Insulin management for insulin delivery during fasting periods

Abstract

A method of insulin management implemented by an insulin delivery system comprising an insulin delivery device (130) is provided. The method comprises: detecting (201) an activation activity associated with a preparation for using an insulin delivery device (130) in the form of an automatic insulin delivery device attachable to the body of the user over the duration of a fasting period over the entire time period; and initiating (202) an automatic delivery of insulin in the form of a corrected bolus dose in response to the periodically received blood glucose measurements during the fasting period.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Provisional Patent Application Serial No. 63 / 332,001, filed on April 18, 2022, entitled “INSULIN MANAGEMENT FOR DELIVERINGINSULIN DURING A FASTING PERIOD,” the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] The present disclosure relates to insulin management. In particular, the present disclosure relates to insulin management for delivering insulin during fasting periods. The present disclosure also relates to coordination of such insulin management with another therapeutic modality. The present disclosure also relates to glucagon management using management systems, devices, and methods equivalent to those described for insulin. Background Art

[0004] At present, many diabetes management methods are used in the form of different insulin treatments. An insulin treatment is a continuous subcutaneous insulin treatment provided by an insulin pump that is used continuously. Known insulin pumps provide continuous subcutaneous insulin infusion (CSII) by being attached to the user's body, wherein a reservoir of insulin inside the pump is delivered via a cannula for subcutaneous insertion. The insulin pump has a controller that can be integrated into the pump body or individually provided, which controls the delivery of insulin. Automatic insulin delivery (AID) is provided by a pump with blood glucose monitoring, which comes from a device attached to the body that obtains regular blood glucose readings.

[0005] Known insulin pump is worn continuously day and night, and therefore, insulin pump delivers single type of quick-acting insulin as the combination of basal insulin and push insulin.Basal insulin is the background insulin required for people to maintain target blood sugar and does not take into account the insulin used or determined for offsetting the blood sugar rise caused by the food taken in. In the case provided by CSII, such quick-acting basal insulin or background insulin is usually provided with preset and / or default basal rate, and is delivered to the user with preset and / or default basal mode, for example, 2 units per hour are delivered with continuous rate or with a series of predetermined doses, and this series of predetermined doses is not calculated or adjusted based on real-time glucose value. On pump, basal rate can change over time, but is usually stable, and represents about 50% of the total insulin demand of type 1 diabetes patients.Compared with CSII basal insulin and / or background insulin, CSII meal push insulin dosage is pumped to cover the food taken in or correct high blood sugar level.Known insulin pump needs to accurately estimate many user-specific variables that must be used to ensure safe and effective insulin delivery in 24 hour cycles.However, accurate estimation may be difficult to determine, and needs to be adjusted over time. Continuous use insulin pumps present high costs and patient inconveniences due to the need to be continuously attached to the body day and night.

[0006] Another popular diabetes management method is to provide regular insulin therapy or flexible insulin therapy through multiple daily injections (MDI). Various treatment regimens are known and may include: supplying bolus insulin (or mealtime insulin) by injecting rapid-acting insulin in an amount proportional to the meal before each meal; and injecting long-acting insulin once or twice a day to provide basal insulin. Compared with CSII, the insulin pen solution used by most patients to provide MDI generally provides patients with lower costs and higher flexibility. However, the use of insulin pens and syringes and inhalable solutions requires awakening to use, resulting in reduced rest and / or reduced glucose control, especially at night, when patients want to rest undisturbed and wake up in a healthy target glucose range.

[0007] Typically, patients with diabetes use a single solution for their diabetes management treatment, at least in part due to the complexity of coordinating different therapies and / or the risks associated therewith. Some risks include unrecognized insulin accumulation and incorrect insulin delivery. Each available diabetes management method has a unique set of behavioral requirements, costs, and potential clinical outcomes. No one solution meets the preferred behavior, cost, and clinical outcome requirements of all diabetic patients. Patients typically follow their doctor's recommendations for a particular method and adjust their lifestyle based on the solution.

[0008] The foregoing discussion of the background to the invention is intended only to facilitate understanding of the invention. It should be appreciated that the discussion is not an acknowledgement or admission that any of the material referred to was part of the common general knowledge in the art at the priority date of the application. Summary of the invention

[0009] Various aspects of the invention are defined in the accompanying claims. Different aspects of the present disclosure are defined in the following paragraphs, and one or more combinations of optional features may be combined with different aspects. According to one aspect of the invention, there is provided a method of insulin management implemented by an insulin system including an insulin delivery device, the method comprising: detecting a start-up activity associated with preparation for use of the insulin delivery device, the insulin delivery device being in the form of an automatic insulin delivery device that can be attached to the user's body for the duration of a fasting period throughout the time period; and initiating automatic delivery of insulin in the form of a corrected bolus dose in response to regularly received blood glucose measurements during the fasting period. The insulin delivery system may be self-contained within the insulin delivery device, wherein a controller performs the method steps. Alternatively, the insulin delivery system may include one or more computing systems that remotely perform one or more of the method steps.

[0010] The method may include: detecting an end activity associated with ending use of the insulin delivery device; and terminating automatic delivery of a correction bolus dose of insulin. The initiation activity may have a primary function other than initiating automatic delivery of insulin from the insulin delivery device, thereby being reused as an indication to initiate automatic delivery of insulin from the insulin delivery device. The initiation activity may include one or more of the following: arrival of a preset time of day; removal of the insulin delivery device from the power charger; and attachment of a disposable insulin dispensing unit to the insulin delivery device. The initiation activity may include one or more of the following: 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 command or selection by the user indicating a desire to initiate automatic delivery of insulin. The initiation activity may include at least one of: proximity or pairing of a controller of the insulin delivery device with 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 with a smart insulin pen; proximity or pairing of a controller of the insulin delivery device with a blood glucose monitor; receiving blood glucose monitor measurements; a fill level of an insulin reservoir of a disposable insulin dispensing unit indicating a fully filled insulin reservoir for initiating automatic delivery of insulin; and movement of a plunger of an insulin reservoir of a disposable insulin dispensing unit indicating a filled insulin reservoir. The method may include: receiving total daily basal dose information from a paired user computing device, the total daily basal dose information being received from a non-fasting insulin management modality during a defined period prior to a fasting period for determining a correction bolus dose. Initiating automatic delivery of insulin may include: preparing the delivery device to prepare to deliver insulin.

[0011] The insulin delivery device can avoid administering basal insulin at a preset or default rate or in a preset or default mode. The method can deliver insulin in the form of a correction bolus dose in response to the received blood glucose measurement result, and the correction bolus dose is compensated by a determined active insulin (insulin on board). The method can deliver at least a first correction bolus dose, which is compensated by a determined active insulin, and the determined active insulin is set to be equal to an assumed active insulin, which is determined based on an assumed external dose calculated to correct the user's initial blood glucose value to a target blood glucose. The method may include calculating the correction bolus dose by the following operations: comparing the assessed blood glucose measurement result with the target blood glucose to obtain a difference, which is adjusted by a user insulin sensitivity factor to obtain a resulting dose amount, and the resulting dose amount is subtracted from the determined active insulin.

[0012] The determined active insulin may include hypothetical active insulin and known insulin delivered from the delivery device. The corrected bolus dose may be based on the user's insulin sensitivity factor derived from total daily basal dose information used in a defined period prior to the fasting period. The total daily basal dose information is the average total number of basal dose units given over the entire period.

[0013] The correction insulin dose may be calculated based on at least one of a fixed target blood glucose 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 divided portion of the total correction bolus dose.

[0014] Various methods can be used to evaluate the evaluated blood glucose measurement results, which can be used alone or in combination. The evaluated blood glucose measurement value is evaluated at least in part by smoothing the received blood glucose measurement results using a low-pass filter to reduce the impact of noise and / or sudden disturbances on the obtained blood glucose value. The evaluated blood glucose measurement result can be evaluated at least in part by retaining the received blood glucose measurement results that are smaller than the rolling average of the previously received blood glucose measurement results of a predetermined number and otherwise retaining the rolling average of the received blood glucose measurement results. The evaluated blood glucose measurement result is evaluated at least in part by forwarding the downward trend of the received blood glucose measurement results and adding the downward trend to the blood glucose measurement result value used in the dose calculation. The downward trend can be determined at least in part based on the maximum negative slope between any received blood glucose measurement results and the reference blood glucose measurement results within a predetermined time range. The evaluated blood glucose measurement result can be evaluated at least in part by fitting the received blood glucose measurement results within a predetermined time range to a trend with an average slope (e.g., a median slope), and the average slope is selected from a plurality of regression fit slopes of different rolling subsets of the received blood glucose measurement results within the predetermined time range. The evaluated blood glucose measurement results can be evaluated at least in part by filtering the received blood glucose measurement results, the filtering including: for increasing received blood glucose measurement results, applying gradually increasing limits on how much each next received blood glucose measurement result can increase compared to the previously received blood glucose measurement result; and for decreasing received blood glucose measurement results, amplifying how much each next received blood glucose measurement result decreases compared to the previously received blood glucose measurement result.

[0015] The method may include dividing the correction dose into delivery portions using a maximum delivery rate for a maximum amount of insulin to be delivered within a given time period. The method may include determining an initial user insulin sensitivity factor for a fasting period based on the total daily basal dose information received. The method may include adjusting the initial user insulin sensitivity factor by a sensitivity safety factor, the sensitivity safety factor being configured to bias the calculation of a periodic correction bolus dose toward a lesser insulin dose. The target blood glucose may be adjusted by a target safety factor based at least in part on a difference between a received blood glucose measurement and a target blood glucose. Adjusting the calculated correction bolus dose by an overall safety factor may be configured to limit the calculated bolus dose to a maximum delivery rate of insulin to be delivered within a time period between the delivery of the correction bolus dose. The target blood glucose may be time-varying, to decrease over time during the fasting period, and the rate of decrease over time of the target blood glucose is determined based on an assumption that the blood glucose level is being reduced by an existing externally administered insulin administered prior to the fasting period. The user insulin sensitivity factor may be initially set at a predetermined value and adjusted over time based at least in part on a difference between a received blood glucose measurement and an expected blood glucose. Evaluating the blood glucose measurements may include filtering for increasing blood glucose values ​​and not filtering for decreasing blood glucose values. Evaluating the blood glucose measurements may include adjusting for a long-term downward trend over a period of hours during a fasting period. Delivering at least a portion of the correction dose may include delivering a first zero dose.

[0016] The method may include delivering insulin from an insulin delivery device in the form of a corrected bolus dose of insulin during a fasting period within the entire time period in response to a received blood glucose measurement, wherein the insulin delivery device avoids administering basal insulin at a preset or default rate or in a preset or default pattern, wherein insulin is received by the user from a non-fasting insulin management modality during a non-fasting period within the entire time period, and the non-fasting insulin management modality provides 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 within the entire time period, and wherein the single fasting period is a major sleep portion of the user's regular daily life.

[0017] The method may include providing coordination between a non-fasting insulin management therapy and a delivery device to a user. Coordination may include providing one or more recommendations to the user related to the non-fasting insulin management therapy and / or the delivery device. Coordination may include providing one or more predictions to the user related to a hypothetical use of the non-fasting insulin management therapy and / or the delivery device. The one or more recommendations include at least one of: a recommendation for the user to utilize the delivery device within a recommended time range at night; and a recommendation for the user to adjust a daily basal dose of insulin from a current value to a different value. 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 within a recommended time range at night; a prediction of the user's waking blood glucose level if the user adjusts the daily basal dose of insulin from a current value to a different value; and a prediction of the user's wake-up blood glucose level if the user does not utilize the delivery device throughout the night.

[0018] Coordination may include: coordinating an end-of-fasting process for a user, wherein coordinating the end-of-fasting process includes: receiving information related to a fasting interruption meal that requires a meal bolus; dividing the end-of-fasting meal bolus into a first part and a second part, the first part being equal to a first part of the remaining insulin in the delivery device at the end of the fasting period, and the second part being delivered to the user using a non-fasting insulin management modality in a non-fasting period immediately following the fasting period; and providing instructions to the user to deliver the second part of the end-of-fasting meal bolus dose from the non-fasting insulin management modality.

[0019] According to one aspect of the present invention, there is provided an insulin management system for an insulin delivery device in the form of an automatic insulin delivery device that can be attached to the user's body for the duration of a fasting period throughout the time period, the system comprising: an activation component configured to detect a start-up activity associated with preparing the use of the insulin delivery device; and a delivery component configured to initiate automatic delivery of insulin in the form of a corrected bolus dose in response to regularly received blood glucose measurements during the fasting period. The system may include an end detection component configured to detect an end activity associated with ending the use of the insulin delivery device. The start-up activity may also have other primary functions in addition to initiating the automatic delivery of insulin from the insulin delivery device, thereby being reused as an indication to initiate the automatic delivery of insulin from the insulin delivery device.

[0020] The activation component can be configured to detect one or more of the following as a startup activity: the arrival of a preset time of day as a startup activity; the removal of the insulin delivery device from the power charger; and the attachment of the disposable insulin dispensing unit to the insulin delivery device. The startup component can be configured to detect one or more of the following as a startup activity: the attachment of the insulin delivery device to the user; the detachment of the applicator of the insulin delivery device from the insulin delivery device; and a desired verbal command or selection by the user indicating the initiation of automatic delivery of insulin. The activation component can be configured to detect one or more of the following as a startup activity: the proximity or pairing of the controller of the insulin delivery device with a user computing device on which a user application associated with the insulin delivery device is installed; the proximity or pairing of the controller of the insulin delivery device with a smart insulin pen; the proximity or pairing of the controller of the insulin delivery device with a blood glucose monitor; receiving blood glucose monitor measurement results; the fill level of the insulin reservoir of the disposable insulin dispensing unit indicating a fully filled insulin reservoir for initiating automatic delivery of insulin; and the movement of the plunger of the insulin reservoir of the disposable insulin dispensing unit indicating the filling of the insulin reservoir. The activation component may be configured to detect receipt of total daily basal dose information from a paired user computing device, the total daily basal dose information received from a non-fasting insulin management modality during a defined period prior to a fasting period for use in determining a correction bolus dose.

[0021] The delivery component may be configured to prime the delivery device to prepare 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.

[0022] The system may also include a mobile user computing device including: a processor and a memory configured to provide non-transitory computer-readable program instructions to the processor to perform the functions of the components; a basal insulin input component configured to request from the user a value of total daily basal dose information used during a defined period prior to the fasting period; and a controller pairing component configured to pair the mobile user computing device with a controller of the delivery device.

[0023] According to one aspect of the invention, there is provided an automatic insulin delivery device capable of being attached to a user's body for the duration of a fasting period, the device comprising: a durable portion including a delivery component configured to control the delivery of insulin in the form of a correction bolus dose in response to a received blood glucose measurement, the delivery component comprising: an activation component configured to detect a start-up activity associated with preparing the insulin delivery device for use; and a delivery component configured to initiate automatic delivery of insulin in the form of a correction bolus dose in response to periodically received blood glucose measurements 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 filled from a non-fasting insulin injection device used during a non-fasting period prior to the fasting period.

[0024] According to one aspect of the invention, there is provided a computer-implemented method for managing the delivery of insulin during a fasting period from a delivery device in the form of a wearable automatic insulin delivery device worn during the fasting period, wherein the method is performed by a computing application provided at a mobile user computing device, the method comprising: requesting from a user a value of total daily basal dose information used during a defined period prior to the fasting period; pairing the mobile user computing device with a controller of the delivery device, the controller monitoring a start-up activity associated with preparing the insulin delivery device for use, thereby initiating automatic delivery of insulin in the form of a corrected bolus dose in response to periodically received blood glucose measurements during the fasting period; and sending information to and receiving information from the controller of the delivery device during the fasting period. The value of the total daily basal dose information from the user may include a typical number of units of basal insulin received from a non-fasting form of insulin therapy.

[0025] The method may include pairing a mobile user computing device with a blood glucose monitor, thereby allowing blood glucose measurements to be transmitted to a delivery device via the mobile user computing device. The method may include providing a display of a session history of information related to a fasting period to the user. The method may include providing user training to the user regarding the use of the delivery device. The method may include coordinating an end of fasting process for the user, including dividing an end of fasting meal bolus into a first portion and a second portion, the first portion being 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 in a non-fasting period immediately following the fasting period using a delivery method different from that of the delivery device.

[0026] According to one aspect of the present invention, there is provided a method of insulin management for use of an insulin delivery device in the form of an automatic insulin delivery device that can be attached to a user's body for the duration of a fasting period throughout the time period, the method comprising: performing a startup activity associated with preparation for use of the insulin delivery device; and receiving automatic delivery of insulin in the form of a corrected bolus dose in response to periodically received blood glucose measurements during the fasting period. The method may provide the insulin delivery device with at least one of: an insulin sensitivity factor; and total daily basal dose information used by the user in a defined period prior to the fasting period.

[0027] The method may include: performing an end activity associated with ending use of the insulin delivery device. Performing the start-up activity may include one or more of the following: removing the insulin delivery device from the power charger; and attaching the disposable insulin dispensing unit to the insulin delivery device. Performing the start-up activity includes one or more of the following: attaching the insulin delivery device to the user; detaching the applicator of the insulin delivery device from the insulin delivery device; and a desired verbal command or selection by the user indicating the start of automatic delivery of insulin. Performing the start-up activity includes at least one of the following: pairing a controller of the insulin delivery device with a user computing device on which a user application associated with the insulin delivery device is installed; pairing a controller of the insulin delivery device with a smart insulin pen; filling an insulin reservoir of a disposable insulin dispensing unit; causing movement of a plunger of an insulin reservoir indicating filling of the insulin reservoir.

[0028] The features and elements of one aspect of the disclosure may be incorporated in other aspects of the disclosure to form various embodiments of systems, apparatus, methods, and computer program products.

[0029] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings. The described features or elements of an embodiment may be used in other embodiments within the scope of the various aspects of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In the attached picture:

[0031] Figure 1A is a schematic diagram illustrating an example implementation of an overall treatment arrangement implementing the present disclosure;

[0032] Figure 1B is a flow chart of an example implementation of a method of insulin management according to an aspect of the present disclosure;

[0033] Figure 1Cshows an overall time period during which two different modes of insulin management may be used in a non-overlapping manner according to some example embodiments;

[0034] FIG. 2A to FIG. 2C is a flow chart of an example implementation of a method of controlling the delivery of insulin according to aspects of the present disclosure;

[0035] FIG. 3A to FIG. 3D is a graph illustrating an example method of processing blood glucose measurements according to aspects of the present disclosure;

[0036] Figure 4 is a block diagram of an example implementation of a system for controlling the delivery of insulin according to an aspect of the present disclosure;

[0037] FIG. 5A to FIG. 5C is a flow chart of an example embodiment of a method of using a delivery device for controlling the delivery of insulin according to aspects of the present disclosure;

[0038] FIG. 6A to FIG. 6M is a series of schematic diagrams illustrating example embodiments of a delivery device according to an aspect of the present disclosure;

[0039] Fig. 7A and Figure 7B is a flow chart of an example implementation 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;

[0040] Figure 7C is a swim-lane flow chart illustrating an example use example for controlling delivery of insulin during a fasting period and / or for coordinating such fasting period insulin management with another therapeutic modality utilized during a non-fasting period according to some example aspects of the present disclosure;

[0041] Figure 8 is a block diagram of an example implementation of a system for providing a computer application for interacting with a delivery device to control the delivery of insulin according to an aspect of the present disclosure;

[0042] Fig. 9 illustrates an example of a computing device in which aspects of the present disclosure may be implemented; and

[0043] FIG. 10A to FIG. 10E is a graph illustrating an example patient storyline during a method of controlling the delivery of insulin according to an aspect of the present disclosure. DETAILED DESCRIPTION

[0044] The present disclosure describes a drug management method, system and delivery device for delivering drugs (e.g., insulin and / or glucagon) from a wearable automatic drug delivery device. The drug delivery device can be used during a fasting period of, for example, less than about 12 hours, wherein the wearable automatic drug delivery device is configured to and is intended to be used only during the fasting period. In the case where the automatic drug delivery device is configured to distribute insulin, the device can be considered to be an automatic insulin delivery device or an AID device. Several embodiments are described below about insulin delivery. However, the present disclosure is not limited thereto, and it is also contemplated that similar or identical embodiments of any other drug configured to deliver an effect on blood sugar levels are also contemplated, such as glucagon for increasing blood sugar concentration when blood sugar concentration drops below a predetermined level (e.g., during sleep, or during exercise or other physical activity requiring energy). In such an embodiment for distributing glucagon, the fasting period can be a period of exercise or activity.

[0045] By definition, diabetics are unable to properly regulate blood glucose due to a substantially complete lack of endogenous insulin secretion (in type 1 diabetics) or due to insufficient endogenous insulin secretion (in type 2 diabetics). Therefore, diabetics require an insulin management process for maintaining blood glucose levels within a desired target range at substantially all times. Therefore, managing automated insulin delivery only during daily fasting periods (e.g., while sleeping) presents several unique challenges.

[0046] First, the user must integrate the supplementary method of insulin administration outside the fasting period (e.g., multiple insulin injections per day to meet the basic and meal push requirements), but for the user, tracking insulin administration between multiple insulin delivery modes may be troublesome. Secondly, since there is a transition between the supplementary non-fasting insulin delivery mode and the automatic fasting insulin delivery mode twice a day, it may be expected to engage and disengage the automatic fasting mode at the appropriate time (e.g., engage at the beginning of the fasting period and disengage at the end of the fasting period), but the natural variation of the timing and duration of these fasting or sleeping periods every day makes it difficult to determine the appropriate time to engage and disengage. Third, since the automatic insulin administration performed only during the fasting period usually occurs when the user is sleeping and fasting, it is very important to prevent excessive insulin distribution and hypoglycemic events caused thereby during the fasting period, but this requires accurate calculation of the insulin already in the user's system at the beginning of the fasting period, and the user is not always good at accurately estimating or calculating the actual active insulin, especially with the time since the last manual insulin injection and the active insulin is gradually metabolized by the body.

[0047] In addition, most patients (type 1 and type 2) with diabetes continue to rely on daily multiple injection (MDI) therapy to carry out diabetes management. Unfortunately, although the patient has many sufficient reasons to select MDI treatment, night control (compared with automatic insulin delivery (AID)) remains the missing element. Up to now, it is impractical or even unachievable to only use AID at night, because setting up conventional insulin pump therapy (especially using AID) is a highly complicated process that needs significant start-up time. In addition, continuous subcutaneous insulin infusion (CSII) is designed to infuse basal and / or background insulin with a predetermined rate, rather than using it together with exogenous basal insulin. For example, conventional AID comprises: basal and / or background insulin are delivered with a predetermined, preset and / or default rate, and the predetermined, preset and / or default rate is not calculated or adjusted in real time (or substantially in real time) based on real-time (or substantially in real time) glucose value. Such basis, baseline and / or background insulin infusion can conflict with daily basal pen dosage, and is impractical for twice a day conversion. Furthermore, switching from an AID to a pen and back typically leaves some active insulin in the body during the transition, which current systems are not equipped to handle.

[0048] Aspects of the present disclosure address each of these potential problems and any number of other potential problems described below, including: 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 that indicate the start and / or end of a fasting period; and / or methods, devices, and systems for automatically calculating and delivering a correction dose of insulin during a fasting period, thereby providing simplified, safe, and effective management of time in range (TIR) ​​during extended fasting periods. Although the embodiments described herein may address one or more of the above challenges, the present disclosure contemplates utilizing and / or combining any feature or features from any embodiment or embodiments with any feature or features of any other embodiment or embodiments described herein.

[0049] The method described herein solves the problem of transition complexity of short-term use and other problems by providing a simplified system that allows easy transition between two different diabetes management modes. In one implementation, the system and method described herein enable seamless, intermittent, situational use of MDI for basal insulin during the day cycle, and use of AID during the night cycle, thereby allowing the user to benefit from low cost, high flexibility and improved clinical results. For example, diabetes management treatment with daily basal and daytime bolus injections is completed by MDI treatment, while nighttime glucose control is achieved by short-term wear insulin pumps, which provide AID control during fasting periods to allow the user to sleep well and wake up within the target glucose range without waking up to correct the bolus injection.

[0050] Embodiments of insulin management methods, systems and delivery devices are described for delivering insulin from a wearable automatic insulin delivery (AID) device during a fasting period, which is designed and expected to be worn only during a fasting period. A delivery algorithm for automatically calculating and delivering a correction dose is provided. This provides simplified, safe and effective management of a time range (TIR) ​​during a fasting period of, for example, less than about 12 hours. Fasting time can be a time period when fasting is expected. This may be during night time or any time period, wherein only a correction bolus is required in the additional sense of any existing basal therapy and meal bolus therapy, which correction bolus can still be "active" throughout the fasting period. Fasting time can be the time when a user falls asleep in a daily cycle. For most users, fasting time may be a night time period between 6 hours and 12 hours, when the user typically lies in a resting position and does not eat during this time.

[0051] The described insulin management implementation is based on the user receiving insulin from the non-fasting insulin management mode during the non-fasting period within the entire time period. The non-fasting period can be the time when the user is awake in the daily cycle; however, the non-fasting period can include a short period of sleep, such as a daytime nap. The fasting period and the non-fasting period can form an overall time period together, such as a 24-hour period or a whole time period for other regularities of users (e.g., shift workers) with non-day-based cycles. The non-fasting insulin management mode provides a basal dose of insulin and a bolus dose of insulin. The entire time period can be 24 hours because this is the user's daily routine; however, for users who need different schedules, such as due to shift work, the entire time period can be adjusted. The non-fasting insulin management mode and the fasting period insulin delivery device are intended to be used as auxiliary, not overlapping. For example, during the wearing of the fasting period insulin delivery device, a dose is usually not given from the non-fasting period insulin management mode. However, the dose applied by the two treatment methods can remain in the body as active insulin during other treatments.

[0052] Embodiments of the insulin management method deliver insulin from a fasting insulin delivery device during a fasting period over a period of time, wherein the fasting insulin delivery device is in the form of an automatic insulin delivery device that can be attached to the user's body for the duration of the fasting period. The fasting insulin delivery device delivers rapid-acting insulin to gradually correct high blood glucose measurements during the fasting period over the fasting period, and these are referred to as correction bolus doses. The fasting insulin delivery device delivers the correction bolus dose in response to the received blood glucose measurements when compared to the target blood glucose. The fasting insulin delivery device avoids administering a background basal dose when it is assumed that the basal dose is obtained from a non-fasting insulin management modality during the non-fasting period portion. For a non-fasting insulin management modality in the form of an injection, the basal dose can be provided by a long-acting insulin injected once or twice a day.

[0053] Wearable AID device can be in the form of a pump worn only during fasting time, for example, a pump worn only during night time. An example of a suitable pump is provided in PCT patent application No. PCT / IB2021 / 060206 (International Publication No. WO 2022 / 097057), the contents of which are incorporated herein by reference. Fasting time wear pump delivers rapid-acting insulin in a small correction dose. Since there is no meal to cover during the fasting period, a small correction dose can be gradually and safely given to keep the user within the target range. Various safety protections are provided in the delivery algorithm to ensure that there is no overcorrection. Since, unlike the continuous wear pump, the fasting time wear pump does not give a basal dose, it is impossible to turn off the basal dose to accommodate overcorrection.

[0054] The described embodiment of the delivery algorithm is designed to perform only a small amount of correction bolus while the user is fasting for a limited time period. No meal bolus or basal rate delivery is provided. The delivery algorithm calculation is simplified and can be based on the maximum amount of insulin in the reservoir of the pump that allows the maximum dose delivered per calculation period. This is informed by the user's regular blood glucose measurements to allow safe and effective delivery of correction bolus insulin without the need for information related to basal rate, carbohydrate ratio or insulin action time. The correction bolus corrects the changes in blood glucose that are not otherwise corrected for the basal insulin dose or bolus insulin dose given during non-fasting time (e.g., daytime), which varies based on daily activity, meal consumption and overall health.

[0055] In the following description, various embodiments of the method, system and device are described with reference to the accompanying drawings. The described individual features of each embodiment in the embodiment can be used in other embodiments. In the case of describing the method in a flowchart, the features described by the steps in the flowchart can be applied to the following. One or more described individual features of the method can be completed by a single step. The individual features described as a single method step can be performed by more than one step. Parts of the described individual features can overlap. The order of the features of the method can also be changed. In a computer-implemented method, it should be understood that each box of the flowchart and / or block diagram and the combination of boxes in the flowchart and / or block diagram can be implemented by computer-readable program instructions.

[0056] Figure 1A 1 is a schematic diagram showing an example implementation of an overall treatment arrangement (100) in which the described insulin management method using a fasting wearable delivery device (130) is used. A user (101) is shown in a sleeping position with a continuous glucose monitor (CGM) (105) attached to their body (102). The CGM (105) can take blood glucose measurements and send the measurements to a base station or mobile computing device (120). The user (101) can sleep during the day, i.e., during Figure 1C The invention relates to an embodiment of the present invention that a user (101) can use an insulin pen (110) such as a smart pen or other MDI method during a non-fasting period (162) of the present invention. The user (101) can use a mobile computing device (120) to manage their insulin use. The mobile computing device (120) can be a dedicated computing device that cooperates with the delivery device (130). Alternatively, the mobile computing device (120) can be a multi-purpose computing device, such as a smart phone. 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 daytime MDI therapy, for example, by interacting with the insulin pen (110).

[0057] The described arrangement provides a fasting time wearable delivery device (130) that is attached to the user's body (102) only during fasting time. Fasting time is typically during the night, but other times may be fasting time, for example if the user is a shift worker. Typically, fasting time is less than about 12 hours. The fasting time wearable delivery device (130) delivers rapid-acting insulin in small correction doses based on periodic blood glucose measurements from the CGM (105). As shown below Figure 1C As shown, the fasting wearable delivery device (130) is used only during the fasting period (164). The fasting wearable delivery device (130) is configured to deliver rapid-acting insulin in small correction doses (180a to 180e) based at least in part on periodic blood glucose measurements from the CGM (105). In some embodiments, the CGM (105) can be incorporated into the delivery device (130). In other embodiments, the CGM (105) can be a separate CGM worn by the user day and night. An islet delivery system for implementing the insulin management method described herein can include a controller of the insulin delivery device (130) combined with any other computing device (e.g., a mobile computing device (120) and / or a cloud computing system (140)) for executing a delivery algorithm.

[0058] In some embodiments, the fasting time wearable delivery device (130) can be provided as a kit. The fasting time wearable delivery device (130) can have a durable unit into which a disposable dispensing unit containing insulin is assembled. The delivery device (130) can include a disposable portion including a reservoir configured to contain insulin and configured to automatically deliver a correction bolus dose to a user. As further described below, the delivery device (130) can have an applicator (135) for filling and applying to the user's body (102). The durable unit can be rechargeable with a charger (e.g., a charging station) (131) that is configured to charge the durable unit during non-fasting time to be ready for use again.

[0059] The durable unit includes a controller (132) for controlling the delivery of insulin from a delivery device (130) according to a delivery algorithm described herein. The delivery algorithm can be completely set on the controller (132). The controller (132) can be set in the form of software and / or hardware components. In a first alternative embodiment, a delivery algorithm that indicates the delivery amount to the controller (132) can be provided remotely. The delivery algorithm can be provided remotely from a cloud computing system (140) or server, from a computer application (122) or other software on a user's mobile computing device (120), or from another form of computing device or system. In a second alternative embodiment, the delivery algorithm can be distributed through different steps or functions performed by one or more of the following: the controller (132), the cloud computing system (140), the software on the mobile computing device (120), and another form of computing device or system.

[0060] Reference Figure 1B , a flowchart (150) shows an example implementation of an insulin management method. The method delivers (151) insulin from a non-fasting insulin management modality during non-fasting periods within the entire time period. The non-fasting insulin management modality provides a basal dose of insulin and a bolus dose of insulin. The first treatment, i.e., the non-fasting insulin management modality, may include any mode, method, device process, treatment, etc. used as an intervention in diabetes treatment, including but not limited to pump delivery of insulin (except for 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, in which insulin is managed without drug intervention at least for some time. In some embodiments, the non-fasting insulin management modality may also or alternatively include any oral medication for type 1 or type 2 diabetes, such as but not limited to GLP-1 and metformin.

[0061] The method includes delivering (152) insulin from a fasting insulin delivery device during a fasting period over the entire time period. This can be considered an adjunct to the first treatment. The fasting insulin delivery device is an automatic insulin delivery device that can be attached to the user's body during the duration of the fasting period, which delivers a correction bolus dose in response to a received blood glucose measurement, and avoids administering any background basal dose of insulin. During the fasting period (when the user is typically asleep), the user is not required to interact with the delivery device (130) to correct the bolus insulin. In some embodiments, the expected fasting period can be from up to about 2 hours before the user falls asleep to about 2 hours after waking up. The correction insulin dose is the amount of insulin to be delivered in addition to the basal insulin and meal bolus insulin provided by the non-fasting insulin management mode during the non-fasting period. The amount of the correction bolus can be determined when glucose is above a target level and can be based on the difference between the current blood glucose and the target blood glucose as well as the insulin sensitivity factor and the amount of active insulin (if available). The correction dose can be delivered at a maximum rate per interval to provide gradual correction and avoid hypoglycemia risk.

[0062] The method can base the correction bolus dose in the fasting period on (153) the user's insulin sensitivity factor (ISF). The ISF is a quantitative variable in the personalized variables and is a measure of how much blood sugar is expected to be reduced for the user by one unit of insulin. For example, if 1 unit of insulin will reduce blood sugar by 25 mg / dL, the insulin sensitivity factor is 1:25. The ISF can be derived based on the total daily basal dose information received from the non-fasting insulin management mode in a defined period before the fasting period. Alternatively, the user's ISF can be known, for example, through the use of another insulin therapy. In another option, the user's ISF can be known during the use of the delivery device. The ISF can be a single ISF that is fixed for the user over the duration of delivery. In an alternative embodiment, the ISF curve can change over time because the user's ISF can 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 curve can use a learning algorithm for adjusting the ISF. This can be adjusted during the delivery session or for the next delivery session.

[0063] The method may include determining (154) a hypothetical active insulin upon initiation of delivery from a fasting insulin delivery device. The hypothetical active insulin may be based on a hypothetical external dose calculated to correct the user's initial blood glucose value to a target blood glucose. In the dose calculation, the hypothetical or assumed dose may be applied as the hypothetical active insulin. Alternatively, if the initial active insulin is known, for example by using another insulin therapy, this may be used as the hypothetical active insulin.

[0064] Delivering (152) insulin from a fasting insulin delivery device during a fasting period can include using a dose calculator at each blood glucose measurement time point to determine when insulin is needed to achieve a target blood glucose for a user. The dose calculator can compare the blood glucose value to the target blood glucose to obtain a difference adjusted by a user insulin sensitivity factor, wherein the resulting dose amount is compensated by the determined active insulin. Once insulin is delivered during the fasting period, the determined active insulin is a combination of the assumed active insulin and the known insulin delivered from the delivery device.

[0065] The received blood glucose measurements may be smoothed using a low pass filter to reduce the effect of noise and / or sudden disturbances on the obtained blood glucose value. In the event that the received blood glucose measurements are trending downward over time, the downward trend may be extrapolated forward and added to the blood glucose value used in the dose calculator. The correction bolus dose during the fasting period may be limited to a defined maximum dose given at any point in time to minimize sudden corrections. A default value of zero dose may be incorporated.

[0066] An example implementation of a method for calculating one or more correction doses is described below. The amount of the correction bolus may be determined when the blood glucose is above the target level and may be based on the difference between the current blood glucose and the target blood glucose and the insulin sensitivity factor and the amount of active insulin. The insulin correction dose calculation is determined at least in part using the following formula (1), and in some cases, one or more safety factors are further applied to one or more of the variables utilized therein (as described anywhere in this disclosure) to effectively guide the user's blood glucose toward the target range and then maintain the user's blood glucose at or near the target during the fasting period.

[0067] (1)Dose_Calculation=[(Current_BG-Target_BG) / ISF]–IOB.

[0068] As described anywhere in this disclosure, Dose_Calculation is the calculated amount of additional insulin required to reduce the user's current blood glucose level to the target blood glucose level. As described anywhere in this disclosure, Current_BG is the user's measured blood glucose value, which can be evaluated before being applied to formula (1). Target_BG is the user's target blood glucose level. ISF (insulin sensitivity factor) is a user-specific factor indicating how many milligrams per deciliter (mg / dl) one unit of insulin is expected to reduce the user's blood glucose.

[0069] An insulin delivery system for implementing an insulin management method is defined as a controller including an insulin delivery device (130) and any other computing device for executing a delivery algorithm. In some embodiments, the controller may perform all processing of the delivery algorithm, and in other embodiments, this may be assigned to other processing devices. The insulin delivery system may include a delivery device (130) having a controller for controlling the delivery of insulin from the insulin delivery device in the form of multiple correction bolus doses of insulin in response to received blood glucose measurements during a fasting period. The correction bolus dose may be compensated by a determined active insulin, and wherein for at least the first correction bolus dose in the multiple correction bolus doses, the determined active insulin is equal to the assumed active insulin. The islet delivery system may include a delivery device and / or other computing systems that perform some of the delivery algorithm processing. For example, the assumed active insulin is determined based on an assumed external dose calculated to correct the user's initial blood glucose value to a target blood glucose.

[0070] Figure 1C An example of an overall time period (160) is shown in which, according to some example embodiments, multiple different modes of insulin management may be used in a non-overlapping manner. In some cases, the overall time period (160) may be 24 hours in length, which is a typical daily routine for most users. However, the overall time period (160) may be adjusted for users who require a different, sometimes more erratic schedule (e.g., due to shift work). The described insulin management is based on the user switching from one or more non-fasting insulin management modalities (e.g., such as insulin administration) during the non-fasting period (162) of the overall time period (160). Figure 1A Shown or combined Figure 1A The insulin pen (110) described herein receives insulin and during a fasting period (164) of the entire time period (160) from different fasting insulin administration modalities (e.g., Figure 1A Shown or combined Figure 1A A fasting wearable delivery device (130) is described for receiving insulin.

[0071] As described herein, non-fasting insulin management mode and fasting period insulin management mode are intended to be used as an auxiliary when non-fasting mode and fasting mode do not actively overlap, for example, supplementary use. For example, as will be described below, basal insulin dose such as (170a, 170b) and meal bolus dose (172a to 172d) are usually not given from non-fasting insulin management mode during fasting period (164), and correction dose (180a to 180e) is usually not given from fasting insulin management mode during non-fasting period (162). Therefore, once non-fasting period (162) begins, it is intended not to use fasting period insulin management mode, and once fasting period (164) begins, it is intended not to use non-fasting insulin management mode. However, at least a portion of the basal dose (170a, 170b) or meal bolus dose (172a to 172d) administered during the non-fasting period (162) may still be active in the body as active insulin during the fasting period (164). For example, when the meal bolus (172a to 172d) is insufficient to compensate for the increase in glucose caused by the meal, or when glucose is still elevated after a meal or meal bolus, the correction dose (180a to 180e) during the fasting period (164) is in addition to the meal bolus (172a to 172d) given during the non-fasting period (162). This deficiency may be due to errors in bolus calculations, errors in reported meal information, errors in treatment parameters used for treatment calculations, hormonal factors, etc.

[0072] The non-fasting period (162) may be a time when the user is awake in the daily cycle; however, the non-fasting period (162) may include short periods of sleep, such as daytime naps. The fasting period (164) may be a time period when fasting is expected. This may be at night or any time period where only a correction bolus is required in addition to any existing basal therapy and meal bolus therapy, which correction bolus can still "take part in" throughout the fasting period (164). Therefore, the fasting period (164) may be a time when the user sleeps in the daily cycle. For most users, the fasting period (164) may be a nighttime period between 6 hours and 12 hours, and typically less than 22 hours, when the user typically lies in a resting position and does not eat during this time.

[0073] exist Figure 1CIn the embodiment of the present invention, a basal dose (170a and / or 170b) and a meal bolus dose (172a to 172d) are administered via a non-fasting insulin management modality during a non-fasting period (162). Basal insulin is the background insulin that a diabetic person needs to maintain blood sugar within a desired range when not eating during a non-fasting period (162). Although needs vary from person to person, basal insulin typically accounts for approximately 50% of the total insulin needs of a person with type 1 diabetes. The basal dose (170a, 170b) may include a slow-acting insulin. In the case of administering one basal dose (170a) per day, the dose (170a) may be configured to meet the user's 24-hour basal need for insulin and may be administered by daily insulin administration, for example via an insulin pen (110) during a non-fasting period (162) (e.g., see Figure 1A Where two basal doses (170a, 170b) are administered per day, each dose (170a, 170b) may be configured to satisfy a user's 12-hour basal requirement for insulin, and the doses (170a, 170b) may be administered during a non-fasting period (162) via a multiple daily injection (MDI) mode.

[0074] In contrast, a meal bolus dose is the amount of insulin required by a diabetic to compensate for the expected rise in blood sugar caused by eating food, where the purpose of the compensation is to bring blood sugar into the target range. Typically, a user who eats a certain amount of carbohydrates requires insulin to avoid causing a rise in glucose. Figure 1C Meal bolus doses (172a-172d) administered via MDI mode during a non-fasting period (162) are shown. Meal bolus doses (172a-172d) may include rapid-acting insulin compared to basal doses (170a, 170b). Although a certain number of meal bolus doses are shown during the non-fasting period (162), they are examples only, and any number of doses is contemplated as needed for the number of meals eaten during the non-fasting period (162).

[0075] During a fasting period (164) within the overall time period (160), the described insulin management method delivers insulin for the duration of the fasting period (164) from a fasting automatic insulin delivery (AID) device attachable to the user's body, such as, for example, from a nighttime wear-only pump provided in PCT Patent Application No. PCT / IB2021 / 060206, the contents of which are incorporated herein by reference. As described in more detail below, during a fasting period (164), the user may receive a dose of insulin from a fasting automatic insulin delivery (AID) device attachable to the user's body, such as, for example, a nighttime wear-only pump provided in PCT Patent Application No. PCT / IB2021 / 060206, the contents of which are incorporated herein by reference. Figure 1ASuch a device (130) is shown in FIG. 1. Since no meal is eaten during the fasting period (162), the device (130) is configured to deliver rapid-acting insulin in the form of correction bolus doses or micro-bolus doses (180a to 180e) to gradually correct the high blood glucose measurements during the fasting period (164), and thereby allow the user to sleep well and wake up within the target glucose range without waking up for a correction bolus. Although a certain number of correction bolus doses are shown during the fasting period (164), they are only examples, and any number of correction doses is contemplated as needed during the fasting period (164).

[0076] Assume that a basal dose (170a, 170b) is obtained from a non-fasting insulin management mode during a non-fasting period (162). It is noteworthy that the fasting insulin delivery device (130) avoids administering background and / or basal insulin to the user. Specifically, the fasting insulin delivery device (130) does not allow, for example, any preset default, basal or background dose of rapid-acting insulin delivery to be performed in consideration of the user's basal insulin needs. In other words, in contrast to the operation of a conventional CSII device, the delivery device (130) does not allow a preset basal rate or preset mode of basal insulin delivery for rapid-acting insulin or slow-acting insulin. The delivery device (130) also does not store such a preset basal rate or preset mode of basal insulin delivery for rapid-acting or slow-acting. The delivery device (130) does not deliver any background insulin. Therefore, the background, baseline and / or basal rate of basal, baseline and / or background insulin delivery is irreversibly fixed at zero because the insulin delivery device (130) can be specifically configured to be unable to perform such basal, baseline and / or background insulin delivery. Thus, the fasting insulin delivery device (130) is designed to perform only a small amount of correction boluses when the user is fasting for a limited period of time, and as described anywhere in this disclosure, in contrast to the CSII device, the fasting insulin delivery device (130) cannot deliver any insulin dose without first running an insulin correction dose calculation based on real and / or estimated real-time (or substantially real-time) blood glucose values. And in some embodiments, the fasting insulin delivery device (130) is also not configured for any meal bolus delivery. This configuration greatly simplifies the requirements for the delivery algorithm so that the fasting insulin delivery device (130) can effectively maintain blood glucose within the target range without requiring information related to basal rate, carbohydrate ratio, or insulin action time.

[0077] As will be described in more detail below, the delivery algorithm tasked with determining the size of the correction dose (180a to 180e) employs various safety factors to adjust one or more variables and ensure that there is no over-administration of insulin or the accompanying over-correction of blood glucose during the non-fasting period (162). In addition, because the user must integrate the non-fasting mode of insulin administration outside of the fasting period, one or more systems, devices, and methods disclosed herein may also provide functionality to integrate this supplemental method of insulin administration used outside of the fasting period (164) with the automatic fasting insulin delivery method of insulin administration used during the fasting period (164). In some embodiments, as will be described in more detail below, in order to facilitate efficient transition between this supplemental method of insulin administration during the non-fasting period (162) and the automatic corrective delivery method during the fasting period (164), one or more systems, devices, and methods disclosed herein may also be configured to accurately detect the start-up activity (190) ( Figure 1C ) and end activity (192)( Figure 1C ), the initiation activity indicating the need, desire, or appropriateness of initiating automatic delivery of insulin from the insulin delivery device (130) at or near the beginning of a fasting period (164), and the termination activity indicating the need, desire, or appropriateness of terminating automatic delivery of insulin from the insulin delivery device (130) at or near the end of a fasting period (164).

[0078] Reference Figure 2A , the flowchart (200) shows that Figure 1A An example embodiment of a method for managing insulin using a delivery device (130) of a device. The method can be performed by a controller of the delivery device, or with some steps performed remotely relative to the controller. The method can be performed by the controller in collaboration with a user application provided on a user's mobile computing device.

[0079] The method may include: detecting (201) a startup activity associated with the preparation for use of an insulin delivery device in the form of an AID that can be attached to the user's body for the duration of a fasting period throughout the time period. Detecting (201) the startup activity associated with the preparation for use of the delivery device may include various different forms of detection of the preparation of the delivery device before it is ready to deliver insulin. Such a startup activity may be any activity that indicates the need, desire, or appropriateness of initiating automatic delivery of insulin from the insulin delivery device (130). Automatic delivery may be initiated without explicit instruction from the user. For example, in some embodiments, such a startup activity may be any activity that is not a direct action for automatic delivery (such as pressing a power button), but is an activity that typically occurs or is expected to typically occur before the start of a fasting period or substantially at the start of a fasting period. In this way, such startup activities have a primary function other than initiating the automatic delivery of insulin from the insulin delivery device (130), so that these startup activities are used for their primary function, and in addition, are simultaneously reused to effectively and accurately indicate the need, desire, or appropriateness of initiating automatic delivery of insulin, because the startup activity is also an activity whose occurrence has a significantly higher correlation with the start of a fasting period. This solves the problem of transition complexity, at least for brief use, by providing a simplified system that allows easy transition between two different diabetes management modalities.

[0080] For example, as will be described in greater detail below, the priming activity may include, but is not limited to, physical activity performed by a user with respect to the delivery device, physical changes to the delivery device, an activity level of a user that meets predetermined criteria, and / or occurs at a preset time of day. As described anywhere in this disclosure, a user performing such priming activity and / or detection of such priming activity by one or more devices and / or device components as described herein may play a role in one or more processes for managing insulin delivery using a different modality during non-fasting periods compared to fasting periods.

[0081] The delivery device (130) may detect its own activation, such as, but not limited to, when a user begins to wear the device (130). Alternatively, where one or more steps and / or calculations are performed remotely by another device (e.g., a mobile device (120) or a remote cloud device (140)), such a method may include detecting or receiving notification of such activation of the delivery device (130) by the other device. In one example, the detection (201) initiation activity may be the receipt of a first blood glucose measurement result. For example, in some embodiments, Figure 4 The activation component (446) of the delivery device (401) can be configured to perform such detection.

[0082] Detection (201) may include detecting one or more physical activities performed by a user with respect to the delivery device. The physical activity may include one or more of: removing a controller of the delivery device from a charger, attaching a dispensing unit to the controller or installing a prefilled insulin cartridge, applying to the user's body, removing an applicator from the controller, completing a manual activation sequence, or an audible or voice command to the controller. Detection (201) may also be at preset times of the day, or may be triggered by the user's activity level, which is detected by the delivery device or another monitor (e.g., a fitness monitor that detects rest periods).

[0083] Detection (201) may include: detecting physical changes to the delivery device. The physical changes may include: detecting movement of the controller due to an accelerometer in the controller, proximity or pairing of the controller with a user computing device (e.g., a smart phone) providing a user application, detecting proximity of a smart pen when filling a dispensing unit, detecting connection of a dispensing unit or cartridge to the controller, detecting 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 dispensing unit, detecting automatic activation of the delivery device. Any of these examples of detecting activation activities may be used as a function of transforming one or more physical activities of a user and / or physical changes to the delivery device into a physical configuration of one or more electrical components and / or one or more electrical signals, the one or more electrical signals and / or physical configurations indicating a need, desire, or appropriateness for initiating automatic delivery of insulin from the insulin delivery device.

[0084] By way of example and not limitation, the primary function of removing the delivery device (130) from the charger (131) is to stop charging of the delivery device (130) rather than to initiate a fasting period. However, because the device (130) is worn by the user during the fasting period, the cessation of charging, removal from the charger (131), and / or detection of physical acceleration of the device (130) during such actions has a significantly higher correlation with the start of a fasting period, and therefore, can be reused for a purpose different from its primary purpose and to indicate the initiation of a fasting period.

[0085] Similarly, the primary function of the insulin pen (110) or mobile device (120) coming within a predetermined distance (e.g., proximity) of the device (130) is to physically move the insulin pen (110) or mobile device (120) rather than to initiate a fasting period. However, since the insulin pen (110) and / or mobile device (120) may be used during a non-fasting period or to fill the insulin reservoir of the device (130) prior to a fasting period, such an action has a significantly higher correlation with the start of a fasting period and may therefore be reused for a purpose different from its primary purpose and to indicate the initiation of a fasting period.

[0086] Similarly, the primary function of inserting an insulin reservoir or pre-filled insulin cartridge into the device (130) is to couple the insulin reservoir or insulin cartridge to the device (130) rather than to initiate a fasting period. However, while the insulin reservoir and / or insulin cartridge must be inserted into the device (130) to be usable during a fasting period, such an action has a significantly higher relevance to the start of a fasting period and can therefore be reused for a purpose different from its primary purpose and to indicate the initiation of a fasting period.

[0087] Similarly, the primary function of the activity level dropping to a level indicative of rest is for the user to rest rather than to initiate a fasting period. However, since the fasting period is a time frame when the user is expected to sleep, the occurrence of the user's activity level dropping to or near the resting rate has a significantly higher correlation with the start of the fasting period, and can therefore be reused for purposes other than its primary purpose and to indicate the initiation of a fasting period. Several additional examples of start-up activities each have a primary function other than initiating automatic delivery of insulin from the insulin delivery device (130), such that these start-up activities are used for their primary function and, in addition, are simultaneously reused to effectively and accurately indicate the need, desire, or appropriateness of initiating automatic delivery of insulin, because the start-up activities are also activities whose occurrence has a significantly higher correlation with the start of a fasting period.

[0088] In some embodiments, initiation of insulin delivery requires a combination of two or more initiation activities. In some embodiments, in response to one or more initiation activities, confirmation is requested or required (on a user interface, etc.). In some embodiments, initiation of insulin delivery is in response to a series of initiation activities that follow predetermined criteria.

[0089] In some embodiments, such a priming event can include reaching a preset time of day and / or a rest period indicative of the user's activity level. Detection of such a priming event can include various forms of detection of preparing the delivery device before preparing to deliver insulin, such as detecting one or more physical activities performed by the user with respect to the delivery device, and / or detecting physical changes to the delivery device.

[0090] The method may initiate (202) automatic delivery of insulin from a delivery device. The initiation (202) may be responsive to detection of an initiation activity and may be performed after a predefined time interval from the initiation activity. Initiating (202) automatic insulin delivery in response to the detected activity may include preparing the delivery device to deliver insulin. The method may deliver (203) insulin in the form of a correction bolus dose in response to a received blood glucose measurement while avoiding administration of any background basal dose of insulin. The delivery device may avoid administering basal insulin at a preset or default rate or in a preset or default mode. The delivery device (203) may include a correction bolus dose based on an assumed active insulin based on an initial assumed correction bolus dose calculated to correct the user's initial blood glucose measurement to a target blood glucose. The delivery (203) may be based on an insulin sensitivity factor of the user based on a total daily basal dose delivered prior to use of the delivery device. The delivery (203) may be determined based on an insulin differential measured from the received blood glucose measurement. The amount to be delivered may be determined without a known carbohydrate factor or carbohydrate ratio, without meal information, and without determining the duration of insulin action. The blood glucose target range may be fixed. For some fasting periods where no correction of insulin is required, the delivery may be zero.

[0091] The method may include detecting (204) an end-of-life activity associated with ending use of the insulin delivery device. The end-of-life activity may include detecting removal of the wearable insulin reservoir from the body, completion of a predetermined time period less than a defined time 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.

[0092] For example, the delivery device (130) and / or the mobile device (120) may be configured to detect such an end 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 an end activity may be any activity that is not a direct action to stop automatic delivery (e.g., pressing a power button to turn off the delivery device (130)), but rather an activity that typically occurs or is expected to typically occur substantially at the end of a fasting period. In this way, such end activities have a primary function other than initiating the cessation of automatic delivery of insulin from the insulin delivery device (130), such that these end activities are used for their primary function and, in addition, are simultaneously reused to effectively and accurately indicate the need, desire, or appropriateness of terminating automatic delivery of insulin, because the end activity is also an activity whose occurrence has a significantly higher correlation with the end of the fasting period. This at least solves the problem of transition complexity for short-term use by providing a simplified system that allows easy transition between two different diabetes management modalities.

[0093] 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 predetermined time period less than a defined time period (e.g., 24 hours, 12 hours, 10 hours, 8 hours, or 6 hours), or returning the durable portion of the delivery device (130) to the charger (131).

[0094] By way of example and not limitation, the primary function of removing the insulin reservoir of the delivery device (130) is to disconnect the insulin reservoir from the delivery device (130), e.g., to refill the reservoir, rather than to terminate the fasting period. However, since the insulin reservoir must be properly disposed within the delivery device (130) for proper function, removal of the insulin reservoir has a significantly higher relevance to the end of the fasting period, and therefore, may be reused for a purpose different from its primary purpose and to indicate the end of the fasting period.

[0095] Similarly, the primary function of reconnecting the device (130) to the charger (131) is to charge the delivery device (130) rather than to terminate the fasting period. However, since the device (130) is worn by the user during the fasting period, reconnecting it to the charger (131) has a significantly higher correlation with the end of the fasting period and, therefore, can be reused for a purpose different from its primary purpose and to indicate a desire to terminate the fasting period.

[0096] Similarly, the primary function of removing the delivery device (130) from the user's body is to detach the device (130) from the user's body rather than to terminate the fasting period. However, since 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 reused for a purpose different from its primary purpose and to indicate the end of the fasting period.

[0097] Similarly, the primary function of a significant rise in activity level above resting level is that the user is active rather than terminating a fasting period. However, since the fasting period is a time frame when the user is expected to sleep, the occurrence of a significant rise in activity level above resting level has a significantly higher correlation with the end of the fasting period, and therefore, can be reused for a purpose different from its primary purpose and to indicate the termination of the fasting period.

[0098] In some embodiments, initiation of insulin delivery requires a combination of two or more end activities. In some embodiments, in response to one or more end activities, confirmation is requested or required (on a user interface, etc.). In some embodiments, initiation of insulin delivery is in response to a series of end activities that follow predetermined criteria.

[0099] Any example of detecting an end activity may function as a function of transforming one or more physical activities of a user and / or a physical change of a delivery device into a physical configuration of one or more electrical components and / or one or more electrical signals that indicate a need, desire, or appropriateness for initiating an end of fasting process and / or for the user to discontinue use of the insulin delivery device (130). As described anywhere in this disclosure, the use of performing such an end activity and / or detection of such an end activity by one or more devices and / or device components as described herein may function in one or more processes of managing insulin delivery using a different modality during non-fasting periods as compared to fasting periods.

[0100] In one embodiment, the method may coordinate (205) an end of fasting process for the user. The end of fasting process may include delivering at least a portion of an end of fasting bolus at the end of the session. For example, this may be a meal bolus. As an example, there is a time when the user wakes up with elevated glucose, because delivery is conservative assuming that the user may still sleep for many more hours. In this case, an end of fasting bolus may be required, which is not necessarily associated with a meal. The user may prompt an end of fasting bolus in the form of a final correction bolus. This may be only a portion of the required end of fasting bolus using the remaining insulin in the delivery device. The final end of fasting correction bolus may be a mixed correction bolus and meal bolus administered at or near the end of the fasting period to correct for the elevated glucose upon awakening, and further, in anticipation of the consumption of a meal during a subsequent non-fasting period after the end of the fasting period. The delivery algorithm may have a number of safeguards to avoid overcorrection during the fasting period; therefore, once the user wakes up, a full correction dose may be required.

[0101] Reference Figure 1C Since the entire period (160) is a repeating period (e.g., in some cases a 24-hour period), coordination of the end-of-fasting process, or if coordination of the end-of-fasting process is not included, detection of the end-of-fasting activity (204) can be forwarded back to the step of detecting (201) the start-of-fasting activity when the next entire period (160) immediately following the non-fasting period (162) is initiated. In addition, the repeating nature of the entire period (160) requires transitioning from the non-fasting period (162) and its associated insulin administration mode (e.g., MDI) to the fasting period (164) and its automatic administration of correction doses (180a to 180e), and transitioning back to the next non-fasting period (162) and its associated insulin administration mode at the end of the fasting period (164). Thus, some methods, devices, and systems configured for integrating a supplemental method of insulin administration outside of a fasting period (164) may include providing one or more correction doses (180a-180e) provided by a delivery device (130) during a fasting period (164) in conjunction with administration of insulin via a non-fasting modality (e.g., Figure 1A Coordination of one or more basal doses (170a, 170b) or meal doses (172a to 172d) provided by an insulin pen (110)).

[0102] Reference Figure 2B , flow chart (220) shows the control of the fasting time wearable delivery device (e.g., Figure 1AAn example embodiment of a method for delivering insulin from a delivery device (130) that is intended to be worn only during fasting periods. The method delivers insulin during a fasting period from a delivery device that is intended to be worn only during fasting periods, and wherein the delivery device does not deliver a basal dose. The method may be used to deliver insulin during a fasting period (164) from a delivery device (130) that is intended to be utilized only during fasting periods (164). The delivery device (130) does not deliver a basal dose of insulin. Such a method may solve the problem of calculating active insulin from a non-fasting delivery modality without any user interaction or input, and without any prior or direct knowledge of the amount of insulin actually administered to the user from such a non-fasting delivery modality. Such a method may be used in applications such as Figure 1A at and / or executed by a controller of a controller (132) of a delivery device (130) shown in Figure 4 and / or at and / or by the delivery device (401) or mobile computing device (402) shown in and / or 8, and / or remotely on a server, computing device (e.g. Fig. 9 The method may be executed at a location such as the computing device (900) shown in FIG. 1 ) and / or by a server, computing device, etc., and then send the instruction to the controller. In some embodiments, some steps may be executed by such a controller of the delivery device, and / or some of the steps may be executed remotely relative to the controller. Therefore, in some embodiments, such a method may be executed in cooperation with such a controller and a user application provided on a mobile computing device of a user (e.g., mobile computing device (401)).

[0103] The method may include an initialization phase (221) in which 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. During 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 of how much one unit of insulin is expected to lower the user's blood sugar. In some embodiments, the ISF may be received from the user (i.e., the patient), from a physician, or from a connected device (e.g., a user application or another insulin therapy device, such as Figure 1A The smart insulin pen (110) receives this initial ISF. During the use of fasting time delivery doses for repeated fasting time periods, the user ISF can be learned and improved over time. In some embodiments, this can be the only user input required by the method, rather than regular blood glucose measurement results. This greatly simplifies the user's interaction with the devices and systems of the present disclosure. In some embodiments, Figure 4The ISF receiving component (431) of the delivery device (401) may be configured to perform the functions of the initialization phase (221).

[0104] The initial user ISF can be based on the total daily basal dose (TDBD) information received. The TDBD information can be provided by the user or doctor via a user application or a smart insulin pen. The TDBD or daily basal amount is the amount of basal insulin taken in a 24-hour period, and it is usually constant every day for the user. For example, the user's TDBD can be determined by the amount of basal insulin injected from an insulin pen in a 24-hour period. In such an embodiment, receiving an ISF may include: receiving a TDBD (e.g., Figure 1C The sum of the MDI (170a, 170b) in the formula (170a, 170b); and the ISF is estimated based on the received TDBD. For example, as described in the following formulas (2) to (4), there is a strong relationship between TDBD, total daily dose (TDD) and ISF:

[0105] (2)ISF=800 / TDBD.

[0106] (3)TDBD=0.47×TDD.

[0107] (4)ISF=1700 / TDD.

[0108] In some embodiments, the ISF can be determined based at least in part on the user's weight. In some embodiments, the user's ISF can be learned during use of the delivery device (130). In some embodiments, the ISF curve can change over time because the user's ISF can 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 curve can use a learning algorithm that is configured to set and / or adjust the ISF during a delivery session or in advance for the next delivery session.

[0109] The method of delivery algorithm determines the insulin required for the user to gradually reach the target blood glucose. The delivery algorithm is based on calculating the correction dose of insulin by comparing the blood glucose measurement result of the assessment with the target blood glucose (wherein the difference is adjusted by the user ISF). The resulting correction amount can be compensated by the determined active insulin. The compensation can be minus the determined active insulin by the resulting dose. The target blood glucose can be a set amount for all users or different categories of users, and can be time-varying, so as to decrease over time during the fasting period. The rate at which the target blood glucose decreases over time can be assumed: the blood glucose level is reduced by the existing externally applied insulin used before the fasting period.

[0110] The method may receive (223) a first blood glucose measurement result. For example, a first blood glucose measurement result may be periodically obtained from a blood glucose monitor (e.g., Figure 1A In some embodiments, the CGM (105) in the apparatus receives blood glucose measurement results. Figure 4 The BG receiving component (451) of the delivery device (401) can be configured to perform the functions of box (223). As will be described in more detail below, an initial blood glucose measurement or a set of initial blood glucose measurements at the beginning of the fasting period (164) or sufficiently close in time to the beginning of the fasting period (164) can be used to determine a hypothetical IOB and, in some cases, one or more safety factors for determining a variable for determining a correction dose in a subsequent step.

[0111] A target blood glucose and one or more safety factors can be set (224). The target blood glucose can be adjusted by the target safety factor to bias the target safety factor. For example, a target blood glucose can be set, and then any one or more of the target blood glucose, ISF, and IOB can be adjusted by applying the safety factor, thereby ultimately manipulating or biasing the insulin dose, or the calculation of such a dose, to prevent over-delivery and the induction of hypoglycemia. The calculated correction dose can also be adjusted by the overall safety factor. One or more of these safety factors can be based on the initial blood glucose measurement result or initial blood glucose measurement result group received (223) at the beginning of the fasting period. One or more of the safety factors can be based on the difference between the assessed blood glucose measurement result and the target blood glucose. The safety factor can be a percentage adjustment, such as 5%, 10%, 15%, or 20% from the baseline value.

[0112] For example, in some embodiments, at the beginning of the fasting period (164), the target blood glucose can be set to a predetermined or constant value for all users, or to a corresponding one of a plurality of constant values ​​for each of a plurality of categories of users. In some embodiments, the target blood glucose is set based at least in part on the first blood glucose measurement received (223), e.g., initially setting or adjusting the target blood glucose to be higher for a higher first blood glucose measurement and initially setting the target blood glucose to be relatively lower for a relatively lower first blood glucose measurement. In some embodiments, a fixed or constant value glucose target means that the method does not allow a user to manually enter or modify a glucose target value. In some embodiments, the target blood glucose level can start at an initial value such as here and be adjusted during the fasting period (164) (as described in more detail below).

[0113] As will be described in more detail below, the safety factor may also be applied to the actual blood glucose measurement in the form of filtering and / or any other modification to the actual blood glucose measurement as described anywhere in this disclosure. However, such adjustments are primarily discussed in the context of evaluating (229) the blood glucose measurement. Similarly, the application of any safety factor to the calculated resulting correction dose may be applied by limiting the correction dose based on the maximum delivery rate.

[0114] The initialization phase (221) of the method may include determining (225) insulin active (IOB), i.e., how much insulin is still active in the user's body. This may be based on a hypothetical external dose calculated to correct the user's initial blood glucose value to the target blood glucose, which will be discussed below with respect to Figure 2C Further described. IOB may include hypothetical active insulin, which is assumed to be provided by non-fasting insulin therapy before using a delivery device (referred to as "external insulin"). It is initially assumed that IOB is sufficient and decreases over time during the fasting period. The rate of decrease over time can be based on the following assumptions: based on the known duration or decay rate of insulin action in the body, blood glucose levels are affected by the existing externally administered insulin administered before the fasting period. When compared with the assessed blood glucose measurement results, the hypothetical active insulin can be adjusted over time during the delivery phase. During the delivery phase, the determined IOB may also include a known device insulin delivered, which is known as a correction dose from the delivery device. The term "external insulin" refers to insulin delivered by a device other than the described fasting delivery device. The term "device insulin" refers to insulin delivered by a fasting delivery device. This is insulin to be delivered by a wearable insulin delivery device, which is used to deliver a correction dose of insulin to a user in the fasting time period.

[0115] The assumed external IOB is based on an assumed or hypothetical amount of external insulin required to correct the user's hyperglycemia based on a comparison of the current BG (or current estimated BG) to the target BG according to equation (6), as derived from equation (5) below:

[0116] (5)[(Current_BG-Target_BG) / ISF]-IOB=0.

[0117] (6) Assumed IOB=[(Current_BG-Target_BG) / ISF].

[0118] The assumed external IOB can be calculated based on the difference between the current blood glucose (or the currently assessed blood glucose as described anywhere in the present disclosure) and the target blood glucose, by ISF scaling, the ISF being set as at box (222) and / or adjusted as at box (224), rather than being derived from known external insulin. In some embodiments, the first blood glucose value on which the assumed IOB is based can be averaged over a set of first blood glucose measurements to filter transient and / or acute changes. In some embodiments, such a set of first blood glucose measurements can be filtered to exclude outliers and / or exclude such outliers from being used for such a rolling average. As described above, considering the assumed initial IOB adequacy means that the controller does not need to accept or use known external IOB amount information from the user. Therefore, the correction dose calculation can be completed without any external IOB input or knowledge. The assumed IOB, at least in the initial stage, does not include insulin input from any previous dose. The initial assumed IOB determined according to equation (5) above is also simpler for the user and can reduce user errors.

[0119] In addition, the assumed IOB can also be used as a safety factor because the IOB in equation (5) is initially assumed or set to be equal to the assumed IOB. In this way, when such a safety factor is reflected as an assumed external IOB that decays over time, any dose calculation that exceeds zero (or the minimum threshold that the delivery device (130) is configured to deliver, such as 0.1 units of insulin) onwards indicates an unexpected BG or incomplete external IOB, which can be safely compensated by delivering the difference (e.g., 0.1 units of insulin).

[0120] The correction bolus dose is compensated by the determined active insulin, and for at least the first correction bolus dose of the plurality of correction bolus doses, the determined active insulin is equal to the assumed active insulin. The method in the initialization phase (221) can deliver (226) a first dose, which may be zero units based on an assumption of the adequacy of the assumed IOB. For example, as described above, the assumed IOB is initially determined based on an assumption of the adequacy of the initial IOB. Therefore, during and / or at the end of the initialization phase, the first correction dose will not include any insulin delivery.

[0121] The method may include a delivery phase (227) in which blood glucose measurements are periodically received (228). For example, blood glucose measurements may be received from a blood glucose monitor (e.g., Figure 1A In some embodiments, the CGM (105) in the apparatus receives blood glucose measurement results. Figure 4The BG amount receiving component (451) of the delivery device (401) can be configured to perform the assessment. In other embodiments, the CGM (105) can perform at least some of the functions of the assessment.

[0122] Preventing over-delivery of insulin or preventing calculated over-delivery of insulin may be better achieved 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 anomalies. Thus, a variety of different methods may be used to evaluate periodically received blood glucose measurements (or a subset thereof) (229). For example, as described below or anywhere else in this disclosure, periodically received blood glucose measurements may be processed and / or filtered to obtain a proxy for 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 anomalies.

[0123] In some embodiments, the blood glucose measurement results (229) can be evaluated by smoothing the received blood glucose measurement results using a low pass filter to reduce the effects of noise and / or sudden disturbances. For example, one or more received blood glucose measurement results can each be replaced by a rolling average of a predetermined number of previous blood glucose measurement results and the received blood glucose measurement result.

[0124] The blood glucose measurement result (229) can be evaluated by filtering the increased blood glucose value without filtering the decreased blood glucose value. For example, when the actual blood glucose value is less than the rolling average of the blood glucose value, the actual blood glucose value can be used. The blood glucose measurement result can be evaluated at least in part by retaining the received blood glucose measurement result that is less than the rolling average of a predetermined number of previously received blood glucose measurements and otherwise retaining the rolling average of the received blood glucose measurements. For example, if the actual CGM value is less than the rolling average of the actual CGM value and the predetermined number of previous CGM values, the actual CGM value can be used, so the BG value is immediately considered to be reduced, but the rolling average can be used in the case where the GM value is greater than the rolling average to avoid determining the insulin dose based on the local blood glucose peak. Peak filtering provides double-sided security for the CGM value used to make decisions by providing additional filtering / smoothing for the increased blood glucose value than the decreased blood glucose value. As will be described below, such double-sided security is also useful in determining or adjusting the IOB, because if the actual IOB is lower than the estimated IBO, it is safe to deliver insulin; however, if the actual IOB is higher than the estimated IBO, insulin will not be delivered.

[0125] In some embodiments, the blood glucose measurement (229) may also be evaluated, at least in part, by extrapolating a downward trend in the received blood glucose measurement forward and adding the downward trend to the blood glucose measurement value used in the dose calculation. This may adjust for a long-term downward trend over a period of several hours during the fasting period (e.g., this may be up to half of the fasting period). The evaluation of the blood glucose measurement may also correct for basal drift. For example, when the true BG value is trending downward over time (e.g., 6 hours), the true blood glucose value may be adjusted downward based on and reflecting the forward extrapolation of the downward trend, effectively reducing the insulin dose for which the BG has drifted downward, preventing inappropriate insulin overdose, and thereby preventing induction of hypoglycemia. This may provide correction for basal drift caused by incorrectly titrated basal insulin doses, meal bolus doses, and / or other physiological factors, as it may compensate (withdraw) the insulin effect to account for the trend adjustment. However, in some methods, adjusting for long-term drift during the fasting period (164) may require determining an appropriate slope for the drift to be compensated. One way this slope can be determined is by performing a least mean squares linear regression analysis on all or a subset of the actual or estimated blood glucose measurements from the time range for which the drift slope is expected. FIG. 3A to FIG. 3D Several additional methods of evaluating received blood glucose measurements are described.

[0126] The IOB, target blood glucose, and / or one or more of the safety factors mentioned 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 during the fasting period (164). In some embodiments, Figure 4 The correction dose calculation component (453) of the delivery device (401) can be configured to perform the functions of box (230).

[0127] The operating assumption is that the assumed IOB is sufficient to cause the initial blood glucose measurements to fall back toward the blood glucose target over time. Thus, in some embodiments, if blood glucose measurements (or their evaluated proxies) received within a predetermined time interval after the start of the fasting period (164) are rising rather than falling from the levels during the initialization phase (when the assumed IOB was initially set), the assumed IOB may be recalculated and / or adjusted upward based on the rising blood glucose measurements and / or their evaluated proxies. Such an upward adjustment or recalculation of the assumed IOB effectively reduces the expected insulin dose in the event that the initial blood glucose measurements received during the initialization phase do not adequately represent the actual rising trajectory of blood glucose under insulin that may have been injected using the non-fasting modality during a previous non-fasting period. In some embodiments, Figure 4The IOB determination component (443) and / or the assumed IOB component (444) of the delivery device (401) may be configured to perform one or more functions of the block (230).

[0128] In some embodiments, the target blood glucose level can be adjusted (230) to change over time (based at least in part on the time that has passed since the initialization of the delivery device). Thus, the target blood glucose level can decrease over time during the fasting period (164) (e.g., see Figure 1C ). In some embodiments, the rate at which the target blood glucose is lowered can be based at least in part on the assumption and expectation that blood glucose levels are currently being lowered by the remaining assumed IOB.

[0129] The method can calculate (231) a correction dose by comparing the estimated blood glucose measurement result to the target blood glucose, wherein the difference is adjusted by the user ISF and the resulting dose is compensated by the determined active insulin. The method can limit the correction dose using a maximum delivery rate that delivers the maximum amount of insulin in a given time period or divide (232) the correction dose into portions. The given time period can be an interval at which blood glucose measurements are received. In some embodiments, Figure 4 The correction dose limiting component (454) of the delivery device (401) can be configured to perform the functions of block (232). For example, the correction dose can be divided into portions (180a to 180e) that include up to a maximum amount of insulin to be delivered in a given time period. The method can then deliver (233) at least a portion of the correction dose, such as the divided portion. In some embodiments, Figure 4 The dose delivery mechanism (431) of the delivery device (401) can be configured to perform the functions of box (233). For example, referring to Figure 1C , the correction dose (180a) may be delivered to the user by the delivery device (130). If the correction dose is greater than the maximum value of each delivery period, the correction dose (180a) may include only a portion of the calculated correction dose that is equal to the maximum value of each delivery period.

[0130] The method may continue to iterate (234) during the delivery phase (227) to adapt to periodically received blood glucose measurements. In one embodiment, the correction dose may be divided into several smaller portions to meet the maximum value delivered, and one of the smaller portions may be given. When the next received blood glucose measurement is received, the method may determine whether to deliver the next divided portion or whether to adjust the dose based on the updated calculation.

[0131] The method may include an end process (235) to accommodate an end-of-fasting bolus as described above. As an example of a use case and not limitation, the user may have elevated blood glucose upon waking because the delivery of the correction dose is conservative, operating under the assumption that the user will sleep for several more hours, in which case a final end-of-fasting correction bolus not associated with a meal (or a portion of such a correction dose that includes remaining insulin in the delivery device) may be administered. As an example of another alternative use case, such as in conjunction with FIG. 5A to FIG. 5C Described in more detail, such a final end-of-fasting correction bolus can be a mixed correction and meal bolus administered at or near the end of the fasting period (164) to achieve both: correction of elevated blood glucose upon waking, and further anticipation of a meal during a subsequent non-fasting period (162) following the end of the fasting period (164).

[0132] See also Figure 2C , flow chart (240) shows the process of delivering a food from a wearable delivery device such as Figure 1A Another example embodiment of a method for controlling insulin delivery by a delivery device (130) using a user. During initial setup of the delivery device, total daily basal dose information may be received (241) from a user, which may be used to estimate (242) the ISF of the user. Target blood glucose (BG) and insulin action time values ​​may be fixed (243) for all users. When a user begins wearing the device, the delivery device may detect (244) activation. The delivery device may receive (245) CGM BG data periodically (typically at 5 minute time points).

[0133] At the beginning of wearing, when the first blood glucose value is received, the dosage calculator can calculate (246) the dosage required to correct the user to the target, and the hypothetical dosage can be immediately added to the IOB as the hypothetical IOB. The hypothetical IOB can be calculated by a common method known to those skilled in the art. The hypothetical dosage is a hypothetical value of external insulin that may have been administered before activating the delivery device. The first blood glucose value on which the hypothetical IOB is based can be averaged and / or filtered over a set of first blood glucose measurements to prevent the use of abnormal values.

[0134] The next BG value, which may have been processed or estimated, may be received (247) from the CGM and may be smoothed using a low pass filter to reduce the effects of noise and sudden disturbances. When the BG values ​​are trending downward over time, the downward trend may be extrapolated forward (248) and added to the actual BG used in the dose calculator, effectively reducing the insulin dose if the BG drifts downward.

[0135] A dose calculator (249) may be run at each CGM time point to determine if insulin is needed to enable the user to reach goal. The basal calculator uses equation (1):

[0136] (1)Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB.

[0137] If the result is positive, the delivery device may deliver a dose of corresponding size, but with the following limitations. The maximum dose given at any point in time may be limited (250) to a small amount (e.g., 0.5 units) to further minimize sudden corrections. The dose may be limited by hardware resolution and the minimum dose increment (e.g., 0.1 units).

[0138] It may be determined (251) whether a next BG value has been received, and if so, the method may loop to repeat filtering (247), trend assessment (248), and dose calculation (249) and delivery (250). When it is determined (251) that there is no next BG value, the method may end (252).

[0139] Example Corrected Dose Calculation Method

[0140] An example implementation of a method for calculating a correction dose is described. The method uses equation (1):

[0141] (1)Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB.

[0142] Current_BG is the measured blood glucose value, which may be evaluated before being applied to the equation, for example, to filter the instantaneous reading or adjust for long-term trends. Target_BG is the user's target blood glucose level and may be set to a constant value for all users at the beginning of a fasting period.

[0143] The target blood glucose level may be increased by a safety factor compared to standard clinical recommendations (e.g., increasing the target to 5%, 10%, 20%, 25% more than the standard recommendation of 100 mg / dL to 120 mg / dL (e.g., 130 mg / dL to 180 mg / dL)). Alternatively, the target blood glucose level may vary over time based on the time elapsed from initialization of the delivery device, such that the target blood glucose level initially increases and decreases over the time of the wear period. The rate of decrease in the target blood glucose level may assume that the blood glucose level is affected (decreased) by the injection or ingestion of external basal insulin during the period of wear of the delivery device.

[0144] Fixed blood glucose target means that the method does not allow the user to modify the blood glucose target value. In one example, an additional 20 mg / dL safety margin above the typical 120 mg / dL BG target is implemented so that the dose calculation is performed based on a 140 mg / dL fixed target to further prevent hypoglycemia. This additional safety margin helps account for expected BG variations due to sensor noise, basal drift, and dose accuracy.

[0145] ISF is how much a unit of insulin is expected to reduce the blood sugar of a specific user. This is based on user-specific input that can be transmitted from an application or a user's smart pen. When the delivery device is repeatedly used during the fasting period, this can be learned over time. The ISF user adaptation parameter is the only user adaptation parameter available in the calculator. In some preferred embodiments, ISF is biased towards less insulin delivery to reduce the risk of hypoglycemia, for example, (5%, 10%, 15%, 20%, 25%) safety factors can be applied, and these safety factors, when used in the push calculator, produce a more conservative calculation of the amount of insulin delivered. In some embodiments, ISF can be initially set to a conservative default and / or predetermined value (for example, a relatively high ISF biased towards a lower insulin dose), and (for example, based on the difference between the actual blood sugar measurement result or the blood sugar measurement result of the assessment and the expected blood sugar) over time and adjusted and / or personalized.

[0146] The ISF can be derived from the total daily basal dose (TDBD) from the user request or provided via an application or smart pen. Using TDBD can reduce variations due to user errors. For example, in order to eliminate the chance of significant ISF errors due to incorrect estimates, the user can be prompted to enter their current TDBD amount (i.e., how much basal insulin they have taken in the past 24 hours), and the ISF is estimated based on this input, rather than allowing the ISF to be set manually. Typically, 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 likelihood that unsafe treatment parameters are entered into the calculator. There is a strong relationship between TDBD insulin use and ISF, and as those skilled in the art will appreciate, the following numbers can be used: ISF = 1700 / TDD, where TDD is the total daily dose, TDBD = 0.47×TDD, and therefore, ISF = 800 / TDBD.

[0147] The hypothetical IOB refers to how much insulin is still active in the body from a previously received external basal or bolus dose, and is subtracted from the correction dose. There are two types of IOBs in this calculator: the hypothetical external IOB, calculated as the hypothetical amount of externally administered insulin required to correct the user's actual BG to the target BG; and the delivered device IOB calculated based on the insulin delivered by the current device as described herein.

[0148] IOB can be viewed as the sum of two subtypes of IOB: (1) a hypothetical IOB, which is the amount of externally administered insulin required to correct the user's actual initial BG to Target_BG, and which is assumed to have been delivered to the user; and (2) a delivered IOB, which is calculated based on the insulin actually delivered to the user by the fasting period delivery device (130) as described herein. Since insulin is metabolized over time, the IOB is adjusted over time based on the known duration of insulin action (DIA). The DIA is the time required for a bolus of insulin to complete the lowering of blood glucose. The DIA time begins at a given bolus and ends when the bolus no longer lowers blood glucose levels. An accurate DIA minimizes insulin accumulation and low blood glucose (hypoglycemia), which can occur when given boluses are too close in time.

[0149] According to the above equation (1), the required insulin that has not yet been delivered is ultimately determined based on: determining the difference between the representation of the user's actual real-time blood glucose level (or the blood glucose level that is close enough in time, such as within 5 minutes) and the target blood glucose, and then scaling the difference according to the representation of the user's insulin sensitivity, and further subtracting the amount of insulin that is calculated to be (or still) active in the user's body. However, the core focus of the disclosed method for calculating and / or controlling the delivery of one or more correction doses of insulin to the user during the fasting period is to prevent over-delivery or calculate over-delivery of insulin and prevent accompanying hypoglycemia, especially because the user is expected to sleep during most of the fasting period and will not eat to provide any exogenous balance to excessive insulin and hypoglycemia. This makes it difficult to guide blood glucose towards a safe and healthy target within a suitable time frame, because many unknown factors can affect the user's actual blood glucose level and short-term dynamics. For example, a user's short-term blood glucose readings can include rapid and sometimes abnormal fluctuations that do not always accurately reflect the long-term trends in the user's current blood glucose levels or the amount of actual active insulin that still acts on these blood glucose levels. Further complicating matters is that a user's insulin sensitivity may vary with the time of day, and of course, based on other physiological factors that are difficult to individually and directly explain, including but not limited to stress (eg, cortisol release).

[0150] Thus, the disclosed 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, solve various technical problems at least in part by utilizing the user's initial conditions (e.g., the user's initial blood glucose level) to determine the amount of insulin (assumption 10B) assumed to be still active in the user's system (from a previous non-fasting period). This assumption of initial insulin sufficiency in the face of initially elevated blood glucose levels prevents insulin accumulation at the beginning of a fasting period, which would result from inappropriate dosing of insulin in response to an initially above-target blood glucose level (for which insulin has been administered).

[0151] In addition, the speed of action of insulin in reducing blood sugar level is limited. In other words, it takes a non-negligible time period to deliver insulin to reduce blood sugar level. Therefore, without knowing the actual insulin already in the body of a specific user, even the most accurate current blood sugar level may not accurately indicate how the actual blood sugar level will be in the short time period in the future. And over time, the body will metabolize active insulin, reducing its effectiveness in reducing blood sugar level. Therefore, without knowing the actual determined insulin action (DIA) time of a specific user, even the most accurate current blood sugar level and actual active insulin may not accurately indicate how the actual blood sugar level will be in the short time period in the future. At least for these reasons, using the most accurate actual blood sugar level at each time point (e.g., each CGM BG reading) may not necessarily be the best way to achieve the goal of preventing over-delivery of insulin or preventing over-delivery of insulin by calculation. On the contrary, by using a proxy of the actual blood sugar level of the user processed, evaluated and / or filtered, it is better to achieve prevention of over-delivery of insulin or prevention of over-delivery of insulin by calculation, the proxy of the actual blood sugar level of the user more accurately represents the long-term trend of the actual blood sugar level of the user, thereby preventing over-delivery of insulin, while also weakening, eliminating or otherwise filtering out short-term noise and / or abnormality. Such a processed, estimated and / or filtered proxy for actual blood glucose may be referred to herein as estimated blood glucose.

[0152] Such methods, devices and / or systems also solve various technical problems at least in part by utilizing one or more safety factors to dynamically adjust (e.g., scale and / or convert) one or more of the variables used to determine insulin dosage (e.g., target blood glucose level, ISF, and / or assumptions and / or delivered portion of IOB) to prevent over-delivery or calculation of over-delivered insulin and prevent associated hypoglycemia.

[0153] The result of above equation (1) is correction dose, and this correction dose can be divided into smaller amount in the form of delivery part based on maximum delivery rate.The maximum delivery rate over time is the amount of the maximum insulin to be delivered in the time interval determined, wherein the amount is in units of insulin, such as 0.1 unit, 0.2 unit, 0.3 unit, 0.4 unit, 0.5 unit, 0.6 unit, 0.7 unit, 0.8 unit.The time interval determined can be a predetermined time interval (such as 5 minutes, 10 minutes, 15 minutes), or can be based on the interval receiving blood glucose data.For example, when the dosage calculation determines that insulin should be delivered, it can deliver no more than the maximum dose amount in 5 minutes, and then rerun the dosage calculation (every 5 minutes or similar interval).The maximum dose amount can be calculated based on the maximum impact on the user in a predetermined time period (such as reducing 10mg / dL every 30 minutes).The maximum dose amount can depend on the ISF calculation drawn according to the total daily basal amount.

[0154] In one example, only small insulin doses are given at every 5 minute interval to gradually reduce BG to the target, with larger corrections implemented as "extended bolus doses". Based on the user's ISF, each dose is limited to a maximum insulin reduction of 20 mg / dL. 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 is calculated as 2 units, it can be divided into 4 using 0.5 unit increments. The first increment of 0.5 units can 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 the BG value changes so that the dose calculation needs to be adjusted.

[0155] The calculated corrected delivery portion is delivered at a fixed zero basal rate because there is no basal delivered with or otherwise by the described delivery device. This is in contrast to known continuous use pumps.

[0156] Measure the user's blood sugar. This can be transmitted from the blood sugar monitor to the delivery algorithm via a connection to an application and / or the cloud. Blood sugar levels are received regularly from a continuous blood sugar sensor and can be processed using one or more of the following methods. The actual BG increase measured quickly can be filtered to reduce the peak. In order to reduce the possibility of excessive insulin based on sporadic CGM noise or local BG fluctuations, the increase of the CGM value can be filtered using a rolling average BG value. If the true CGM value is less than the rolling average, the true CGM value can be used, so the reduced BG value is immediately considered, but the increase will be filtered to avoid medication on the local peak. Peak filtering provides double-sided security for the CGM value used to make decisions by providing additional filtering / smoothing for increased blood sugar values ​​rather than for reduced blood sugar values. Double-sided security can be used because if the actual IOB is low, it is safe to deliver insulin; however, if the actual IOB is high, the method will not deliver insulin. Long-term trends can also be adjusted to infer a downward trend for many hours (e.g., 6 hours) in the future. This provides a correction for basal drift because it compensates (cancels) the insulin effect of trend adjustment.

[0157] The method can provide a safety factor or margin for any of the variables of the dose calculator, including target BG, IOB, and / or can be applied as a separate adjustment to the dose calculation. The safety factor can be based on a comparison of the user's actual BG to the target BG, with the safety margin varying over time. The safety margin can be applied once at the beginning of a treatment session.

[0158] In one embodiment, a safety margin may be applied based on the assumption that the user has taken insulin from another source (referred to as external insulin) prior to applying the described delivery device, and that the insulin taken was sufficient to lower the current BG to the target BG that the user of the delivery device started with. The assumed external IOB is based on an assumed amount of external insulin required to correct the user's hyperglycemia, based on a comparison of the current BG to the target BG, such that:

[0159] [(Current_BG-Target_BG) / ISF]-IOB=0.

[0160] The hypothetical external IOB can be assumed based on the above equation, rather than being derived from known external insulin. The hypothetical IOB can have a time-varying curve based on the duration of insulin action (DIA) based on the time elapsed from initialization of the delivery device, such that the hypothetical IOB decreases over time during the wear period. As the hypothetical IOB decreases, the dose calculation is corrected downward along the curve. The expected rate of decrease in blood glucose level / IOB is based on the assumption that external insulin injected or ingested will affect blood glucose levels during the time period of initialization / wearing of the delivery device.

[0161] Considering the assumed initial IOB sufficiency means that the controller does not need to accept or use known external IOB amount information from the user. Correction dose calculations can be completed without external IOB input or knowledge. The initial assumed external IOB calculated from [(Current_BG-Target_BG) / ISF]-assumed IOB@t=0 (referred to as "assumed IOB") is simpler for the user and reduces user error.

[0162] Calculation of the correction dose insulin delivery amount (including the assumed external IOB applied to the calculation) is performed iteratively with each received actual BG value using the previous equation as follows:

[0163] Dose_Calculation=[(Current_BG-Target_BG) / ISF]-IOB.

[0164] The assumed external IOB provides a safety margin, and the IOB in Dose_Calculation is equal to the assumed external IOB + any effective device IOB, where the effective device IOB is the amount of insulin delivered since the delivery device was used in the fasting period. The assumed external IOB may decay based on the duration of insulin action (DIA). In this way, when the safety margin is embodied as the assumed external IOB that decays over time, any dose calculation exceeding 0 (or a threshold value, such as 0.1 units of insulin) indicates an unexpected BG or an incomplete external IOB, which can be safely compensated by delivering a difference (such as 0.1 units of insulin). The DIA or effective insulin time is the time required for the bolus insulin to complete the reduction of blood sugar. The DIA time starts when the bolus is given, and ends when the bolus no longer reduces the blood sugar level. Accurate DIA minimizes insulin accumulation and hypoglycemia (hypoglycemia), which may occur when the bolus is given too close in time.

[0165] In another implementation, the duration of actual insulin action (DIA) calculated according to actual BG or according to the BG of the assessment described anywhere in the present disclosure is compared with the assumption of external IOB. In another implementation, actual BG is compared with the expected BG calculated according to DIA. These values ​​and / or their comparison can be used to create, calculate, determine, set, reset and / or select a safety factor or margin. These values ​​and / or comparison can also be used to learn from the experience of the previous safety margin of the user, so as to be committed to biasing the insulin dosage calculation towards delivering less insulin under the situation of any unknown factors that may affect blood sugar. The fixed setting of DIA can be used. This eliminates the chance of major DIA errors caused by incorrect estimates. The pharmacokinetics / pharmacodynamics (PK / PD) of rapid-acting insulin has been fully characterized as having a PK / PD peak at about 65 minutes, which is related to the DIA of 6 hours. Therefore, since the delivery device only uses rapid-acting insulin, the DIA can be fixed at a value between about 5 hours and 7 hours, preferably fixed at 6 hours. This can be combined with a fixed time constant of the IOB calculation (of approximately 60 to 70 minutes) to avoid insulin pile-up.

[0166] In some embodiments, the ISF changes over time. For example, many people are more insulin resistant in the morning, so it is desirable to use a lower ISF during the morning portion of the fasting period (164). Therefore, in some embodiments, the ISF can be set or reset based on the time of day. The ISF curve can use a learning algorithm that is configured to adjust the ISF based at least in part on the user's effective ISF during one or more previous fasting periods, blood glucose measurements, and / or a historical record of blood glucose targets. In some embodiments, the ISF can be initially set to a conservative default value and / or predetermined value (e.g., a relatively high ISF) and adjusted / personalized over time based at least in part on a comparison between actual and expected BG trends / curves in the context of a correction dose that has been delivered to the user during the fasting period.

[0167] The delivered insulin from the delivery device can be based on a calculated device correction amount, where the delivery is not informed of the actual external active insulin. In this case, the initial delivered dose is zero because it is based on the assumption that IOB is sufficient. For safety reasons, the delivery delivers at least a portion of the calculated amount, and typically a small portion. For example, if 0.5 units are delivered every 5 minute interval, the 2 unit correction dose will be divided into 4×0.5 delivery portions. Note that after 5 minutes, when a new blood glucose value is received, the calculation can be rerun and the ongoing correction delivery portion can be increased (more than 0.5 units) or decreased (less than 0.5 units).

[0168] Alternatively, delivery may be a single correction dose; however, delivery in smaller delivery portions at the maximum delivery rate allows for a slower, and therefore safer, correction, which is confirmed or updated by each iteration of a new actual BG received.

[0169] Since the described delivery device may be in the form of a fasting time wearable delivery device, the user will use another treatment (e.g., MDI) during non-fasting time. For example, the delivery device can be worn at night, and the user uses the MDI during the day. Using the MDI during non-fasting time means the presence of an external IOB. Therefore, using the delivery device without assuming the IOB or without a known IOB will be high risk because the external insulin amount will not be informed. In other embodiments, the IOB can be known from the first treatment used during the non-fasting period, and therefore the assumed external IOB calculation may not be required.

[0170] Refer to the following FIG. 3A to FIG. 3D Continue with the following questions about how blood glucose measurements can be evaluated (e.g., based on Figure 2B Each of these methods can also be considered as a method of achieving a safety factor that allows for a bias toward less insulin delivery in the event of any unknown factors that may affect blood glucose values.

[0171] Combination Figure 3A A method for determining this drift compensation slope is described, Figure 3A A use case is shown for determining a drift slope for a plurality of actual or estimated blood glucose measurements within a time range (300). The estimated blood glucose measurements are evaluated at least in part by extrapolating a downward trend of the received blood glucose measurements forward and adding the downward trend to the blood glucose measurement values ​​used in the dose calculation. The downward trend is determined at least in part based on a maximum negative slope between any received blood glucose measurement and a reference blood glucose measurement within a predetermined time range.

[0172] In some implementations, the time range (300) may include Figure 1CThe portion of the fasting period (164) of the reference blood glucose measurement result (302) is established. In some embodiments, a predetermined time range (310) is established before a reference (e.g., the most recent or last) blood glucose measurement result (302) (e.g., occurring between T1 or a time earlier than T1 before T0 reference and T2 or a time later than T2 before T0, where T2>T1), and the predetermined time range is, for example, between T1 and T2, and is 15 minutes to 30 minutes or 30 minutes to 60 minutes before the reference measurement result (302). The slope of each straight line connecting one of the blood glucose values ​​(303 to 306) within the predetermined time range (310) and the reference measurement result (302) is determined, the maximum slope is selected as representative of the drift within the time range (300), and the amount of downward adjustment is determined based on the selected slope and the length L of the expected period during which the downward drift is to be extended (e.g., the reference 302 is reduced by an amount equal to their product to the evaluation value 301). Selecting the maximum slope from blood glucose values ​​that precede the reference measurement (302) by a sufficient time period solves the problem of underestimating blood glucose excursions and thereby overestimating insulin requirements by preemptively adjusting the actual blood glucose value downward to account for future excursions based on the fastest indication of a long-term drop in blood glucose during a predetermined time frame.

[0173] In some embodiments, evaluating a received blood glucose measurement comprises combining Figure 3B The received blood glucose measurement result is filtered as described, Figure 3B A use case is shown in which a drift slope is to be determined for a plurality of actual or estimated blood glucose measurements in a time range (320). The estimated blood glucose measurements are evaluated at least in part by fitting the received blood glucose measurements in a predetermined time range to a trend having a median slope selected from a plurality of regression fit slopes for different rolling subsets of the received blood glucose measurements in the predetermined time range.

[0174] In some implementations, the time range (320) may include Figure 1CThe linear regression fit slope (e.g., S1) is determined for all blood glucose measurements in a rolling window (322) of a predetermined interval (e.g., a 60 minute window from the first blood glucose measurement to the last blood glucose measurement in the window). The rolling window (322) is advanced by one or more blood glucose measurements, and the linear regression fit slope (e.g., S2, S3) is re-determined for all blood glucose measurements in the advancing rolling window (322). Thus, for each blood glucose value rolling window (322) advances, a previous blood glucose value used in a previous regression fit will fall outside the back of the window, and the next blood glucose value not yet used in a previous regression fit will enter the front of the window. In some embodiments, for each of these slopes (e.g., S1, S2, S3), a rolling average can be determined by averaging the values ​​of each slope and a predetermined number of previous or immediately adjacent slopes. This serves to smooth out small changes in the rate of change of the slope (e.g., reducing the volatility of the change). Then, the median value (or other form of average) of the initial slope (e.g., S1, S2, S3) or the rolling average of each of these slopes (e.g., slope S2) in the time range (320) is selected as a representative of the trend of the blood glucose value in the time range (320), and the actual blood glucose value (black point) is filtered or adjusted to match the selected trend line extending from the first blood glucose value (321) of the time range (320) (e.g., see the white point with a black outline). The median slope (e.g., S2) is selected from the regression fit slopes (e.g., S1, S2, S3) of the blood glucose values ​​in the rolling window (322), or in some cases from the rolling average of the regression fit slopes, ensuring that the value selected as an indication of the blood glucose trend in the time range (320) is not driven by any extreme disturbances in either direction occurring in the time range (320). This solves the problem of over-delivering insulin in the case of any unknown variables that may affect the blood glucose value by limiting the rate of change of blood glucose changes based on a moderately representative slope of the received blood glucose values ​​in the time range of interest.

[0175] In some embodiments, evaluating a received blood glucose measurement comprises combining Figure 3C The received blood glucose measurement result is filtered as described, Figure 3C A plurality of actual and / or estimated blood glucose measurements 903 to 909 from a recent time range (340) are shown within which a blood glucose trend can be determined. The slope of the line connecting each pair of adjacent blood glucose measurements (e.g., S 2-3 , S 3-4 , S 4-5 , S 5-6 , S 6-7 , S7-8 , S 8-9 In some embodiments, a rolling average of the slopes can be determined by averaging each slope with a predetermined number of previous or immediately adjacent slope values. This serves to smooth out smaller changes in the rate of change of the blood glucose measurement (e.g., to reduce the volatility of the change). Then, the median value of the initial slope or rolling average slope in the time range (340) is selected (e.g., the slope S 6-7 ) as a representation of the trend of blood glucose values ​​within the time range (340), and filtering or adjusting the actual blood glucose values ​​(342 to 349) (black dots) to match the selected trend line extending from the first blood glucose value of the time range (340) (e.g., see the white dots with black outlines). Selecting the median slope from the individual slopes between adjacent actual blood glucose values, or in some cases from the rolling average of the individual slopes between adjacent actual blood glucose values, can allow for representation of the blood glucose trend within the time range (340), which will better prevent over-delivery of insulin while still effectively directing the user's blood glucose toward the target range, and then maintaining blood glucose near the target during the fasting period (164). This solves the problem of over-delivering insulin in the presence of any unknown variable that may affect the blood glucose value by limiting the rate of change of blood glucose changes based on a moderate slope between adjacent received blood glucose values ​​within the time range of interest.

[0176] In some embodiments, evaluating a received blood glucose measurement comprises combining Figure 3D The received blood glucose measurement result is filtered as described, Figure 3D A plurality of actual or estimated blood glucose measurements (363 to 368) from a recent time range (360) are shown within which a blood glucose trend may be determined. The estimated blood glucose measurements are evaluated at least in part by filtering the received blood glucose measurements, the filtering comprising: for increasing received blood glucose measurements, applying progressively increasing limits on how much each next received blood glucose measurement may increase compared to a previous received blood glucose measurement; and for decreasing received blood glucose measurements, amplifying how much each next received blood glucose measurement decreases compared to a previous received blood glucose measurement.

[0177] It is observed that the blood glucose measurements (368, 367, 366) follow an increasing trend, then flatten with measurement (365), and then begin to decrease with measurements (364, 363, 362). In some embodiments, the evaluation of the true received blood glucose measurements includes: when the true blood glucose value increases (e.g., when the slope between adjacent true blood glucose values ​​is positive), applying gradually increasing limits (e.g., L1, L2, and L3) on how much the next blood glucose value can increase compared to the previous value, the evaluation results in the deviation from the true BG measurement shown for the measurements (366 and 367), but when the true blood glucose value decreases (e.g., when the slope between adjacent true blood glucose values ​​is negative), the decrease (e.g., D1, D2, and D3) between the blood glucose value and the next blood glucose value is amplified, the evaluation results in the deviation from the true BG measurement shown for the measurements (362, 363, and 364). For example, while each real blood glucose value is greater than or equal to the previous real blood glucose value within the time range (360), if the next real blood glucose value is greater than the previous estimated blood glucose value by more than a predetermined amount (e.g., L1, L2, and L3), the next estimated blood glucose value is set to be greater than the previous estimated blood glucose value by only the predetermined amount, the predetermined amount is increased, and the evaluation is repeated for the next real blood glucose value. However, when the next real blood glucose value is less than the previous real blood glucose value, the next estimated blood glucose value is set to be lower than the previous estimated blood glucose value by a multiple (e.g., any decimal value greater than 1, 2x is shown) of the difference between the next real blood glucose value and the previous real blood glucose value (e.g., D1, D2, and D3). This addresses the issue of over-delivery of insulin in the presence of any unknown variables that may affect blood glucose values ​​by allowing the assessed received blood glucose measurement to slowly merge with the rising CGM line which rounds off higher and wider peaks rather than typically smoothing higher and wider peaks by a rolling average of the blood glucose measurements, but allowing the assessed received blood glucose measurement to quickly merge with the falling CGM line, thereby allowing a trend of blood glucose over the time frame (360) to be represented which will be better biased to prevent over-delivery of insulin while still effectively guiding the user's blood glucose towards the target range and then maintaining blood glucose near the target during the fasting period (164).

[0178] The delivery algorithm of the method for controlling the delivery of insulin from a fasting wearable delivery device (130) can be implemented as a stand-alone algorithm in a controller (132) of the delivery device (130), or all or some of the delivery algorithm can be implemented using external processing. For example, some of the evaluation of blood glucose measurements can be performed by a blood glucose monitor.

[0179] 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 in conjunction with the user's existing basal and mealtime bolus insulin, so unlike other pump systems, the fasting time delivery device only dispenses a correction dose. The delivery algorithm uses a typical dose calculation to adjust the actual BG to the target BG based on the user's ISF and IOB. The delivery algorithm includes safety mechanisms to reduce the chance of overcorrection and subsequent hypoglycemia.

[0180] See also Figure 4 , the block diagram shows a delivery device (401) (e.g., such as Figure 1A An example embodiment of the system of the delivery device (130) with the controller (132) described is shown in . The controller (410) may include: a power supply (433) and a charging connector (434). The controller (410) may include: a wireless communication module (413) for communicating with a continuous glucose monitor (GCM) (403) via a wireless network (405) for receiving blood glucose measurements of a user. The controller (410) may also communicate with a mobile computing device (402) such as a mobile phone, laptop computer, or desktop computer via the wireless network (405). In some embodiments, the mobile computing device (402) may communicate with Figure 1A In some embodiments, the blood glucose monitor (403) may be connected to the mobile computing device (120). Figure 1A Corresponding to the CGM (105).

[0181] The controller (410) may include: a microcontroller in the form of a processor (411) having firmware (412) for controlling the operation of the delivery device (401). The firmware (412) may be provided by components of the controller (410). The processor (411) may be a hardware module or circuit for performing the functions of the described components, and the described components may be software units executed on at least one processor (411). The memory may be configured to provide computer instructions to the processor (411) to perform the functions of the components.

[0182] The controller (410) may include a delivery component (420) that can communicate with the mobile computing device (402) and / or the user's blood glucose monitor (403) and determine when and how much of a dose is to be dispensed from a reservoir (432) of the delivery device (401) via a 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 components described in the delivery component (420) may be provided herein, particularly with reference to Figure 2A , Figure 2B and Figure 2C The steps of the flow chart correspond to the functions of the described drug delivery method.

[0183] In some embodiments, the controller (410) can also be configured to cause the dose delivery mechanism (431) (or a similar separate mechanism for glucagon in the device (401)) to deliver a predetermined and / or calculated amount of glucagon from a corresponding reservoir for glucagon (similar to (432)) based at least in part on blood glucose levels falling below a predetermined low level (e.g., 40 mg / dl), and / or to maintain blood glucose levels above a predetermined safety level during periods of intense user activity (e.g., exercise).

[0184] 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 based on total daily basal dose information received from a non-fasting insulin management modality during a defined period prior to the fasting period for determining a correction bolus dose. The initialization component (440) may include a safety factor component (442) for providing a safety factor to a parameter on which the dose correction is based. The initialization component (440) may include an active insulin determination component (443) including an assumed active insulin component (444) for calculating an initial assumed correction bolus dose that corrects the user's initial blood glucose measurement result to a target blood glucose and a device active insulin component (445) for determining a known delivered insulin from the delivery device.

[0185] The delivery phase component (450) may include a blood glucose measurement result receiving component (451) for periodically receiving blood glucose measurement results based on which the correction bolus dose for the fasting period is based. The delivery phase component (450) may include a measurement result evaluation component (452) for smoothing the received blood glucose measurement results using a low pass filter to reduce the impact of noise or sudden disturbances on the obtained blood glucose value. The measurement result evaluation component (452) can be used to forward-project the received blood glucose measurement results that are trending downward over time. The delivery phase component (450) may include a correction dose calculation component (453) for determining the correction bolus dose for the fasting period at each blood glucose measurement time point to determine when insulin is needed to enable the user to reach the target blood glucose. The correction dose calculation component (453) compares the blood glucose value with the target blood glucose to obtain a difference, which is adjusted by the user's insulin sensitivity factor, wherein the dose blood glucose amount is compensated by the determined active insulin. The delivery phase component (450) may include a correction dose limiting component (454) for limiting the correction bolus dose for the fasting period to a defined maximum dose given at any point in time to minimize sudden corrections. The correction dose limiting component (454) may be used to limit the correction bolus dose for the fasting period to a minimum dose given at any point in time based on the delivery device hardware. The delivery phase component (450) may include an end process component (455) for coordinating the end of the bolus delivery at the end of the fasting period. The delivery phase component (450) may also include an end detection component (456) for detecting an end activity associated with ending use of the insulin delivery device.

[0186] Reference Figure 5A , flow chart (500) illustrates an example embodiment of a method of delivering insulin during a fasting period using a delivery device in the form of a wearable automatic insulin delivery (AID) device intended to be worn during fasting periods.

[0187] The user may use (501) a first therapy during non-fasting periods within a time period (e.g., a 24 hour period) to receive a basal dose of insulin and a bolus dose of insulin. The first therapy in the form of a non-fasting insulin management modality may include: a mode, method, device treatment, treatment, etc. used as a diabetes treatment intervention. This may include: pump delivery of insulin, pen or syringe injection of insulin, inhaled insulin, oral insulin, or any form of insulin management used while the user is awake. The non-fasting insulin management modality may also include diet and exercise, wherein insulin is managed without drug intervention at least some of the time.

[0188] The user can use (510) a fasting insulin delivery device as an adjunct to the first treatment during a fasting period within the entire time period. As described herein, a fasting insulin delivery device is an automatic insulin delivery device that can be attached to the user's body for the duration of the fasting period, which delivers a correction bolus dose in response to received blood glucose measurements and avoids administering a background basal dose. During the fasting period (typically when the user is sleeping), the user does not need to interact with the delivery device to correct the bolus insulin. The expected fasting time period can be up to about 2 hours before the user goes to bed, and less than about 2 hours after waking up.

[0189] In one embodiment, the user can fill (502) the fasting insulin delivery device with insulin before use during the fasting period. Filling can be performed by using insulin available from the first treatment. Since the insulin comes from a single source, it is possible to monitor total insulin use. Alternatively, filling can be provided from a separate source, particularly when the type of insulin used in the delivery device is different from the first treatment. Filling can be performed by inserting a pre-filled cartridge or a partially filled cartridge from a previous use phase. Filling can be performed from a medicine bottle, a syringe, a pen, or other insulin delivery device.

[0190] The user can apply (503) the fasting insulin delivery device to his body during the fasting period. It can be applied immediately after the last meal of the non-fasting period, or it can be applied within a few hours. The user can apply the delivery device before bedtime or after completing his daily meals. The delivery device can be applied to the body with an adhesive to keep the delivery device in place, and wherein the needle / cannula is placed under the skin. The user can determine when to apply and remove the delivery device based on the personal day and night cycle. The duration of the fasting period and the time of day may vary due to different uses of the same user. The user can be assisted in using and applying the delivery device by a user application provided on the user's mobile computing device (e.g., smart phone). The user application can suggest when to apply / remove the delivery device. The user application can provide coordination with the first treatment.

[0191] The user may provide (504) insulin sensitivity information to set up the fasting insulin delivery device. This may be a one-time requirement when the user first uses the delivery device. This may be provided via the first treatment with or without the user's participation. For example, the smart insulin pen may provide this information directly to the delivery device or via a user application. The insulin sensitivity information may be total daily basal dose information as received from the first treatment in a previous time period. For example, the user may provide the user's usual daily basal insulin dose as provided by the first treatment. The insulin sensitivity information may be provided at least when the user of the delivery device first uses it, wherein the delivery device includes a durable portion that is reused during multiple fasting periods. The method may not allow the user to provide information related to one or more of the following parameters to the delivery device: the amount of insulin to be delivered; the duration of insulin action; target blood glucose; basal rate (i.e., specifically, the rate of administration of basal, background and / or baseline insulin required to maintain blood glucose at the target, excluding meal bolus doses); IOB; and the ratio of insulin to carbohydrates. The method may not allow the user to provide such parameters by not including any input device that causes the parameters to reach the delivery device.

[0192] The user may perform (505) a start-up activity associated with preparing the insulin delivery device for use during the fasting period. The user may receive insulin from the fasting insulin delivery device during the fasting period throughout the time period. The fasting insulin delivery device may be an automatic insulin delivery device that is attachable to the user's body for the duration of the fasting period. The user may receive (506) a correction bolus dose in response to the received blood glucose measurement from the fasting insulin delivery device without receiving any background basal dose.

[0193] At the end of the fasting period, the user can remove (507) the delivery device from his body. Removal means stopping the delivery of insulin via the delivery device by separating the delivery device from the body. Removal can be done before or after a meal that ends the initial fast. The user can remove the delivery device after about 2 hours of waking up or within about 2 hours of waking up. Figure 5C As further described, the user may remove the delivery device after determining the amount of additional insulin needed to cover the meal for the fasting interruption.

[0194] When the fasting period ends and the delivery device has been removed from the user's body, the user can revert (508) to the first treatment. However, it is not necessary to remove the delivery device before resuming the first treatment. The reservoir of the delivery device can store only the amount of insulin required for the fasting period, and thus the reservoir can be almost or completely empty. In addition, any remaining amount in the reservoir can be used by the end-of-fasting bolus or a portion thereof.

[0195] 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 can be a smart pen. The pump can be configured to be filled by the insulin pen so that the delivered insulin is from a single source and can therefore be calculated.

[0196] Non-fasting insulin management mode and fasting insulin delivery device can provide auxiliary use in the form of supplementary use of one mode to another mode, so that treatment is provided to the user. Fasting insulin delivery device can be used at fixed or unfixed intervals. For example, in a 24-hour period, the user can use the delivery device during fixed sleeping time (for example, 12 hours, 10 hours, 8 hours or 6 hours of sleeping time). However, other users may have a more unstable lifestyle and may need a fasting period at an unfixed time and an unfixed time period.

[0197] The fasting insulin delivery device is personalized for the user, and the delivery algorithm can be learned based on the repeated use of the delivery device by the user. The delivery algorithm can learn one or more of the following: ISF, DIA, and TDBD can be recommended. The fasting insulin delivery device can provide a correction bolus dose. The correction bolus dose during the fasting period is a supplement to the meal bolus given during the non-fasting period, for example, when the meal bolus is not enough to cover the blood sugar increase caused by the meal, or when the blood sugar is still elevated after the meal or meal bolus. This deficiency may be due to bolus calculation errors, reported meal information errors, treatment parameter errors for treatment calculations, etc. Fasting period blood sugar control is achieved by short-term wearing of an insulin pump, which provides AID control during fasting to allow the user to sleep well and wake up within the target blood sugar range without waking up for correction bolus. Daytime basis and daytime bolus are achieved by other types of treatment (e.g., MDI treatment).

[0198] The described method solves the problem of conversion complexity during transient use by providing a simplified system that allows easy conversion between two different diabetes management modes. In one implementation, the system and method described herein enable seamless, intermittent, sporadic use of MDI during the day cycle, and use of AID during the night cycle, allowing the user to benefit from low cost, high flexibility and improved clinical results. For example, diabetes management treatment using daily basal and daytime bolus injections is achieved by MDI treatment, while nighttime blood sugar control is achieved by short-term wearing of an insulin pump that provides AID control during fasting to allow the user to sleep well and wake up within the target blood sugar range without waking up for correction bolus injections.

[0199] Reference Figure 5B , a flow chart (520) illustrates an example implementation of a method for delivering insulin during a fasting period using a delivery device in the form of a wearable automatic insulin delivery (AID) device that is worn only during fasting periods. According to the described delivery method, the delivery device for delivering a correction dose of insulin during a fasting period is a simple wearable insulin delivery device in which user input or control is limited due to safety protections and safety factors incorporated into the delivery algorithm. The delivery device only accepts and processes rapid-acting insulin for the correction dose.

[0200] The use of the delivery device is based on the assumption that prior to using the delivery device, daily basal and mealtime bolus insulin is provided by the user during non-fasting periods using MDI therapy (521). MDI therapy may include external injection, ingestion or inhalation of insulin. In an example embodiment, MDI therapy is provided by a smart insulin pen.

[0201] The user removes (522) the delivery device from the charger. Since the user only uses the delivery device during fasting periods, the delivery device can be charged during non-fasting periods (e.g., during daytime). The user can fill (523) the reservoir of the delivery device with a certain amount of insulin. In one embodiment, the user can use an MDI therapy device to fill (523) the reservoir so that the amount of insulin added to the reservoir is known and accounted for in the MDI therapy. For example, the user can use a smart insulin pen to fill (523) the delivery device.

[0202] The user may apply (524) the delivery device to their body and activate the delivery device to prepare the delivery device to begin delivery of a correction dose of insulin according to the described delivery algorithm applied by the controller of the delivery device. The user may provide (525) information of the ISF, either directly or via a user application or a cloud server, which is provided to the controller of the delivery device. This may be provided at the first repeated use of the delivery device, for example, when the delivery device is used each night. The ISF may be derived from the total daily basal dose (TDBD) requested by the user, or may be provided via an application or smart pen.

[0203] The controller is configured to iteratively calculate a correction dose of insulin based on the following equation: Correction_Dose = [(Current_BG - Target_BG) / ISF] - IOB. The method does not know other information from the user except for the information of ISF. The method does not require, accept or use other information from the following parameters or information: amount of insulin to be delivered; duration of insulin action; target blood glucose; basal rate; IOB; insulin to carbohydrate ratio. The delivery algorithm does not require filling of the reservoir during use.

[0204] The user receives (526) a correction dose from the delivery device during the fasting period. The user may optionally receive (527) an end-of-fasting dose to accommodate an end-of-fasting meal. The end-of-fasting dose may be based on the amount of insulin remaining in the reservoir. The user may remove (528) the delivery device from their body and return the delivery device to the charger. The correction dose is the only insulin delivered by the delivery device. No basal dose is given. The user cannot modify the amount of insulin to be delivered by the delivery device unless the delivery device is removed from their body. When the dose calculation determines that insulin should be delivered, the dose amount delivered within a defined interval (e.g., 5 minutes) does not exceed the maximum dose amount.

[0205] The duration of insulin action (DIA or effective insulin time) can be fixed and cannot be modified by the user. In order to remove the chance of major DIA errors caused by incorrect estimates, fixed settings are used. Target blood glucose can also be fixed and cannot be modified by the user, and can have an additional safety factor. As described above, the IOB is assumed based on the initial blood glucose reading and is also determined by the delivery dose given by the delivery device. The user does not need an insulin to carbohydrate ratio because no meal bolus dose is delivered except for the optional end-of-fasting bolus. The insulin reservoir of the delivery device can be filled before wearing and will not be refilled during the wearing time. In addition to the removal of the wearable device, the delivery of insulin is fully automated without user control. The delivery device does not require alarms or alarms.

[0206] Reference Figure 5C , flow chart (520) illustrates an example embodiment of a method of delivering insulin during a fasting period using a delivery device in the form of a wearable automatic insulin delivery (AID) device intended to be worn during a fasting period. Flow chart (520) illustrates an end of fast process in which at least a portion of an end of fast meal bolus may be provided from remaining insulin in a reservoir of the delivery device.

[0207] The user may receive (541) a correction bolus dose from the described delivery device during the fasting period. The user may provide (542) information related to a fasting interruption meal that requires a meal bolus at the end of the fasting period. A meal bolus refers to the amount of insulin required to compensate for an expected increase in blood sugar caused by eating for a person with diabetes. The compensation is intended to bring blood sugar into a target range. Typically, a user who consumes a certain amount of carbohydrates requires insulin to avoid causing a blood sugar increase. Providing (542) information associated with a fasting interruption meal may include: providing information via a connected insulin pen or through user input from a user software application. The information may include meal information in the form of carbohydrates. The meal information may include blood sugar and IOB information.

[0208] The amount of bolus insulin recommended for covering meals can be calculated based on meal information, blood glucose data and / or IOB information. The amount of insulin can be determined by a delivery device dosage calculator of a delivery device, by a first treatment method or by a separate bolus calculator. When the user ends the fasting period in the target blood glucose range, the meal bolus calculation drives the delivery recommendation. When the user ends the fasting period under the condition of elevated blood glucose, additional units can be recommended to cover the elevation.

[0209] The user may receive (543) at least a portion of the total recommended bolus from the delivery device. 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 include the entire total recommended bolus, the dose may be split.

[0210] The calculated recommended insulin bolus amount can be split into a first part and a second part. Splitting means dividing the total recommended bolus amount into two different parts, which add up to the total recommended bolus amount. The first part can be determined based on the amount of insulin remaining in the insulin reservoir of the delivery device. This can be known, measured or allocated, and then reported. Fig. 7A or Figure 7BFurther described, this can include automatic delivery from the delivery device, wherein confirmation is provided from the user application. Alternatively, this can be distributed by using the control button on the delivery device, until the maximum value required for the recommended insulin bolus amount. For example, if there are 4 units of insulin remaining in the reservoir of the delivery device, the remainder will not be wasted when the patch is removed, but the remainder can be delivered to the user. The second part can be provided by another form of insulin therapy modality. This can be a first form of non-fasting treatment, wherein the user is currently at the beginning of the non-fasting period. The second part is determined according to the difference between the amount of the bolus insulin remaining in the reservoir of the recommended bolus amount and 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 an insulin pen.

[0211] The user may receive (544) instructions to administer the second portion via a non-fasting treatment. Alternatively, this may be automatically sent to a treatment device (e.g., a smart insulin pen). Instructions to deliver the second portion using the first treatment may be delivered to the user via a connected device (e.g., 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 continuous delivery of insulin. This may be delivered to the user via a user application or smart insulin pen. Fig. 7A Further description of the user application or via Figure 7B The individual treatment coordination user application described further above performs the coordination. The user receives (545) any second portion from the non-fasting treatment and may remove (546) the delivery device if not already removed.

[0212] Reference FIG. 6A to FIG. 6M , an example implementation of a delivery device in the form of an AID delivery device (130) is shown as a series of diagrams of a user population and application process. Fig. 6AA packaging arrangement (600) of a delivery device and associated equipment is shown. A durable portion of the delivery device in the form of a controller (132) is provided with a plurality of sealed packages (605), such as blister packages, each package containing a disposable dispensing unit (601). The dispensing units (601) each include a plunger (603) supported on a base (606) and a reservoir (602), wherein the plunger (603) is configured to controllably deliver insulin from the reservoir (602) to a user via a cannula. The controller (132) is attached to the dispensing unit (133) to form a delivery device (130). In one arrangement, the dispensing unit (601) may be provided with an attached coupler (604), and the dispensing unit (602) may be configured to be filled from an MDI therapy pen or syringe by positioning the MDI therapy pen or syringe using the coupler (604) without any insulin in its reservoir (602). The packaging arrangement (600) may also include an applicator (135) and a charger (131) with a charging cord (608).Alternative embodiments may be configured to receive pre-filled cartridges in lieu of a reservoir.

[0213] A dispensing unit (601) is provided in a sealed package (605) and a user can open the sealed package (605) to take out Figure 6B The dispensing unit (601) shown in FIG. 6 is supported on a base (606). The dispensing unit (601) may include a coupler (604) for attaching (611) an insulin pen (110) (eg, Figure 6C ) to fill the reservoir (602). Fig.6D As shown in FIG. 6 , during filling of the reservoir ( 602 ), the plunger ( 603 ) is pushed back ( 612 ). The plunger ( 603 ) may be colored to allow the user to see the movement of the plunger ( 603 ). Fig. 6E As shown in FIG. , the insulin pen ( 110 ) is removed ( 613 ) and can be used with Fig. 6F , together with or after the removal (614) of the coupler (604) shown in FIG. 6 to leave the distribution unit (601). Figure 6G As shown in , the controller (132) is attached (615) to the dispensing unit (601) to form the delivery device (130).

[0214] like Figure 6H As shown in FIG. 6 , the push applicator ( 135 ) is configured to be attached ( 616 ) to the upper portion of the delivery device ( 130 ) to allow the delivery device to be removed ( 617 ) from the base ( 606 ) (eg, Fig.6I ). Figure 6J As shown in FIG, a delivery device (130) held within an applicator (135) is positioned on the user's body. Figure 6KAs shown in FIG, the push button (607) of the applicator is pushed down (618) to apply a pushing force by the user via the applicator (135), thereby adhering the delivery device to the user's body through adhesive attachment. Figure 6L As shown in , the applicator (135) is removed (619) from the delivery device (130), and the delivery device (130) is then ready to deliver the correction dose during the fasting period. Figure 6M As shown in , at the end of the fasting period, the delivery device (130) is removed from the user's body and placed back (620) to the power charger (135).

[0215] The applicator (135) can wrap around and hold the upper portion of the delivery device so that the delivery device can be removed from the base (606) or can be positioned on the user's body with one hand. The push button (607) of the applicator (135) can generate the appropriate force to separate the delivery device from the applicator (135) and push the delivery device 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 to deliver insulin.

[0216] Reference Fig. 7A , a flow chart (700) illustrates an example implementation of a method for managing the delivery of insulin during a fasting period from a delivery device in the form of a wearable automatic insulin delivery device for wear during a fasting period. The method is performed by a computer software application provided on a mobile computing device (e.g., a smart phone or tablet). The computer software application may be an application for managing the described fasting period delivery device.

[0217] The method may register (701) a user of the application and may provide (702) a training step to instruct the user on how to use the delivery device, including filling from an insulin pen. This may be performed when the user first uses the delivery device. The method may request (703) user input of an insulin sensitivity factor or total daily basal dose information to use this information 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 usually taken every 24 hours. If the information changes, the user can update the information. In order to set a delivery device for a fasting period, the method may pair (704) a mobile communication device running the application with a controller of the delivery device. The method may also pair (705) a mobile communication device running the application with a blood glucose monitor worn by the user. Pairing may be performed via near field communication technology, such as using Bluetooth. The application may include instructions for pairing. The method may provide (706) the user's ISF to a delivery algorithm of the controller of the delivery device for calculating a correction dose.

[0218] During the fasting period (707), the method can receive (708) a record of blood glucose measurements monitored from the blood glucose monitor, and these records can be sent to the controller for calculating the correction bolus dose. Alternatively, these records can be sent directly from the blood glucose monitor to the controller. In another alternative, the blood glucose monitor can be integrated into the delivery device and set in the controller. Filtering and inference of the blood glucose measurements can be performed in the application to send the estimated blood glucose value to the controller for use in the delivery algorithm. The method can receive (709) a record of the correction bolus dose given by the delivery device.

[0219] The method may include an end of fasting procedure, during which the method receives (710) an end of fasting input from a user and may send the input to a delivery device controller. The method may receive (711) details of an end of fasting bolus dose from the controller. The method may notify (712) the user of the end of fasting procedure and instruct the user to replenish the delivery device end of fasting dose using their insulin pen. Steps (710) and (711) may be performed during a fasting period (707) or at a time when the user interrupts fasting. The method may provide (713) a session history, including a display of a correction dose given by the delivery device and blood glucose measurement results, and additional statistical information including user information. A session history of previous sessions may also be provided.

[0220] Reference Figure 7B , flow chart (720) illustrates an example implementation of a method for managing the delivery of insulin from a delivery device in the form of a wearable automatic insulin delivery device for wear during fasting periods when using fasting periods. The method is performed by a computer software application provided on a mobile computing device (e.g., a smart phone or tablet). The computer software application can be a coordination application for coordinating the use of a fasting delivery device with a non-fasting insulin therapy (e.g., an MDI therapy using a smart insulin pen).

[0221] The method may register (721) a user of the application and may record user information related to the user's insulin needs. The method may receive (722) information related to the non-fasting insulin therapy used by the user throughout the period. This may be received from a non-fasting therapy device (e.g., a smart insulin pen or an application that manages the use of the non-fasting therapy device). Alternatively, this may be received from the user. The method may receive (723) information related to the fasting delivery device delivering a correction bolus dose during the fasting period of the entire period. This information may be received from a controller of the delivery device or from a separate application that manages the use of the delivery device.

[0222] The method may provide coordination between non-fasting and fasting treatments and doses (724). The method may include providing a recommendation to the user (725). Coordination may include providing an ISF for the delivery device based on the use of the non-fasting treatment. Coordination may include providing an ISF at the end of the use of the delivery device. Coordination may provide additional parameter information for coordination between treatments, including active insulin and basal drift when switching between treatments.

[0223] The recommendation may include daily basal dose optimization to help the user adjust their basal insulin during non-fasting periods. The recommendation may include indicating the amount of insulin to be filled into the delivery device during the fasting period. The recommendation may include whether and when to use the delivery device throughout the time period, including the timing of when to apply the delivery device throughout the time period. The recommendation may include adjustments to the treatment or treatment parameters.

[0224] The method may provide predicted results (726) associated with adjustments to a treatment or treatment parameter of a non-fasting treatment and a fasting delivery device (e.g., improved time in range), where the adjustments are represented by hypothetical scenarios. For example, the following scenario may be predicted: if the user wears the delivery device at night, what the user's blood glucose level may be between x hours and y hours. Another example may be what the likely outcome is if the user does not wear the delivery device at night. Yet another example may be what the likely outcome is if the daily basal amount is changed from x to y. In one embodiment, an implementation may be where the user's data may be uploaded and analyzed to determine the relative benefit of the described delivery device over an existing non-fasting treatment, for example based on increased time in range (TIR).

[0225] Figure 7C Use cases are shown according to some example embodiments, with time extending vertically from the top of the graph to the bottom of the graph and interactions are shown as horizontal lines with arrows extending between devices and / or entities involved in a method of insulin management for delivering insulin during a fasting period (164) and / or coordinating such fasting period (164) insulin management with another therapeutic modality utilized during a non-fasting period (162). Figure 7C A non-limiting example use case is shown 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 as described elsewhere in this disclosure). In a non-limiting example, the user (101) may be a type 1 diabetic requiring continued insulin therapy both during non-fasting periods (162) and during fasting periods (164).

[0226] As shown, the user (101) is first in a non-fasting period (162), during which the user (101) can self-administer a 24-hour slow-acting basal insulin dose (170a) and a fast-acting meal bolus dose (172a to 172d), for example, using a different insulin pen (e.g., insulin pen (110)).

[0227] At some time during the non-fasting period (162), a user may interact with a mobile device (120) (e.g., running a coordination application for use with a fasting delivery device (130) and non-fasting insulin therapy) to register the user with the application (701, 721). After registration, the coordination application may be configured to provide a training step (702) to the user, instructing the user on how to use the delivery device (130), including filling from an insulin pen (110). The coordination application may then pair (704 / 705) (e.g., wireless communication pairing) with a controller and CGM (e.g., shown as integrated with the delivery device (130), but may also be a separate device) of the delivery device (130). Once registration and pairing are complete, the coordination application may request (703) and the user may provide (706) an ISF or TDBD to the mobile device (120) for use in determining the ISF (as described anywhere in this disclosure). In the event that the ISF is determined rather than provided by the user, the mobile device (120) may determine the ISF (as described anywhere herein) and provide the ISF to the delivery device (130) (eg, delivery device controller (132)).

[0228] Then, as described anywhere in this disclosure, the user can perform a startup activity (201). In some embodiments, such as in conjunction with at least FIG. 6A to FIG. 6M As described, this may include filling the delivery device (130) with insulin. For example, upon detecting (201) the initiation activity, the delivery device (130) calculates and delivers a correction dose (180a to 180d) (as described anywhere in this disclosure) to the user (101) during the fasting period (164) in response to the user's actual and / or estimated blood glucose values.

[0229] At some point, the user performs an end activity (204) to signal an end of fasting process at the end of the fasting period (164). Upon detection of the end activity (204), the end of fasting process may be entered. In some embodiments where the user's blood glucose is at target or within a target range after initiating the end of fasting process, the final correction dose (180e) may not be delivered to the user. However, if (e.g., for reasons described anywhere in this disclosure) the user's blood glucose is above target, the delivery device (130) may deliver an end of fasting bolus (180e) to the user.

[0230] In yet another embodiment, the user intends to eat at the beginning of an upcoming non-fasting period (162). In such an embodiment, the user provides information (710) about the expected upcoming fasting interruption meal (e.g., carbohydrate information, etc.) to the mobile device (120), and the mobile device (120) provides such details to the delivery device (130). Based on the meal information and the current blood glucose level, the delivery device (130) determines the fasting interruption meal dose and delivers it to the user as a bolus (180e). As previously described, in some cases, the calculated fasting interruption meal dose is greater than the amount of insulin remaining in the delivery device (130). In such a case, the bolus (180e) includes the remaining portion of the insulin in the delivery device (130), and then the delivery device (130) sends and the mobile device (120) receives (711) details of the end-of-fasting bolus (180e), which may include how much insulin remains to be delivered via the smart pen (110). The remainder of the calculated fasting interruption 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 (712) the user of an end-of-fasting procedure in which the user delivers an end-of-fasting 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 dosage information for the end-of-fasting bolus to the smart pen (110), so that the smart pen (110) may be preset to deliver the end-of-fasting bolus.

[0231] Reference Figure 8 , a block diagram illustrates an example implementation of a system including a mobile computing device (402) (e.g., a mobile phone, a laptop computer, or a desktop computer). The mobile computing device (402) can communicate with a delivery device (401) (e.g., the described delivery device (130)) via a wireless network (405). The mobile computing device (402) can also communicate with a continuous glucose monitor (GCM) (403) via the wireless network (405) to receive blood glucose measurements of a user. The mobile computing device (402) can include a wireless communication module (806).

[0232] 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 executed on the mobile computing device (402). The software unit may be stored in a memory unit (804) and may provide instructions to the processor (802) to perform the functions of the described components. In some cases, such as in a cloud computing implementation, a software unit arranged 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 a software application that may be downloaded to the mobile computing device (402) and executed on the mobile computing device (402).

[0233] A 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 users of the application; and a user training component (812) for providing training steps to guide 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 to use this information to set an ISF for the user. The delivery device application (810) may include: a controller pairing component (814) for pairing a mobile communication device (402) running the delivery device application (810) with a controller of the delivery device (401). The delivery device application (810) may include: a blood glucose monitor pairing component (815) for pairing a 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 providing component (816) for providing the user's ISF to a delivery algorithm of a controller of the delivery device (401) for use in calculating a correction dose.

[0234] The delivery device application (810) may include: a blood glucose providing component (817) for receiving blood glucose measurements monitored from the blood glucose monitor (403) and sending these measurements to the controller for use in calculating a correction bolus dose. The application (810) may include: a dose calculation component (818) for performing one or more steps in calculating a correction bolus dose (e.g., as described anywhere in the present disclosure). The dose calculation component (818) may work in conjunction with the controller (310) of the delivery device (301). The dose calculation component (818) may work in conjunction with a remote server. The application (810) may include: a dose receiving component for receiving a record of a correction bolus dose given by the delivery device.

[0235] The delivery device application (810) may include: an end of fasting component (819) for providing an end of fasting process in which the delivery device application (810) receives an end of fasting input from the user and may send the input to the controller and may receive details of an end of fasting bolus dose from the controller to notify the user of instructions to use their insulin pen or other treatment to replenish the delivery device end of fasting dose. The delivery device application (810) may include: a session history component (820) for providing a session history including a display of a correction dose given by the delivery device together with blood glucose measurement results and additional statistics including user information. A session history of previous sessions may also be provided.

[0236] A treatment coordination application (820) may be provided by a hardware or software unit for managing the described fasting delivery device. The treatment coordination application (820) may be provided independently of the delivery device application (810). The treatment coordination application (820) may be combined with or interact with the delivery device application (810). The treatment coordination application (820) may include: a registration component (821) for registering users of the application and for recording user information related to the user's insulin needs. The treatment coordination application (820) may include: a non-fasting treatment component (822) for receiving information related to the non-fasting insulin treatment used by the user during the overall period. This may be received from the non-fasting treatment device (e.g., a smart insulin pen or an application that manages the use of the non-fasting treatment device). Alternatively, this may be received from the user. The treatment coordination application (823) may include: a delivery device treatment component (823) for receiving information related to the fasting delivery device delivering a correction bolus dose during the fasting period of the overall period. This information may be received from a controller of the delivery device or from the delivery device application (810).

[0237] The therapy coordination application (820) may include: a coordination component (824) for providing coordination between non-fasting and fasting treatments and doses. The therapy coordination application (820) may include: a recommendation component (825) for providing recommendations to the user. The recommendations may include: recommending that the user use the delivery device within the recommended time range at night; and recommending that the user adjust the daily basal dose of insulin from a current value to a different value. The therapy coordination 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: predicting the user's wake-up blood glucose level if the user uses the delivery device within the recommended time range at night; predicting the user's wake-up blood glucose level if the user adjusts the daily basal dose of insulin from a current value to a different value; and predicting the user's wake-up blood glucose level if the user does not use the delivery device overnight.

[0238] Fig. 9An example of a computing device (900) that can implement various aspects of the present disclosure is shown. The computing device (900) can be implemented as any form of data processing equipment, including a personal computing device (e.g., a laptop or desktop computer), a server computer (which can be self-contained, physically distributed in multiple locations), a client computer, or a communication device (e.g., a mobile phone (e.g., a cellular phone), a satellite phone, a tablet computer, a personal digital assistant, etc.). Different implementations of the computing device can specify the inclusion or exclusion of various components or subsystems described below.

[0239] The computing device (900) may be suitable for storing and executing computer program code. The various participants and elements in the previously described system diagram may use 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 communication infrastructure (905) (e.g., a communication 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 the following: a CPU, a graphics processing unit (GPU), a microprocessor, a field programmable gate array (FPGA), an application-specific integrated circuit (ASIC), etc. In some configurations, multiple processors may be provided and the multiple processors may be arranged to perform calculations simultaneously. In some implementations, the various subsystems or components of the computing device (900) may be distributed in multiple physical locations (e.g., in a distributed, clustered, or cloud-based computing configuration), and appropriate software units may be arranged to manage and / or process data on behalf of remote devices.

[0240] The memory component may include a system memory (915), which may include a read-only memory (ROM) and a random access memory (RAM). A basic input / output system (BIOS) may be stored in the ROM. System software (including operating system software) may be stored in the system memory (915). The memory component may also include an auxiliary memory (920). The auxiliary memory (920) may include a fixed disk (921) such as a hard disk drive, and may optionally include one or more storage interfaces (922) for docking with a storage component (923), such as a removable storage component (e.g., a tape, an optical disk, a flash drive, an external hard disk drive, a removable memory chip, etc.), a network attached storage component (e.g., a NAS drive), a remote storage component (e.g., a cloud-based storage), etc.

[0241] The computing device (900) may include an external communication interface (930) for operating the computing device (900) in a networking environment that enables data to be delivered between multiple computing devices (900) and / or the Internet. The data delivered via the external communication interface (930) may be in the form of a signal, which may be an electronic signal, an electromagnetic signal, an optical signal, a radio signal, or other type of signal. The external communication interface (930) may enable data communication between the computing device (900) and other computing devices including servers and external storage facilities. Web services may be accessed by and / or from the computing device (900) via the communication interface (930).

[0242] The external communication interface (930) may be configured to connect to a wireless communication channel (e.g., a cellular telephone 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 delivery 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 associated keys and an international mobile subscriber identity for identifying and authenticating a user using the computing device (900). One or more subscriber identity modules may be removable from the computing device (900) or embedded in the computing device (900).

[0243] The external communication interface (930) may also 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 delivery element (e.g., an antenna). The contactless element (950) may be associated with (e.g., embedded in) the computing device (900), and data or control instructions sent via a cellular network may be applied to the contactless element (950) by means of a contactless element interface (not shown). The contactless element interface may be used to allow data and / or control instructions to be exchanged between a computing device circuit (and thus a cellular network) and the contactless element (950). The contactless element (950) may be capable of delivering and receiving data using a near field communication capability (or near field communication medium) typically based on a standardized protocol or data delivery mechanism (e.g., ISO 14443 / NFC). The near field communication capability may include a short-range communication capability, such as radio frequency identification (RFID), Bluetooth, infrared, or other data delivery capabilities that may be used to exchange data between the computing device (900) and the interrogation device. Thus, the computing device (900) is able to communicate and deliver data and / or control instructions via both a cellular network and near field communication capabilities.

[0244] Computer readable media in the form of various memory components may provide storage of computer executable instructions, data structures, program modules, software elements, and other data. A computer program product may be provided by a computer readable medium having stored thereon computer readable program code executable by the central processor (910). The computer program product may be provided by a non-transitory or non-transitory computer readable medium, or may be provided via a signal or other transient or transitory means via the communication interface (930).

[0245] The interconnection via the communication infrastructure (905) enables one or more processors (910) to communicate with each subsystem or component and to control the execution of instructions from the memory component and the exchange of information between the subsystems or components. Peripheral devices (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.) can be coupled to the computing device (900) directly or via an I / O controller (935) or integrated with the computing device (500). One or more displays (945) (which can be touch-sensitive displays) can be coupled to the computing device (900) or integrated with the computing device (500) via a display or video adapter (940).

[0246] The computing device (900) may include a geolocation element (955) that is arranged to determine the geographic location of the computing device (900). The geolocation element (955) may be implemented, for example, by a global positioning system (GPS) or similar receiver module. In some implementations, the geolocation element (955) may use, for example, a cellular phone or Wi-Fi network and / or beacons (e.g., Bluetooth Low Energy (BLE) beacons, iBeacons, etc.). TM The indoor positioning system is implemented by using a communication channel (such as a GPS) to determine or roughly estimate the geographic location of the computing device (900). In some implementations, the geographic location component (955) can implement inertial navigation to track and determine the geographic location of the communication device using an initial set point and inertial measurement data.

[0247] FIG. 10A to FIG. 10E is a graph showing an exemplary storyline for a user using a fasting time delivery method during a session during a fasting period (e.g., at night). The lines can represent either BG or IOB, as one can be derived from the other. Although the axis is labeled blood glucose (BG) (as represented by the graph), the lines can represent either BG or IOB (of course IOB has different labels and values), as one can be derived from the other. As can be appreciated by those skilled in the art, actual BG and expected BG can be derived from actual IOB and assumed IOB, and vice versa.

[0248] Fig. 10A 1010 is a graph showing blood glucose over time during a fasting wear session. The solid line represents the actual BG trend / curve over time as measured by the CGM. The line with small dashes represents the expected BG trend / curve based on an assumed external IOB curve over time, which is calculated at the beginning of the session based on the assumption of insulin sufficiency described above. The line with large dashes represents the device IOB calculated based on the insulin that has been delivered by the delivery device.

[0249] Fig. 10B 1020 is a graph showing blood glucose over time during a fasting wear session. The line with small dashes represents the actual BG trend / curve measured by the CGM over time. The solid line represents the expected BG trend / curve based on the assumed external IOB. In the example of this wear session, the actual BG / IOB matches the expected / assumed BG / IOB, so the assumption that external insulin is sufficient is correct and there is no need to deliver device insulin. Note that in the absence of a safety factor and / or in the absence of any unknown factors that may affect blood glucose values, there is no bias towards reducing insulin delivery (as described herein, particularly the calculation and utilization of the assumed IOB), if the external insulin is not known, the device will mistakenly deliver insulin at the beginning of the session, which will lead to a dangerous nocturnal hypoglycemic event.

[0250] Fig. 10C is a graph (1030) showing blood glucose over time during a session. The solid line represents the BG trend / curve over time as measured by the CGM, showing the following example: the actual blood glucose is not trending downward as expected, which means that the user may not have taken enough meal boluses at dinner time or before applying the delivery device and starting the fasting period. The line with small dashes represents the expected BG trend / curve based on the assumed external IOB curve over time, which is calculated at the beginning of the session based on the assumption of insulin sufficiency described above. The vertical lines schematically represent the time periods during which insulin is delivered in small doses. Note that although the external IOB is assumed to be at a level that is inconsistent with reality, the algorithm is able to quickly learn that the external IOB is insufficient and can deliver correction insulin to ensure that the user wakes up within the target range.

[0251] Fig. 10D1040 is a graph showing blood glucose over time during a session where BG drops below expected at night. The dashed line represents the actual BG trend / curve measured by the CGM over time, showing that during the session, the actual blood glucose unexpectedly drops toward hypoglycemia early, which means that the user has taken too much meal bolus insulin at dinner time or before applying the delivery device. The solid line represents the expected BG trend / curve based on the assumed external IOB curve over time, which is calculated based on the assumption that insulin is sufficient at the beginning of the session as described above. Note that due to the implementation of the safety factor as described herein and / or the bias towards reducing insulin delivery in the context of any unknown factors that may affect blood glucose values, the delivery device does not deliver insulin at the beginning of the session despite the blood glucose value being above the target. This use case also shows the benefit of adjusting the assumed IOB upward when the initial blood glucose level rises at the beginning of the fasting period. By adjusting the assumed IOB upward to handle such an initial rise in blood glucose instead of injecting insulin, a potentially dangerous hypoglycemic event is further avoided. If insulin is delivered in response to an initial blood glucose above standard clinical targets, the result will be an even more severe nocturnal hypoglycemic event.

[0252] Fig.10E 1050 is a graph representing blood glucose over time during a session, showing a session in which the actual BG slowly rises toward the end of the session (e.g., dawn effect). The solid line represents the actual BG trend / curve over time measured by the CGM, showing an example of actual blood glucose rising toward the end of the session (dawn effect), which may be caused by external basal insulin or other physiological factors. The vertical line generally represents the time period during which a correction dose of insulin is delivered by the delivery device dose calculation. Note that the safety margin decreases over time due to the assumption that the possibility of external insulin is reduced, so the delivery device delivers enough insulin to reduce the "dawn effect" that some MDI users would otherwise experience. Advantageously, the delivery algorithm allows daytime MDI diabetes management users to benefit from continuous wearing of the AID at night, increasing the time in range without increasing the risk of hypoglycemia.

[0253] The foregoing description has been presented for purposes of illustration and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Those skilled in the relevant art will appreciate that many modifications and variations are possible in light of the above disclosure.

[0254] Any step, operation, component or process described herein can be performed or implemented with one or more hardware or software units individually or in combination with other devices. In one embodiment, the software unit is implemented with a computer program product, which includes a non-transient or non-transient computer-readable medium containing a computer program code, which can be executed by a processor to perform any or all steps, operations or processes described. The software unit or function described in this application can be implemented as a computer program code using any suitable computer language, such as Java, C++ or Perl using traditional technology or object-oriented technology. The computer program code can be stored as a series 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 disk drive or an optical medium such as a CD-ROM. Any such computer-readable medium can also reside on a single computing device or in a single computing device, and can be present on different computing devices in a system or network or in different computing devices in a system or network.

[0255] This paper uses the flow chart and block diagram of the method, system and computer program product according to the embodiment.Each frame in the flow chart and / or block diagram and the combination of frames in the flow chart and / or block diagram can provide the function that can be implemented by computer-readable program instructions.In some alternative embodiments, the function identified by the frame can occur in an order different from the order shown in the flow chart.

[0256] 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 implement the described methods.

[0257] 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 (e.g., the accompanying flow charts) are typically used by those skilled in the art of data processing to effectively convey the substance of their work to others skilled in the art. Although these operations are described functionally, computationally, or logically, it is understood that these operations are implemented by computer programs or equivalent circuits, microcodes, etc. The described operations may be embodied in software, firmware, hardware, or any combination thereof.

[0258] The language used in the specification is selected primarily for readability and instructional purposes, and the language is not selected to describe or limit the subject matter of the present invention. Therefore, the scope of the present invention is not intended to be limited by this detailed description, but by any claims issued on an application based thereon. Therefore, the disclosure of the embodiments of the present invention is intended to illustrate, but not to limit the scope of the present invention set forth in any appended claims.

[0259] Finally, throughout the specification and any appended claims, unless the context requires otherwise, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

Claims

1. A method of insulin management implemented by an insulin delivery system including an insulin delivery device (130), comprising: detecting (201) a start-up activity associated with preparation for use of the insulin delivery device (130) in the form of an automatic insulin delivery device attachable to a user's body for the duration of a fasting period throughout the time period; as well as Automatic delivery of insulin in the form of a correction bolus dose is initiated (202) during the fasting period in response to periodically received blood glucose measurements.

2. The method according to claim 1, comprising: detecting (204) a termination activity associated with terminating use of the insulin delivery device; as well as Automatic delivery of the correction bolus dose of insulin is terminated.

3. The method according to claim 1 or 2, wherein: The initiation activity has a primary function other than initiating automatic delivery of insulin from the insulin delivery device, and thus is simultaneously reused as an instruction to initiate automatic delivery of insulin from the insulin delivery device.

4. The method according to any one of claims 1 to 3, wherein: The startup activities include one or more of the following: Arrive at a preset time of day; removing the insulin delivery device from the power charger; and A disposable insulin dispensing unit is attached to the insulin delivery device.

5. The method according to any one of claims 1 to 4, wherein: The startup activities include one or more of the following: attaching the insulin delivery device to the user; The insulin delivery device applicator is detached from the insulin delivery device; and A verbal command or selection by the user indicating a desire to initiate automatic delivery of insulin.

6. The method according to any one of claims 1 to 5, wherein: The startup activity includes at least one of the following: proximity or pairing of a controller of the insulin delivery device with a user computing device on which a user application associated with 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 a controller of the insulin delivery device with a blood glucose monitor; receiving blood glucose monitor measurement results; a fill level of an insulin reservoir of a disposable insulin dispensing unit indicating a sufficiently filled insulin reservoir for initiating automatic delivery of insulin; and Movement of the plunger of the insulin reservoir of the disposable insulin dispensing unit indicating filling of said insulin reservoir.

7. A method according to any one of the preceding claims, comprising: Total daily basal dose information is received from a paired user computing device, the total daily basal dose information being received from a non-fasting insulin management modality over a defined period prior to the fasting period, for use in determining the correction bolus dose.

8. A method according to any one of the preceding claims, wherein: Initiating (202) automatic delivery of insulin includes priming the delivery device to prepare for delivery of the insulin.

9. A method according to any one of the preceding claims, wherein: The insulin delivery device (130) avoids administering basal insulin at a preset or default rate or in a preset or default pattern.

10. A method according to any one of the preceding claims, comprising: In response to the received blood glucose measurement, insulin is delivered (203) in the form of the correction bolus dose, the correction bolus dose being compensated by the determined active insulin.

11. The method according to claim 10, comprising: At least a first correction bolus dose is delivered, the first correction bolus dose being compensated by a determined active insulin set equal to a hypothetical active insulin determined based on a hypothetical external dose calculated to correct the user's initial blood glucose value to a target blood glucose.

12. The method according to claim 10 or 11 includes calculating (231) a correction bolus dose by comparing the assessed blood glucose measurement result with the target blood glucose to obtain a difference, the difference being adjusted by a user insulin sensitivity factor to obtain a resulting dose amount, the resulting dose amount being compensated by the determined active insulin.

13. The method according to any one of claims 10 to 12, wherein: The determined active insulin includes the hypothetical active insulin and the known insulin delivered from the delivery device.

14. The method according to any one of claims 10 to 13, wherein: The correction bolus dose is based on an insulin sensitivity factor of the user derived from total daily basal dose information used during a defined period prior to the fasting period.

15. The method according to claim 14, wherein: The total daily basal dosage information is the average total number of basal dosage units given over the entire time period.

16. An insulin management system for an insulin delivery device (130, 401) in the form of an automatic insulin delivery device attachable to a user's body for the duration of a fasting period throughout a period of time, the system comprising: an activation component (446) configured to detect a start-up activity associated with preparation for use of the insulin delivery device; as well as A delivery component (420) is configured to initiate automatic delivery of insulin in the form of a correction bolus dose during the fasting period in response to periodically received blood glucose measurements.

17. The system according to claim 16, comprising: A termination detection component (456) is configured to detect a termination activity associated with terminating use of the insulin delivery device.

18. The system according to claim 16 or 17, wherein: The initiation activity has a primary function other than initiating automatic delivery of insulin from the insulin delivery device, and thus is simultaneously reused as an instruction to initiate automatic delivery of insulin from the insulin delivery device.

19. A system according to any one of claims 16 to 18, wherein: The activation component (446) is configured to detect one or more of the following as the startup activity: Arriving at a preset time of day as the initiation activity; removing the insulin delivery device from the power charger; as well as A disposable insulin dispensing unit is attached to the insulin delivery device.

20. A system according to any one of claims 16 to 19, wherein: The activation component (446) is configured to detect one or more of the following as the startup activity: attaching the insulin delivery device to the user; The insulin delivery device applicator is detached from the insulin delivery device; and A verbal command or selection by the user indicating a desire to initiate automatic delivery of insulin.

21. A system according to any one of claims 16 to 20, wherein: The activation component (446) is configured to detect one or more of the following as the startup activity: proximity or pairing of a controller of the insulin delivery device with a user computing device on which a user application associated with 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 a controller of the insulin delivery device with a blood glucose monitor; receiving blood glucose monitor measurement results; a fill level of an insulin reservoir of a disposable insulin dispensing unit indicating a sufficiently filled insulin reservoir for initiating automatic delivery of insulin; and Movement of the plunger of the insulin reservoir of the disposable insulin dispensing unit indicating filling of said insulin reservoir.

22. The system of claim 21, wherein: The activation component (446) detects receipt of total daily basal dose information from a paired user computing device, the total daily basal dose information received from a non-fasting insulin management modality during a defined period prior to the fasting period for use in determining the correction bolus dose.

23. A system according to any one of claims 16 to 22, wherein: The delivery component (420) is configured to prime the delivery device to prepare to deliver the insulin.

24. The system of any one of claims 16 to 23, comprising a mobile user computing device (402), the mobile user computing device comprising: a processor (802) and a memory (804), the memory being configured to provide non-transitory computer-readable program instructions to the processor to perform the functions of the component; a basal insulin input component (813) configured to request from a user a value of total daily basal dose information used during a defined period prior to the fasting period; as well as A controller pairing component (814) is configured to pair the mobile user computing device with a controller of the delivery device.

25. An automatic insulin delivery device (130, 401) attachable to a user's body for the duration of a fasting period, the device comprising: a durable portion comprising a delivery component (420) configured to control delivery of insulin in the form of a correction bolus dose in response to a received blood glucose measurement, the delivery component comprising: an activation component (446) configured to detect a start-up activity associated with preparation for use of the insulin delivery device; a delivery component (420) configured to initiate automatic delivery of insulin in the form of a correction bolus dose during the fasting period in response to periodically received blood glucose measurements; and A disposable part includes a reservoir (432) configured to contain insulin and configured to automatically deliver the correction bolus dose to the user.

26. The device according to claim 25, wherein The reservoir (432) is configured to be filled from a non-fasting insulin injection device used during a non-fasting period preceding the fasting period.

27. A computer-implemented method for managing the delivery of insulin during a fasting period from a delivery device (130, 401), the delivery device being in the form of a wearable automatic insulin delivery device worn during the fasting period, wherein: The method is performed by a computing application provided at a mobile user computing device (402), the method comprising: requesting (703) from the user a value of total daily basal dose information used during a defined period prior to the fasting period; pairing (704) the mobile user computing device (402) with a controller (420) of the delivery device, the controller (420) detecting a start-up activity associated with preparation for use of the insulin delivery device to initiate automatic delivery of insulin in the form of a correction bolus dose during the fasting period in response to periodically received blood glucose measurements; and Information is sent to and received from a controller (420) of the delivery device (130, 401) during the fasting period.

28. The method according to claim 27, wherein: The value of the total daily basal dose information from the user includes the typical number of units of basal insulin received from a non-fasting form of insulin therapy.

29. The method according to claim 27 or 28, wherein: The method includes pairing (705) the mobile user computing device (402) with a blood glucose monitor (105), thereby allowing blood glucose measurements to be transmitted to the delivery device (401) via the mobile user computing device (402).

30. A method according to any one of claims 27 to 29, comprising: The user is provided with a display of a session history of information related to the fasting period.

31. A method according to any one of claims 27 to 30, comprising: User training is provided to the user regarding the use of the delivery device.

32. A method according to any one of claims 27 to 31, comprising: Coordinating (724) an end-of-fasting process for the user includes dividing an end-of-fasting 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 to be delivered to the user during a non-fasting period immediately following the fasting period using a delivery method different from that of the delivery device.

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