Systems and methods for risk-based insulin delivery transformation

Abstract

Systems and methods are provided for managing hyperglycemia and hypoglycemia by adjusting received data to provide safe and reliable range control using automatic bolus determination where the rate of insulin delivery is dependent on the level of hyperglycemic or hypoglycemic risk. Additionally, some embodiments are directed to converting insulin delivery to a rate based on glycemic risk.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 145,224, entitled "SYSTEMS AND METHODS FOR RISK BASED INSULIN DELIVERY CONVERSION," filed February 3, 2021, the contents of which are incorporated by reference in their entirety herein. [Background technology]

[0002] The availability and reliability of glucose time series data has increased in recent years with the growing adoption of continuous glucose monitoring (CGM) systems and connected devices. However, despite the availability of reliable glucose data, accurate tracking of insulin and meal data, as well as optimized and effective timing of mealtime insulin boluses, continues to be a problem for many people with diabetes, resulting in poor glucose control.

[0003] Conventional diabetes management algorithms have been developed iteratively over time and contain numerous modules that may have overlapping or even competing functions in an attempt to provide flexibility for various user considerations and interactions.

[0004] It is with respect to these and other considerations that the various aspects and embodiments of the present disclosure are presented. Summary of the Invention [Means for solving the problem]

[0005] Systems and methods are provided for managing hyperglycemia and hypoglycemia by adjusting received data to provide safe and reliable control to range using automatic bolus determination where the rate of insulin delivery is determined by the level of hyperglycemic or hypoglycemic risk. Additionally, some embodiments are directed to converting insulin delivery to a rate based on glycemic risk.

[0006] In one embodiment, the risk-based insulin delivery rate converter comprises a comparator including a model agreement evaluator configured to receive insulin data and glucose data and configured to identify discrepancies between separately derived estimates of metabolic and behavioral data derived from the insulin and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin; and a blood glucose risk evaluator configured to quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data. and an insulin delivery monitor configured to adjust the insulin delivery rate based on data from the comparator and glycemic risk assessor.

[0007] In one embodiment, a risk-based insulin delivery rate conversion method includes receiving insulin data and glucose data at a comparison unit; identifying a deviation between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement evaluator of the comparison unit; quantifying a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessor; and adjusting an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor using an insulin delivery monitor.

[0008] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive insulin data and glucose data at a comparison unit, use a model agreement evaluator of the comparison unit to identify deviations between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin, use a glycemic risk assessor to quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data, and use an insulin delivery monitor to adjust an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor.

[0009] In one embodiment, the risk-based insulin delivery rate converter comprises a comparator including a model agreement evaluator configured to receive insulin data and glucose data and to identify discrepancies between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin; a glycemic risk assessor configured to quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data; an insulin delivery monitor configured to adjust the insulin delivery rate based on data from the comparator and the glycemic risk assessor; and a reference insulin rate updater configured to determine a reference insulin rate (RIR), where the RIR is an internal reference for insulin that is considered to achieve equilibrium.

[0010] In one embodiment, the risk-based insulin delivery rate conversion method includes receiving insulin data and glucose data at a comparison unit; identifying a discrepancy between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement assessment unit of the comparison unit; quantifying a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit; adjusting an insulin delivery rate based on data from the comparison unit and the glycemic risk assessment unit using an insulin delivery monitoring unit; and determining an RIR using a reference insulin rate (RIR) update unit, where the RIR is an internal reference for insulin that is believed to achieve equilibrium.

[0011] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive insulin data and glucose data at a comparison unit, identify deviations between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement evaluator of the comparison unit, quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessor, adjust an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor using an insulin delivery monitor, and determine an RIR using a reference insulin rate (RIR) updater, the RIR being an internal reference for insulin that is believed to achieve balance.

[0012] In one embodiment, the method includes receiving a plurality of inputs at a comparison unit, identifying deviations between separately derived estimates of metabolic and behavioral data derived from the inputs, quantifying a current or future risk of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit, and adjusting an insulin delivery rate based on data from the comparison unit and from the glycemic risk assessment unit using an insulin delivery monitor unit.

[0013] In one embodiment, the system comprises a comparator configured to receive a plurality of inputs and identify deviations between separately derived estimates of metabolic and behavioral data derived from the inputs; a glycemic risk assessor configured to quantify a current or future risk of hyperglycemia or hypoglycemia based on the glucose data; and an insulin delivery monitor configured to adjust an insulin delivery rate based on data from the comparator and from the glycemic risk assessor.

[0014] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive a plurality of inputs at a comparison unit, identify deviations between separately derived estimates of metabolic and behavioral data derived from the inputs, quantify a current or future risk of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit, and adjust an insulin delivery rate using an insulin delivery monitor unit based on data from the comparison unit and from the glycemic risk assessment unit.

[0015] This Summary introduces a selection of concepts in a simplified form that are further described below in the Detailed Description. As such, this Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.

[0016] The foregoing summary, as well as the following detailed description of exemplary embodiments, will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the embodiments, there are shown in the drawings exemplary configurations of the embodiments. The embodiments are not limited to the specific methods and instrumentalities disclosed. The drawings are as follows: [Brief description of the drawings]

[0017] [Figure 1] FIG. 1 is a high level functional block diagram of one embodiment of the present invention. [Diagram 2] FIG. 1 is a block diagram of one implementation of a risk-based insulin delivery rate converter. [Diagram 3] FIG. 1 is a flow diagram of one embodiment of a method for risk-based insulin delivery rate conversion. [Figure 4] FIG. 13 is a block diagram of one embodiment of a comparator used in risk-based insulin delivery rate conversion. [Diagram 5] FIG. 1 is a flow diagram of one embodiment of a comparison method used in risk-based insulin delivery rate conversion. [Figure 6] FIG. 1 is a block diagram of one implementation of a glycemic risk assessor for use in risk-based insulin delivery rate conversion. [Figure 7] FIG. 1 is a flow diagram of one embodiment of a method for glycemic risk assessment for use in risk-based insulin delivery rate conversion. [Figure 8] FIG. 1 is a block diagram of one embodiment of an insulin delivery monitor for use in risk-based insulin delivery rate conversion. [Figure 9] FIG. 1 is a flow diagram of one embodiment of a method for insulin delivery monitoring for use in risk-based insulin delivery rate conversion. [Figure 10] 1 illustrates an exemplary computing environment in which exemplary embodiments and aspects may be implemented. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] The claimed subject matter is described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the claimed subject matter. However, it may be apparent that the claimed subject matter may be practiced without these specific details. In other instances, structures and devices are shown in block diagram form to facilitate description of the claimed subject matter.

[0019] 1 is a high-level functional block diagram 100 of one embodiment of the present invention. Processor 130 communicates with insulin device 110 and glucose monitor 120, which communicate with patient 140 to deliver insulin to patient 140 and monitor glucose levels of patient 140, respectively. Processor 130 is configured to perform calculations and other operations and functions described further herein. Insulin device 110 and glucose monitor 120 may be implemented as separate devices or as a single device, within a single device, or across multiple devices. Processor 130 may be implemented locally in insulin device 110, glucose monitor 120, or as a standalone device (or in any combination of two or more of insulin device 110, glucose monitor 120, or standalone device). Processor 130 or portions of the illustrated system may be located remotely, such as in a server or cloud-based system.

[0020] Examples of insulin devices, such as insulin device 110, include insulin syringes, external pumps, and patch pumps that deliver insulin to a patient, typically into subcutaneous tissue. Insulin devices 110 also include devices that deliver insulin by different means, such as insulin inhalers, insulin jet injectors, intravenous infusion pumps, and implantable insulin pumps. In some embodiments, a patient uses a combination of two or more insulin delivery devices, for example injecting long-acting insulin with a syringe and using inhaled insulin before meals. In other embodiments, these devices can deliver other drugs that help control glucose levels, such as glucagon, pramlintide, or glucose-like peptide-1 (GLP-1).

[0021] Examples of glucose monitors, such as glucose monitor 120, include continuous glucose monitors that record glucose values ​​at regular intervals, such as 1, 5, or 10 minutes. These continuous glucose monitors can be, for example, inserted percutaneously, fully implanted, or use electrochemical or optical sensors that measure tissue non-invasively. Examples of glucose monitors, such as glucose monitor 120, also include devices that periodically draw blood or other fluids to measure glucose, such as intravenous blood glucose monitors, microperfusion sampling, or periodic fingersticks. In some embodiments, glucose readings are provided in near real time. In other embodiments, glucose readings determined by the glucose monitor can be stored in the glucose monitor itself for subsequent retrieval.

[0022] The insulin device 110, glucose monitor 120, and processor 130 may be implemented using a variety of computing devices, such as a smartphone, a desktop computer, a laptop computer, and a tablet. Other types of computing devices may also be carried. A suitable computing device is shown in FIG. 10 as computing device 1000 and cloud-based applications.

[0023] The insulin device 110, glucose monitor 120, and processor 130 may communicate through a network. The network may be a variety of network types including a public switched telephone network (PSTN), a cellular network, and a packet-switched network (e.g., the Internet). Although only one insulin device 110, one glucose monitor 120, and one processor 130 are shown in FIG. 1, there is no limit to the number of insulin devices, glucose monitors, and processors that may be carried. The activity monitor 150 and / or smartphone 160 may also be used to collect dietary and / or activity data from or about the patient 140 and provide the dietary and / or activity data to the processor 130.

[0024] The processor 130 may execute an operating system and one or more applications. The operating system may control which applications are executed by the insulin device 110 and / or glucose monitor 120 and how the applications interact with one or more sensors, services, or other resources of the insulin device 110 and / or glucose monitor 120.

[0025] The processor 130 may be configured and / or used to receive data from the insulin device 110 and the glucose monitor 120, and in some embodiments, from the patient 140, and to perform one or more of the calculations, operations, and / or functions further described herein.

[0026] The risk-based insulin delivery transformation contemplated and described herein is applicable to any conventional diabetes management platform designed to determine and / or deliver insulin delivery rates to a patient. Applicable embodiments include, but are not limited to, conventional fully manual open loop therapy, decision-aided therapy, range controlled automated insulin delivery (AID), control to target AID, model predictive control (MPC), linear quadratic Gaussian (LQG), proportional integral derivative (PID), etc. In some implementations, as described further herein, an insulin delivery monitor (e.g., insulin delivery monitor 245, further described herein) adjusts the insulin delivery rate based on the deviation of the predicted metabolic state versus the actual metabolic state and the hyperglycemic risk level.

[0027] Still further, in accordance with some embodiments, an artificial pancreas (AP) algorithm is provided that manages hyperglycemia by adjusting received data to provide safe and reliable range control using automatic bolus determination where the rate of insulin delivery is dependent on the level of hyperglycemic risk. Further embodiments may be implemented to address hypoglycemic risk. Additionally, some embodiments are directed to converting insulin delivery to a rate based on glycemic risk.

[0028] 2 is a block diagram of one embodiment of a risk-based insulin delivery rate converter 230. The risk-based insulin delivery rate converter 230 includes a comparison component 235, a glycemic risk assessment component 240, and an insulin delivery monitor component 245.

[0029] Inputs to the risk-based insulin delivery rate converter 230 include continuous glucose monitoring system (CGM) data 205, other sensed input data 210, insulin data 215, user input data 220, and configuration and / or setup input data 203. External process data 225 (e.g., proposed basal rate and / or proposed bolus rate) are also input to the insulin delivery monitor portion 245 of the risk-based insulin delivery rate converter 230. Outputs 290 of the risk-based insulin delivery rate converter 230 include the approved basal rate and / or the approved bolus rate.

[0030] The risk-based insulin delivery rate converter 230 operates periodically and / or on-demand to provide an approved basal rate and / or an approved bolus rate for the next time interval based on glycemic risk and model deviation. On / off criteria for the risk-based insulin delivery rate converter 230 may be applied, for example, when the patient is starting a bolus or based on data reliability. In some embodiments, the risk-based insulin delivery rate converter 230 operates periodically, for example, every 5 minutes, whenever new CGM values ​​are received, etc.

[0031] Input CGM data 205 (e.g., glucose data), other sensed input data 210, and input insulin data 215 (e.g., previously administered basal / bolus insulin per insulin on board (IOB) calculation) include the respective data up to the present time (i.e., up to the present). In some embodiments, CGM data may be replaced with predicted data when CGM data is missing or unreliable for a particular time interval. User input data 220 may include data based on meals and / or exercise and / or other activities. Meals and exercise and other activities may be explicitly ignored or not allowed in some embodiments.

[0032] Additional inputs may include external process data 225, such as a suggested basal rate and / or a suggested bolus rate from an external process, which may include a pre-programmed basal profile (e.g., from an insulin pump), another AP algorithm (e.g., an AID system), patient-initiated insulin delivery (basal or bolus), etc. The systems and methods described herein convert the suggested or externally derived bolus and / or basal rate into an approved bolus and / or basal rate, as described in more detail with respect to the insulin delivery monitor 245. It should be noted that while arrows leading to and from certain components are shown at a high level, the inputs to or from any process (and resulting outputs) may be inputs to another process simultaneously, sequentially, post-processing, etc., as can be understood by one of ordinary skill in the art.

[0033] If the input includes a default basal insulin delivery profile, which typically defines a minimum amount of insulin per time interval during a 24-hour continuous subcutaneous insulin infusion (CSII), either defined by the patient or another system, it is contemplated that this profile may have a feedback loop from the risk-based insulin delivery rate converter 230 described herein. However, in some embodiments, the basal insulin delivery profile may be defined by the patient. Without wishing to be bound by theory, the patient may modify the basal rate to compensate for a missed bolus or a missed meal, e.g., to minimize or avoid a bolus meal that may adversely affect the techniques, processes, and / or algorithms provided herein. Thus, the systems and methods described herein are designed to monitor (i.e., convert and approve, if necessary) the proposed bolus rate and / or basal rate from an external source before outputting to the patient or the system, or to other users, entities, components, modules, or devices.

[0034] The comparator 235 is configured to identify discrepancies between separately derived estimates of metabolic and behavioral data (e.g., with and without CGM data) by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin (and optionally additional data, e.g., carbohydrate records).

[0035] 3 is a flow diagram of one embodiment of a risk-based insulin delivery rate conversion method 300. Method 300 may be performed by risk-based insulin delivery rate converter 230.

[0036] At 310, input is received, for example at the comparison unit 235. The input may include, for example, glucose data (e.g., CGM data 205), insulin data 215, other sensed input data 210, user input data 220, and / or configuration and / or setup input data 203, etc.

[0037] At 320, a discrepancy (D) between separately derived estimates of metabolic and behavioral data derived from the insulin and glucose data is identified by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin.

[0038] At 330, the glycemic risk assessor 240 is used to quantify the current or future risk of hyperglycemia and / or hypoglycemia based on the glucose data.

[0039] At 340 , the insulin delivery rate is modified by the insulin delivery monitor 245 based on the data from the comparator 235 and from the glycemic risk assessor 240 .

[0040] 4 is a block diagram of one embodiment of a comparator, such as comparator 235. As shown in FIG. 4, comparator 235 includes a state estimator 420, a model match evaluator 430, and a reference insulin rate (RIR) updater 440.

[0041] The state estimator 420 may provide an estimate of the patient's physiological and / or behavioral state based on CGM feedback, other sensed inputs, and / or user input. The state estimator 420 may include a model-based state observer, such as a Kalman filter or similar, that generates estimates of the patient's physiological state (e.g., mass or concentration of glucose, insulin, or other substances in various compartments) and / or behavioral state (e.g., (current or recent) feeding or physical activity). Output from the state estimator 420 may be provided to a model match evaluator 430, which then generates one or more quantitative deviations D435. In some embodiments, the deviations may optionally be computed against a baseline insulin rate (RIR) 425. The output may be in the form of multiple vectors / matrices including the deviations D435 or RIR 425, which in some embodiments may optionally include a history thereof.

[0042] In some embodiments, the state estimator 420 provides one or more metabolic state estimates that may be based on an individualized physiological model to generate the following outputs: the adjusted estimated metabolic input, the patient's estimated metabolic state for the duration of the input data, a numerical assessment of the reliability of the estimated state, and a numerical assessment of the reliability of the adjusted estimated metabolic input. The state estimator 420 is configured to receive the (optionally filtered) extrapolation force, any extracted states, and model parameters to the extent that an individualized physiological model is used by the estimator 420. Different estimators can be used depending on the implementation. In one implementation, the estimator 420 performs an open-loop estimation of the metabolic state from the best estimate of the metabolic state vector at the start of the time series into the future, and plays the individualized physiological model forward all the way to the end of the prediction horizon. Examples and embodiments are described in U.S. Patent Application No. 17 / 096785, entitled "JOINT STATE ESTIMATION PREDICTION THAT EVALUATES DIFFERENCES IN PREDICTED VS. CORRESPONDING RECEIVED DATA," filed November 12, 2020, by inventor Stephen D. Patek, which is incorporated by reference in its entirety.

[0043] The model match evaluator 430 may be or include a process or module that evaluates the discrepancy between two different models of metabolic and / or behavioral states for one or more state variables. In other words, the model match evaluator 430 calculates the discrepancy D435 as the difference between the state estimator variables (based on all available data) and what the model would have predicted for the same variables in the absence of CGM data (open loop estimates), where the discrepancy is the difference between the two versions of the variables. In particular, if metabolism can be perfectly modeled / predicted, CGM data is not required. However, metabolism cannot be perfectly modeled / predicted, and the insulin delivery monitor 245 described herein can use the discrepancy.

[0044] Exemplary state variables include: plasma glucose concentration or mass, interstitial glucose concentration or mass, glucose in other compartments of the body, fast-acting or long-acting insulin in subcutaneous tissue in one or more compartments, insulin in plasma, liver, or periphery resulting from subcutaneous or intravenous infusion or from endogenous secretion, states describing the uptake, action, clearance of insulin or glucose in various compartments of the body, pharmacokinetic and / or pharmacodynamic states associated with pharmaceuticals, states associated with the absorption of carbohydrates in the diet, etc.

[0045] In one embodiment, the difference value is calculated as a measure of the extent to which recent CGM data does not match the physiological model used for state estimation. In one example, the deviation between two different open-loop predictions of metabolic and / or behavioral states is quantified in delta, e.g., by comparison of state observers (including Kalman filters) to other states in other compartmental models with other open-loop estimates. In one such embodiment, for each internal state x, a delta Dx is calculated (if possible) that is believed to match the open-loop prediction with the CGM recording. Examples are described in U.S. Patent Application Serial No. 15 / 580,935, filed December 8, 2017, by inventor Breton, entitled "INSULIN MONITORING AND DELIVERY SYSTEM AND METHOD FOR CGM BASED FAULT DETECTION AND MITIGATION VIA METABOLIC STATE TRACKING," which is incorporated herein by reference in its entirety. For example, a delta can be calculated that is related to the insulin action state of the model. However, the model match evaluator 430 may quantify these deviations D435 as variances, difference values, delta variables, etc. The continuity of the CGM signal may be taken into account by the model match evaluator 430 along with the values ​​and / or trends of recent CGM data. In another embodiment, (i) all information including blood glucose (BG) and (ii) all information excluding BG are used to quantify the deviation between the artificial intelligence (AI) model and the machine learning (ML) model. Other useful models include compartmental models of glucose-insulin kinetics (e.g., minimal models, etc.) that may or may not be fine-tuned to the patient's particular physiology, including states corresponding to insulin action, Kalman filters to estimate the patient's insulin action state based on blood glucose measurements, recent insulin delivery, and carbohydrate records, open-loop estimation of insulin action state (using only recent insulin records), etc.

[0046] The RIR updater 440 can determine an internal reference insulin rate 450. The RIR 450 may overlap with a patient-defined basal profile, but is distinct from a basal profile defined by the patient, a physician, or an external process that is specifically designed for compensation for meals and other behavioral events. Rather, the RIR 450 is an internal reference for what constitutes insulin that is considered to achieve equilibrium. The RIR 450 may be a time-averaged basal rate, adapted over time, patient-dependent, fixed, zero, programmed, learned, prescribed, etc., or a combination thereof. The RIR 450 may be further derived from total daily basal (total daily insulin or TDI), correction factor, and / or body mass index (BMI) / weight. The RIR 450 may be updated, for example, every 5 minutes, or may be defined by the data acquisition rate (from the CGM). The RIR 450 may be used by the state estimator 425 to improve state estimation, BG prediction, and interpretation of deviations from the model match evaluator 430. In response, the RIR updater 440 may replace the time-varying basal rate as the basis for insulin delivery.

[0047] In some embodiments, the reference insulin rate RIR (450) is returned to the state estimator 420 as a reference point for insulin (shown as RIR 425) in state estimation and prediction. Additionally or alternatively, in some embodiments, the deviation D (435) or the reference insulin rate RIR (450) is provided to the glycemic risk assessor 240 (shown in FIG. 6 as D (622 and 642) and RIR (625 and 645), respectively), where the RIR can serve as a reference point for interpreting past insulin delivery in quantifying risk of hypoglycemia or hyperglycemia, as an alternative to the patient's preprogrammed basal rate profile. Additionally or alternatively, in some embodiments, the deviation D (435) or reference insulin rate RIR (450) is provided to the insulin delivery monitor 245 (shown in FIG. 8 as D at 822 and RIR at 825, respectively), where the RIR may serve as a reference point in interpreting past and future suggested basal and / or bolus recommendations from the external process data 225, instead of the patient's preprogrammed basal rate profile. The preprogrammed basal rate profile may have time of day characteristics that make it inappropriate as an insulin reference, such as partial management of normal meals with elevated basal rates.

[0048] 5 is a flow diagram of one embodiment of a comparison method 500 for use in risk-based insulin delivery rate conversion. Method 500 can be performed using comparison component 235.

[0049] Input is received at 510. The input may include, for example, glucose data (e.g., CGM data 205), insulin data 215, other sensed input data 210, user input data 220, and / or configuration and / or setup input data 203, etc.

[0050] At 520, the patient's physiological and / or behavioral state is estimated based on the received input using a state estimator, such as state estimator 420. The output is provided to a model match evaluator, such as model match evaluator 430. Additionally or alternatively, the output may be provided to other components and / or modules for later use.

[0051] At 530, the discrepancy D435 between two different models of metabolic and / or behavioral state is evaluated for one or more state variables. For example, the difference between the state estimator variable and what the model would have predicted for the same variable in the absence of CGM data is calculated, the discrepancy being the difference between the two versions of the variable. The discrepancy D may be provided to other components and / or modules for later use.

[0052] At 540, an internal RIR is determined and provided to various components and / or modules (described further herein) for subsequent use.

[0053] 6 is a block diagram of one embodiment of a glycemic risk assessor, such as glycemic risk assessor 240. Glycemic risk assessor 240 determines hyperglycemic risk 620 and hypoglycemic risk 640. Hyperglycemic risk 620 and hypoglycemic risk 640 may be determined using the output of state estimator 420. Additionally or alternatively, hyperglycemic risk 620 and hypoglycemic risk 640 may be determined using model match assessor deviations D622 (for hyperglycemic risk) and D642 (for hypoglycemic risk), respectively. Additionally or alternatively, hyperglycemic risk 620 and hypoglycemic risk 640 may be determined using reference insulin rate RIR625 and reference insulin rate RIR645, respectively.

[0054] The glycemic risk assessor 240 quantifies the current and future risk of hyperglycemia and / or hypoglycemia, respectively. The glycemic risk assessor 240 calculates the level of risk from inputs such as blood glucose data, insulin data, user input data, state estimator output, RIR, and model match assessor deviation D, and in some embodiments may be based on predicted glucose. In some embodiments, the glycemic risk (e.g., calculated hypoglycemia and / or calculated hyperglycemia) uses prediction / state estimation. The glycemic risk assessor 240 may be a glycemic risk spatial quantification such as in low blood glucose index (LBGI) / high blood glucose index (HBGI) and / or examples and implementations described in U.S. Patent No. 10,638,981, entitled "METHOD, SYSTEM AND COMPUTER READABLE MEDIUM FOR ASSESSING ACTIONABLE GLYCEMIC RISK" by inventor Stephen D. Patek, which is incorporated herein by reference in its entirety.

[0055] Each assessment of hyperglycemia and / or hypoglycemia may be multivariate, which may include a predicted BG (either for a particular range, or for the entire trajectory, or for the "hurricane path"). In one embodiment, the glycemic risk assessor 240 may include deltas as described in Breton, such as the examples described in U.S. Patent Application Serial No. 15 / 580,935, filed December 8, 2017, by inventor Breton, entitled "INSULIN MONITORING AND DELIVERY SYSTEM AND METHOD FOR CGM BASED FAULT DETECTION AND MITIGATION VIA METABOLIC STATE TRACKING," which is incorporated herein by reference in its entirety. The glycemic risk assessor 240 may be configured to assess hyperglycemic risk alone or in combination with hypoglycemic risk, such as that described in U.S. Patent Application Serial No. 14 / 659,500, entitled "GLYCEMIC URGENCY ASSESSMENT AND ALERTS INTERFACE," filed March 16, 2015, by inventor Rack-Gomer, which is incorporated herein by reference in its entirety. The fit of the risk function may be parameterized. A normalized risk, such as that described in U.S. Patent No. 10,638,981, entitled "METHOD, SYSTEM AND COMPUTER READABLE MEDIUM FOR ASSESSING ACTIONABLE GLYCEMIC RISK," by inventor Stephen D. Patek, which is incorporated herein by reference in its entirety, allows for parameterization of the shape of the risk function in a more natural way. Exemplary risk-based windows may be, for example, over 5 minutes, over 30 minutes, a basal / bolus combination, a function of time, etc.

[0056] 7 is a flow diagram of one embodiment of a method 700 for glycemic risk assessment for use in risk-based insulin delivery rate conversion. Method 700 can be performed using the glycemic risk assessor 240.

[0057] At 710, inputs such as blood glucose data, insulin data, user input data, state estimator output, RIR, and / or model match evaluator deviation D are received.

[0058] At 720, the current and / or future risk of hyperglycemia is determined (eg, quantified).

[0059] At 730, the current and / or future risk of hypoglycemia is determined (eg, quantified).

[0060] At 740, the risk is output to an insulin delivery monitor (eg, insulin delivery monitor 245), the patient, a physician, or other medical professional or caregiver, or the like.

[0061] 8 is a block diagram of an embodiment of an insulin delivery monitor, such as insulin delivery monitor 245. Insulin delivery monitor 245 includes nominal insulin planning component 820 and monitor 840.

[0062] The insulin delivery monitor 245 adjusts the insulin delivery rate based on data from the comparator 235 and the glycemic risk assessor 240. The insulin delivery monitor 245 also takes into account suggested bolus and / or basal rates from an external process, if available. In many cases, suggested (basal or bolus) insulin rates are available, for example, from traditional fully manual open loop therapy (CSII basal insulin profile), decision support therapy (recommended algorithms), range controlled automatic insulin delivery (AID), target controlled AID, MPC, LQG, PID, etc. However, the systems and methods described herein can function within fully standalone algorithms and some implementations.

[0063] Depending on the implementation, the insulin delivery monitor 245 may include intensifying (increasing the rate) of insulin based on hyperglycemic risk, attenuating (decreasing the rate) of insulin based on hypoglycemic risk, or both. In some embodiments, the insulin delivery monitor 245 calculates the insulin rate for a time window during which the required amount of insulin will be delivered, the time window being determined from the level of glycemic risk, e.g., hyperglycemic risk or hypoglycemic risk. In some embodiments, the insulin rate is calculated based on the comparator 235, e.g., the model match evaluator 430.

[0064] In one embodiment, the insulin delivery monitor 245 adapts the proposed basal rate to the approved basal rate by adapting the proposed value according to the risk of hyperglycemia to ensure that BG remains below an upper envelope of acceptable values, where the upper envelope is a function of time (e.g., may be the time of day or may vary with respect to other parameters), as further described herein.

[0065] The nominal insulin planner 820 takes into account the risk of hyperglycemia and / or hypoglycemia (and optionally uses the estimated impairment state and RIR 825) to determine a future insulin target trajectory, which is converted into a suggested basal and / or bolus rate. The nominal insulin planner 820 can function as a support layer for existing algorithms or within a stand-alone algorithm.

[0066] The normative insulin planning unit 820 determines the amount of insulin required to minimize the deviation determined by the model match assessment unit 430 of the comparison unit 235. This amount may be a standard amount of insulin required, such as ISOB (insulin that should be on board) (residual insulin required) as described in U.S. Patent Application No. 15 / 580,935, entitled “INSULIN MONITORING AND DELIVERY SYSTEM AND METHOD FOR CGM BASED FAULT DETECTION AND MITIGATION VIA METABOLIC STATE TRACKING,” inventor Marc D. Breton, filed December 8, 2017, and published as U.S. Patent Application Publication No. 2019 / 0254595(A1), which is incorporated by reference in its entirety, or may be provided in terms of future plasma insulin or other physiological terms.

[0067] In one exemplary embodiment (e.g., as described in U.S. Patent Application Serial No. 15 / 580,935, incorporated herein by reference in its entirety), the condition evaluated is IOB vs. ISOB based on how much insulin would be required to bring the patient back to the upper BG envelope curve, where the upper BG envelope is a time-of-day dependent curve, e.g., curve values ​​are higher during the day (e.g., 160 mg / dl) and drop during the night (e.g., 120 mg / dl). In some embodiments, the upper BG envelope is calculated based on a current estimate of BG designed to allow BG to drop to a final value during a time window. In some embodiments, the systems and methods described herein ensure a substantial response to hyperglycemia risk by imposing a maximum curve value to solve the problem of inadequate response to hyperglycemia that sometimes occurs. Of note, the upper envelope is used as a target by ISOB, which is not the same as the target of the control algorithm to fine-tune insulin delivery. In some embodiments, the nominal insulin planner 820 calculates ISOB based on a goal defined by an upper BG envelope curve that is generated on demand based on the estimated BG. In some embodiments, the envelope is determined from a sleep profile, although this is not a requirement and may not actually be done in a particular implementation. In some embodiments, ISOB may be calculated as a function of both upper and lower BG envelopes, for example, ISOB may be calculated to achieve a BG somewhere between a hyperglycemic upper envelope curve value and a low BG envelope according to an insulin cutoff threshold or logic.

[0068] In some embodiments, insulin may be expressed directly in terms of subcutaneous insulin delivery (see, e.g., ISOB described in U.S. Patent Application No. 15 / 580,935, which is incorporated herein by reference in its entirety) relative to a user-provided basal rate profile or relative to a reference insulin rate (RIR). In some embodiments, the output of the nominal insulin planning component may be based on the BG upper envelope curve or other mechanisms to optimize the patient's theoretical insulin trajectory.

[0069] The time window (sometimes called the "rate window") used to determine the insulin delivery rate (which will indicate the level of concordance or mismatch) may be a function of the risk of glycemia (e.g., hyperglycemia or hypoglycemia) and is therefore variable. For example, if there is a high risk of hyperglycemia, the entire amount of insulin required may be delivered as fast as possible, i.e., as a bolus.

[0070] The monitoring unit 840 may be combined with or separate from the nominal insulin planning unit 820. The monitoring unit 840 adjusts the suggested basal rate (and optionally the suggested bolus rate) from an external source (e.g., external process data 225) with the insulin requirement identified by the nominal insulin planning unit 820 to determine the approved basal rate (and / or bolus) for the next periodic update. U.S. Patent Application No. 15 / 580,935, which is incorporated herein by reference in its entirety, describes an embodiment that determines insulin requirement by calculating ISOB and comparing it to IOB. However, other methods of determining insulin requirement may be used.

[0071] In addition to inputs from the original inputs, the monitor 840 may process the output of the state estimator 420, the output of the model match evaluator 430 (i.e., the deviation D), the output of the RIR updater 440 (i.e., the RIR 450), and may further include inputs from an externally derived process describing basal insulin and optionally bolus insulin (i.e., external process data 225). Thus, the monitor 840 may be useful for coordinating external processes with the systems and methods described herein for insulin planning.

[0072] In some embodiments, the insulin delivery monitor 245 may convert the bolus recommendation to a combination of bolus and basal, e.g., an amount delivered at a maximum rate and an amount delivered as an elevated basal rate over a period of time. The conversion can be based on the state of the system and glycemic risk and can be fed back to previous steps and / or modules of the methods and / or systems described herein. In some implementations, the conversion can be informed by when the next decision can be made. In some implementations, the risk-based insulin delivery rate converter 230 takes the output of any open-loop or closed-loop artificial pancreas algorithm designed to generate a rate of insulin delivery and converts that rate to a mix of basal rate and individual bolus. In some implementations, the individual (correction) bolus is coordinated with the basal rate based on hyperglycemic risk, i.e., the insulin delivery monitor 245 converts the recommended correction bolus to a rate where the rate window is calculated as a function of hyperglycemic risk (rather than a fixed rate window such as 30 minutes).

[0073] In one example, predicted blood glucose is used to calculate hyperglycemic risk, which is used by the model matching evaluator 430 to quantify the variance between glycemic and / or insulin states, where the greater the risk of hyperglycemia, the shorter the rate window. In other words, at the highest level of hyperglycemia, the required amount of insulin is delivered as a separate bolus. Thus, the rate window is variable, such that the higher the calculated risk of hyperglycemia, the closer the rate window is to 5 minutes (or any periodic rate of data acquisition refresh and / or controller update). As an example, if the risk-based insulin delivery rate converter 230 calculates that the difference between ISOB and IOB is 3 units, this may be delivered in 5 minutes at a high level of hyperglycemic risk, but over 30 minutes at a low level of hyperglycemic risk. In particular, here, the pre-intervention hyperglycemic risk is used to convert ISOB to a rate of insulin delivery that will be applied until the next controller update, such that at high hyperglycemic risk, ISOB is delivered as a separate bolus. However, in some embodiments, the conversion of ISOB to a rate may be based on both pre-intervention and post-intervention predicted BG information. In contrast to standard model predictive control (MPC), the speed value is a modified ISOB value, which is not the result of optimization.

[0074] Although the above example describes the use of hyperglycemic risk, the conversion of ISOB to a rate may be based on both hyperglycemic and hypoglycemic risk information.

[0075] The rate window can be the denominator for conversion of an individual bolus to a rate based on hyperglycemic risk, as shown in the equation below. Insulin delivery rate = (amount of insulin required based on level of concordance) / (risk-based time window during which the amount of insulin required will be delivered).

[0076] In this case, the resulting recommendation from the monitor 840 may be large enough to achieve the effect of individual corrections and / or meal boluses, or small enough to include a low basal delivery rate.

[0077] In some embodiments, the aggressiveness of the insulin delivery monitor 245 may be constrained based on an assessment of the patient's total daily insulin requirement (TDI). For example, parameters needed to calculate an appropriate response to the difference between IOB and ISOB may be constrained as a function of the TDI. Ongoing modifications of the TDI adjust how aggressive the normative insulin planning component is allowed to be. A saturation value for the correction factor may be used as a separate check on how aggressive the control algorithm is allowed to be. Limits on the correction factor may now be implemented.

[0078] Output 290 from insulin delivery monitor 245 includes the approved basal rate and optionally the approved bolus rate. Output 290 may also include messages sent to the patient, to a physician or other medical professional or administrator, to a display, computing device, etc. For example, a predicted BG trajectory may be displayed along with an explanation of uncertainties. Recommended values ​​or amounts of insulin delivery may be provided or described for specific time intervals and / or with respect to various conditions (e.g., "if," "when," "based on," "time in range without meal announcement," etc.).

[0079] 9 is a flow diagram of one embodiment of a method 900 of insulin delivery monitoring for use in risk-based insulin delivery rate conversion. Method 900 can be performed using insulin delivery monitor 245.

[0080] At 910, inputs such as current and / or future risk of hyperglycemia and / or hypoglycemia, the output of the state estimator 420, the output of the model match assessor 430 (i.e., the deviation D), the output of the RIR updater 440 (i.e., the RIR 450), and inputs from an externally derived process describing basal insulin and optionally bolus insulin are received.

[0081] At 920, a future insulin target trajectory is determined.

[0082] At 930, a nominal insulin planner is used to determine the amount of insulin required to minimize the deviation D from the model fit evaluator 430 and / or to minimize the risk of hyperglycemia.

[0083] At 940, the proposed basal rate and / or the proposed bolus rate are adjusted with the insulin needs identified by the nominal insulin planning component to determine an approved basal rate and / or an approved bolus rate.

[0084] At 950, the approved basal rate and / or the approved bolus rate are output, for example, to a delivery device, a patient, a physician or other medical professional or administrator, a display device, a computing device, or the like.

[0085] Example 1 - Monitoring the performance of conventional insulin pump therapy

[0086] In one embodiment, the systems and methods described herein are operatively used with an insulin pump therapy system (external process) having a user programmed basal rate profile and a functional pre-prandial insulin bolus calculated using carbohydrate estimates, carbohydrate ratios, correction factors, and IOBs. In this example, the system / method operates as follows:

[0087] The comparator 235 quantitatively adjusts the open-loop and CGM-based estimates of the current metabolic state vector in various ways, including one or more of the following: by attributing the level of agreement (or discrepancy) to failure of insulin delivery (e.g., pump blockage) → setting a pump failure state estimate, by attributing the agreement / disagreement to unexpected low / high "insulin action" → recognizing the fact that the insulin sensitivity parameter is too small / too large, and / or by attributing the quantified agreement / disagreement to an unannounced meal (or a meal with a higher carbohydrate content than the patient approved) → incrementally adapting the model agreement assessor 430 deviation (D) for insulin action.

[0088] The glycemic risk assessor 240 estimates a quantitative value of the applicable hyperglycemic and / or hypoglycemic risk over a specified planning period, note that this does not assume any further intervention from the user.

[0089] The insulin delivery monitor 245 (knowing the user-programmed basal rate profile from an operatively connected insulin delivery device) can optionally look at the current bolus request from the patient and, without assuming any future intervention from the patient, estimate the effect of the basal rate profile over the specified planning period and decide to modify the current bolus request (if any) or issue an unrequested insulin bolus, modify the basal rate profile for the duration of the planning period, and / or specify that a bolus be delivered at some point in the future during the planning period.

[0090] In one exemplary situation (set of conditions) according to this embodiment, when the preprogrammed basal profile is elevated relative to the patient's fasting basal profile (or RIR), the elevated basal rate may represent a user's attempt to partially cover an unannounced meal with basal insulin delivery, in which case the monitor serves to accelerate the effect of the elevated basal rate by converting a portion of it into a separate bolus.

[0091] In another exemplary situation (set of conditions) according to this embodiment, if the comparison unit 235 can determine that either (i) unannounced / underestimated carbohydrates are present or (ii) reduced insulin sensitivity is the most likely explanation for the model mismatch, the glycemic risk assessment unit 240 can estimate a clinically significant elevated risk R of hyperglycemia, and if the user has recently specified an individual bolus B, the insulin delivery monitor unit 245 will either: It may now decide to deliver a bolus equal to a percentage F of the total amount of insulin plus B (the percentage is calculated as a function of the estimated risk of hyperglycemia R (e.g., F=k*R / (1+k*R), where k is a parameter)) and deliver the remaining percentage of insulin (1-F) as a new, reduced, temporary basal rate for the specified planning period T, or, at the user's discretion, deliver only B and wait for a future opportunity for the monitor to preemptively convert basal insulin to a bolus (this may depend on various factors such as reliability of the data).

[0092] In yet another exemplary situation (set of conditions) according to this embodiment, if the comparison unit 235 estimates that unexpectedly high insulin action (suggesting momentarily high insulin sensitivity) is the most likely explanation for the model mismatch, the glycemic risk assessment unit 240 estimates a clinically significant elevated risk R of hypoglycemia, and if the user has recently entered an individual bolus B≧0, the insulin delivery monitor unit 245 may set a temporary basal rate for the specified planning period based on the risk. For example, based on a desire to achieve a particular IOB, if the user's bolus B is known, the basal rate can be set to achieve that IOB within a specified time frame, where both the target IOB and the time frame are calculated as a function of the estimated risk of hypoglycemia. Additionally or alternatively, the insulin delivery monitor unit 245 may warn the user about the bolus, suggesting that the bolus may worsen the risk of hypoglycemia in the absence of additional carbohydrates.

[0093] Example 2 - Automatic Insulin Delivery (AID) Algorithm Monitoring

[0094] In this second exemplary embodiment, the systems and methods described herein are operatively used in conjunction with an automatic insulin delivery therapy system (external process) that includes automatic adjustment of basal rate and / or automatic insulin bolus with or without the patient having the opportunity to request a bolus. The comparator 235 quantitatively adjusts the open-loop and CGM-based estimates of the current metabolic state vector as described in Example 1 and further based on the estimated RIR.

[0095] The glycemic risk assessor 240 estimates a quantitative value of the applicable hypoglycemic risk over the specified planning period (note: assuming no further intervention from the user).

[0096] Based on the patient's RIR, and depending on the basal rate recommendation and / or insulin bolus request / recommendation higher than the RIR, the insulin delivery monitor 245 may decide to modify the current bolus request / recommendation (if any) or introduce a new bolus, modify the AID basal rate recommendation, and / or specify that a bolus be delivered at some point in the future within a specified planning period, assuming no future intervention from the patient.

[0097] In one exemplary situation (set of conditions) according to this second embodiment, if the comparator 235 determines that either (i) unannounced / underestimated carbohydrates are present or (ii) reduced insulin sensitivity is the most likely explanation for the model mismatch, the glycemic risk profiler estimates a clinically significant elevated risk of hyperglycemia R, and in the absence of a bolus recommendation or request, the insulin delivery monitor 245 may now deliver a bolus equal to a percentage F of the total amount of insulin associated with the AID-recommended basal rate profile for the specified planning period T (the percentage is calculated as a function of the estimated risk of hyperglycemia R (e.g., F=k*R / (1+k*R), where k is a parameter)) and deliver the remaining percentage of insulin associated with the AID basal rate recommendation (1-F) as the reduced new basal rate. Additionally or alternatively, the bolus introduced above may be calculated as a function of the difference between the AID-recommended basal rate and the patient's RIR.

[0098] In another exemplary situation (set of conditions) according to this second embodiment, if the comparison unit 235 recognizes that either (i) unannounced / underestimated carbohydrates are present or (ii) reduced insulin sensitivity is the most likely explanation for the model mismatch, the glycemic risk assessment unit 240 estimates a clinically significant elevated risk of hyperglycemia R, and if the user has specified only an individual bolus B, the insulin delivery monitor unit 245 determines to now deliver a bolus equal to B plus a certain percentage F of the total amount of insulin associated with the AID-recommended basal rate profile for the specified planning period T (the certain percentage is calculated as a function of the estimated risk of hyperglycemia R, e.g., F=k*R / (1+k*R), where k is a parameter), and to deliver the remaining percentage of insulin associated with the AID's basal rate recommendation (1-F) as the new reduced basal rate. Alternatively, the insulin delivery monitor 245 may deliver only B at the user's discretion and wait for a future opportunity for the monitor to preemptively convert basal insulin to a bolus, which may be based, for example, on data reliability or fail-safe features.

[0099] In yet another exemplary situation (set of conditions) according to this second embodiment, when the comparator 235 recognizes that unexpectedly high insulin action (suggesting momentarily high insulin sensitivity) is the most likely explanation for the model mismatch, the glycemic risk assessor 240 estimates a clinically significant elevated risk of hypoglycemia R, and if the user specifies only an individual bolus B≧0, the insulin delivery monitor 245 decides to set a temporary basal rate for a specified planning period, for example, based on a desire to achieve a specific IOB, if the user's bolus B is known, the basal rate can be set to achieve that IOB within a specified time frame, where both the target IOB and the time frame are calculated as a function of the estimated risk of hypoglycemia. If it turns out that a reduced basal rate was necessary (e.g., to compensate for unannounced carbohydrates), the difference can be introduced later as a compensated elevated basal rate or as an individual bolus. Additionally or alternatively, the monitor may decide to leave bolus B unchanged, but may display / warn the user about the bolus unless B=0, suggesting that in the absence of additional carbohydrates the bolus may exacerbate the risk of hypoglycemia.

[0100] 10 illustrates an exemplary computing environment in which exemplary embodiments and aspects may be implemented. The computing device environment is only one example of a suitable computing environment and is not intended to suggest any limitation as to the scope of use or functionality.

[0101] Numerous other general purpose or special purpose computing device environments or configurations may be used. Examples of well-known computing devices, environments, and / or configurations that may be suitable for use include, but are not limited to, personal computers, server computers, handheld or laptop devices, multiprocessor systems, microprocessor-based systems, networked personal computers (PCs), minicomputers, mainframe computers, embedded systems, distributed computing environments that include any of the above systems or devices, and the like.

[0102] Computer-executable instructions such as program modules executed by a computer may be used. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Distributed computing environments may be used in which tasks are performed by remote processing devices that are linked through a communications network or other data transmission medium. In a distributed computing environment, program modules and other data may be located in both local and remote computer storage media, including memory storage devices.

[0103] 10, an exemplary system for implementing aspects described herein includes a computing device, such as computing device 1000. In its most basic configuration, computing device 1000 typically includes at least one processing unit 1002 and memory 1004. Depending on the exact configuration and type of computing device, memory 1004 may be volatile (such as random access memory (RAM)), non-volatile (such as read-only memory (ROM), flash memory, etc.), or some combination of the two. This most basic configuration is illustrated in FIG. 10 by dashed line 1006.

[0104] Computing device 1000 may have additional features / functionality. For example, computing device 1000 may include additional storage (removable and / or non-removable) including, but not limited to, magnetic or optical disks or tape. Such additional storage is illustrated in FIG. 10 by removable storage 1008 and non-removable storage 1010.

[0105] Computing device 1000 typically includes a variety of computer readable media. Computer readable media can be any available media that can be accessed by device 1000 and includes both volatile and nonvolatile media, removable and non-removable media.

[0106] Computer storage media includes volatile and non-volatile, removable and non-removable media implemented in any method or technology for storage of information such as computer readable instructions, data structures, program modules, or other data. Memory 1004, removable storage 1008, and non-removable storage 1010 are all examples of computer storage media. Computer storage media include, but are not limited to, RAM, ROM, electrically erasable program read-only memory (EEPROM), flash memory or other memory technology, CD-ROM, digital versatile disk (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium that can be used to store the desired information and that can be accessed by computing device 1000. Any such computer storage media may be part of computing device 1000.

[0107] Computing device 1000 may contain communication connections 1012 that allow the device to communicate with other devices. Computing device 1000 may also have input devices 1014, such as a keyboard, mouse, pen, voice input device, touch input device, etc. Output devices 1016, such as a display, speakers, printer, etc. All of these devices are well known in the art and need not be discussed at length here.

[0108] In one embodiment, the risk-based insulin delivery rate converter comprises a comparator including a model agreement evaluator configured to receive insulin data and glucose data and configured to identify discrepancies between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin; a glycemic risk assessor configured to quantify a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data; and an insulin delivery monitor configured to adjust the insulin delivery rate based on data from the comparator and the glycemic risk assessor.

[0109] In one embodiment, a risk-based insulin delivery rate conversion method includes receiving insulin data and glucose data at a comparison unit; identifying a deviation between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement evaluator of the comparison unit; quantifying a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessor; and adjusting an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor using an insulin delivery monitor.

[0110] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive insulin data and glucose data at a comparison unit, use a model agreement evaluator of the comparison unit to identify deviations between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin, use a glycemic risk assessor to quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data, and use an insulin delivery monitor to adjust an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor.

[0111] Implementations may include some or all of the following features: The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the model match evaluator to evaluate the deviation between two different models of the metabolic or behavioral state and provide the deviation as an output for later use. The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the model match evaluator to quantify the deviation between two different open-loop predictions of the metabolic or behavioral state as a variance. The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the state estimator of the comparator to estimate at least one of the patient's physiological or behavioral state based on at least one of continuous glucose monitoring system (CGM) feedback, other sensed input, or user input and provide an output to the model match evaluator. The state estimate is used by the model match evaluator. The computer readable medium further includes instructions, when executed by the at least one processor, that cause the system to assess a hyperglycemic risk by the glycemic risk assessment unit, where the hyperglycemic risk is used to adjust a time window used to calculate an insulin rate by the insulin delivery monitoring unit. The insulin delivery monitoring unit considers at least one of a suggested bolus rate or a basal rate from an external process. The insulin delivery monitoring unit calculates an insulin rate for a time window in which the amount of insulin required will be delivered. The time window is determined from the level of glycemic risk quantified by the glycemic risk assessment unit. The computer readable medium further includes instructions, when executed by the at least one processor, that cause the system to determine, by an insulin planning unit of the insulin delivery monitoring unit, an amount of insulin required to minimize the deviation determined by the comparison unit. The computer readable medium further includes instructions, when executed by the at least one processor, that cause the system to adjust, by a monitoring unit of the insulin delivery monitoring unit, a suggested basal rate from an external source with the insulin need identified by the insulin planning unit to determine an approved basal rate for the next periodic update.The computer readable medium further includes instructions that, when executed by the at least one processor, cause the system to convert an approved basal rate into a mixture of a basal rate and a separate bolus using the insulin delivery monitor.

[0112] In one embodiment, the risk-based insulin delivery rate converter comprises a comparison unit including a model agreement evaluator configured to receive insulin data and glucose data and to identify discrepancies between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin; a glycemic risk assessment unit configured to quantify a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data; an insulin delivery monitor configured to adjust the insulin delivery rate based on data from the comparison unit and the glycemic risk assessment unit; and a reference insulin rate update unit configured to determine a reference insulin rate (RIR), where the RIR is an internal reference for insulin that is considered to achieve equilibrium.

[0113] In one embodiment, the risk-based insulin delivery rate conversion method includes receiving insulin data and glucose data at a comparison unit; identifying a discrepancy between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement assessment unit of the comparison unit; quantifying a risk of at least one of current or future hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit; adjusting an insulin delivery rate based on data from the comparison unit and the glycemic risk assessment unit using an insulin delivery monitoring unit; and determining an RIR using a reference insulin rate (RIR) update unit, where the RIR is an internal reference for insulin that is believed to achieve equilibrium.

[0114] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive insulin data and glucose data at a comparison unit, identify deviations between separately derived estimates of metabolic and behavioral data derived from the insulin data and glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin using a model agreement evaluator of the comparison unit, quantify a current or future risk of at least one of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessor, adjust an insulin delivery rate based on data from the comparison unit and the glycemic risk assessor using an insulin delivery monitor, and determine an RIR using a reference insulin rate (RIR) updater, the RIR being an internal reference for insulin that is believed to achieve balance.

[0115] Implementations may include some or all of the following features: The RIR update unit is included within the comparison unit. The RIR is used by the comparison unit. The glycemic risk assessment unit is configured to receive the RIR and use the RIR to quantify a risk of at least one of current or future hyperglycemia or future hypoglycemia. The insulin delivery monitor unit is configured to receive the RIR and use the RIR to determine a future insulin target trajectory and an amount of insulin needed to minimize the deviation. The insulin delivery monitor unit is further configured to receive the deviation data and use the deviation data to determine a future insulin target trajectory and an amount of insulin needed to minimize the deviation. The computer readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the model match assessment unit to assess a deviation between two different models of a metabolic or behavioral state and provide the deviation as an output for later use. The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the model match evaluator to quantify the deviation between two different open-loop predictions of metabolic or behavioral states as variance. The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the state estimator of the comparator to estimate at least one of the patient's physiological or behavioral state based on at least one of continuous glucose monitoring system (CGM) feedback, other sensed input, or user input, and provide an output to the model match evaluator. The state estimate is used by the model match evaluator. The computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to assess hyperglycemic risk by the glycemic risk evaluator, which is used to adjust a time window used to calculate an insulin rate by the insulin delivery monitor. The insulin delivery monitor considers at least one of a proposed bolus rate or a basal rate from an external process. The insulin delivery monitor calculates an insulin rate for a time window during which the required amount of insulin will be delivered. The time window is determined from the level of glycemic risk quantified by the glycemic risk assessment component.The computer readable medium further includes instructions that, when executed by the at least one processor, cause the system to determine, by an insulin planning portion of the insulin delivery monitoring portion, an amount of insulin needed to minimize the deviation determined by the comparison portion. The computer readable medium further includes instructions that, when executed by the at least one processor, cause the system to cause, by a monitoring portion of the insulin delivery monitoring portion, to reconcile a suggested basal rate from an external source with the insulin need identified by the insulin planning portion to determine an approved basal rate for the next periodic update. The computer readable medium further includes instructions that, when executed by the at least one processor, cause the system to convert the approved basal rate into a mix of a basal rate and a separate bolus using the insulin delivery monitoring portion.

[0116] In one embodiment, the method includes receiving a plurality of inputs at a comparison unit, identifying deviations between separately derived estimates of metabolic and behavioral data derived from the inputs, quantifying a current or future risk of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit, and adjusting an insulin delivery rate based on data from the comparison unit and data from the glycemic risk assessment unit using an insulin delivery monitor unit.

[0117] In one embodiment, the system comprises a comparator configured to receive a plurality of inputs and identify deviations between separately derived estimates of metabolic and behavioral data derived from the inputs; a glycemic risk assessor configured to quantify a current or future risk of hyperglycemia or hypoglycemia based on the glucose data; and an insulin delivery monitor configured to adjust an insulin delivery rate based on data from the comparator and from the glycemic risk assessor.

[0118] In one embodiment, the system comprises at least one processor and a non-transitory computer readable medium including instructions that, when executed by the at least one processor, cause the system to receive a plurality of inputs at a comparison unit, identify deviations between separately derived estimates of metabolic and behavioral data derived from the inputs, quantify a current or future risk of hyperglycemia or hypoglycemia based on the glucose data using a glycemic risk assessment unit, and adjust an insulin delivery rate using an insulin delivery monitor unit based on data from the comparison unit and data from the glycemic risk assessment unit.

[0119] An embodiment may include some or all of the following features: The input includes at least one of glucose data, insulin data, sensed input data, or user input data. Identifying the discrepancy includes quantifying the extent to which the recent blood glucose measurements are inconsistent with the recent insulin. The computer-readable medium further includes instructions, when executed by the at least one processor, that cause the system to estimate, in the comparison unit, a physiological or behavioral state of the patient based on the received input using a state estimator, and cause a model match assessor to provide an output, evaluate a discrepancy between two different models of metabolic or behavioral state for one or more state variables, and output the discrepancy. Evaluating the discrepancy includes calculating a difference between a state estimator variable and what the model would have predicted for the same variable in the absence of continuous glucose monitoring (CGM) data, the discrepancy being the difference between the two versions of the variable. The computer-readable medium further includes instructions, when executed by the at least one processor, that cause the system to determine an internal reference insulin rate (RIR) and output the RIR. The computer readable medium further includes instructions, which when executed by the at least one processor, cause the system to determine, in the glycemic risk assessment portion, a current or future risk of hyperglycemia, determine a current or future risk of hypoglycemia, and output the current or future risk of hyperglycemia and the current or future risk of hypoglycemia. The computer readable medium further includes instructions, which when executed by the at least one processor, cause the system to determine, in the insulin delivery monitoring portion, a future insulin target trajectory, determine, using a normative insulin planning portion, an amount of insulin required to minimize the deviation determined by the model match assessment portion, adjust a proposed basal rate or a proposed bolus rate with the insulin need identified by the normative insulin planning portion to determine an approved basal rate or an approved bolus rate, and output the approved basal rate or the approved bolus rate.

[0120] It should be understood that the various techniques described herein may be implemented in connection with hardware or software components, or, where appropriate, a combination of both. Exemplary types of hardware components that may be used include Field-programmable Gate Arrays (FPGAs), Application-specific Integrated Circuits (ASICs), Application-specific Standard Products (ASSPs), System-on-a-chip systems (SOCs), Complex Programmable Logic Devices (CPLDs), and the like. The methods and apparatus of the presently disclosed subject matter, or certain aspects or portions thereof, may take the form of program code (i.e., instructions) embodied in a tangible medium, such as a floppy diskette, CD-ROM, hard drive, or any other machine-readable storage medium, which when loaded and executed by a machine, such as a computer, causes the machine to become an apparatus for implementing the presently disclosed subject matter.

[0121] Although exemplary implementations may refer to utilizing aspects of the disclosed subject matter in the context of one or more stand-alone computer systems, the subject matter is not so limited, but rather may be implemented in connection with any computing environment, such as a network or distributed computing environment. Furthermore, aspects of the subject matter disclosed herein may be implemented in or across multiple processing chips or devices, as well as stored across multiple devices. Such devices may include, for example, personal computers, network servers, and handheld devices.

[0122] Although the systems and techniques have been described in language specific to structural features and / or methodological acts, it should be understood that the systems and techniques defined in the appended claims are not necessarily limited to the specific features or acts described. Rather, the specific features and acts described above are disclosed as example forms of implementing the claims. [Explanation of symbols]

[0123] 100 High-level functional block diagram 110 Insulin Device 120 Glucose Monitor 130 processors 140 patients 150 Activity Monitor 160 Smartphones 203 Setup Input Data 205 CGM data 210 Other Sensed Input Data 215 Insulin Data 220 User-entered data 225 External Process Data 230 Insulin Delivery Rate Transducer 235 Comparison Section 240 Department of Glycemic Risk Assessment 245 Insulin Delivery Monitor 290 Output 420 State Estimation Unit 425 Reference Insulin Rate (RIR) 430 Model Matching Evaluation Unit 435 Deviation 440 Reference Insulin Rate (RIR) Update Section 450 Internal Reference Insulin Rate 605 Input 620 Hyperglycemia Risk 640 Hypoglycemia risk 820 Prescriptive Insulin Planning Section 840 Monitoring Department 1000 devices 1002 Processing unit 1004 Memory 1006 dashed line 1008 Removable storage device 1010 Non-removable storage device 1012 Communication connection 1014 Input Devices 1016 Output Device

Claims

1. A system comprising: At least one processor; A non-transitory computer-readable medium that, when executed by the at least one processor, provides the system with: receiving input data including insulin data and glucose data at a comparison unit; using a model agreement assessment unit of the comparison unit to identify a deviation between separately derived estimates of metabolic data derived from the insulin data and the glucose data by quantifying the extent to which recent blood glucose measurements are inconsistent with recent insulin, wherein the deviation is calculated as a difference between an estimate of the metabolic data made using an individualized physiological model and the input data and an estimate of the metabolic data made using the individualized physiological model and the input data without using the glucose data; Quantifying a level of future risk of hyperglycemia or hypoglycemia based on the predicted glucose data using a glycemic risk assessment component; Using the insulin delivery monitor determining the amount of insulin required to minimize said deviation; adjusting a suggested basal rate from an external source with the determined insulin need to determine an approved basal rate, the approved basal rate being calculated for a time window during which the amount of insulin required will be delivered, the time window being determined from the quantified level of risk; outputting the approved basal rate; and a non-transitory computer readable medium comprising instructions for adjusting an insulin delivery rate based on data from the comparison component and the glycemic risk assessment component by Including, the system.

2. The system described in claim 1, wherein the insulin delivery monitoring unit further takes into account a bolus rate suggested from an external process.

3. The system described in claim 1 or 2, wherein the non-transitory computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to use the insulin delivery monitoring unit to convert the approved basal rate into a mixture of a basal rate and an individual bolus.

4. The system of any one of claims 1 to 3, wherein the non-transitory computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to determine a reference insulin rate (RIR) by a reference insulin rate update unit, the RIR being an internal reference for insulin that is deemed to achieve equilibrium.

5. The system of claim 4, wherein the non-transitory computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to receive the RIR in the glycemic risk assessment unit and use the RIR to quantify the risk of future hyperglycemia or future hypoglycemia.

6. The system described in claim 4 or 5, wherein the non-transitory computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to receive the RIR in the insulin delivery monitoring unit and use the RIR to determine a future insulin target trajectory and the amount of insulin required to minimize the deviation.

7. A system as described in any one of claims 1 to 6, wherein the basal rate suggested from the external source is due to a pre-programmed basal profile, patient-initiated insulin delivery, or an artificial pancreatic algorithm.

8. The non-transitory computer-readable medium further includes instructions that, when executed by the at least one processor, cause the system to quantify a level of future hyperglycemic risk, wherein for higher levels of hyperglycemic risk, a shorter time window is determined as the time window within which the required amount of insulin will be delivered. A system as described in any one of claims 1 to 7.

9. A system as described in any one of claims 1 to 8, wherein the glucose data is received from a continuous glucose monitor.

10. A system described in any one of claims 1 to 9, wherein the insulin data includes previously administered basal / bolus insulin.

11. A system described in any one of claims 1 to 10, wherein the estimate of the metabolic data is estimated using a Kalman filter.

12. A system described in any one of claims 1 to 11, wherein the approved basal rate is output to an insulin delivery device.

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