplicated. The order of the method features may also be changed. It will be understood that in a computer-implemented method, each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, may be implemented by computer-readable program instructions.

[0042] FIG. 1A is a schematic diagram showing an exemplary embodiment of an overall treatment setup (100) in which the described insulin management method of a fasting-worn delivery device (130) is used. A user (101) is shown in a sleeping position with a continuous glucose monitor (CGM) (105) attached to his body (102). The CGM (105) can obtain and transmit blood glucose measurements to a base station or a mobile computing device (120). The user (101) may use an insulin pen (110), such as a smart pen, or other MDI method during the day, i.e., during the non-fasting period (162) of FIG. 1C. The user (101) may use a mobile computing device (120) to manage insulin usage. The mobile computing device (120) may be a dedicated computing device for cooperation with the delivery device (130). Alternatively, the mobile computing device (120) may be a general-purpose computing device, such as a smartphone. In one embodiment, a known application (121) provided by the mobile computing device (120) can receive blood glucose measurements from the CGM (105) and can manage MDI therapy during the day, for example by interacting with an insulin pen (110).

[0043] The described configuration provides a fasting-worn delivery device (130) that is attached to the user's body (102) only during fasting periods. The fasting periods are typically overnight, but other times may be fasting periods, for example if the user is a shift worker. Typically, the fasting periods are less than about 12 hours. The fasting-worn delivery device (130) delivers small correction doses of fast-acting insulin based on periodic blood glucose measurements from the CGM (105). The fasting-worn delivery device (130) is utilized only during fasting periods (164), as shown in FIG. 1C below. The fasting-worn delivery device (130) is configured to deliver small correction doses of fast-acting insulin based at least in part on periodic blood glucose measurements from the CGM (105). In some embodiments, the CGM (105) may be incorporated into the delivery device (130). In other embodiments, the CGM (105) may be a separate CGM worn by the user day and night. An insulin delivery system for implementing the insulin management methods described herein may include a controller for the insulin delivery device (130) in combination with any other computing devices used to execute the delivery algorithms, such as a mobile computing device (120) and / or a cloud computing system (140).

[0044] In some embodiments, the fasting-worn delivery device (130) may be provided as a kit. The fasting-worn delivery device (130) may have a durable unit into which a disposable supply unit containing insulin fits. The delivery device (130) may include a disposable portion including a reservoir configured to contain insulin and to automatically deliver a correction bolus dose to the user. The delivery device (130) may have an applicator (135) for filling and application to the user's body (102), as described further below. The durable unit may be rechargeable by a charger (e.g., a charging station) (131) provided to charge the durable unit during non-fasting times so that it is ready for reuse.

[0045] The durable unit includes a controller (132) for controlling the delivery of insulin from the delivery device (130) according to a delivery algorithm described herein. The delivery algorithm may be provided entirely on the controller (132). The controller (132) may be provided in the form of software and / or hardware components. In a first alternative embodiment, a delivery algorithm may be provided remotely to the controller (132) instructing the amount to be delivered. The delivery algorithm may be provided remotely from a cloud computing system (140) or server, from a computer application (122) or other software on the user's mobile computing device (120), or from another form of computing device or system. In a second alternative embodiment, the delivery algorithm may be distributed with different steps or functions performed by one or more of the controller (132), the cloud computing system (140), the software on the mobile computing device (120), and another form of computing device or system.

[0046] Referring to FIG. 1B, a flow chart (150) illustrates an exemplary embodiment of an insulin management method. The method delivers insulin from a non-fasting insulin management modality during non-fasting periods of the overall time period (151). The non-fasting insulin management modality provides a basal dose of insulin and a bolus dose of insulin. The first therapy, i.e., the non-fasting insulin management modality, may include any mode, method, device process, therapy, etc. used as an intervention in diabetes treatment, including but not limited to pump delivery of insulin (other than the fasting period delivery device (130)), MDI pen or syringe injection of insulin, inhaled insulin, oral insulin, or any form of insulin management used when the user is awake. The non-fasting insulin management modality may also include diet and exercise, where insulin is administered at least part of the time without pharmaceutical intervention. In some embodiments, the non-fasting insulin control modality may additionally or alternatively include any oral medication for type 1 or type 2 diabetes, including, but not limited to, GLP-1 and metformin.

[0047] The method includes delivering insulin from a fasting insulin delivery device (152) during the fasting period within the entire period. This may be considered an adjunct to the first therapy. The fasting insulin delivery device is an automatic insulin delivery device wearable on the user's body for the duration of the fasting period, which delivers a correction bolus dose in response to a received blood glucose measurement and refrains from administering a background basal dose of insulin. The user does not need to interact with the delivery device (130) to correct the bolus insulin during the fasting period when the user is normally asleep. In some embodiments, the intended period of fasting can be from up to about 2 hours before the user goes to sleep to about 2 hours after waking up. The correction bolus dose is an amount of insulin delivered in addition to the basal insulin and prandial bolus insulin provided by the non-fasting insulin management modality during the non-fasting period. The amount of the correction bolus may be determined when the blood glucose value is above the target value and may be based on the difference between the current blood glucose value and the target blood glucose value, as well as the insulin sensitivity factor and the amount of insulin on-board, if available. Correction doses may be delivered at the maximum rate every interval to provide a gradual correction and avoid the risk of hypoglycemia.

[0048] The method may determine the correction bolus dose during the fasting period based on the user's insulin sensitivity factor (ISF) (153). The ISF is a quantified variable of an individualized variable and is a measure of how much one unit of insulin is expected to lower the user's blood glucose level. For example, if one unit of insulin lowers blood glucose level by 25 mg / dL, the insulin sensitivity factor is 1:25. The ISF may be derived from total daily basal dose (TDBD) information received from a non-fasting insulin management modality for a defined period prior to the fasting period. Alternatively, the user's ISF may be known, for example, through the use of another insulin therapy. In another option, the user's ISF may be learned during use of the delivery device. The ISF may be a single ISF for the user that is fixed for the duration of delivery. In an alternative embodiment, the ISF profile may change over time, as the user's ISF may change at different times of the day. For example, many people are more insulin resistant in the morning and therefore require a stronger correction factor. The ISF profile may use a learning algorithm that adjusts the ISF. The ISF may be adjusted during a delivery session or for the next delivery session.

[0049] The method may include determining (154) an assumed insulin onboard at the start of delivery from the fasting insulin delivery device. The assumed insulin onboard may be based on an assumed external dose calculated to correct the user's initial blood glucose level to a target blood glucose level. The assumed dose or virtual dose may be applied to the dose calculation as the assumed insulin onboard. Alternatively, if the initial insulin onboard is known, for example from the use of another insulin therapy, this may also be used as the assumed insulin onboard.

[0050] Delivering insulin from a fasting insulin delivery device during the fasting period (152) may include using a dose calculator at each blood glucose measurement to determine when insulin is needed to bring the user to a target blood glucose level. The dose calculator may compare the blood glucose level to the target blood glucose level to obtain a difference adjusted by the user's insulin sensitivity factor, and the resulting dose is compensated by a determined insulin onboard. The determined insulin onboard is a combination of the expected insulin onboard and the known delivered insulin from the delivery device during the fasting period after insulin has been delivered once.

[0051] Received blood glucose measurements may be smoothed with a low pass filter to reduce the effects of noise and / or sudden perturbations to obtain blood glucose values. If the received blood glucose measurements are trending downward over time, the downward trend may be projected forward and added to the blood glucose value used in the dose calculator. Correction bolus doses for fasting periods may be limited to a defined maximum dose administered at any one time to minimize sudden corrections. A default to a zero dose may be built in.

[0052] Exemplary embodiments of methods for calculating one or more correction doses are described below. The amount of the correction bolus may be determined when the blood glucose value exceeds the target value, and may be determined based on the difference between the current blood glucose value and the target blood glucose value, as well as an insulin sensitivity factor and the amount of insulin on-board. The calculation of the insulin correction dose is determined at least in part using the following formula (1), optionally further applying one or more safety factors to one or more of the variables utilized therein, to effectively guide the user's blood glucose value into the target range and then maintain the user's blood glucose value at or near the target during fasting periods, as described elsewhere in this disclosure.

[0053] (1) Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB

[0054] Dose_calc is the calculated amount of additional insulin needed to lower the user's current blood glucose level to the target blood glucose level, as described elsewhere in this disclosure. Current_BG is the user's measured blood glucose level, which may be evaluated before applying to equation (1), as described elsewhere in this disclosure. Target_BG is the user's blood glucose level goal. ISF (insulin sensitivity factor) is a user-specific factor that indicates how many milligrams per deciliter (mg / dl) one unit of insulin is expected to lower the user's blood glucose level.

[0055] An insulin delivery system for implementing the insulin management method is defined as including a controller of the insulin delivery device (130) in combination with any other computing devices used to execute the delivery algorithm. In some embodiments, the controller can execute all processing of the delivery algorithm, while in other embodiments, the processing of the delivery algorithm can be distributed to other processing devices. The insulin delivery system can include a delivery device (130) with a controller that controls the delivery of insulin from the insulin delivery device with insulin in the form of multiple correction bolus doses during fasting periods in response to received blood glucose measurements. The correction bolus doses may be compensated by a determined insulin onboard, where for at least a first correction bolus dose of the multiple correction bolus doses, the determined insulin onboard is equal to the assumed insulin onboard. The insulin delivery system can include a delivery device and / or other computing systems that execute part of the delivery algorithm processing. For example, the assumed insulin onboard is determined based on an assumed external dose calculated to correct the user's initial blood glucose value to a target blood glucose value.

[0056] FIG. 1C illustrates an example of a total period (160) in which multiple different insulin management modes may be used in a non-overlapping manner, according to some exemplary embodiments. In some circumstances, the total period (160) may be 24 hours long, as is the normal daily routine for most users. However, the total period (160) may be adjusted for users who require a different, sometimes more irregular schedule, for example, due to shift work. The described insulin management is based on the user receiving insulin from one or more non-fasting insulin management modalities (e.g., insulin pens (110) shown in or described in conjunction with FIG. 1A) during non-fasting periods (162) of the total period (160) and from a different fasting insulin management modality (e.g., fasting-worn delivery device (130) shown in or described in conjunction with FIG. 1A) during fasting periods (164) of the total period (160).

[0057] As described herein, the non-fasting insulin control modalities and the fasting period insulin control modalities are intended to be used additively, e.g., adjunctively, without operational overlap between the non-fasting and fasting modalities. For example, as described below, neither basal insulin dose(s), e.g., (170a, 170b), nor prandial bolus doses (172a-172d) are typically administered from a non-fasting insulin control modality during a fasting period (164), and correction doses (180a-180e) are typically administered from a fasting insulin control modality during a non-fasting period (162). Thus, once a non-fasting period (162) begins, a fasting period insulin control modality is not intended for use, and once a fasting period (164) begins, a non-fasting insulin control modality is not intended for use. However, at least a portion of the basal doses (170a, 170b) or meal bolus doses (172a-172d) administered during the non-fasting period (162) may still be active in the body as insulin on-board during the fasting period (164). The correction doses (180a-180e) during the fasting period (164) supplement the meal boluses (172a-172d) administered during the non-fasting period (162), for example, when the meal boluses (172a-172d) do not sufficiently cover the rise in blood glucose level resulting from a meal, i.e., when blood glucose level remains elevated after the meal or meal bolus. This shortfall may be due to an error in the bolus calculation, an error in the reported meal information, an error in the treatment parameters used in the treatment calculation, hormonal factors, etc.

[0058] The non-fasting period (162) may be the time during which the user is awake in the daily cycle. However, the non-fasting period (162) may also include short periods of sleep, such as daytime naps. The fasting period (164) may be the time of intended fasting. This may be overnight, or any period during which only a correction bolus is needed in an additional sense to any existing basal and meal bolus regimen. This may allow one to remain "on board" throughout the fasting period (164). Thus, the fasting period (164) may be the time during which the user is asleep in the daily cycle. For most users, the fasting period (164) may be an overnight period between 6 and 12 hours, typically less than 22 hours, during which the user typically lies in a resting position and does not eat during this time.

[0059] In FIG. 1C, basal doses (170a and / or 170b) and meal bolus doses (172a-172d) are administered via a non-fasting insulin management modality during non-fasting periods (162). Basal insulin is the background insulin that a diabetic person requires to maintain blood glucose levels in a desired range without meals during non-fasting periods (162). Although the amount required varies from user to user, basal insulin typically accounts for approximately 50% of a type 1 diabetes patient's total insulin needs. The basal doses (170a, 170b) may include slow acting insulin. If the basal dose (170a) is administered once a day, the dose (170a) may be configured to meet the user's 24-hour basal requirements for insulin. The dose (170a) may be administered by daily injection of insulin doses during non-fasting periods (162), for example, via an insulin pen (110) (see, e.g., FIG. 1A). When the basal dose (170a) is administered twice daily, each of the doses (170a, 170b) may be configured to meet the user's 12-hour basal need for insulin, and the doses (170a, 170b) may be administered via a multiple daily injection (MDI) mode during the non-fasting period (162).

[0060] In contrast, a meal bolus dose is the amount of insulin required to compensate for the expected rise in blood glucose in a diabetic resulting from a meal, the compensation being aimed at bringing blood glucose levels into a target range. Typically, a user who eats a certain amount of carbohydrates will require insulin to avoid the resulting rise in blood glucose levels. FIG. 1C shows meal bolus doses (172a-172d) administered by the MDI mode during a non-fasting period (162). In contrast to the basal doses (170a, 170b), the meal bolus doses (172a-172d) may include fast-acting insulin. Although a specific number of meal bolus doses are shown in the non-fasting period (162), they are for illustrative purposes only, and any number of doses required by the number of meals eaten during the non-fasting period (162) are contemplated.

[0061] During the fasting period (164) within the overall period (160), the described insulin management method administers insulin from a fasting automatic insulin delivery (AID) device wearable on the user's body for the duration of the fasting period (164), for example, a pump worn only at night, such as that provided in PCT Patent Application No. PCT / IB2021 / 060206, the contents of which are incorporated herein by reference. Such a device (130) is shown in FIG. 1A, as described in more detail below. Because no food is consumed during the fasting period (162), the device (130) is configured to deliver fast-acting insulin in the form of correction bolus or microbolus doses (180a-180e) to gradually correct high blood glucose readings during the fasting period (164). This allows the user to sleep soundly and wake up in the target blood glucose range without having to wake up for a correction bolus. Although a specific number of correction bolus doses are shown during the fasting period (164), they are merely for illustration and any number of correction doses required during the fasting period (164) are contemplated.

[0062] The basal doses (170a, 170b) are assumed to be taken from the non-fasting insulin management modality during the non-fasting period (162). In particular, the fasting insulin delivery device (130) refrains from administering background insulin and / or basal insulin to the user. In particular, the fasting insulin delivery device (130) does not allow the delivery of any preset default dose, basal dose or background dose of fast-acting insulin, for example to take into account the basal insulin needs of the user. In other words, in contrast to the operation of conventional CSII devices, the delivery device (130) does not allow a preset basal rate of basal insulin delivery or a preset pattern of basal insulin delivery, for either fast-acting or slow-acting insulin. The delivery device (130) also does not store such a preset basal rate or preset pattern of fast-acting or slow-acting basal insulin delivery. The delivery device (130) does not deliver any background insulin. Thus, the background rate, baseline rate and / or basal rate of basal insulin delivery, baseline insulin delivery and / or background insulin delivery are fixed at zero and invariant, because the insulin delivery device (130) may be specifically configured such that such basal insulin delivery, baseline insulin delivery and / or background insulin delivery is not possible. Thus, the fasting insulin delivery device (130) is designed to perform only small correction boluses while the user is fasting for a limited period of time, and in contrast to the CSII device, cannot deliver any insulin dose without first performing an insulin correction dose calculation based on true and / or estimated real-time (or substantially real-time) blood glucose values, as described elsewhere in this disclosure. Also, in some embodiments, the fasting insulin delivery device (130) is not configured for meal bolus delivery at all.This configuration greatly simplifies the requirements for the delivery algorithm to enable the fasting insulin delivery device (130) to effectively maintain blood glucose levels in the target range without requiring information regarding basal rates, carbohydrate ratios, or insulin action duration.

[0063] As described in more detail below, the delivery algorithm responsible for determining the size of the correction doses (180a-180e) uses various safety factors to adjust one or more variables to ensure there is no over-dosing of insulin or the associated over-correction of blood glucose levels during non-fasting periods (162). Additionally, because a user must integrate a non-fasting mode of insulin administration outside of fasting periods, one or more of the systems, devices and methods disclosed herein may also provide the ability to integrate this supplemental method of insulin administration utilized outside of fasting periods (164) with an automated fasting insulin delivery method of insulin administration utilized during fasting periods (164). In some embodiments, to facilitate an efficient transition between this supplemental method of insulin administration during non-fasting periods (162) and the automated corrective method of delivery during fasting periods (164), one or more of the systems, devices, and methods disclosed herein may also be configured to accurately detect one or both of an initiation activity (190) (FIG. 1C) indicating the need, desire, or appropriateness for initiating automated delivery of insulin from the insulin delivery device (130) at or near the beginning of the fasting period (164) and a termination activity (192) (FIG. 1C) indicating the need, desire, or appropriateness for terminating automated delivery of insulin from the insulin delivery device (130) at or near the end of the fasting period (164), as described in more detail below.

[0064] Referring to Figure 2A, a flow chart (200) illustrates an exemplary embodiment of a method for managing insulin by a delivery device, such as delivery device (130) of Figure 1A. The method may be performed by a controller of the delivery device, or some steps may be performed remotely to the controller. The method may be performed in cooperation with the controller and a user application provided on a user's mobile computing device.

[0065] The method may include detecting (201) a starting activity associated with preparing for use an insulin delivery device in the form of an AID wearable on the user's body for the duration of a fasting period within an overall period. Detecting (201) a starting activity associated with preparing for use of a delivery device may include detecting a variety of different forms of preparing the delivery device before it is ready to deliver insulin. Such starting activity may be any activity that indicates the need, desire, or appropriateness of initiating an automatic delivery of insulin from the insulin delivery device (130). The automatic delivery may be initiated without an explicit instruction from the user. For example, in some embodiments, such starting activity may be any activity that is not a direct action to automate delivery, such as pressing a power button, but instead is an activity that typically occurs or is expected to typically occur prior to or substantially at the beginning of a fasting period. In this manner, such starting activities have primary functions other than initiating automatic delivery of insulin from the insulin delivery device (130), and such starting activities are used for those primary functions while being repurposed to effectively and accurately indicate the need, desire, or appropriateness of initiating automatic delivery of insulin. Because the onset activity is also the activity whose occurrence is significantly highly correlated with the onset of the fasting period. This at least solves the issue of transition complexity for transient use by providing a simplified system that allows for an easy transition between two different diabetes management modalities.

[0066] For example, as described in more detail below, the initiating activity may include, but is not limited to, physical activity performed by a user with respect to the delivery device, a physical change to the delivery device, a user activity level meeting a predefined criterion, and / or the occurrence of a pre-set time of day. A user performing such an initiating activity and / or detection of such an initiating activity by one or more devices and / or device components described herein may play a role in one or more processes for managing insulin delivery using different modalities during non-fasting periods as compared to fasting periods, as described elsewhere in this disclosure.

[0067] The delivery device (130) may detect its own activation, for example, but not limited to, when a user begins wearing the device (130). Alternatively, if one or more steps and / or calculation procedures are performed remotely by another device, such as the mobile device (120) or a remote cloud device (140), such a method may include detecting such activation of the delivery device (130) or receiving a notification by the other device. In one example, detecting the initiation activity (201) may be the receipt of a first blood glucose measurement. For example, in some embodiments, the activation component (446) of the delivery device (401) of FIG. 4 may be configured to perform such detection.

[0068] Detecting (201) may include detecting one or more physical activities performed by the user with respect to the delivery device, which may include one or more of removing the controller of the delivery device from a charger, attaching a supply unit or a pre-filled insulin cartridge to the controller, applying to the user's body, removing the applicator from the controller, completing a manual priming sequence, or giving an audible or voice command to the controller. Detecting (201) may also occur at preset times of day or may be triggered by the user's activity level detected by the delivery device or another monitor (such as a fitness monitor that detects rest periods).

[0069] Detecting (201) may include detecting physical changes in the delivery device. Physical changes may include detecting movement of the controller via an accelerometer in the controller, proximity or pairing of the controller to a user computing device such as a smartphone on which a user application is provided, detecting proximity of a smart pen when filling a supply unit, detecting connection of a supply unit or cartridge to the controller, detecting the fill level of an insulin reservoir by the controller, detecting removal of an applicator from the controller, detecting removal of a controller from a base, detecting movement of a plunger in a supply unit, detecting automatic priming of a delivery device. Any of these examples of detecting an initiating activity may function to translate one or more physical activities of a user and / or physical changes in the delivery device into one or more electrical signals and / or a physical configuration of one or more electrical components indicative of the need, desire, or appropriateness of initiating automatic delivery of insulin from the insulin delivery device.

[0070] By way of example and not limitation, removal of the delivery device (130) from the charger (131) does not initiate a fasting period, but rather has a primary function of interrupting charging of the delivery device (130). However, because the device (130) is worn by a user during a fasting period, the interruption of charging, removal from the charger (131), and / or detection of the physical acceleration of the device (130) during such actions may have a significantly higher correlation with the onset of a fasting period, and thus may be repurposed for purposes other than its primary purpose, and to indicate the onset of a fasting period.

[0071] Similarly, the insulin pen 110 or mobile device 120 coming within a predetermined distance (e.g., proximity) of the device 130 has the primary function of physically moving the insulin pen 110 or mobile device 120 rather than initiating a fasting period. However, because the insulin pen 110 and / or mobile device 120 may also be utilized during non-fasting periods or to fill the insulin reservoir of the device 130 immediately prior to a fasting period, such an action has a significantly higher correlation with the onset of a fasting period and may therefore be repurposed for purposes other than its primary purpose and to indicate the onset of a fasting period.

[0072] Similarly, the insertion of an insulin reservoir or pre-filled insulin cartridge into device 130 has the primary function of coupling the insulin reservoir or cartridge to device 130, rather than initiating a fasting period. However, because the insulin reservoir and / or cartridge must be inserted into device 130 to be usable during a fasting period, such an action has a significantly higher correlation with the onset of a fasting period and therefore may be repurposed for purposes other than its primary purpose, and to indicate the onset of a fasting period.

[0073] Similarly, the decrease in activity level to a level indicative of resting has the primary function of indicating that the user is at rest, rather than initiating a fasting period. However, because fasting periods are time frames in which a user is expected to sleep, the occurrence of the user's activity level decreasing to or near a resting rate has a significantly high correlation with the start of a fasting period, and therefore may be repurposed for purposes other than its primary purpose, and to indicate the start of a fasting period. Several additional examples of initiating activities each have a primary function other than initiating automatic delivery of insulin from the insulin delivery device (130), and such initiating activities are used for their primary function while simultaneously being repurposed to effectively and accurately indicate the need, desire, or appropriateness of initiating automatic delivery of insulin, because the initiating activities are also activities whose occurrences have a significantly high correlation with the start of a fasting period.

[0074] In some embodiments, a combination of two or more initiating actions is necessary to initiate insulin delivery. In some embodiments, confirmation is requested or required, such as in a user interface, in response to one or more of the initiating actions. In some embodiments, initiation of insulin delivery is in response to a series of initiating actions that follow predetermined criteria.

[0075] In some embodiments, such an initiating activity may include the arrival of a preset time of day and / or the arrival of a user activity level indicative of a period of rest. Detection of such an initiating activity may include a variety of different forms of detection that prepares the delivery device before it is ready to deliver insulin, such as detecting one or more physical activities performed by the user with respect to the delivery device and / or detecting a physical change in the delivery device.

[0076] The method can initiate (202) automatic delivery of insulin from a delivery device. The initiating (202) can be in response to detection of an initiating activity or can occur after a predefined time interval from the initiating activity. Initiating (202) automatic insulin delivery in response to the detected activity can include priming the delivery device so that it is ready to deliver insulin. The method can deliver insulin in the form of a correction bolus dose in response to a received blood glucose measurement while refraining from administering a background basal dose of insulin (203). The delivery device can refrain from administering basal insulin at a pre-set or default rate or in a pre-set or default pattern. The delivering (203) can include a correction bolus dose based on an assumed insulin onboard, which can be based on an initial virtual correction bolus dose calculated to correct the user's initial blood glucose measurement to a target blood glucose value. The delivering (203) can be based on a user's insulin sensitivity factor, which can be based on a user's insulin sensitivity factor based on a total daily basal dose delivered prior to use of the delivery device. The amount to deliver (203) may be determined from the insulin deficit measured from the received blood glucose measurements. The amount to be delivered may be determined without a known carbohydrate factor or carbohydrate ratio, without meal information, and without determining the insulin action time. The target range of blood glucose levels may be fixed. In some fasting periods where insulin is not needed for correction, the delivery may be zero.

[0077] The method can detect a termination activity associated with terminating activity of the insulin delivery device (204). The termination activity can include detecting removal of the wearable insulin reservoir from the body, completion of a predefined period of time that is less than a prescribed period (e.g., 24 hours, 12 hours, 10 hours, 8 hours, or 6 hours), or returning a durable portion of the delivery device to a charging port.

[0078] For example, the delivery device (130) and / or the mobile device (120) may be configured to detect such a termination activity, which may be any activity that indicates the need, desire, or appropriateness of terminating the automatic delivery of insulin from the insulin delivery device (130). For example, in some embodiments, such a termination activity may be any activity that is not a direct action to stop the automatic delivery, such as, for example, pressing a power button to turn off the delivery device (130), but instead is an activity that typically occurs or is expected to typically occur at the substantial end of a fasting period. In this way, such termination activities have primary functions other than initiating the cessation of the automatic delivery of insulin from the insulin delivery device (130), and such termination activities are used for those primary functions while at the same time being reused to effectively and accurately indicate the need, desire, or appropriateness of terminating the automatic delivery of insulin. Because termination activities are also activities whose occurrence has a significantly high correlation with the end of a fasting period. This at least solves the transition complexity problem for episodic use by providing a simplified system that allows for an easy transition between two different diabetes management modalities.

[0079] Such termination activities may include detecting removal of the wearable insulin reservoir from the device (130), detecting removal of the device (130) from the body, completion of a predefined period of less than a specified period (e.g., 24 hours, 12 hours, 10 hours, 8 hours, or 6 hours), or returning a durable portion of the delivery device (130) to the charger (131).

[0080] By way of example and not limitation, removal of the insulin reservoir of the delivery device (130) does not terminate the fasting period, but rather has a primary function of disconnecting the insulin reservoir from the delivery device (130), for example, to refill the reservoir. However, because the insulin reservoir must be properly positioned within the delivery device (130) for proper function, removal of the insulin reservoir has a significantly higher correlation with the end of the fasting period, and therefore may be repurposed for purposes other than its primary purpose, and to indicate the end of the fasting period.

[0081] Similarly, reconnecting the device (130) to the charger (131) has the primary function of charging the delivery device (130) rather than terminating the fasting period. However, because the device (130) is worn by the user during the fasting period, reconnecting to the charger (131) has a significantly higher correlation with the end of the fasting period and therefore may be repurposed for purposes other than its primary purpose and to indicate a desire to end the fasting period.

[0082] Similarly, removal of the delivery device (130) from the user's body has the primary function of disconnecting the device (130) from the user's body, rather than terminating the fasting period. However, because the delivery device (130) must be properly worn by the user for proper function, removal of the delivery device (130) from the user has a significantly higher correlation with the end of the fasting period, and therefore may be repurposed for purposes other than its primary purpose, and to indicate the end of the fasting period.

[0083] Similarly, an increase in activity level significantly above a resting level has the primary function of indicating that the user is active, rather than ending a fasting period. However, because fasting periods are time frames in which the user is expected to sleep, the occurrence of a user's activity level increasing significantly above a resting level has a significantly higher correlation with the end of a fasting period, and therefore may be repurposed for purposes other than its primary purpose, and to indicate the end of a fasting period.

[0084] In some embodiments, a combination of two or more termination actions is required to initiate insulin delivery. In some embodiments, confirmation is requested or required, such as in a user interface, in response to one or more termination actions. In some embodiments, initiation of insulin delivery is in response to a sequence of termination actions that conform to predetermined criteria.

[0085] Any example of detecting a termination activity may function to convert one or more physical activities of the user or physical changes in the delivery device into one or more electrical signals and / or a physical configuration of one or more electrical components that indicate the need, desire, or appropriateness of initiating a fasting termination procedure and / or for the user to cease use of the insulin delivery device (130). The user performing such a termination activity and / or detecting such a termination activity by one or more devices and / or device components described herein may play a role in one or more processes for managing insulin delivery using different modalities during non-fasting periods as compared to fasting periods, as described elsewhere in this disclosure.

[0086] In one embodiment, the method can adjust (205) a fasting termination procedure for the user. The fasting termination procedure can include delivering at least a portion of a fasting termination bolus at the end of the session. For example, this can be a meal bolus. As an example, assuming the user may sleep for many more hours, the user may wake up with elevated blood glucose levels due to a conservative delivery. In this case, a fasting termination bolus that is not necessarily related to a meal may be required. The user can prompt for a fasting termination bolus in the form of a final correction bolus. This may be only a portion of the required fasting termination bolus that uses the remaining insulin in the delivery device. The final fasting termination correction bolus can be a hybrid correction and meal bolus, administered both at or near the end of the fasting period to correct the elevated blood glucose levels upon awakening, and also after the fasting period has ended, with the expectation that a meal will be consumed during the subsequent non-fasting period. The delivery algorithm can have numerous safeguards to avoid over-correction during the fasting period. Thus, a full correction dose may be required when the user wakes up.

[0087] 1C , because the total period (160) is a repetitive period (e.g., a period of 24 hours in some cases), adjustments to the fasting termination procedure, or if not included, the detection of termination activity (204) may return to the detection of initiation activity step (201) at the beginning of a non-fasting period (162) of the next total period (160) immediately following a fasting period (164). Furthermore, the repetitive nature of the total period (160) necessitates a transition from the non-fasting period (162) and its associated insulin delivery modality (e.g., MDI) to the fasting period (164) and its automatic administration of correction doses (180a-180e), and another transition to the next non-fasting period (162) and its associated insulin administration mode at the end of the fasting period (164). Accordingly, some methods, devices, and systems configured to integrate supplemental methods of insulin administration outside of fasting periods (164) may include coordinating one or more correction doses (180a-180e) provided by a delivery device (130) during fasting periods (164) with one or more basal doses (170a, 170b) or prandial doses (172a-172d) provided via a non-fasting modality (e.g., the insulin pen (110) of FIG. 1A) during non-fasting periods (162).

[0088] Referring to FIG. 2B, a flow chart (220) illustrates an exemplary embodiment of a method for controlling delivery of insulin from a fasting-worn delivery device, such as the delivery device (130) of FIG. 1A. The method delivers insulin during fasting periods from a delivery device that is intended to be worn only during fasting periods and where no basal dose is provided by the delivery device. The method may be utilized to deliver insulin during fasting periods (164) from a delivery device (130) that is intended to be utilized only during fasting periods (164). No basal dose of insulin is provided by the delivery device (130). Such a method may solve the problem of accounting for insulin onboarding from non-fasting administration modalities without user interaction or input, and without prior or direct knowledge of the amount of insulin actually administered to the user from such non-fasting administration modalities. Such methods may be performed in and / or by a controller, such as the controller (132) of the delivery device (130) shown in FIG. 1A, and / or by the delivery device (401) or mobile computing device (402) shown in FIG. 4 and / or FIG. 8, and / or by a server, computing device, etc., such as the computing device (900) shown in FIG. 9, whereupon instructions are sent to the controller. In some embodiments, certain steps may be performed by such a controller of the delivery device, and / or some of the steps may be performed remotely to the controller. Thus, in some embodiments, such methods may be performed in cooperation with such a controller using a user application provided on a user's mobile computing device, such as the mobile computing device (401).

[0089] The method may include an initialization phase (221) where various parameters and safety factors are set for the delivery algorithm. Some of the steps of the initialization phase (221) may be updated during the delivery phase. In the initialization phase (221), the method may receive or determine (222) an initial user insulin sensitivity factor (ISF). The ISF is a user-specific factor that represents how much one unit of insulin is expected to lower the user's blood glucose level. In some embodiments, this initial ISF may be received from the user (i.e., the patient), from a physician, or from a connected device such as a user application or another insulin therapy device such as the smart insulin pen (110) of FIG. 1A. The user ISF may be learned and refined over time during use of fasting delivery doses for repeated fasting periods. In some embodiments, this may be the only user input required for the method other than periodic blood glucose measurements. This greatly simplifies user interaction with the devices and systems of the present disclosure. In some embodiments, the ISF receiving component (431) of the delivery device (401) of FIG. 4 may be configured to perform the functions of the initialization phase (221).

[0090] The initial user ISF may be based on received total daily basal dose (TDBD) information. The TDBD information may be provided by the user or a physician via a user application or a smart insulin pen. The TDBD, or total daily basal dose, is the amount of basal insulin taken in a 24-hour period and is typically constant for a user from day to day. The user's TDBD may be determined, for example, by the amount of basal insulin injected from an insulin pen in a 24-hour period. In such an embodiment, receiving the ISF may include receiving the TDBD (e.g., the sum of the MDIs (170a, 170b) in FIG. 1C) and estimating the ISF from the received TDBD. For example, there is a strong relationship between the TDBD, total daily dose (TDD) and ISF, as shown by the following equations (2)-(4).

[0091] (2)ISF=800 / TDBD (3) TDBD = 0.47 × TDD (4)ISF=1700 / TDD

[0092] In some embodiments, the ISF may be determined based at least in part on the user's weight. In some embodiments, the user's ISF may be learned during use of the delivery device (130). In some embodiments, the ISF profile may change over time as the user's ISF may change at different times of the day. For example, many people are more insulin resistant in the morning, which requires a stronger correction factor. The ISF profile may use a learning algorithm configured to set and / or adjust the ISF during a delivery session or in advance for the next delivery session.

[0093] The method of the delivery algorithm determines the insulin required to gradually bring the user to the target blood glucose level. The delivery algorithm is based on calculating a correction dose of insulin by comparing the evaluated blood glucose measurement (hereinafter referred to as the "evaluated blood glucose measurement") with the target blood glucose level and adjusting the difference by the user ISF. The resulting correction amount can be compensated by the determined insulin onboard. The compensation can reduce the resulting dose by the determined insulin onboard. The target blood glucose level can be an amount set for all users or for different categories of users and can be time-varying so that it decreases over time during the fasting period. The rate of decrease of the target blood glucose level over time can assume that the blood glucose level is lowered by the existing externally administered insulin administered before the fasting period.

[0094] The method can receive an initial blood glucose measurement (223). For example, the blood glucose measurement may be periodically received from a glucose monitor (e.g., CGM (105) of FIG. 1A). In some embodiments, a BG receiving component (451) of the delivery device (401) of FIG. 4 can be configured to perform the functions of block (223). As described in more detail below, an initial blood glucose measurement or set of initial blood glucose measurements at the start of the fasting period (164) or at a time sufficiently close to the start of the fasting period (164) may be used to determine an assumed IOB in subsequent steps, and possibly one or more safety factors for variables utilized in determining a correction dose.

[0095] A target blood glucose value and one or more safety factors may be set (224). The target blood glucose value may be adjusted by the target safety factor to bias it towards the target safety factor. For example, a target blood glucose value may be set and then any one or more of the target blood glucose value, ISF and IOB may be adjusted by applying a safety factor, thereby ultimately manipulating or biasing the insulin dose or the calculation of such a dose to prevent over-delivery and inducing hypoglycemia. The calculated correction dose may also be adjusted by an overall safety factor. One or more of these safety factors may be based on an initial blood glucose measurement or a group of initial blood glucose measurements received at the beginning of the fasting period (223). The one or more safety factors may be based on the difference between the evaluation blood glucose measurement and the target blood glucose value. The safety factor may be a percentage adjustment, such as 5%, 10%, 15% or 20% from the baseline value.

[0096] For example, in some embodiments, the blood glucose target value may be set at a predefined or constant value for all users at the start of the fasting period (164), or may be set to a respective one of a plurality of constant values ​​for each of a plurality of categories of users. In some embodiments, the blood glucose target value is set at least in part based on the initial blood glucose measurement received (223), e.g., initially setting or adjusting the blood glucose target value higher if the initial blood glucose measurement is high, and setting or adjusting the blood glucose target value relatively lower if the initial blood glucose measurement is relatively low. In some embodiments, a fixed or constant blood glucose target value means that the method does not allow the user to manually input or modify the blood glucose target value. In some embodiments, the blood glucose target value may begin at an initial value as described herein and be adjusted over the fasting period (164) as described in more detail below.

[0097] As described in more detail below, a safety factor may also be applied to the actual blood glucose measurement in the form of filtering and / or any other correction thereto, as described elsewhere in this disclosure. However, such adjustments are primarily discussed as evaluating the blood glucose measurement (229). Similarly, the application of any safety factor to the calculated resulting correction dose may be applied by limiting the correction dose based on a maximum delivery rate.

[0098] The initialization phase (221) of the method may include determining (225) insulin on-board (IOB), which is the amount of insulin still active in the user's body. This may be based on an assumed external dose calculated to correct the user's initial blood glucose value to a target blood glucose value. This is further described below in relation to FIG. 2C. The IOB may include an assumed insulin on-board (referred to as "external insulin") that is assumed to be provided by a non-fasting insulin therapy before use of the delivery device. The IOB is assumed to be sufficient initially and to decrease over time during the fasting period. The rate of decrease over time may be based on the assumption that blood glucose values ​​are affected by existing externally administered insulin administered before the fasting period based on known decay rates or duration of insulin action in the body. The assumed insulin on-board may be adjusted over time in the delivery phase compared to the evaluated blood glucose measurements. During the delivery phase, the determined IOB may also include a known delivery device insulin, as known from the delivered correction dose from the delivery device. The term "external insulin" refers to insulin delivered by a device other than the fasting delivery device described. The term "device insulin" refers to insulin delivered by a fasting delivery device, which is insulin delivered by a wearable insulin delivery device to deliver a correction dose of insulin to a user intended for fasting periods.

[0099] The assumed external IOB is based on the amount of hypothetical or assumed external insulin needed to correct the user's hyperglycemia based on a comparison of the current BG (i.e., the current evaluated BG) and the target BG according to equation (6), which is derived from equation (5) below:

[0100] (5) [(Current_BG-Target_BG) / ISF]-IOB=0 (6) Expected IOB = [(Current_BG - Target_BG) / ISF]

[0101] The assumed external IOB may be calculated from the difference between the current blood glucose value (i.e., the current assessed blood glucose value as described elsewhere in this disclosure) and the target blood glucose value, scaled by the ISF, set in block (222), and / or adjusted in block (224), not resulting from known external insulin. In some embodiments, the initial blood glucose value(s) on which the assumed IOB is based may be averaged over the initial set of blood glucose measurements to filter out transient and / or acute changes. In some embodiments, such initial set of blood glucose measurements may be filtered to exclude outliers and / or to exclude such outliers from use in such rolling average. As mentioned above, considering the sufficiency of the assumed initial IOB means that the controller does not need to accept or use a known amount of external IOB information from the user. Thus, the calculation of the correction dose can be accomplished without any input or knowledge of the external IOB. The assumed IOB for at least the initial period does not include insulin input from previous administrations. The initial assumed IOB determined from equation (5) above is also simpler for the user and reduces user error.

[0102] Additionally, the assumed IOB may also function as a safety factor, in that the IOB in equation (5) is initially assumed or set to be equal to the assumed IOB. In this way, if such a safety factor is embodied as an assumed external IOB that decays over time, any dose calculation that exceeds 0 (or a minimum threshold that the delivery device (130) is configured to deliver, such as 0.1 units of insulin) represents an unexpected BG, or an incomplete external IOB, which may be safely compensated for by delivering the difference (e.g., 0.1 units of insulin).

[0103] The correction bolus dose is compensated by the determined insulin onboard, and for at least a first correction bolus dose of the multiple correction bolus doses, the determined insulin onboard is equal to the assumed insulin onboard. The method in the initialization phase (221) can deliver a first dose (226), which may be zero units, based on an assumption of assumed IOB sufficiency. For example, as described above, the assumed IOB is initially determined based on an assumption of initial IOB sufficiency. Thus, the first correction dose during and / or at the end of the initialization phase will not include any insulin delivery.

[0104] The method can include a delivery stage (227) in which blood glucose measurements are periodically received (228). For example, the blood glucose measurements may be received from a glucose monitor, such as the CGM (105) of FIG. 1A. In some embodiments, the BG measurement receiving component (451) of the delivery device (401) of FIG. 4 can be configured to perform the evaluation. In other embodiments, the CGM (105) can perform at least some of the functions of the evaluation.

[0105] Preventing over-delivery of insulin or preventing calculations that over-deliver insulin may be better accomplished by utilizing a processed, evaluated, and / or filtered proxy of the user's actual blood glucose level that more accurately represents the long-term trend of the user's actual blood glucose level, while also attenuating, eliminating, or otherwise filtering out short-term noise and / or aberrations. Thus, the periodically received blood glucose measurements (or a subset thereof) may be evaluated (229) using a variety of different methods. For example, the periodically received blood glucose measurements (hereinafter "received blood glucose measurements") may be processed and / or filtered as described below or elsewhere in this disclosure to obtain a proxy of the user's actual blood glucose level that more accurately represents the long-term trend of the user's actual blood glucose level, while also attenuating, eliminating, or otherwise filtering out short-term noise and / or aberrations.

[0106] In some embodiments, the blood glucose measurements may be evaluated by smoothing the received blood glucose measurements utilizing a low pass filter to reduce the effects of noise and / or rapid perturbations (229). For example, one or more received blood glucose measurements may each be replaced with a rolling average of the received blood glucose measurement and a predetermined number of previous blood glucose measurements.

[0107] The blood glucose measurement may be evaluated (229) by filtering for increases in blood glucose and not filtering for decreases in blood glucose. For example, the true blood glucose value may be used if it is less than the rolling average of the blood glucose value. The blood glucose measurement may be evaluated at least in part by retaining received blood glucose measurements that are less than the rolling average of a predefined number of previous received blood glucose measurements and retaining the rolling average for the remaining received blood glucose measurements. For example, if the true CGM value is less than the rolling average of the true CGM value and the predefined number of previous CGM values, the true CGM value may be used so that decreases in BG are immediately considered. However, if the true CGM value is greater than the rolling average, the rolling average may be used to avoid insulin delivery based on localized blood glucose peaks. Peak filtering provides a double-sided safety for the CGM value used in decision making by providing additional filtering / smoothing for increases in blood glucose over decreases in blood glucose. Such double-sided safety may also be useful in determining or adjusting IOB, as described below. This is because when the actual IOB is lower than the estimated value, it is safe to deliver insulin, but when the actual IOB is higher than the estimated value, no insulin is delivered.

[0108] In some embodiments, the blood glucose measurements may also be evaluated (229) at least in part by projecting forward the downward trend of the received blood glucose measurements and adding the downward trend to the blood glucose measurements used for dose calculation. This can adjust for long-term downward trends over several hours during the fasting period (e.g., this may be up to half of the fasting period). The evaluation of the blood glucose measurements can also correct for basal drift. For example, if the true BG value is trending downward over time (e.g., 6 hours), the true blood glucose value can be adjusted downward based on and to reflect the forward projection of the downward trend, effectively reducing insulin dosing if the BG has already drifted downward, preventing inappropriate over-delivery of insulin and thereby preventing the induction of hypoglycemia. This provides for correction of basal drift caused by incorrectly adjusted basal insulin dosing, meal bolus dosing, and / or other physiological factors in terms of compensating (backing off) the insulin effect, taking into account the trend adjustment. However, adjusting for long-term drift during the fasting period (164) may require, in some approaches, the determination of the appropriate slope of the drift to be compensated for. One way this slope may be determined is by a least mean squares fit linear regression analysis to all or a subset of the true or evaluated blood glucose measurements from the time frame for which the drift slope is desired. Several additional methods for evaluating the received blood glucose measurements are described in connection with Figures 3A-3D.

[0109] The IOB, the target blood glucose level, and / or one or more of the safety factors described above may be adjusted (230). For example, the assumed IOB varies based on the time elapsed since initialization of the delivery device and the duration of insulin action (DIA), such that the assumed IOB should generally decrease over the fasting period (164). In some embodiments, the correction dose calculation component (453) of the delivery device (401) of FIG. 4 may be configured to perform the functions of block (230).

[0110] The operating assumption is that the assumed IOB is sufficient to bring the initial blood glucose measurements back up to the blood glucose target over time. Thus, in some embodiments, if blood glucose measurements (or their evaluated surrogates) received within a predefined time interval after the start of the fasting period (164) rise rather than fall from their levels during the initiation phase (when the assumed IOB was initially set), the assumed IOB may be recalculated and / or adjusted upward based on the increased blood glucose measurement(s) and / or their evaluated surrogate(s). Such upward adjustment or recalculation of the assumed IOB effectively reduces the predicted insulin delivery if the initial blood glucose measurements received during the initialization phase underrepresent the actual upward trajectory of blood glucose levels where insulin may have already been delivered during a non-fasting period prior to utilizing the non-fasting modality. In some embodiments, the IOB determination component (443) and / or the assumed IOB component (444) of the delivery device (401) of FIG. 4 may be configured to perform one or more functions of block (230).

[0111] In some embodiments, the target blood glucose level may be adjusted to change over time based at least in part on the time elapsed since initialization of the delivery device (230). Thus, the target blood glucose level may decrease over time during the fasting period (164) (see, e.g., FIG. 1C). In some embodiments, the rate at which the target blood glucose level decreases may be based, at least in part, on the assumption and expectation that blood glucose levels are currently being lowered by remaining assumed IOB.

[0112] The method can calculate a correction dose by comparing the evaluated blood glucose measurement to a target blood glucose, adjusting the difference by the user ISF, and correcting the resulting dose by the determined insulin on-board (231). The method can limit or divide the correction dose into portions having a maximum delivery rate for a maximum amount of insulin delivered over a given period of time (232). The given period of time can be an interval during which blood glucose measurements are received. In some embodiments, the correction dose limiting component (454) of the delivery device (401) of FIG. 4 can be configured to perform the functions of block (232). For example, the correction dose can be divided into portions (180a-180e) that include a maximum amount of insulin delivered over a given period of time. The method can then deliver at least a portion of the correction dose, such as the divided portions (233). In some embodiments, the dose delivery mechanism (431) of the delivery device (401) of FIG. 4 can be configured to perform the functions of block (233). For example, with reference to Figure 1C, a correction dose (180a) may be delivered to a user by the delivery device (130). If the correction dose is greater than the maximum value per delivery period, the correction dose (180a) may include only a portion of the calculated correction dose equal to the maximum value per delivery period.

[0113] The method may continually repeat (234) during the delivery phase (227) to accommodate periodically received blood glucose measurements. In one embodiment, the correction dose may be divided into several smaller portions to meet the maximum value for delivery, and one of the smaller portions may be given. When the next incoming blood glucose measurement is received, the method may determine whether to deliver the next portion or adjust the dose based on the updated calculation.

[0114] The method may include an end procedure (235) to accept a fasting-ending bolus, as described above. A non-limiting use case may be that the user wakes up with elevated blood glucose levels due to conservative delivery of correction doses and operating under the assumption that the user will sleep for a few more hours. In this case, a final fasting-ending correction bolus (or a portion of such a correction dose that includes residual insulin in the delivery device) that is not meal-related may be administered. As another alternative use case, such a final fasting-ending correction bolus may be a hybrid correction and meal bolus administered at or near the end of the fasting period (164) to correct for elevated blood glucose levels upon awakening, with the expectation that a meal will be consumed during the subsequent non-fasting period (162) after the fasting period (164) has ended, as described in more detail in connection with FIGS. 5A-5C.

[0115] Referring to FIG. 2C, a flow chart (240) illustrates another exemplary embodiment of a method for controlling delivery of insulin from a fasting-worn delivery device, such as the delivery device (130) of FIG. 1A. During initial setup of the delivery device, total daily basal information can be received from the user (241), which can be used to estimate the ISF for that user (242). Target blood glucose (BG) and insulin action time values ​​can be fixed for all users (243). The delivery device can detect activation when the user begins wearing the device (244). The delivery device can accept CGM BG data periodically, typically at 5 minutes (245).

[0116] At the start of wear, when the first blood glucose value is received, the dose calculator can calculate the dose that would be needed to correct the user to the target value, and this virtual dose can be immediately added to the IOB as an assumed IOB (246). The assumed IOB can be calculated by common methods known to those skilled in the art. This virtual dose is an assumed amount of external insulin that may have been administered before activation of the delivery device. The first blood glucose value on which the assumed IOB is based can be averaged over the set of first blood glucose measurements and / or filtered to prevent outliers from being used.

[0117] The next BG value, which may have been processed or evaluated, is received from the CGM and may be smoothed with a low pass filter to reduce the effects of noise and sudden perturbations 247. If the BG value is trending downward over time, this downward trend may be projected forward and added to the actual BG used in the dose calculator 248, effectively decreasing the insulin dose if the BG is drifting downward.

[0118] A dose calculator may be run at each CGM time point to determine if insulin is needed to bring the user to goal (249). The basic calculator uses equation (1):

[0119] (1) Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB

[0120] If the result is a positive number, the delivery device can deliver a dose of the corresponding size, with the following limitations: The maximum dose given at any one time may be limited to a small amount (e.g., 0.5 units) to further minimize sudden corrections (250). The dose may be limited by the hardware resolution and the minimum dose increment (e.g., 0.1 units).

[0121] It may be determined whether a next BG value has been received (251). If a next BG value has been received, the method may loop to repeat filtering (247), trend evaluation (248), and dose calculation (249) and delivery (250). If it is determined (251) that there is not a next BG value, the method may end (252).

[0122] Exemplary Methods for Calculating Correction Dose An exemplary embodiment of a method for calculating the correction dose is described, which uses equation (1).

[0123] (1) Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB

[0124] Current_BG is the measured blood glucose level that may be evaluated before applying to the formula, for example to filter the instantaneous reading or to adjust for long term trends. Target_BG is the user's target blood glucose level, which may be set as a constant value for all users at the start of the fasting period.

[0125] The target blood glucose level can be a safety factor higher compared to standard clinical recommendations (e.g., the target is 5%, 10%, 20%, 25% higher than the standard recommendation of 100-120 mg / dL (e.g., 130-180 mg / dL)). The target blood glucose level can optionally be time-varying based on the time elapsed since initialization of the delivery device, such that the target blood glucose level starts out rising and drops over the time of the wear period. The rate at which the target blood glucose level drops can be assumed to be influenced (dropped) by exogenous basal insulin injected or ingested during the time period of progressive wear of the delivery device.

[0126] A fixed blood glucose target means that the method does not allow the user to modify the blood glucose target. In one example, a safety margin of 20 mg / dL is added above the typical 120 mg / dL BG target, and dose calculations are performed based on a fixed target of 140 mg / dL to further prevent hypoglycemia. This additional safety margin helps account for expected BG fluctuations due to sensor noise, basal drift, and dosing accuracy.

[0127] The ISF indicates how much one unit of insulin is expected to lower a particular user's blood glucose level. This is based on user-specific input, which may be sent from the application or the user's smart pen. It may be learned over time if the delivery device is used repeatedly over fasting periods. The ISF user-adapted parameter is the only user-adapted parameter available to the calculator. In some preferred embodiments, the ISF is biased towards less insulin delivery to reduce the risk of hypoglycemia, e.g., a safety factor (of 5%, 10%, 15%, 20%, 25%) may be applied, which, when used in the bolus calculator, results in a more conservative calculation of insulin delivery. In some embodiments, the ISF is initially set to a conservative default and / or pre-defined value (e.g., a relatively high ISF biased towards lower insulin administration) and may be adjusted and / or individualized over time, e.g., based on the difference between actual or assessed blood glucose measurements and expected blood glucose levels.

[0128] The ISF may be derived from the total daily basal dose (TDBD) requested by the user or provided via an application or smart pen. Using the TDBD can reduce variability due to user error. For example, to eliminate the chance of significant ISF error due to incorrect estimation, the user may be prompted to input the current TDBD amount (i.e., how much basal insulin has been taken in the past 24 hours), and the ISF is estimated based on this input rather than allowing it to be set manually. In general, the user is more likely to know this value and it is more likely to be accurate. Basing the ISF on the TDBD can reduce the probability of unsafe treatment parameters being entered into the calculator. There is a strong relationship between TDBD insulin usage and ISF, and as will be appreciated by those skilled in the art, the following numerical values ​​may be used: ISF=1700 / TDD (where TDD is the total daily dose, TDBD=0.47×TDD, and therefore ISF=800 / TDBD).

[0129] The assumed IOB indicates how much insulin is still active in the body from the previously externally received basal or bolus dose, which is subtracted from the correction dose. There are two types of IOB in this calculator: an assumed external IOB, calculated as a hypothetical amount of externally administered insulin required to correct the user's actual BG to the target BG, and a delivery device IOB, calculated based on the insulin delivered by the device described herein.

[0130] IOB can be considered as the sum of two subtypes of IOB: (1) Assumed IOB, which is the amount of externally administered insulin that would be needed to correct the user's actual initial BG to target_BG, and is assumed to have already been administered to the user; and (2) Delivered IOB, which is calculated based on the insulin actually delivered to the user by the fasting period delivery device (130) described herein. Since insulin is metabolized over time, IOB is adjusted over time based on the known duration of insulin action (DIA). DIA is the time it takes for a bolus of insulin to finish lowering blood glucose levels. The DIA time starts when the bolus is given and ends when the bolus no longer lowers blood glucose levels. An accurate DIA minimizes insulin stacking and low blood glucose levels (hypoglycemia) that can occur if boluses are administered too close together.

[0131] According to equation (1) above, the required insulin to be delivered is finally determined based on the difference between the user's actual real-time (or sufficiently recent in time, e.g. within 5 minutes) blood glucose level representation and the target blood glucose level. It is then scaled according to the user's insulin sensitivity representation and further reduced by the amount of insulin calculated to be already (or still) active in the user's body. However, the central focus of the disclosed method for calculating and / or controlling the delivery of one or more correction doses of insulin to a user during a fasting period is to prevent over-delivery or calculation of over-delivery of insulin and the associated hypoglycemia, especially since the user is expected to be asleep for most of the fasting period and has not eaten to provide any exogenous counterbalance to the insulin overshoot to the hypoglycemia. This makes it difficult to effectively guide blood glucose levels to a safe and healthy target in an appropriate time frame, since many unknown factors may affect the user's actual blood glucose level and short-term dynamics. For example, a user's short-term blood glucose readings can contain rapid and sometimes erratic fluctuations that do not necessarily accurately reflect long-term trends in the user's current blood glucose levels or the actual amount of insulin on-board that still affects those blood glucose levels. Further complicating the difficulty is that a user's insulin sensitivity can vary over time and certainly based on other physiological factors that are difficult to account for individually and directly, including but not limited to stress (e.g., cortisol release).

[0132] Thus, methods for calculating and / or controlling the delivery of one or more correction doses of insulin to a user during a fasting period, and devices and / or systems configured to perform such methods, at least partially solve various technical problems by utilizing the user's initial state(s) (e.g., the user's initial blood glucose level) to determine the amount of insulin (assumed IOB) that is assumed to still be active in the user's system from a previous non-fasting period. This assumption that initial insulin is sufficient despite initially elevated blood glucose levels prevents insulin stacking at the beginning of a fasting period that would result from inappropriately administering insulin in response to an initially above-target blood glucose level when insulin has already been administered.

[0133] Moreover, insulin has a finite rate of action to lower blood glucose levels. In other words, it takes a non-negligible amount of time for the delivered insulin to lower blood glucose levels. Thus, even the most accurate current blood glucose value is not necessarily an accurate indicator of what the actual blood glucose level will be, even for a short period of time in the future, without knowledge of the actual insulin already in the body for a particular user. And as time goes on, the body metabolizes the insulin onboard, reducing its effectiveness in lowering blood glucose levels. Thus, even the most accurate current blood glucose value and actual insulin onboard is not necessarily an accurate indicator of what the actual blood glucose level will be, even for a short period of time in the future, without knowledge of the actual determined insulin action (DIA) time for a particular user. For at least these reasons, utilizing the most accurate actual blood glucose value at each time point (e.g., each CGM BG reading) may not necessarily best achieve the goal of preventing over-delivery of insulin or calculations that over-deliver insulin. Rather, preventing over-delivery of insulin or preventing calculations that over-deliver insulin may be better accomplished by utilizing processed, estimated, and / or filtered surrogates of the user's actual blood glucose levels that more accurately represent long-term trends in the user's actual blood glucose levels in a manner that biases against over-delivery of insulin, while also attenuating, eliminating, or otherwise filtering out short-term noise and / or anomalies. Such processed, estimated, and / or filtered surrogates of actual blood glucose levels may be referred to herein as estimated blood glucose levels.

[0134] Such methods, devices and / or systems also solve, at least in part, various technical problems by utilizing one or more safety factors to dynamically adjust (e.g., scale and / or transform) one or more of the variables utilized to determine insulin dosage (e.g., target blood glucose level, ISF and / or expected and / or delivered portion of IOB) to prevent over-delivery of insulin or calculations to over-deliver insulin and associated hypoglycemia.

[0135] The result of the above formula (1) is a correction dose that can be divided into smaller amounts in the form of delivery portions based on the maximum delivery rate. The maximum delivery rate over time is the maximum amount of insulin administered over a determined time interval, the amount being in units of insulin, for example, 0.1 units, 0.2 units, 0.3 units, 0.4 units, 0.5 units, 0.6 units, 0.7 units, 0.8 units. The determined time interval can be a predefined time interval, for example, 5 minutes, 10 minutes, 15 minutes, or can be based on the interval at which blood glucose data is received. For example, if the dose calculation determines that insulin should be delivered, no more than the maximum dose of insulin can be delivered for 5 minutes, after which the dose calculation is re-run (every 5 minutes or a similar interval). The maximum dose can be calculated based on the maximum effect on the user over a predefined period of time, for example, a decrease of 10 mg / dL per 30 minutes. The maximum dose can depend on an ISF calculation derived from the total daily basal dose.

[0136] In one example, only small insulin doses are administered every 5 minute interval to gradually reduce the BG to the target, with larger corrections as "extended bolus doses." Each dose is limited to a maximum insulin reduction of 20 mg / dL based on the user's ISF. For example, for a user with an ISF of 40 mg / dL per unit, the maximum insulin given per interval is limited to a maximum of 0.5 units. For example, if the dose calculation is 2 units, this may be divided into 4 using 0.5 unit increments. The first increment of 0.5 units may be delivered, and when the next BG value reaches the 5 minute mark, the dose calculator will know that 0.5 units have been delivered and will continue to deliver the next 0.5 units, and so on, unless there is a change in the BG value such that the dose calculation requires an adjustment.

[0137] The calculated correction delivery portion is delivered at a fixed zero basal rate since there is no basal delivered by the described delivery device or otherwise, which is different compared to known continuous use pumps.

[0138] A blood glucose level is measured at the user. This may come from the blood glucose monitor to the application and / or via a connection to the cloud to the delivery algorithm. Blood glucose levels are received periodically from a continuous glucose sensor and may be processed in one or more of the following ways: Sudden increases in the measured actual BG may be filtered to reduce spikes. Increasing CGM values ​​may be filtered using a rolling average BG value to reduce the chance of overdosing insulin based on sporadic CGM noise or local BG fluctuations. The true CGM value may be used if it is less than the rolling average, so decreasing BG values ​​are taken into account immediately, but increases are filtered to avoid dosing at local peaks. Peak filtering provides a two-sided safety for the CGM values ​​used for decision making by providing additional filtering / smoothing for increasing blood glucose levels, but not decreasing blood glucose levels. Two-sided safety may be used since when the actual IOB is low, delivery of insulin is safe. However, when the actual IOB is higher, the method will not deliver insulin. Long-term trends may also be adjusted to forecast downward trends many hours into the future (e.g., 6 hours into the future). This provides a correction for basal drift in that it compensates (backs out) the insulin effect for trend adjustment.

[0139] The method may provide a safety factor or margin for any of the dose calculator's variables, including the target BG, IOB, and / or may be applied as a separate adjustment to the dose calculation. The safety factor may be based on the user's actual BG compared to the target BG, and the safety margin is time-varying. The safety margin may be applied once at the beginning of a session.

[0140] In one embodiment, a safety margin may be applied based on the assumption that the user has taken insulin from another source (called exogenous insulin) prior to application of the described delivery device, and that the taken insulin is sufficient to lower the current BG to the target BG at the user's initiation of the delivery device. The assumed exogenous IOB is based on a hypothetical amount of exogenous insulin required to correct the user's hyperglycemia, and is based on a comparison of the current BG to the target BG as follows:

[0141] [(Current_BG-Target_BG) / ISF]-IOB=0

[0142] The assumed external IOB is assumed from the above formula and may not be derived from known external insulin. The assumed IOB may have a time-varying profile based on the time elapsed since delivery device initialization based on the duration of insulin action (DIA), so that the assumed IOB decreases over the wear period. As the assumed IOB decreases, the dose calculation is corrected downward along the curve. The rate of decrease in the predicted blood glucose level / IOB is based on the assumption that blood glucose levels are affected by external insulin injected or ingested during the ongoing initialization / wear of the delivery device.

[0143] Considering the sufficiency of the assumed initial IOB means that the controller does not need to accept or use a known amount of external IOB information from the user. The corrective dose calculation can be accomplished without or knowledge of the external IOB input. The initial assumed external IOB (called the "assumed IOB") calculated from [(current_BG-target_BG) / ISF]-assumed IOB@t=0 is simpler for the user and reduces user error.

[0144] The calculation of the correction dose insulin delivery amount, including the assumed external IOB applied in the calculation, is performed iteratively with each received actual BG value using the preceding formula:

[0145] Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB

[0146] The assumed external IOB provides a safety margin, and the IOB in the dose_calculation is equal to the assumed external IOB + any active device IOB, where the active device IOB is the amount of insulin delivered after the start of use of the delivery device in the fasting period. The assumed external IOB can be decayed based on the duration of insulin action (DIA). In this way, if the safety margin is embodied as an assumed external IOB that decays over time, any dose calculation above 0 (or a threshold such as 0.1 units of insulin) represents an unexpected BG, or an incomplete external IOB, which is safely compensated for by delivering the difference (e.g., 0.1 units of insulin). The DIA or active insulin time is the time it takes for a bolus of insulin to finish lowering blood glucose levels. The DIA time starts when the bolus is given and ends when the bolus no longer lowers blood glucose levels. An accurate DIA minimizes insulin stacking and low blood glucose levels (hypoglycemia) that can occur if boluses are administered very close together.

[0147] In another implementation, the expected external IOB is compared to an actual duration of insulin action (DIA) calculated from actual or estimated BG as described elsewhere in this disclosure. In another implementation, the actual BG is compared to an expected BG calculated from the DIA. These values ​​and / or their comparisons can be used to create, calculate, determine, set, reset and / or select a safety factor or margin. The values ​​and / or comparisons can also be used to learn from the user's past experience with the safety margin to bias the insulin dose calculation towards delivery of less insulin in any unknown situation that may affect blood glucose levels. A fixed setting of the DIA may be used. This removes the opportunity for significant DIA error due to erroneous estimation. The pharmacokinetics / pharmacodynamics (PK / PD) of fast-acting insulins are well characterized to have a PK / PD peak at approximately 65 minutes, which correlates with a 6 hour DIA. Therefore, since the delivery device uses only fast-acting insulin, the DIA may be fixed at a value between approximately 5-7 hours, and is preferably fixed at 6 hours. This can be combined with a fixed time constant for IOB calculations (approximately 60-70 min) to avoid insulin stacking.

[0148] In some embodiments, the ISF varies over time. For example, many people are more insulin resistant in the morning, so a lower ISF is desirable during the morning portion of the fasting period (164). Thus, in some embodiments, the ISF may be set or reset based on the time of day. The ISF profile may use a learning algorithm configured to adjust the ISF based at least in part on the history of the user's effective ISF, blood glucose measurements and / or blood glucose target(s) during one or more previous fasting periods. In some embodiments, the ISF may be initially set to a conservative default value and / or a predefined value (e.g., a relatively high ISF) and adjusted / individualized over time based at least in part on a comparison between actual and expected BG trends / profiles in the context of correction doses already delivered to the user during the fasting period.

[0149] The insulin delivered from the delivery device can be based on the calculated device correction amount, with delivery uninformed by the actual external insulin onboard. In this case, the initial delivery dose is zero, since it is based on the assumption of a hypothetical situation where the IOB is sufficient. The delivery delivers at least a portion of the calculated amount, typically a small amount, for safety. For example, if a delivery portion of 0.5 units per 5-minute interval is set, a correction of 2 units is divided into a delivery portion of 4 x 0.5. In particular, after 5 minutes, when a new blood glucose value is received, the calculation may be re-run, and the ongoing correction delivery portion may be increased (more than 0.5 units) or decreased (less than 0.5 units).

[0150] The delivery may alternatively be a single correction dose, however delivery at the maximum delivery rate in smaller delivery portions allows for a slower and therefore safer correction, which is confirmed or updated each time a new actual BG is repeatedly received.

[0151] The described delivery device may be in the form of a fasting worn delivery device, so that the user would have used another therapy, such as an MDI, during non-fasting times. For example, the delivery device may be worn at night by a user who uses an MDI during the day. Use of an MDI during non-fasting times implies the presence of an external IOB. Thus, using a delivery device without an assumed IOB or without a known IOB is risky, as it is not informed by the amount of external insulin. In other embodiments, the IOB may be known from a first therapy used during non-fasting periods, and thus calculation of an assumed external IOB may not be required.

[0152] For example, a description of how blood glucose measurements may be evaluated according to block (229) of Figure 2B follows below with reference to Figures 3A-3D. Each of these may also be thought of as a way to implement a safety factor that allows for a bias towards less insulin delivery in any unknown circumstances that may affect blood glucose levels.

[0153] A method for determining such a slope for drift compensation is described in relation to Figure 3A. Figure 3A illustrates a use case in which a drift slope is determined for multiple true or evaluated blood glucose measurements within a time frame (300). The evaluated blood glucose measurements are evaluated at least in part by projecting forward a downward trend of the received blood glucose measurements and adding the downward trend to the blood glucose measurements used for dose calculation. The downward trend is determined based at least in part on the maximum negative slope between any received blood glucose measurement and the reference blood glucose measurement within a predefined time frame.

[0154] In some embodiments, the time window (300) may include a portion of the fasting period (164) of FIG. 1C. In some embodiments, a predefined time window (310) (e.g., a time greater than or equal to T1 occurs before the TO reference and a time less than or equal to T2 occurs before TO, T2>T1) before the reference (e.g., most recent or last) blood glucose measurement (302) is established, e.g., between T1 and T2 is 15-30 minutes or 30-60 minutes before the reference measurement (302). A slope is determined for each line connecting one of the blood glucose values ​​(303-306) within the predefined time window (310) with the reference measurement (302), the maximum slope is selected as representative of the drift over the time window (300), and an amount of downward adjustment is determined based on the selected slope and the length L of the expected period over which the downward drift should be extended (e.g., the reference 302 is reduced by an amount equal to its product with respect to the evaluation value 301). Selecting the maximum slope from the blood glucose level sufficient time prior to the reference measurement (302) solves the problem of underestimating blood glucose drift and thereby overestimating insulin requirements by proactively adjusting the true blood glucose level downward based on the fastest indicator of long-term decline in blood glucose during a predefined time frame to account for future drift.

[0155] In some embodiments, evaluating the received blood glucose measurements includes filtering the received blood glucose measurements as described in connection with Figure 3B. Figure 3B illustrates a use case in which a drift slope is determined for multiple true or evaluated blood glucose measurements within a time window (320). The evaluated blood glucose measurements are evaluated at least in part by fitting the received blood glucose measurements within a predefined time window to a trend having a median slope selected from multiple regression fitting slopes for different rolling subsets of the received blood glucose measurements within the predefined time window.

[0156] In some embodiments, the time frame (320) may include a portion of the fasting period (164) of FIG. 1C. In some embodiments, a linear regression fitting slope, e.g., S1, is determined for all blood glucose readings within a rolling window (322) of a predefined interval (e.g., a 60 minute window from the first blood glucose reading to the last blood glucose reading in the window). The rolling window (322) is advanced by one or more blood glucose readings, and the linear regression fitting slopes, e.g., S2, S3, are redetermined for all blood glucose readings within the advanced rolling window (322). Thus, each time the blood glucose rolling window (322) advances, one previous blood glucose reading used in the previous regression fit moves out of the back of the window, and one next blood glucose reading not yet used in the previous regression fit moves in front of the window. In some embodiments, a rolling average may be determined for each of these slopes (e.g., S1, S2, S3) by averaging the value of each slope with a predefined number of previous slopes or immediately adjacent slopes. This serves to smooth out smaller fluctuations in the rate of change of the slopes (e.g., reducing the volatility of the changes). Next, the median (or other form of average) of the initial slopes (e.g., S1, S2, S3) in the time frame (320), or the median (or other form of average) of the rolling averages of each of those slopes, is selected as representative of the trend of blood glucose levels over the time frame (320) (e.g., slope S2), and the true blood glucose levels (black dots) are filtered or adjusted to match the selected trend line (e.g., see white dots with black outline) extending from the initial blood glucose level (321) in the time frame (320). Selecting a median slope (e.g., S2) from among the regression fitting slopes (e.g., S1, S2, S3) of blood glucose levels within a rolling window (322), or possibly from a rolling average of the regression fitting slopes, ensures that the value selected as indicative of the blood glucose trend over the time frame (320) is not driven by extreme perturbations in either direction occurring within the time frame (320).This solves the problem of over-delivering insulin in the context of any unknown variables that may affect blood glucose levels by limiting the rate of change of blood glucose fluctuations based on a moderately representative slope of the incoming blood glucose levels within the time frame of interest.

[0157] In some embodiments, evaluating the received blood glucose measurements includes filtering the received blood glucose measurements as described in connection with Figure 3C. Figure 3C shows a number of true and / or evaluated blood glucose measurements 903-909 from a recent time frame (340) from which blood glucose trends may be determined. A line, e.g., S, connecting each pair of adjacent blood glucose measurements is shown. 2-3 , S 3-4 , S 4-5 , S 5-6 , S 6-7 , S 7-8 , S 8-9 , the slopes are determined. In some embodiments, a rolling average of these slopes may be determined by averaging each slope value with a predetermined number of previous or immediately adjacent slopes. This serves to smooth out smaller fluctuations in the rate of change of the blood glucose measurement (e.g., reducing the volatility of the changes). The median of the initial slopes over the time frame (340), or the median of the rolling averaged slopes, is then selected as representative of the trend of the blood glucose levels over the time frame (340) (e.g., the slope S 6-7), along with the true blood glucose values ​​(342-349) (black dots) are filtered or adjusted to match a selected trend line (see, e.g., white dots with black outline) extending from the initial blood glucose value for the time frame (340). Selecting a median slope from among the individual slopes between adjacent true blood glucose values, or possibly from among a rolling average of the individual slopes between adjacent true blood glucose values, allows for a representation of the blood glucose trend over the time frame (340) and may better prevent over-delivery of insulin while still effectively guiding the user's blood glucose value towards the target range, and then maintaining blood glucose levels near the target during the fasting period (164). This solves the problem of over-delivering insulin in the context of any unknown variables that may affect blood glucose levels, by limiting the rate of change of blood glucose fluctuations based on the median slope between adjacent received blood glucose values ​​in the time frame of interest.

[0158] In some embodiments, evaluating the received blood glucose measurements includes filtering the received blood glucose measurements as described in connection with FIG. 3D. FIG. 3D shows a number of true or evaluated blood glucose measurements (363-368) from a recent time frame (360) from which blood glucose trends may be determined. The evaluated blood glucose measurements are evaluated at least in part by filtering the received blood glucose measurements. The filtering includes imposing progressively increasing limits on how much each next received blood glucose measurement may increase compared to the previous received blood glucose measurement for increasing received blood glucose measurements, and amplifying how much each next received blood glucose measurement may decrease compared to the previous received blood glucose measurement for decreasing received blood glucose measurements.

[0159] It is observed that the blood glucose readings (368, 367, 366) follow an increasing trend, plateauing at reading (365) and beginning to decline at readings (364, 363, 362). In some embodiments, the evaluation of the true received blood glucose readings includes imposing progressively increasing limits (e.g., L1, L2, and L3) on how much the next blood glucose reading may increase compared to the previous one if the true blood glucose reading is increasing (e.g., if the slope between adjacent true blood glucose readings is positive), the evaluation resulting in a deviation from the true BG reading indicated for readings (366 and 367), but amplifying the decrease (e.g., D1, D2, and D3) between the blood glucose reading and the next blood glucose reading if the true blood glucose reading is decreasing (e.g., if the slope between adjacent true blood glucose readings is negative), the evaluation resulting in a deviation from the true BG reading indicated for readings (362, 363, and 364). For example, if the next true blood glucose value is greater than the previous evaluated blood glucose value by a predetermined amount (e.g., L1, L2, and L3) while each true blood glucose value is greater than or equal to the previous value in the time frame (360), the next evaluated blood glucose value is set to be greater than the previous evaluated blood glucose value by a predetermined amount, increased by the predetermined amount, and the evaluation is repeated for the next true blood glucose value. However, if the next true blood glucose value is lower than the previous true blood glucose value, the next evaluated blood glucose value is set to a multiple (e.g., any decimal value greater than 1, 2 times is shown) of the difference between the next true blood glucose value and the previous true blood glucose value that is lower than the previous evaluated blood glucose value (e.g., D1, D2, and D3). This solves the problem of over-delivering insulin in the context of any unknown variables that may affect blood glucose values ​​by allowing the evaluated incoming blood glucose measurement to merge slowly with a rising CGM line that is rounding off a higher and wider peak than would typically be smoothed by a rolling average of blood glucose measurements, but quickly with a falling CGM line. This allows for the trending of blood glucose levels over a time frame (360) to more bias insulin over-delivery while effectively guiding the user's blood glucose levels towards the target range and then maintaining blood glucose levels near the target during fasting periods (164).

[0160] The delivery algorithm of the method for controlling delivery of insulin from a fasting-worn delivery device 130 may be implemented as self-contained in the controller 132 of the delivery device 130, or may be implemented using external processing for all or part of the delivery algorithm. For example, part of the evaluation of blood glucose measurements may be performed by a blood glucose monitor.

[0161] The controller (132) may be implemented in firmware that accepts GM blood glucose values ​​(e.g., via a Bluetooth interface or other wireless communication). The delivery algorithm works with the user's existing basal and meal bolus insulin so that, unlike other pump systems, the fasting delivery device only delivers correction doses. The delivery algorithm uses typical dose calculations and adjusts actual BG to target BG based on the user's ISF and IOB. The delivery algorithm includes safety mechanisms to reduce the possibility of over-correction and subsequent hypoglycemia.

[0162] Referring to FIG. 4, a block diagram illustrates an exemplary embodiment of a system including a delivery device (410) having a controller (410), such as the delivery device (130) described above having a controller (132) as shown in FIG. 1A. The controller (410) may include a power source (433) and a charging connector (434). The controller (410) may include a wireless communication module (413) for communicating over a wireless network (405) with a continuous glucose monitor (GCM) (403) for receiving a user's blood glucose measurement. The controller (410) may also communicate over the wireless network (405) with a mobile computing device (402), such as a mobile phone, laptop, or desktop computer. In some embodiments, the mobile computing device (402) may correspond to the mobile computing device (120) of FIG. 1A. In some embodiments, the glucose monitor (403) may correspond to the CGM (105) of FIG. 1A.

[0163] The controller (410) may include a microcontroller in the form of a processor (411) having firmware (412) that controls the operation of the delivery device (401). The firmware (412) may be provided by a component of the controller (410). The processor (411) may be a software unit that executes on at least one processor (411) or may be a hardware module or circuit that performs the functions of the described component. The memory may be configured to provide computer instructions to the processor (411) to perform the functions of the component.

[0164] The controller (410) may include a delivery component (420) that may communicate with the mobile computing device (402) and / or the user glucose monitor (403) and that determines when and how much of a dose to deliver from the reservoir (432) of the delivery device (401) via the dose delivery mechanism (431) of the delivery device (401). The delivery component (420) may include an initialization component (440) for an initial configuration phase of the delivery component (420) and a delivery phase component (450) for a delivery phase. The described components of the delivery component (420) may provide functionality corresponding to the drug delivery methods described herein, with particular reference to the steps of the flowcharts of Figures 2A, 2B, and 2C.

[0165] In some embodiments, the controller (410) may also be configured to cause the dose delivery mechanism (431) (or a similar separate mechanism of the glucagon device (401)) to deliver a predetermined and / or calculated amount of glucagon from a respective glucagon reservoir (similar to (432)) based at least in part on the blood glucose level falling below a predetermined low level (e.g., 40 mg / dl) and / or to maintain the blood glucose level at or above a predetermined safe level during episodes of intense user activity (e.g., exercise).

[0166] The initialization component (440) may include an activation component (446) for detecting activation of the delivery device to begin delivery of insulin. The initialization component (440) may include an insulin sensitivity factor (ISF) receiving component (441) for deriving an insulin sensitivity factor from total daily basal dose information received from the non-fasting insulin management modality for a defined period prior to the fasting period for use in determining a correction bolus dose. The initialization component (440) may include a safety factor component (442) for providing a safety factor to the parameters on which the dose correction is based.

[0167] The initialization component (440) may include an insulin on-board determination component (443) that includes an assumed insulin on-board component (444) for calculating an initial virtual correction bolus dose to correct the user's initial blood glucose measurement to a target blood glucose level, and a device insulin on-board component (445) for determining known delivered insulin from the delivery device.

[0168] The delivery phase component (450) may include a blood glucose measurement receiving component (451) for periodically receiving blood glucose measurements on which correction bolus doses during fasting periods are based. The delivery phase component (450) may include a measurement evaluation component (452) for smoothing the received blood glucose measurements using a low pass filter to reduce the effects of noise or sudden perturbations to obtain blood glucose values. The measurement evaluation component (452) may be for projecting forward received blood glucose measurements that are trending downward over time. The delivery phase component (450) may include a correction dose calculation component (453) for determining a correction bolus dose during fasting periods at each blood glucose measurement to determine when insulin is needed to bring the user to a target blood glucose value. The correction dose calculation component (453) may compare the blood glucose value to the target blood glucose value to obtain a difference adjusted by the user insulin sensitivity factor, and the dose blood glucose amount is compensated by the determined insulin on board. The delivery phase component (450) may include a correction dose limiting component (454) for limiting correction bolus doses during fasting periods to a defined maximum dose given at any time to minimize abrupt corrections. The correction dose limiting component (454) may be for limiting correction bolus doses during fasting periods to a minimum dose given at any time based on the delivery device hardware. The delivery phase component (450) may include a termination procedure component (455) for adjusting termination bolus delivery at the end of a fasting period. The delivery phase component (450) may also include a termination detection component (456) for detecting termination activity associated with the end of use of the insulin delivery device.

[0169] Referring to FIG. 5A, a flow chart (500) illustrates an exemplary embodiment of a method of using a delivery device for delivering insulin during fasting periods in the form of a wearable automatic insulin delivery (AID) device intended to be worn during fasting periods.

[0170] A user may receive basal and bolus doses of insulin using a first therapy during non-fasting periods within an overall period (such as a 24-hour period) (501). A first therapy in the form of a non-fasting insulin management modality may include a mode, method, device process, therapy, etc. used as an intervention in diabetes treatment. This may include pump delivery of insulin, pen or syringe injection of insulin, inhaled insulin, oral insulin, or any form of insulin management used when the user is awake. A non-fasting insulin management modality may also include a diet and exercise regimen in which insulin is administered at least part of the time without pharmaceutical intervention.

[0171] The user may use the fasting insulin delivery device during the fasting period of the entire period as an adjunct therapy to the first therapy (510). The fasting insulin delivery device is an automated insulin delivery device described herein wearable on the user's body for the duration of the fasting period that delivers a correction bolus dose in response to received blood glucose measurements and refrains from administering a background basal dose. The user does not need to interact with the delivery device to correct the bolus insulin during the fasting period when the user is normally asleep. The intended fasting period may be up to about 2 hours before the user goes to sleep and less than about 2 hours after waking up.

[0172] In one embodiment, a user may fill (502) the fasting insulin delivery device with insulin prior to use during a fasting period. Filling may be done by using insulin available from a first therapy. This allows for total insulin usage to be monitored since insulin is provided from a single source. Alternatively, filling may be provided from a separate source, especially if a different type of insulin is used in the delivery device compared to the first therapy. Filling may be performed by inserting a pre-filled cartridge or a partially filled cartridge from a previous usage session. Filling may be done from a vial, syringe, pen or other insulin administration device.

[0173] The user may apply the fasting insulin delivery device to their body during the fasting period (503). Application may be immediately or within a few hours after the last meal of the non-fasting period. The user may apply the delivery device before going to bed or after finishing their daily meal. The delivery device may be applied to the body with an adhesive to hold it in a predetermined position and a needle / cannula placed under the skin. The user may decide when to apply and remove the delivery device based on the individual's day-night cycle. The duration and time of the fasting period may vary from use to use for the same user. The user may be assisted in the use and application of the delivery device by a user application provided on the user's mobile computing device, e.g., a smartphone. The user application may recommend when to apply and remove the delivery device. The user application may provide coordination with the first therapy.

[0174] The user may provide insulin sensitivity information to set up the fasting insulin delivery device (504). This may be a one-time requirement when the user first uses the delivery device. This may be provided by the first therapy with or without the user's involvement. For example, a smart insulin pen may provide this information to the delivery device directly or via a user application. The insulin sensitivity information may be total daily basal dose information received from the first therapy in the preceding period. For example, the user may provide a normal daily dose of basal insulin provided by the first therapy. The insulin sensitivity information may be provided for at least the first use by the user of the delivery device, the delivery device including a durable portion for repeated use during multiple fasting periods. The method may not allow the user to provide information to the delivery device regarding one or more of the following parameters: amount of insulin delivered; duration of insulin action; target blood glucose level; basal rate (i.e., the delivery rate of basal insulin, background insulin, and / or baseline insulin required to maintain blood glucose level at the target value, specifically not including meal bolus doses); IOB; and insulin to carbohydrate ratio. The method may not allow the user to provide such parameters by not including parameter input means in the delivery device.

[0175] The user may perform start-up activities related to preparing the insulin delivery device for use during the fasting period (505). The user may receive insulin from the fasting insulin delivery device during the fasting period within the overall period. The fasting insulin delivery device may be an automatic insulin delivery device that is wearable on the user's body for the duration of the fasting period. The user may receive a correction bolus dose in response to the received blood glucose measurement without receiving any background basal dose from the fasting insulin delivery device (506).

[0176] The user may remove the delivery device from their body at the end of the fasting period 507. Removing means stopping the delivery of insulin via the delivery device by removing the delivery device from the body.

[0177] Removal may occur before or after an initial fast-breaking meal. The user may remove the delivery device after waking up or within about 2 hours of waking up. The user may remove the delivery device after determining the amount of additional insulin needed to cover a fast-breaking meal, as further described in connection with FIG. 5C.

[0178] The user may return to the first therapy when the fasting period ends and the delivery device is removed from the user's body (508). However, it is not necessary that the delivery device be removed before the first therapy is resumed. The reservoir of the delivery device may hold only the amount of insulin required for the fasting period, and therefore the reservoir may be nearly or completely empty. Any remaining amount in the reservoir may also be used by the fasting end bolus or a portion thereof.

[0179] In one embodiment, the fasting insulin delivery device is a wearable insulin reservoir pump that provides automatic insulin delivery (AID) without user interaction, and the first therapy is an insulin pen, which may be a smart pen. The pump may be configured such that the insulin delivered is from a single source and is filled by the insulin pen, as may be described accordingly.

[0180] Non-fasting insulin management modalities and fasting insulin delivery devices can provide adjunctive use in the form of complementary use of one modality with another to provide therapy to a user. Fasting insulin delivery devices can be used at regular or irregular intervals. For example, in a 24-hour period, a user can use the delivery device during regular sleep times, e.g., 12-hour, 10-hour, 8-hour, or 6-hour sleep times. However, other users may have a more irregular lifestyle and may require fasting periods to be at irregular times and durations.

[0181] The fasting insulin delivery device is individualized to the user and the delivery algorithm can learn from repeated use of the delivery device by the user. The delivery algorithm may learn one or more of the ISF, DIA, and can recommend a TDBD. The fasting insulin delivery device can provide a correction bolus dose. The correction bolus dose during the fasting period is supplemental to the meal bolus given during the non-fasting period, for example, when the meal bolus does not adequately cover the rise in blood glucose resulting from a meal, or when blood glucose remains elevated after a meal or meal bolus. This underfilled state can be due to an error in the bolus calculation, an error in the reported meal information, an error in the treatment parameters used in the treatment calculation, etc. Glycemic control during the fasting period is achieved by a short-term wearable insulin pump that provides AID control during fasting, allowing the user to sleep soundly and wake up in the target blood glucose range without having to wake up for a correction bolus. Daytime basal and daytime bolus doses are achieved by other types of therapy, such as MDI therapy.

[0182] The described method solves the problem of transition complexity for episodic use by providing a simplified system that allows for easier transition between two different diabetes management modalities. In one implementation, the system and method described herein allows seamless, intermittent, episodic use of MDI during the daytime cycle and AID during the nighttime cycle, thereby allowing users to benefit from lower costs, greater flexibility, and improved clinical outcomes. For example, diabetes management therapy with daily basal and daytime bolus administration is achieved by MDI therapy, while nighttime glycemic control is achieved by a short-term worn insulin pump that provides AID control during fasting. This allows users to sleep soundly and wake up in the target glycemic range without having to wake up for a correction bolus.

[0183] Referring to Figure 5B, a flow chart (520) illustrates an exemplary embodiment of a method of using a delivery device for delivering insulin during fasting periods in the form of a wearable automatic insulin delivery (AID) device that is worn only during fasting periods. The delivery device for delivering correction doses of insulin during fasting periods according to the described delivery method is a simple wearable insulin delivery device with limited user input or control due to safeguards and safety factors built into the delivery algorithm. The delivery device only accepts and handles fast-acting insulin for correction doses.

[0184] Use of the delivery device is based on the assumption of daily basal insulin and prandial bolus insulin provided by an MDI therapy (521) used by the user during non-fasting periods prior to use of the delivery device. MDI therapy may include external injection, ingestion or inhalation of insulin. In an exemplary embodiment, MDI therapy is provided by a smart insulin pen.

[0185] The user removes the delivery device from the charger (522). The delivery device may be charged during non-fasting periods, e.g., during the day, since it is only used by the user during fasting periods. The user may fill the reservoir of the delivery device with an amount of insulin (523). In one embodiment, the user may fill the reservoir using an MDI therapy device (523) such that the amount of insulin added to the reservoir is known and accounted for in MDI therapy. For example, the user may fill the delivery device using a smart insulin pen (523).

[0186] The user can apply the delivery device to their body and activate the delivery device (524) so ​​that it is ready to begin delivering insulin correction doses according to the described delivery algorithm applied by the controller of the delivery device. The user can provide information for an ISF (525) that is provided to the controller of the delivery device, either directly or via a user application or cloud server. This may be provided at the first time of repeated use of the delivery device, for example, if the delivery device is used every night. The ISF may be derived from a total daily basal dose (TDBD) requested by the user or provided via an application or smart pen.

[0187] The controller is configured to iteratively calculate a correction dose of insulin based on the following formula: Correction_Dose=[(Current_BG-Target_BG) / ISF]-IOB. This method does not obtain any other information from the user, except for information regarding ISF. This method does not require, accept, or use any other information from the following parameters or information: amount of insulin delivered; duration of insulin action; target blood glucose level; basal rate; IOB; insulin to carbohydrate ratio. The delivery algorithm does not require the reservoir to be filled during use.

[0188] The user receives correction doses from the delivery device during the fasting period (526). The user can optionally receive a fasting ending dose to cover a fast-ending meal (527). The fasting ending dose may be based on the remaining amount of insulin in the reservoir. The user can remove the delivery device from their body and place the delivery device back on the charger (528). The correction dose is the only insulin delivered by the delivery device. No basal dose is given. The amount of insulin delivered by the delivery device cannot be changed by the user other than by removing the delivery device from the body. If the dose calculation determines that insulin should be delivered, not more than the maximum dose of insulin is delivered over a defined interval (e.g., 5 minutes).

[0189] The duration of insulin action (DIA or active insulin time) may be fixed and cannot be changed by the user. A fixed setting is used to eliminate the chance of significant DIA error due to incorrect estimation. The target blood glucose value may also be fixed and cannot be changed by the user and may have an additional safety factor. The IOB is assumed as described above based on the initial blood glucose reading and is determined by the delivered dose given by the delivery device. An insulin to carbohydrate ratio is not required from the user since there are no meal bolus doses delivered, except for the optional fasting termination bolus. The insulin reservoir of the delivery device may be filled before wearing and is not refilled during the wearing time. The delivery of insulin is fully automated and there is no user control except for removal of the wearable device. No alerts or alarms are required in the delivery device.

[0190] 5C, a flow chart (520) illustrates an exemplary embodiment of a method of using a delivery device for delivering insulin during fasting periods in the form of a wearable automatic insulin delivery (AID) device intended to be worn during fasting periods. The flow chart (520) illustrates a fasting termination procedure in which at least a portion of the fasting termination meal bolus may be provided from residual insulin in a reservoir of the delivery device.

[0191] The user can receive correction bolus doses from the described delivery device during the fasting period (541). The user can provide information regarding a breaking fasting meal that requires a meal bolus at the end of the fasting period (542). A meal bolus refers to the amount of insulin required to compensate for the expected rise in blood glucose in a diabetic patient due to ingesting food. This compensation aims to bring the blood glucose level within a target range. Generally, a user who ingests some amount of carbohydrates will need insulin to avoid a resulting rise in blood glucose. Providing information related to the breaking fasting meal (542) can include providing information via user input via a connected insulin pen or user input from a user software application. The information can include meal information in the form of carbohydrates. The meal information can include blood glucose and IOB information.

[0192] The amount of bolus insulin recommended to cover the meal may be calculated based on the meal information, blood glucose data, and / or IOB information. The amount of insulin may be determined by a delivery device dose calculator in the delivery device, by the first therapy, or by a separate bolus calculator. If the user ends the fasting period within the target blood glucose range, the meal bolus calculation drives the delivery recommendation. If the user ends the fasting period with elevated blood glucose levels, additional units may be recommended to cover the increase.

[0193] The user may receive at least a portion of the total recommended bolus from the delivery device (543). The amount received from the delivery device may be based on the amount of insulin available in the delivery device at the end of the fasting period. If the delivery device does not contain the entire recommended bolus, the dose may be split.

[0194] The calculated recommended insulin bolus amount may be divided into a first portion and a second portion. By divided, we mean dividing the total recommended bolus amount into two separate portions that add up to the total recommended bolus amount. The first portion may be determined based on the remaining amount of insulin in the insulin reservoir of the delivery device. The remaining amount may be known, measured, or delivered and then reported. This may include automatic delivery from the delivery device with confirmation provided from the user application, as further described in connection with FIG. 7A or FIG. 7B. Alternatively, this may be using a control button on the delivery device to deliver the remaining insulin up to the maximum amount required for the recommended insulin bolus amount. For example, if 4 units of insulin remain in the reservoir of the delivery device, this will not be wasted when removing the patch, but rather the remainder may be delivered to the user. The second portion may be provided by another form of insulin therapy modality. This may be a first form of non-fasting therapy for a user who is currently at the beginning of a non-fasting period. The second portion is determined from the difference between the recommended bolus amount and the amount of bolus insulin remaining in the reservoir of the first modality. For example, if the meal bolus is 8 units, 4 units can be provided from the remainder in the reservoir and 4 units can be delivered by the insulin pen.

[0195] The user may receive instructions to administer the second portion via the non-fasting therapy (544). Alternatively, this may be automatically sent to a therapy device such as a smart insulin pen. Instructions to deliver the second portion with the first therapy may be sent to the user via a connected device such as a user smart insulin pen or via a user application. The IOB may also be sent to the user application or smart insulin pen for continuation of insulin delivery. This may be adjusted via a user application, which will be further described in connection with FIG. 7A, or via a separate therapy adjustment user application, which will be further described in connection with FIG. 7B. The user may receive any second portion from the non-fasting therapy (545) and remove the delivery device if not already removed (546).

[0196] 6A-6M, an exemplary embodiment of a delivery device in the form of an AID delivery device (130) is shown in a series of views of a user filling and application process. FIG. 6A shows a packaging arrangement (600) of the delivery device and associated equipment. A durable portion of the delivery device in the form of a controller (132) comprises a number of sealed packages (605), e.g., blister packs, each containing a disposable supply unit (601). The supply units (601) each include a reservoir (602) supported on a base (606) and a plunger (603) provided for controlled delivery of insulin from the reservoir (602) to a user via a cannula. The controller (132) is attached to the supply unit (133) to form the delivery device (130). In one configuration, the supply units (601) can include an attached coupler (604) that does not contain insulin in their reservoirs (602) for filling from an MDI treatment pen or syringe by using the coupler (604) to position the pen or syringe. The packaging configuration (600) may also include an applicator (135) and a charger (131) with a charging cable (608). Alternative embodiments may be configured to receive a pre-filled cartridge instead of a reservoir.

[0197] The supply unit (601) is provided in a sealed package (605) that is opened by a user to remove the supply unit (601) supported on a base (606), as shown in FIG. 6B. The supply unit (601) may include a coupler (604) for attaching (611) an insulin pen (110), as shown in FIG. 6C, to fill the reservoir (602). During filling of the reservoir (602), the plunger (603) is pushed backwards (612), as shown in FIG. 6D. The plunger (603) may be colored to allow the user to see the movement of the plunger (603). The insulin pen (110) is removed (613), as shown in FIG. 6E, and separated from the supply unit (601) with or following removal (614) of the coupler (604), as shown in FIG. 6F. The controller (132) is attached (615) to the supply unit (601) to form a delivery device (130) as shown in Figure 6G.

[0198] The push applicator (135) is attached (616) to the top of the delivery device (130) as shown in FIG. 6H and is configured to allow the delivery device to be detached (617) from the base (606) as shown in FIG. 6I. The delivery device (130) held within the applicator (135) is placed on the user's body as shown in FIG. 6J. The applicator's push button (607) is depressed (618) as shown in FIG. 6K, and a pushing force is applied by the user through the applicator (135) to attach the delivery device to the user's body by adhesive attachment. The applicator (135) is detached (619) from the delivery device (130) as shown in FIG. 6L, and the delivery device (130) is then ready to deliver correction doses during the fasting period. At the end of the fasting period, the delivery device (130) is removed (620) from the user's body as shown in FIG. 6M and placed back on the charger (135).

[0199] The applicator (135) can encircle and hold the top of the delivery device so that the delivery device can be removed from the base (606) with one hand or placed on the user's body with one hand. A push button (607) on the applicator (135) can create the appropriate force to remove the delivery device from the applicator (135) and press it onto the user's skin, so that the adhesive surface on the underside of the delivery device attaches to the user's skin and the cannula on the underside of the delivery device pierces the user's skin ready for insulin delivery.

[0200] 7A, a flow chart (700) illustrates an exemplary embodiment of a method for managing the delivery of insulin during fasting periods from a delivery device in the form of a wearable automatic insulin delivery device worn during fasting periods. The method is performed by a computer software application provided on a mobile computing device such as a smartphone or tablet. The computer software application may be an application for managing the described fasting period delivery device.

[0201] The method may register a user of the application (701) and provide a training step to instruct the user on how to use the delivery device, including filling from an insulin pen (702). The training step may be performed the first time the user uses the delivery device. The method may request user input of insulin sensitivity factor or total daily basal dose information (703), which may be used to set an ISF for the user. This may request the type of long-acting insulin used by the user, and how many units of long-acting insulin are typically taken per 24 hours. If this changes, the user may update this information. To set up the delivery device during fasting periods, the method may pair a mobile communication device running the application with a controller of the delivery device (704). The method may also pair a mobile communication device running the application with a blood glucose monitor worn by the user (705). The pairing may be via short-range wireless communication technology, for example using Bluetooth. The application may include instructions for pairing. The method may provide the user's ISF to a delivery algorithm in the controller of the delivery device for use in calculating correction doses (706).

[0202] During the fasting period (707), the method can receive records of monitored blood glucose measurements from the glucose monitor and send these to the controller for calculation of correction bolus doses (708). Alternatively, these can be sent directly from the glucose monitor to the controller. In another alternative, the glucose monitor can be integrated into the delivery device and provided within the controller. Filtering and prediction of blood glucose measurements can be performed in the application to send estimated blood glucose values ​​to the controller for use in the delivery algorithm. The method can receive records of correction bolus doses given by the delivery device (709).

[0203] The method may include a fasting termination procedure in which the method may receive fasting termination input from the user and send the input to the delivery device controller (710). The method may receive details of a fasting termination bolus dose from the controller (711). The method may notify the user of the fasting termination procedure (712) with instructions to supplement the fasting termination dose of the delivery device with an insulin pen. Steps (710) and (711) may be performed during the fasting period (707) or at the time the user breaks a fast. The method may provide a session history (713) including a display of a correction dose provided by the delivery device along with the blood glucose measurement and with additional statistics for user information. Session history for previous sessions may also be provided.

[0204] Referring to Figure 7B, a flow chart (720) illustrates an exemplary embodiment of a method for managing delivery of insulin when using fasting periods from a delivery device in the form of a wearable automatic insulin delivery device worn during fasting periods. The method is performed by a computer software application provided on a mobile computing device such as a smartphone or tablet. The computer software application may be a reconciliation application for reconciling a non-fasting insulin therapy, such as an MDI therapy using a smart insulin pen, with the use of a fasting delivery device.

[0205] The method can register (721) a user of the application and record user information regarding the user's insulin needs. The method can receive (722) information regarding a non-fasting insulin regimen used by the user for the entire period. This information may be received from a non-fasting regimen device, such as a smart insulin pen or an application managing the use of the non-fasting regimen device. Alternatively, this information may be received from the user. The method can receive (723) information regarding a fasting delivery device that delivers a correction bolus dose within the entire period of fasting. This information can be received from a controller of the delivery device or from a separate application managing the user of the delivery device.

[0206] The method can provide adjustments between non-fasting and fasting therapies and doses (724). The method can include providing recommendations to the user (725). The adjustments can include providing ISF to the delivery device based on use of the non-fasting therapy. The adjustments can include providing ISF at the end of use of the delivery device. The adjustments can provide additional parameter information for adjustments between therapies including insulin onboard and basal drift at transitions between therapies.

[0207] The recommendations may include optimizing a daily basal dose to help a user adjust basal insulin during non-fasting periods. The recommendations may include indicating the amount of insulin to load into the delivery device during fasting periods. The recommendations may include whether and when to use a delivery device within an overall period, including when to apply the delivery device within the overall period. The recommendations may include adjusting a therapy or therapy parameters.

[0208] The method can provide (726) predicted outcomes associated with adjustments to treatment or treatment parameters (e.g., improved time in range) of the non-fasting therapy device and fasting delivery device, where the adjustments are represented by hypothetical scenarios. For example, a scenario can be predicted of what would happen to the user's blood glucose levels if the user wears the delivery device for x to y hours overnight. In another example, a scenario can be predicted of what would happen if the user does not wear the delivery device overnight, and the possible outcomes. In a further example, a scenario can be predicted of what could be the possible outcomes if the daily basal dose is changed from x to y. In one embodiment, the implementation can upload and analyze a user's data to determine the relative benefit of the described delivery device over an existing non-fasting therapy, for example, based on an increase in time in range (TIR).

[0209] Figure 7C illustrates a use case with time extending vertically from the top to the bottom of the diagram and interactions shown as horizontal lines with arrows extending between devices and / or entities involved in a method of insulin management for delivering insulin during fasting periods (164) and / or a method of coordinating insulin management of such fasting periods (164) with another treatment modality utilized during non-fasting periods (162), according to some exemplary embodiments. Figure 7C illustrates a non-limiting exemplary use case including a user (101), an insulin pen (110), a delivery device (130), and a mobile device (120), as previously described in connection with Figure 1A or elsewhere in this disclosure. In a non-limiting example, the user (101) may be a type 1 diabetes patient who requires consistent insulin therapy during both non-fasting periods (162) and fasting periods (164).

[0210] As shown, a user (101) initially operates a non-fasting period (162) during which the user (101) can self-administer a slow-acting 24-hour basal insulin dose (170a) and fast-acting prandial bolus doses (172a-172d), for example, utilizing a different insulin pen, e.g., insulin pen (110).

[0211] At some point during the non-fasting period (162), the user may interact with the mobile device (120) and execute a calibration application for using the fasting delivery device (130) with a non-fasting insulin regimen, for example, to register the user with the app (701, 721). Upon registration, the calibration app may be configured to provide a user training process (702) that instructs the user on how to use the delivery device (130), including refilling from an insulin pen (110). The calibration app may then pair (e.g., wireless communication pairing) (704 / 705) with the controller of the delivery device (130) and the CGM (e.g., shown integral with the delivery device (130), but which may be separate devices). Once registration and pairing are complete, the calibration app may request (703) an ISF or TDBD to determine an ISF, and the user may provide (706) the ISF or TDBD to the mobile device (120), as described elsewhere in this disclosure. If the ISF is determined rather than provided by a user, the mobile device (120) may determine the ISF as described elsewhere herein and provide the ISF to the delivery device (130) (e.g., the delivery device controller (132)).

[0212] The user may then perform an initiating action (201) as described elsewhere in this disclosure. In some embodiments, this may include loading the delivery device (130) with insulin, as described in connection with at least Figures 6A-6M. Once the initiating action is detected (201), the delivery device (130) calculates and delivers correction doses (180a-180d) to the user (101) in response to the user's actual and / or assessed blood glucose levels during the fasting period (164), for example, as described elsewhere in this disclosure.

[0213] At some point, the user performs a termination activity (204) to signal a fasting termination procedure at the end of the fasting period (164). When this termination activity (204) is detected, the fasting termination procedure may be entered. In some embodiments, where the user's blood glucose level is at target or within the target range after the fasting termination procedure begins, a final correction dose (180e) may not be delivered to the user. However, if the user's blood glucose level is above target, for example, for reasons described elsewhere in this disclosure, the delivery device (130) may deliver a fasting termination bolus (180e) to the user.

[0214] In yet another embodiment, the user intends to eat a meal at the beginning of the upcoming non-fasting period (162). In such an embodiment, the user provides information (710) about the expected next fast-breaking meal (e.g., carbohydrate information, etc.) to the mobile device (120), which provides such details to the delivery device (130). Based on the meal information and the current blood glucose level, the delivery device (130) determines a fast-breaking meal bolus and delivers it as a bolus to the user (180e). As mentioned above, in some cases, the calculated fast-breaking meal bolus is greater than the amount of insulin remaining in the delivery device (130). In such a case, the bolus (180e) includes the remaining insulin in the delivery device (130), which then transmits the fast-ending bolus (180e) details (including how much insulin is still to be delivered via the smart pen (110)) to the mobile device (120) which receives (711). The remainder of the calculated fast-ending meal bolus is manually delivered by the user via the smart insulin pen (110) during the non-fasting period (162). For example, the mobile device (120) may notify the user of an ending procedure (712) in which the user delivers a fasting ending bolus via the smart pen (110) during the non-fasting period (162). In some embodiments, the mobile device (120) may be configured to send instructions and / or dosing information for this fasting ending bolus to the smart pen (110), thereby allowing the smart pen (110) to be pre-configured to deliver this fasting ending bolus.

[0215] Referring to Figure 8, a block diagram illustrates an exemplary embodiment of a system including a mobile computing device (402), such as a mobile phone, laptop, or desktop computer. The mobile computing device (402) may communicate with a delivery device (401), such as the delivery device (130) described above, via a wireless network (405). The mobile computing device (402) may also communicate with a continuous glucose monitor (GCM) (403) via the wireless network (405) for receiving a user's blood glucose measurements. The mobile computing device (402) may include a wireless communication module (806).

[0216] The mobile computing device (402) may include a processor (802) for performing the functions of the components described below, which may be provided by hardware or by a software unit executing on the mobile computing device (402). The software unit may be stored in a memory component (804), and instructions for performing the functions of the described components may be provided to the processor (802). In some cases, for example in cloud computing implementations, a software unit configured to manage and / or process data on behalf of the mobile computing device (402) may be provided remotely. Some or all of the components may be provided by software applications downloadable and executable on the mobile computing device (402).

[0217] The delivery device application (810) may be provided by a hardware or software unit for managing the described fasting delivery device. The delivery device application (810) may include a registration component (811) for registering a user of the application and a user training component (812) for providing a training process instructing the user on how to use the delivery device, including filling from an insulin pen. The delivery device application (810) may include a basal insulin input component (813) for prompting and receiving user input of total daily basal dose information, which is used to set an ISF for the user. The delivery device application (810) may include a controller pairing component (814) for pairing the mobile communication device (402) running the delivery device application (810) with the controller of the delivery device (401). The delivery device application (810) may include a glucose monitor pairing component (815) for pairing the mobile communication device (402) running the application (810) with a blood glucose monitor (403) worn by the user. The delivery device application (810) may include an ISF provision component (816) for providing the user's ISF to a delivery algorithm of the controller of the delivery device (401) for use in calculating the correction dose.

[0218] The delivery device application (810) may include a blood glucose providing component (817) for receiving monitored blood glucose measurements from the glucose monitor (403) and transmitting these to the controller for calculation of a correction bolus dose. The application (810) may include a dose calculating component (818) for performing one or more of the steps of calculating a correction bolus dose, for example, as described elsewhere in this disclosure. The dose calculating component (818) may function in conjunction with the controller (310) of the delivery device (301). The dose calculating component (818) may function in conjunction with a remote server. The application (810) may include a dose receiving component for receiving a record of a correction bolus dose provided by the delivery device.

[0219] The delivery device application (810) may include a fasting termination component (819) for providing a fasting termination procedure in which the delivery device application (810) may receive fasting termination input from the user, transmit the input to the controller, receive fasting termination bolus dose details from the controller, and notify the user with instructions to supplement the delivery device's fasting termination dose with an insulin pen or other therapy. The delivery device application (810) may include a session history component (820) for providing a session history, including a display of correction doses provided by the delivery device along with blood glucose measurements, and additional statistics for user information. Session history for previous sessions may also be provided.

[0220] The therapy adjustment application (820) may be provided by a hardware or software unit for managing the described fasting delivery device. The therapy adjustment application (820) may be provided independently of the delivery device application (810). The therapy adjustment application (820) may be combined with or interact with the delivery device application (810). The therapy adjustment application (820) may include a registration component (821) for registering users of the application and may record user information regarding the user's insulin needs. The therapy adjustment application (820) may include a non-fasting therapy component (822) for receiving information regarding a non-fasting insulin therapy used by the user at any given time. This information may be received from a non-fasting therapy device, such as a smart insulin pen, or an application managing the use of the non-fasting therapy device. Alternatively, this information may be received from the user. The therapy adjustment application (823) may include a delivery device therapy component (823) for receiving information regarding a fasting delivery device that delivers a correction bolus dose within a total fasting period. This information may be received from a controller of the delivery device or from the delivery device application (810).

[0221] The therapy adjustment application (820) may include an adjustment component (824) for providing an adjustment between non-fasting and fasting therapy and dosage. The therapy adjustment application (820) may include a recommendation component (825) for providing recommendations to the user. The recommendations may include recommending that the user utilize the delivery device for a recommended time frame overnight; and recommending that the user adjust the daily basal dose of insulin to a different value from the current value. The therapy adjustment application (820) may include a prediction component (826) for providing predictions to the user. The one or more predictions may include one or more of the following: a prediction of the user's awake blood glucose level if the user utilizes the delivery device for a recommended time frame overnight; a prediction of the user's awake blood glucose level if the user adjusts the daily basal dose of insulin to a different value from the current value; and a prediction of the user's awake blood glucose level if the user does not utilize the delivery device overnight.

[0222] 9 illustrates an example of a computing device (900) capable of implementing various aspects of the present disclosure. The computing device (900) may be embodied as any form of data processing device, including a personal computing device (e.g., a laptop or desktop computer), a server computer (which may be self-contained or physically distributed across multiple locations), a client computer, or a communications device, such as a mobile phone (e.g., a cellular phone), a satellite phone, a tablet computer, a personal digital assistant, etc. Different embodiments of the computing device may dictate the inclusion or exclusion of various components or subsystems described below.

[0223] The computing device (900) may be adapted to store and execute computer program code. The various participants and elements of the foregoing system diagrams may employ any suitable number of subsystems or components of the computing device (900) to facilitate the functions described herein. The computing device (900) may include subsystems or components interconnected via a communications infrastructure (905) (e.g., a communications bus, a network, etc.). The computing device (900) may include one or more processors (910) and at least one memory component in the form of a computer-readable medium. The one or more processors (910) may include one or more of a CPU, a graphical processing unit (GPU), a microprocessor, a field programmable gate array (FPGA), an application specific integrated circuit (ASIC), and the like. In some configurations, multiple processors may be provided and may be configured to perform calculations simultaneously. In some implementations, various subsystems or components of the computing device (900) may be physically distributed across multiple locations (e.g., in a distributed, clustered, or cloud-based computing configuration), and appropriate software units may be configured to manage and / or process data on behalf of the remote devices.

[0224] The memory component may include a system memory (915), which may include read-only memory (ROM) and random access memory (RAM). A basic input / output system (BIOS) may be stored in the ROM. System software may be stored in the system memory (915), including operating system software. The memory component may also include a secondary memory (920). The secondary memory (920) may include a fixed disk (921), such as a hard disk drive, and optionally one or more storage interfaces (922) for interfacing with a storage component (923). The storage component (923) may be a removable storage component (e.g., magnetic tape, optical disk, flash memory drive, external hard drive, removable memory chip, etc.), a network attached storage component (e.g., NAS drive), a remote storage component (e.g., cloud-based storage), etc.

[0225] The computing device (900) may include an external communication interface (930) for operation of the computing device (900) in a network environment that enables transfer of data between multiple computing devices (900) and / or the Internet. Data transferred via the external communication interface (930) may be in the form of electrical, electromagnetic, optical, radio, or other types of signals. The external communication interface (930) may enable communication of data between the computing device (900) and other computing devices, including servers and external storage facilities. Web services may be accessible by and / or from the computing device (900) via the communication interface (930).

[0226] The external communication interface (930) may be configured to connect to a wireless communication channel (e.g., a cellular network, a wireless local area network (e.g., using Wi-Fi), a satellite telephone network, a satellite Internet network, etc.) and may include associated wireless transfer elements such as an antenna and associated circuitry. The external communication interface (930) may include a subscriber identity module (SIM) in the form of an integrated circuit that stores an international mobile subscriber identifier and associated keys used to identify and authenticate a subscriber using the computing device (900). One or more subscriber identity modules may be removable from the computing device (900) or may be incorporated into the computing device (900).

[0227] The external communication interface (930) may further include a contactless element (950), which is typically implemented in the form of a semiconductor chip (or other data storage element) with an associated wireless transfer element such as an antenna. The contactless element (950) may be associated with (e.g., embedded in) the computing device (900), and data or control instructions transmitted over the cellular network may be applied to the contactless element (950) by a contactless element interface (not shown). The contactless element interface may function to enable the exchange of data and / or control instructions between the computing device circuitry (and thus the cellular network) and the contactless element (950). The contactless element (950) may be capable of transmitting and receiving data using a near-field communication capability (or near-field communication medium), typically according to a standardized protocol or data transfer mechanism (e.g., ISO 14443 / NFC). The near-field communication capabilities may include short-range communication capabilities, such as radio frequency identification (RFID), Bluetooth, infrared, or other data transmission capabilities, and may be used to exchange data between the computing device 900 and an interrogation device. Thus, the computing device 900 may be capable of communicating and transmitting data and / or control instructions via both a cellular network and near-field communication capabilities.

[0228] Computer-readable media in the form of various memory components may provide storage of computer-executable instructions, data structures, program modules, software units, and other data. A computer program product may be provided by a computer-readable medium having computer-readable program code stored thereon that is executable by a central processing unit, the processor (910). The computer program product may be provided by a non-transient or non-transitory computer-readable medium, or may be provided by a signal or other transitory or transitory means via the communications interface (930).

[0229] Interconnected via a communications infrastructure (905), one or more processors (910) may communicate with each subsystem or component and control the execution of instructions from the memory components and the exchange of information between the subsystems or components. Peripherals (e.g., printers, scanners, cameras, etc.) and input / output (I / O) devices (e.g., mice, touch pads, keyboards, microphones, touch-sensitive displays, input buttons, speakers, etc.) may be coupled to the computing device (900) directly or through an I / O controller (935) or may be integrally formed with the computing device (900). One or more displays (945), which may be touch-sensitive displays, may be coupled to the computing device (900) through a display or video adapter (940) or may be integrally formed with the computing device (900).

[0230] The computing device (900) may include a geographic location element (955) configured to determine a geographic location of the computing device (900). The geographic location element (955) may be implemented, for example, by a Global Positioning System (GPS) or similar receiver module. In some implementations, the geographic location element (955) may implement an indoor positioning system that determines or approximates the geographic location of the computing device (900) using communication channels such as, for example, cellular or Wi-Fi networks and / or beacons (e.g., Bluetooth Low Energy (BLE) beacons, iBeacons, etc.). In some implementations, the geographic location element (955) may implement inertial navigation to track and determine the geographic location of the communication device using initialization points and inertial measurement data.

[0231] 10A-10E are graphs illustrating an exemplary storyline of a user using a fasting delivery method, for example, during an overnight fasting session. The lines may represent either BG or IOB, since one may be derived from the other. The axis represents blood glucose (BG) as depicted by the graph, but the lines may represent either BG or IOB (with different labels and values ​​for IOB, of course), since one may be derived from the other. Actual BG and predicted BG may be derived from actual IOB and assumed IOB, or vice versa, as would be understood by one skilled in the art.

[0232] 10A is a graph (1010) depicting blood glucose levels over time during a fasting wearing session. The solid line represents the actual BG trend / profile over time as measured by the CGM. The small dashed line represents the predicted BG trend / profile over time based on an assumed external IOB profile calculated at the start of the session based on assumed insulin sufficiency as described above. The larger dashed line represents the device IOB calculated from the insulin delivered by the delivery device.

[0233] FIG. 10B is a graph (1020) depicting blood glucose levels over time during a fasting wear session. The small dashed line represents the actual BG trend / profile over time as measured by the CGM. The solid line represents the predicted BG trend / profile based on an assumed external IOB. In this example of a wear session, the actual BG / IOB matches the predicted / assumed BG / IOB, so the assumption that external insulin was sufficient was true and there was no need to administer device insulin. In particular, without the safety factor and / or any unknown circumstances that may affect blood glucose levels as described herein, particularly biasing towards less insulin delivery in conjunction with the assumed IOB calculation and utilization, the device would have erroneously delivered insulin at the beginning of the session if not informed by external insulin, resulting in a dangerous overnight hypoglycemic event.

[0234] FIG. 10C is a graph (1030) representing blood glucose levels over time during a session. The solid line represents the actual BG trend / profile over time as measured by the CGM, showing an example where the actual blood glucose level is not trending downward as expected. This means that the user likely did not take a sufficient meal bolus at dinner or before applying the delivery device to start the fasting period. The small dashed line represents the predicted BG trend / profile based on the assumed external IOB profile over time calculated at the start of the session based on assumed insulin sufficiency as described above. The vertical lines represent diagrammatically the period(s) where insulin was administered at a low dose. Notably, the assumed external IOB was actually at an incorrect level, but the algorithm was able to quickly learn that the external IOB was not sufficient and was able to deliver correction insulin to ensure the user woke up within the target range.

[0235] FIG. 10D is a graph (1040) representing blood glucose levels over time during a session where BG drops more than expected overnight. The dashed line represents the actual BG trend / profile over time as measured by the CGM, showing an example where the actual blood glucose level dropped unexpectedly towards hypoglycemia early during the session. This means that the user took too much meal bolus insulin at dinner or before applying the delivery device. The solid line represents the expected BG trend / profile based on the assumed external IOB profile over time calculated at the beginning of the session based on the assumed insulin sufficiency as described above. Notably, the delivery device did not deliver insulin at the beginning of the session despite being above target because it implemented a safety factor and / or biased to deliver less insulin in any unknown situation that may affect blood glucose levels as described herein. This use case also shows the benefit of adjusting the assumed IOB upwards when initial blood glucose levels rise at the beginning of the fasting period. By adjusting the assumed IOB upwards to account for such an initial rise in blood glucose levels instead of administering insulin, a potentially dangerous hypoglycemic event was further avoided. If insulin had been delivered in response to an initial blood glucose level higher than the standard clinical target, the result would have been a more severe overnight hypoglycemic event.

[0236] FIG. 10E is a graph (1050) representing blood glucose levels over time during a session, showing a session where the actual BG slowly rises towards the end of the session (e.g., dawn effect). The solid line represents the trend / profile of actual BG over time as measured by the CGM, showing an example of actual blood glucose rising towards the end of the session (dawn effect), which may be caused by external basal insulin or other physiological factors. The vertical lines generally represent the period(s) during which a correction dose of insulin was delivered by the delivery device dose calculation. As the safety margin decreases over time, particularly assuming a decreasing likelihood of external insulin, the delivery device delivered enough insulin to mitigate the "dawn effect" that some MDI users would otherwise experience. Advantageously, the delivery algorithm allows daytime MDI diabetes management users to benefit from continuous AID wear at night, increasing time in range without increasing hypoglycemia risk.

[0237] The above description has been presented for purposes of illustration and is not intended to be exhaustive or to limit the invention to the precise form disclosed. Those skilled in the art will recognize that many modifications and variations are possible in light of the above disclosure.

[0238] Any of the steps, operations, components or processes described herein may be executed or implemented in one or more hardware or software units, alone or in combination with other devices. In one embodiment, the software units are implemented in a computer program product including a non-transient or non-transient computer readable medium containing computer program code that can be executed by a processor to perform any or all of the described steps, operations or processes. The software units or functions described in this application may be implemented as computer program code using any suitable computer language, such as, for example, Java, C++, or Perl, using conventional or object-oriented techniques. The computer program code may be stored as a sequence of instructions or commands on a non-transient computer readable medium, such as a random access memory (RAM), a read-only memory (ROM), a magnetic medium such as a hard drive, or an optical medium such as a CD-ROM. Any such computer readable medium may also be present on or within a single computing device, or on or within different computing devices in a system or network.

[0239] Flowchart diagrams and block diagrams of methods, systems, and computer program products according to the embodiments are used herein. Each block of the flowchart diagrams and / or block diagrams, and combinations of blocks in the flowchart diagrams and / or block diagrams, may provide functions that may be implemented by computer-readable program instructions. In some alternative implementations, the functions identified by the blocks may occur in an order different from that shown in the flowchart diagrams.

[0240] The computer program product may include one or more computer-readable hardware storage devices having computer-readable program code stored therein, the program code being executable by one or more processors to perform the methods described.

[0241] Some portions of this specification describe embodiments of the invention in terms of algorithms and symbolic representations of operations on information. These algorithmic descriptions and representations, such as the accompanying flowcharts, are commonly used by those skilled in the data processing arts to effectively convey the substance of their work to others skilled in the art. These operations, while described functionally, computationally, or logically, are understood to be implemented by computer programs or equivalent electrical circuits, microcode, or the like. The described operations may be embodied in software, firmware, hardware, or any combination thereof.

[0242] The language used herein has been selected primarily for ease of reading and explanation purposes, and may not have been selected to delineate or limit the subject matter of the invention. Accordingly, it is intended that the scope of the invention be limited not by this detailed description, but rather by any claims asserted in an application based hereon. Accordingly, the disclosure of embodiments of the invention is intended to be illustrative, but not limiting, of the scope of the invention, which is set forth in the appended claims.

[0243] Finally, throughout this specification and the appended claims, unless the context indicates otherwise, the word "comprise" or variations such as "comprises" or "comprising" are understood to imply the inclusion of a stated integer element or group of integers, but not the exclusion of any other integer element or group of integer elements.

Claims

1. An insulin management system for an insulin delivery device (130, 401) in the form of an automated insulin delivery device that can be worn on the user's body during fasting periods throughout the entire period, A startup component (446) configured to detect initiation activity related to preparing the insulin delivery device for use, A delivery component (420) configured to initiate automatic delivery of insulin in the form of a corrected bolus dose in response to received blood glucose measurements regularly received during the fasting period, A system that includes this.

2. The system according to claim 1, further comprising an termination detection component (456) configured to detect termination activity related to the termination of use of the insulin delivery device.

3. The system according to claim 1, wherein the initiation activity has a primary function other than initiating the automatic delivery of insulin from the insulin delivery device, and is simultaneously reused as an instruction to initiate the automatic delivery of insulin from the insulin delivery device.

4. The startup component (446) performs the following as the start activity: The aforementioned initiation activity is the arrival of a predetermined time each day. Removal of the insulin delivery device from the charger, and Attachment of a disposable insulin supply unit to the insulin delivery device, The system according to claim 1, configured to detect one or more of the following.

5. The startup component (446) performs the following as the start activity: The attachment of the insulin delivery device to the user, Removal of the applicator of the insulin delivery device from the insulin delivery device, and A verbal instruction or selection by the user indicating a desire to initiate automated insulin delivery, The system according to claim 1, configured to detect one or more of the following.

6. The startup component (446) performs the following as the start activity: Proximity or pairing of the controller of the insulin delivery device with a user computing device on which a user application related to the insulin delivery device is installed. Proximity or pairing of the controller of the insulin delivery device with the smart insulin pen, Proximity or pairing of the controller of the insulin delivery device with the blood glucose monitor, Receiving blood glucose monitor readings, The fill level of the insulin reservoir of the disposable insulin supply unit, indicating that the insulin reservoir is sufficiently filled to initiate the automatic delivery of insulin, and The movement of the plunger in the insulin reservoir of the disposable insulin supply unit, showing the filling of the aforementioned insulin reservoir. The system according to claim 1, configured to detect one or more of the following.

7. The activation component (446) uses to determine the corrected bolus dose received from the non-fasting insulin management modality during a defined period prior to the fasting period. The system according to claim 6, which detects that the total daily basic dose information has been received from the paired user computing device.

8. The system according to claim 1, wherein the delivery component (420) is configured to prime the delivery device so that it is ready to deliver the insulin.

9. Includes a mobile user computing device (402) having a processor (802) and memory (804), The aforementioned memory (804) consists of the following components: User-generated total daily basal dose information used during the defined period prior to the aforementioned fasting period. A basal insulin input component (813) configured to request a value, and A controller pairing component (814) configured to pair the mobile user computing device with the controller of the delivery device, The system according to claim 1, configured to provide the processor (802) with non-temporary computer-readable program instructions in order to perform the function of

10. An automated insulin delivery device (130) that can be worn on the user's body during the duration of a fasting period, A durable portion comprising a delivery component (420) configured to control insulin delivery in the form of a corrected bolus dose in response to an received blood glucose measurement, wherein the delivery component comprises an activation component (446) configured to detect initiation activity related to preparing the insulin delivery device for use, and a delivery component (420) configured to initiate automatic insulin delivery in the form of a corrected bolus dose in response to received blood glucose measurements received periodically during the fasting period, A disposable portion including a reservoir (432) configured to contain insulin and to automatically deliver the corrected bolus dose to the user, Delivery devices, including

11. The delivery device according to claim 10, wherein the reservoir (432) is configured to be refillable from a non-fasting insulin injection device used during a non-fasting period preceding the fasting period.

12. A computer implementation method for managing the delivery of insulin during a fasting period from a delivery device (130, 401) in the form of a wearable automated insulin delivery device worn during the fasting period, which is executed by a computing application provided on a mobile user computing device (402), (703) Requesting a value from the user for the total daily basal dose information used during the defined period prior to the fasting period, Pairing (704) the mobile user computing device (402) with the controller (420) of the delivery device, wherein the controller (420) detects an initiation activity related to preparing the insulin delivery device for use and initiates automatic delivery of insulin in the form of a corrected bolus dose in response to received blood glucose measurements received periodically during the fasting period. During the fasting period, information is transmitted and received between the delivery device (130, 401) and the controller (420), Computer implementation methods, including those mentioned above.

13. The computer implementation method according to claim 12, wherein the user's value for the total daily basal dose information includes the usual number of basal insulin units received from non-fasting insulin therapy.

14. The computer implementation method according to claim 12, comprising pairing the mobile user computing device (402) with a blood glucose monitor (105) (705) in order to enable the transfer of blood glucose measurements to the delivery device (401) via the mobile user computing device (402).

15. The computer implementation method according to claim 12, further comprising providing the user with a session history display of information regarding fasting periods.

16. The computer implementation method according to claim 12, further comprising providing the user with user training on the use of a delivery device.

17. The computer implementation method according to claim 12, comprising adjusting a fasting termination procedure for the user (724), which includes dividing a fasting termination meal bolus into a first portion equal to the remaining insulin in the delivery device at the end of the fasting period and a second portion delivered to the user by a delivery method other than the delivery device during a non-fasting period immediately following the fasting period.

18. A mobile user computing device for managing the delivery of insulin during a fasting period from a delivery device (130, 401) in the form of a wearable automatic insulin delivery device worn during a fasting period, wherein the mobile user computing device comprises a processor and a memory configured to provide the processor with computer program instructions to execute a computing application having a method, the method being Requesting a value from the user for the total daily basal dose information to be used during the defined period prior to the fasting period (703), Pairing (704) the mobile user computing device (402) with the controller (420) of the delivery device, wherein the controller (420) detects an initiation activity related to preparing the insulin delivery device for use and initiates automatic delivery of insulin in the form of a corrected bolus dose in response to received blood glucose measurements received periodically during the fasting period. During the fasting period, information is transmitted and received between the delivery device (130, 401) and the controller (420), Mobile user computing devices, including [specific devices].

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