Prandial blood glucose excursion optimization method via computation of time-varying optimal insulin profiles and system thereof

• US 8,527,208 B2
• Filed: 11/17/2008
• Issued: 09/03/2013
• Est. Priority Date: 11/17/2008
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics International AG (Roche Holding AG)
• Inventors: Prud'homme, Thierry, Cris, Catalin
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US12/272,155
• Publication Number:
  US 20100125241A1
• Time in Patent Office: 1,751 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: G16H 10/60 for patient-specific data, e.g. for electronic patient records
• CPC Class Codes: G16H 20/17 delivered via infusion or injection
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems

Abstract

A method and system for optimizing post prandial blood glucose excursions for persons with diabetes via computation of time-varying optimal insulin profiles are disclosed. The method builds upon a mathematical model based on the physiologic description of the human glucoregulatory system. Model parameter values are specific for each patient and meal type, and are determined from measured data by minimizing differences between both measurements and model predictions, and which are used to provide the optimal insulin profiles that are useful to diabetics in managing their chronic disease.

Claims

1. A method of operating an electronic device to compute an optimal insulin infusion profile which is used as a postprandial blood glucose control for a specific patient/meal combination, said method comprising:

providing a pre-meal measurement of blood glucose concentration to the electronic device;

providing a meal intake comprising size and composition of a meal to be consumed by a patient to the electronic device;

providing pre-meal history of insulin infusion to the electronic device,

providing a chosen insulin infusion pattern for the postprandial blood glucose control which defines a target blood glucose trace to the electronic device;

providing a model having model parameters which are predetermined for the specific patient/meal combination to the electronic device, wherein said model parameters describe a relationship between the infused insulin, the meal intake and the blood glucose concentration of the specific patient/meal combination which values differs from other patient/meal combinations and define a predicted blood glucose trace for specific patient/meal combination;

computing automatically on the electronic device the optimal insulin infusion profile for the meal intake before an amount of insulin is delivered by optimizing the chosen insulin infusion pattern via minimizing an objective function which defines a relationship between the target blood glucose trace and the predicted blood glucose trace for the specific patient/meal combination, wherein the value of the objective function will be lower for an insulin profile which represents the best postprandial blood glucose control for the specific patient/meal combination, and said minimizing resulting in the optimal insulin infusion profile; and

providing, via the electronic device, the optimal insulin infusion profile for the meal intake.

2. The method of claim 1, wherein the pre-meal measurement of blood glucose concentration is provided via spot measurements performed during routine therapy.

3. The method of claim 1, wherein the pre-meal measurement of blood glucose concentration is provided via continuous measurements performed during routine therapy.

4. The method of claim 1, further comprises providing information concerning the absorption speed and carbohydrate content of the meal to be consumed.

5. The method of claim 1, further comprises using an insulin pump to provide the pre-meal insulin infusion history.

6. The method of claim 1, further comprises using a blood glucose meter to provide the pre-meal measurement of blood glucose concentration.

7. The method of claim 1, further comprises using a portable electronic device to record data concerning the pre-meal insulin infusion history, the pre-meal measurement of blood glucose concentration, and the size and composition of a meal to be consumed, and providing the recorded data concerning the pre-meal insulin infusion history, the pre-meal measurement of blood glucose concentration, and the size and composition of a meal to be consumed to the electronic device.

8. The method of claim 1, wherein the model is selected from the group of models consisting of a set of linear or nonlinear ordinary differential equations, a set of linear or nonlinear partial differential equations, a set of linear or nonlinear ordinary difference equations, a set of linear or nonlinear partial difference equations, a set of linear or nonlinear stochastic ordinary differential equations, a set of linear or nonlinear stochastic partial differential equations, a set of linear or nonlinear stochastic ordinary difference equations, a set of linear or nonlinear stochastic partial difference equations, an autoregressive moving average model, and a neural network model.

9. The method of claim 1 wherein a meal related glucose absorption is computed from a meal related carbohydrate intake rate for use in the objective function.

10. The method of claim 1, further comprises performing parameter identification to predetermine the model parameters.

11. The method of claim 10, wherein the parameter identification is a parameter identification method selected from the group consisting of maximum likelihood estimation, maximum a posteriori estimation, maximum a posteriori estimation with Bayesian priors, least squares fitting, and nonlinear least squares fitting.

12. The method of claim 1, wherein the objective function is minimized using means selected from the group consisting of global optimization, genetic algorithms, simulated annealing, linear programming, stochastic optimization, and calculus of variations.

13. The method of claim 1, wherein the objective function is defined by:

14. The method of claim 10, wherein said electronic device is selected from the group consisting of a desktop computer, and a portable electronic device providing a diabetes therapy guidance system.

15. The method of claim 1, wherein the optimal insulin infusion profile is provided to an insulin pump of the patient.

16. The method of claim 1, further comprises modifying insulin dosage and timing sequence of insulin infusion according to the optimal insulin infusion profile when the patient indicates at a subsequent time that the meal is to be consumed.

17. The method of claim 16, wherein the modifying is carried out automatically on an insulin pump of the patient.

18. The method of claim 1, wherein the optimal insulin infusion profile is provided to a display of the electronic device, and said method further comprises permitting acceptance of the displayed optimal insulin profile before use as the postprandial blood glucose control for the patient/meal combination.

20. The method of claim 1, wherein the insulin infusion profile is a piecewise constant function.

19. A system which provides an optimal insulin infusion profile useful as a postprandial blood glucose control for a specific patient/meal combination, said system comprising:

an input device configured to receive information about a pre-meal measurement of blood glucose concentration, and a meal intake comprising size and composition of a meal to be consumed;

a memory which contains additional information about a pre-meal history of insulin infusion, a chosen insulin infusion pattern for the postprandial blood glucose control which defines a target blood glucose trace, and a dynamical minimal model having model parameters which are predetermined for the patient/meal combination and describe a relationship between the infused insulin, the meal intake and the blood glucose concentration of the specific patient/meal combination which values differs from other patient/meal combinations and define a predicted blood glucose trace for specific patient/meal combination;

a processor programmed to use the received information and the additional information to compute automatically the optimal insulin infusion profile for the meal intake before an amount of insulin is delivered by optimizing the chosen insulin infusion pattern via minimizing an objective function which defines a relationship between the target blood glucose trace and the predicted blood glucose trace for the specific patient/meal combination, wherein the value of the objective function will be lower for an insulin profile which represents the best postprandial blood glucose control for the specific patient/meal combination, and wherein said minimizing of the objective function results in the optimal insulin infusion profile; and

a display configured to display the optimal insulin infusion profile.