Closed-loop blood glucose control systems and methods
Inventors
ROUSSON, Sylvain • BLANC, ROMAIN • DORON, Maeva
Assignees
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Publication Number
US-11484652-B2
Publication Date
2022-11-01
Expiration Date
Abstract
An automated closed-loop blood glucose control system comprises a continuous glucose-monitoring sensor (101), a subcutaneous insulin delivery device (103); and a controller (105) which determines a maximal allowable insulin injection amount and determines an insulin delivery control signal on the basis of the maximal allowable insulin injection amount and the quantity of insulin to inject.
Core Innovation
The invention relates to an automated closed-loop blood glucose control system for the controlled delivery of insulin to a patient. The control system comprises a continuous glucose-monitoring sensor providing glucose measurement values at associated measurement times, a subcutaneous insulin delivery device configured to deliver exogenous insulin in subcutaneous tissue in response to an insulin delivery control signal, and a controller programmed to receive the glucose measurement values and provide the delivery control signal. The controller determines a quantity of insulin to inject at at least one time step based on a predicted glucose level computed using a physiological model of the glucose-insulin system.
The physiological model comprises a system of differential equations describing the evolution of a plurality of state variables as a function of time. The controller computes a maximal allowable insulin injection amount and determines the insulin delivery control signal based on both the maximal allowable insulin injection amount and the quantity of insulin to inject at the at least one time step. The maximal allowable insulin injection amount is a function of patient insulin sensitivity defined as a ratio between a variation in blood glucose level and a variation in a quantity of insulin present in a second compartment of the subcutaneous layer.
The patient insulin sensitivity is a decreasing function of a glucose level of the patient, and the maximal allowable insulin injection amount is proportional to an inverse of the patient sensitivity to insulin. The described sensitivity behavior decreases as glucose level increases, with different slope behaviors around an intermediate glucose level, and the document also describes an optional sensitivity-to-glucose decreasing function represented by a precomputed sensitivity-to-glucose curve derived from averaged simulated experiments.
The document further specifies that the maximal allowable insulin injection amount can be proportional to at least a predefined basal insulin and a personalized reactivity coefficient, and can optionally be made dependent on heart rate via physiological monitoring. The controller applies the constraint by computing the insulin delivery control signal so that the injected insulin quantity is capped based on the computed maximal allowable insulin injection amount, while also using model-based prediction and cost optimization and periodic self-calibration of model parameters and states using prior glucose, insulin, and meal indicators.
Claims Coverage
The partial content provides three independent claims (clm-00001, clm-00011, clm-00014). Each independent claim centers on predicting glucose with a physiological glucose-insulin model using differential-equation state variables and constraining the computed insulin injection using a maximal allowable insulin injection amount based on a patient insulin sensitivity that decreases with glucose level and is used via an inverse relationship.
Physiological model-based glucose prediction with differential-equation state variables
The controller determines a quantity of insulin to inject at at least one time step on the basis of a predicted glucose level determined by computing a physiological model of glucose-insulin system in the patient, the model comprising a system of differential equations describing the evolution of a plurality of state variables as a function of time.
Maximal allowable insulin injection amount driven by insulin sensitivity
The controller computes a maximal allowable insulin injection amount and determines the insulin delivery control signal on the basis of the maximal allowable insulin injection amount and the quantity of insulin to inject at at least one time step, wherein the maximal allowable insulin injection amount is a function of a sensitivity of the patient to insulin, the sensitivity being representative of a ratio between a variation in a blood glucose level and a variation in a quantity of insulin present in a second compartment of the subcutaneous layer, the sensitivity being a decreasing function of a glucose level of the patient, and wherein the maximal allowable insulin injection amount is proportional to an inverse of said sensitivity of the patient to insulin.
Capped insulin delivery control signal based on maximal allowable amount
The insulin delivery control signal is determined on the basis of the maximal allowable insulin injection amount and the quantity of insulin to inject at at least one time step, wherein the control signal constrains delivered insulin so that the insulin quantity to inject is based on the computed maximal allowable insulin injection amount.
Basal- and reactivity-coefficient-parametrized maximum as a product with inverse sensitivity
For the system of the claim, the maximal allowable insulin injection amount is a function of a predefined basal amount of continuously infused insulin and/or bolus insulin of the patient, and wherein the maximal allowable insulin injection amount is a product of at least said predefined basal amount, a predefined personalized reactivity coefficient and an inverse of said sensitivity of the patient to insulin.
Across the independent claims, the coverage is centered on closed-loop subcutaneous insulin delivery driven by controller prediction from a physiological glucose-insulin model expressed as differential equations, and on a safety-constraining maximal allowable insulin injection amount computed from a patient insulin sensitivity defined via a glucose-change/insulin-change ratio in a second subcutaneous compartment that decreases with glucose level and is used through an inverse sensitivity relationship.
Stated Advantages
Constrains insulin delivery by computing a maximal allowable insulin injection amount based on patient insulin sensitivity that decreases with glucose level.
Determines insulin delivery control signals based on both the predicted glucose level and the maximal allowable insulin injection amount.
Provides a maximum insulin injection amount configured as a function of predefined basal insulin and a personalized reactivity coefficient (in product form with inverse sensitivity).
Documented Applications
Automated closed-loop blood glucose control using continuous glucose-monitoring sensor measurements to control subcutaneous insulin delivery (continuous infusion and/or bolus insulin).
Controlled delivery of insulin to a patient using a method that includes continuously monitoring glucose, computing insulin quantities using a physiological glucose-insulin model with differential equations, and constraining delivery with a maximal allowable insulin injection amount.
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