This application is a national stage filing under 35 U.S.C. 371 of International Patent Application Serial No. PCT/FR2017/052511, filed Sep. 19, 2017, which claims priority to French patent application FR16/58881, filed Sep. 21, 2016. The entire contents of these applications are incorporated herein by reference in their entirety.

BACKGROUND

The present application relates to the field of automated blood sugar regulation systems, also called artificial pancreases.

DISCUSSION OF THE RELATED ART

An artificial pancreas is a system enabling to automatically regulate the insulin intake of a diabetic patient based on his/her blood sugar history, on his/her meal history, and on his/her insulin injection history.

MPC-type regulation systems or model predictive control systems, where the regulation of the delivered insulin dose takes into account a prediction of the future evolution of the patient's blood sugar, obtained from a physiological model describing the assimilation of insulin by the patient's body and its impact on the patient's blood sugar, are here more particularly considered.

It would be desirable to be able to improve the performance of model predictive control artificial pancreases and, more particularly, to be able to improve the quality of the prediction of the patient's future blood sugar, to be able to control with a better relevance insulin intakes and to limit risks of placing the patient in a hyperglycemia or hypoglycemia situation.

It would further be desirable to be able to limit risks for the patient due to a possible failure of the physiological model used to predict the patient's future blood sugar.

SUMMARY

Thus, an embodiment provides an automated system of regulation of a patient's blood sugar, comprising:

a blood sugar sensor;

an insulin injection device; and

a processing and control unit capable of predicting the future evolution of the patient's blood sugar from a physiological model and of controlling the insulin injection device by taking the prediction into account, wherein:

the physiological model comprises a differential equation system describing the time variation of a plurality of state variables; and

the processing and control unit is capable of implementing a step of automatic calibration of the physiological model comprising a step of estimation of initial values of the state variables by minimization of a quantity representative of the error, during a past observation period, between the blood sugar estimated based on the physiological model and the blood sugar measured by the sensor.

According to an embodiment, the quantity is representative of the area between a first curve ĝ representative of the time variation of the blood sugar estimated based on the model over the observation period, and a second curve g representative of the time variation of the blood sugar measured by the sensor over the observation period.

According to an embodiment, the quantity is defined as follows:

m=1Δ⁢⁢T⁢∑t=t0t0+Δ⁢⁢T⁢⁢g⁡(t)-g^⁡(t)2

where t is a discretized time variable, is t0the time of beginning of the observation phase, and t0+ΔT is the end time of the observation phase.

According to an embodiment, the calibration method further comprises a step of estimation of parameters of the differential equation system by minimization of said quantity.

According to an embodiment, the calibration method comprises a plurality of successive iterations of the following steps a) and b):

a) estimating the parameters of the differential equation system by minimization of said quantity by setting the initial values of the state variables; and

b) estimating the initial values of the state variables by minimization of said quantity by setting the parameters of the differential equation system.

According to an embodiment, at the first iteration of step a), the initial values of the state variables are analytically determined by making the assumption that all the derivatives of the differential equation system are zero.

According to an embodiment, the simulate the evolution of the patient's blood sugar based on the physiological model, the processing and control unit takes into account the history of the insulin injected to the patient by the injection device and the history of the glucose ingested by the patient.

According to an embodiment, the physiological model is Hovorka's model.

Another embodiment provides a method of automated regulation of a patient's blood sugar, comprising:

a step of calculating, by means of a processing and control unit, a prediction of the future evolution of the patient's blood sugar based on a physiological model comprising a differential equation system describing the time variation of a plurality of state variables;

a step of controlling an insulin injection device taking this prediction into account; and

a step of automatic calibration of the physiological model comprising a step of estimation of initial values of the state variables by minimization of a quantity representative of the error, during a past observation period, between the blood sugar estimated based on the physiological model and the blood sugar measured on the patient by a blood sugar sensor.

According to an embodiment, the method further comprises a step of estimation of parameters of the differential equation system by minimization of said quantity.

According to an embodiment, the calibration step comprises a plurality of successive iterations of the following steps a) and b):

a) estimating the parameters of the differential equation system by minimizing said quantity by setting the initial values of the state variables; and

b) estimating the initial values of the state variables by minimizing said quantity by setting the parameters of the differential equation system.

Another embodiment provides an automated system of regulation of a patient's blood sugar, comprising:

a blood sugar sensor;

an insulin injection device; and

a processing and control unit capable of predicting the future evolution of the patient's blood sugar based on a physiological model and of controlling the insulin injection device by taking the prediction into account,

wherein the processing and control unit is capable of:

a) implementing a step of automatic calibration of the physiological model by taking into account a history of the blood sugar measured by the sensor during a past observation period;

b) at the end of the calibration step, determining whether the model is satisfactory or not based on at least one numerical indicator representative of the error between the blood sugar estimated based on the model and the real blood sugar measured by the sensor; and

c) if the quality of the model is not satisfactory, controlling the insulin injection device without taking into account the prediction made from the model.

According to an embodiment, the numerical indicator comprises an indicator m representative of the area between a first curve ĝ representative of the time variation of the blood sugar estimated based on the model over the observation period, and a second curve g representative of the time variation of the blood sugar measured by the sensor over the observation period.

According to an embodiment, indicator m is defined as follows:

m=1Δ⁢⁢T⁢∑t=t0t0+Δ⁢⁢T⁢⁢g⁡(t)-g^⁡(t)2

where t is a discretized time variable, is t0the time of beginning of the observation phase, and t0+ΔT is the end time of the observation phase.

According to an embodiment, the numerical indicator comprises an indicator m1representative of the difference between the blood sugar estimated based on the model and the blood sugar measured by the sensor at a given time.

According to an embodiment, the numerical indicator comprises an indicator m2representative of the difference between the derivative of the blood sugar estimated based on the model and the derivative of the blood sugar measured by the sensor at a given time.

According to an embodiment, at step c), the control of the insulin injection device is a model predictive control based on a simplified physiological model.

According to an embodiment, at step c), the insulin injection device is controlled to deliver preprogrammed insulin doses corresponding to a reference basal rate prescribed to the patient.

According to an embodiment, the physiological model comprises a differential equation system describing the time variation of a plurality of state variables, and step a) of automatic calibration of the model comprises a step of estimation of parameters of the differential equation system by minimization of a quantity representative of the error, during a past observation period, between the blood sugar estimated based on the physiological model and the blood sugar measured by the sensor.

According to an embodiment, step a) of automatic calibration of the model further comprises a step of determination of initial values of the state variables.

Another embodiment provides a method of automated regulation of a patient's blood sugar, comprising:

a step of calculating, by means of a processing and control unit, a prediction of the future evolution of the patient's blood sugar based on a physiological model; and

a step of control of an insulin injection device taking this prediction into account, the method further comprising:

a) a step of automatic calibration of the physiological model taking into account a history of the blood sugar measured by a blood sugar sensor during a past observation period;

b) at the end of the calibration step, a step of determination of the quality of the physiological model based on at least one numerical indicator representative of the error between the blood sugar estimated based on the model and the real blood sugar measured by the sensor; and

c) if the quality of the model is considered unsatisfactory, a step of control of the insulin injection device without taking into account the prediction made from the model.

