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CN-121985907-A - Method for controlling blood sugar and artificial pancreas system for performing the same

CN121985907ACN 121985907 ACN121985907 ACN 121985907ACN-121985907-A

Abstract

The present invention relates to a method for controlling glucose in a flexible structured bi-hormonal artificial pancreas, the method managing optional meals and/or exercise alarms by means of coordinated control actions, the method comprising measuring plasma glucose signals, calculating an incremental plasma glucose measurement (y), defining an incremental plasma glucose model, defining carbohydrate intake as a function of estimated carbohydrate content of the patient, defining an expected postprandial incremental plasma glucose from administered insulin bolus Defining corrected delta plasma glucose Insulin infusion after correction And corrected carbon hydrate uptake Defining virtual control behavior It has a modulating action And counterregulatory behavior Between allocations, with a nominal value S) the 2-DOF feedback controller of the pre-filter to calculate the control behavior.

Inventors

  • Ricardo Sans Diaz
  • Jorge Bondia Kompany
  • Jose Louis. Dies Ruano
  • Pedro Jose Garcia Hill
  • Ivan Sara Mira

Assignees

  • 瓦伦西亚理工大学

Dates

Publication Date
20260505
Application Date
20240823
Priority Date
20230825

Claims (20)

  1. 1. A method for controlling glucose in a flexible structured bi-hormonal artificial pancreas, the method being capable of managing optional meal notifications and optional exercise notifications by means of coordinated control actions, the method comprising the steps of: -measuring a plasma glucose signal (G (t)) by means of a Continuous Glucose Monitor (CGM); -calculating an incremental plasma glucose measurement by means of the formula: Wherein the method comprises the steps of Is the baseline glucose value; -taking into account carbohydrate intake (d), infusion relative to baseline Incremental insulin infusion (u), glucagon administration (v) and rescue carbohydrate administration (w), the model for increasing plasma glucose (y) was defined as: Wherein the method comprises the steps of , And is also provided with And wherein Is a time-invariant linear transfer function, correlates carbohydrate intake (d), delta insulin infusion (u), glucagon administration (v) and rescue carbohydrate administration (w) with delta plasma glucose (y), and is subjected to And The number of the molecular order of the matrix is not more than the limit of the number of the denominator; -defining carbohydrate intake as: Wherein the method comprises the steps of Is an estimated carbohydrate content of the patient notification; definition of expected postprandial increase in plasma glucose The method comprises the following steps: Wherein the method comprises the steps of Insulin bolus(s) administered in association with a manual meal notification of the patient; -defining corrected delta plasma glucose Insulin infusion after correction And corrected carbon intake of the hydrate The method comprises the following steps: -defining virtual control behavior The method comprises the following steps: Such that: -controlling behavior Divided into regulatory control actions And counterregulatory control behavior : -Assigning the counterregulatory behaviour as follows Wherein the method comprises the steps of Represents a counterregulatory effect by means of glucagon infusion, and Represents a counterregulatory effect carried out by means of carbohydrate intake such that: -calculate the regulatory and counterregulatory behaviour as follows: Wherein the method comprises the steps of Is a function of defining the change between regulatory and anti-regulatory behavior, and Is a tunable factor, and wherein Is the previously obtained controller gain, and Is defined as: Wherein the method comprises the steps of Calculated as a prefilter with nominal value 2-DOF feedback controller of (c) as follows: And wherein Is designed for a stabilization system And attenuate interference A central linear controller of(s), -Calculating the counterregulatory behaviour in the form of: Wherein the method comprises the steps of Is an adjustable parameter, y -Calculating the control behavior as follows:
  2. 2. the method of claim 1, wherein the model Obtained as follows: Wherein the method comprises the steps of , , And Is a transfer function of the form: Wherein the method comprises the steps of , , And Is a parameter representing the delay and is used to determine, , , , , , , , , , , And Is a previously obtained parameter and j is an index representing the patient.
  3. 3. The method according to any one of claims 1 to 2, further comprising the step of performing corrections for regulatory and anti-regulatory behaviour in the form of: Wherein the method comprises the steps of Is a function of defining the change between regulatory and anti-regulatory behavior, and Is an adjustable factor.
  4. 4. A method according to any one of claims 1 to 3, wherein Equal to Or with a specific sample window Is a moving average filter of (c).
  5. 5. The method according to any one of claims 1 to 4, further comprising the step of, for a pair of The correction is performed as follows: Defining feedback behavior ) And feedforward behavior ) The following are provided: Wherein the method comprises the steps of Is relative to Is added to the nominal value of glucose.
  6. 6. The method of any one of claims 1 to 5, wherein the controller Is defined as: And a filter And Is defined as: Wherein the method comprises the steps of , , And Is a previously calculated parameter, and r is relative to Is added to the nominal value of glucose.
  7. 7. The method according to any one of claims 1 to 6, wherein according to a condition in which the one counterregulatory behavior is more favorable than the other, Is variable over time.
  8. 8. The method according to any one of claims 1 to 5, wherein rescue carbohydrates are used as quantified levels ) Is calculated as follows: And wherein Is the minimum threshold for activating the recommended accumulated carbohydrates, And: Wherein the method comprises the steps of Is to define a time range Inner pair Is used for the prediction of (a), And A predetermined threshold for predicting glucose and measuring glucose, respectively, and wherein: Wherein BW is the weight (kg) of the user, Is the sampling period, and Is the clearance rate.
  9. 9. The method according to claim 8, wherein for The predictive calculation of (2) is as follows: Is a discretization of the filtered glucose derivative (discretisation): Wherein the method comprises the steps of Is a previously determined time constant.
  10. 10. The method according to any one of claims 1 to 9, wherein glucagon is used as a quantitive level ± ) Is calculated as follows: And wherein Is the minimum threshold for activating the recommended cumulative glucagon, And: Wherein the method comprises the steps of Is to define a time range Inner pair Prediction of (c), and And A predetermined threshold for predicting glucose and measuring glucose, respectively, and wherein: Wherein BW is the weight (kg) of the user, Is the sampling period Is the clearance rate.
  11. 11. The method of claim 10, wherein for The predictive calculation of (2) is as follows: is the discretization of the filtered glucose derivative Wherein the method comprises the steps of Is a previously determined time constant.
  12. 12. The method according to any one of claims 8 to 11, wherein At a rate of 60 mg/dl, Is 54 mg/dl and is in a time range 60 Min.
  13. 13. A method according to any one of claims 8 to 12, wherein the expected postprandial increase in plasma glucose is calculated by adding a specific dose of the term corresponding to the counterregulatory behaviour Such as: Wherein the method comprises the steps of And Is an adjustable gain.
  14. 14. The method of claim 13, wherein the gain is adjustable And Is determined to be when the counterregulatory behavior (v, w) is equal to the quantization level [ ] , ) Achieving the desired maximum output increase The required gain is obtained as follows: Wherein the method comprises the steps of Representing an inverse Laplace transform operator, and Is prepared from the quantization level , ) Resulting in a desired output change.
  15. 15. A method according to any one of claims 1 to 14, wherein postprandial incrementation of plasma glucose is expected Saturation is as follows:
  16. 16. The method of claim 15, wherein 180 And is 180 70.
  17. 17. The method of any one of claims 6 to 16, wherein the controller Is to be used in the present invention Is defined as 。
  18. 18. The method of any of claims 6 to 16, wherein the gain is adjustable Is defined as: Wherein the method comprises the steps of Is inverse Laplace transform, and And Is an adjustable parameter, wherein Represents the worst case expected meal size, and Is responsive to the meal Is a lower tolerance limit for postprandial glucose.
  19. 19. The method of claim 18, wherein Is defined as the size of the meal notified by the patient every time an optional meal notification is made ) A kind of electronic device Is defined to be responsive to the meal The calculated k value is kept in an adjustable time window from the time of meal notification to the lower tolerance limit of postprandial glucose.
  20. 20. The method of any one of claims 1 to 19, wherein insulin bolus administered as a result of optional meal notification ) Meal size notified from the patient ) Is calculated as by A bolus of the definition wherein Is a feedforward controller, given by:

Description

Method for controlling blood sugar and artificial pancreas system for performing the same Technical Field The invention belongs to the technical field of glucose control. In particular, the invention relates to a regulatory control behaviour by means of insulin administration, and a counterregulatory control behaviour by means of glucagon and/or rescue carbohydrate (rescue carbohydrates) administration, more effective in controlling glucose levels. It is an object of the present invention to provide a glucose control method that enables the management of optional meals and exercise notifications by means of a flexible structured bi-hormonal control system. A second object of the present invention is to provide a flexible structure of a bi-hormonal artificial pancreas for administering insulin, glucagon and/or rescue carbohydrates in a coordinated manner. Background Type 1 diabetes (DMT 1) is an autoimmune disorder that destroys pancreatic beta cells, resulting in the inability to secrete insulin. This hormone plays a key role in glucose homeostasis as it is responsible for lowering plasma glucose concentrations. Thus, people with DMT1 often have high glucose levels (hyperglycemia) for long periods of time, resulting in serious long-term health problems such as cardiovascular disease, nephropathy, retinopathy and neuropathy. This is why exogenous insulin administration is required. The Artificial Pancreas (AP) system has emerged as a technical treatment for DMT1 that improves glycemic control compared to traditional treatments. However, daytime control remains a challenge because meal intake and exercise result in significant fluctuations in glucose levels. Existing hybrid AP systems are based on meal bolus with carbohydrates adapted to compensate for glucose elevation due to the meal. In open-loop therapy (open-loop), the patient has had to assume responsibility for estimating and informing the system of carbohydrates (meal notifications). Thus, some patients may not be aware of the usefulness of the AP, thereby giving up its continued use. Thus, the AP system must be able to have acceptable performance without meal notification responsibilities. However, a complete system (fully automated) without meal notification may not be suitable for all patients. Some patients with rich carbohydrate estimation experience may tend to assume (at least in some cases) responsibility for meal notification to enhance postprandial control. Meal notifications, however, as a kind of feed forward behavior, may interact with feedback behavior in APs designed to work in a fully automated way without said notifications, leading to an overdose of insulin and thus to hypoglycemia (abnormally low glucose levels). Thus, the AP system must include a mechanism that allows the user to provide meal notifications without increasing the risk of hypoglycemia. Motion is another major problem that challenges AP system performance. Although very high intensity exercise events may lead to hyperglycemia (abnormally high glucose levels), light to moderate aerobic exercises, which are most commonly performed by non-athletes, reduce glucose levels. Existing hybrid systems require the user to plan the movement several hours before the start of the movement to reduce insulin infusion. To eliminate the motion notification, the AP system must have a counterregulatory control action that increases the glucose level. Carbohydrate supplementation is the most practical option for treating mild exercise-related hypoglycemia. However, people with concerns about weight gain may prefer to administer glucagon subcutaneously as a non-caloric treatment for hypoglycemia. In clinical trials, the bi-hormonal AP system with automatic insulin and glucagon administration has been effective in shortening exercise-induced hypoglycemic time. Persons with less exercise and a low tendency to have hypoglycemia may consider the additional cost of the bi-hormonal AP system to be justified for timely administration of glucagon. For these patients, self-administration of low-dose glucagon pens may be a more suitable option for safely and effectively alleviating non-severe hypoglycemia. Based on the above analysis, the following three features are recommended in an AP system: 1) Effectively compensating for meals without any meal notification; 2) Allowing the patient to provide meal notifications (if they are willing to do so) without compromising the performance of the feedback controller, and 3) Counterregulatory control actions are provided to manage hypoglycaemic relief, for example in a notification-free exercise event. Many methods of eliminating meal notifications have been proposed, but none have a mechanism to reduce feedback behavior interactions with the event that the patient provides a meal notification. As for feed forward as a result of unintended movement, most glucagon-insulin systems lack a carbohydrate advice module and vice versa. A few strategies that can wor