Estimation of glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization from continuous glucose sensors and subcutaneous insulin deliver

• US 10,297,353 B1
• Filed: 05/08/2018
• Issued: 05/21/2019
• Est. Priority Date: 05/08/2018
• Status: Active Grant

• Current Assignee: Prince Sultan University
• Original Assignee: Prince Sultan University
• Inventors: Al-Matouq, Ali Ahmed
• Primary Examiner(s): Wang, Jack K
• Application Number:
  US15/974,451
• Time in Patent Office: 378 Days
• Field of Search: 3405731, 604506, 600365
• CPC Class Codes: A61B 5/0002 Remote monitoring of patients using telemetry, e.g. transmission of vital signals via a communication network A61B5/07 takes precedence; transmission systems for measured values G08C; transmission H04B; transmission of digital information H04L; wireless communication networks H04W
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7271 Specific aspects of physiological measurement analysis A61B5/316, A61B5/349 and A61B5/374 take precedence
• CPC Class Codes: A61M 2005/14208 with a programmable infusion control system, characterised by the infusion program
• CPC Class Codes: A61M 2205/52 with memories providing a history of measured variating parameters of apparatus or patient
• CPC Class Codes: A61M 5/142 Pressure infusion, e.g. using pumps
• CPC Class Codes: A61M 5/1723 using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G16H 10/20 for electronic clinical trials or questionnaires
• CPC Class Codes: G16H 20/13 delivered from dispensers
• CPC Class Codes: G16H 20/60 relating to nutrition control, e.g. diets
• CPC Class Codes: G16H 40/63 for local operation
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

Method and system for determining glucose flux profiles in plasma during meals using continuous glucose sensors and insulin delivery. A database of plausible glucose flux profiles is encoded in dictionaries using sparse dictionary learning. A constrained Lasso minimization problem is formed that integrates a transport model for a patient with the dictionaries for estimating the glucose fluxes. Meal carbohydrates consumed by a patient is incorporated in the minimization problem through convex constraints. The estimated glucose fluxes resulting from solving the constrained Lasso minimization problem are glucose rate of appearance from the intestine, endogenous glucose production from the liver and insulin dependent glucose utilization. A method for determining patient carbohydrate to insulin ratio at the time of the meal by calculating the area under the curve of the estimated insulin dependent glucose utilization.

Claims

1. A measurement system for measuring glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization comprising:

a receiver configured to receive subcutaneous glucose concentration data from a continuous glucose sensor that is coupled to a patient, the receiver further configured to receive insulin infusion data from an insulin infusion device or from the user through an input device, the receiver further configured to receive meal information data from the user through an input device, the receiver further configured to receive information regarding the initial condition for the glucose/insulin model of the patient used;

processing logic configured to determine a blood glucose and insulin concentration in the subject in response to a glucose disturbance and/or insulin infusion or a combination of both; and

processing logic configured to determine an estimated glucose rate of appearance from the intestine, an estimated endogenous glucose production from the liver and an estimated insulin dependent glucose utilization in response to received subcutaneous glucose concentration data and subcutaneous insulin delivery data, initial condition data in response to the glucose disturbance and/or insulin infusion or a combination of both and the rate of glucose appearance from the intestine, rate of endogenous glucose production and rate of insulin dependent glucose utilization of the subject.

2. The measurement system for measuring glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 1 wherein the subcutaneous glucose concentration data is noisy subcutaneous glucose concentration data and insulin infusion data is noisy subcutaneous insulin infusion data.

3. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 2 wherein the processing logic configured to determine an estimated glucose rate of appearance from the intestine, endogenous glucose production and insulin dependent glucose utilization is further configured to determine a filtered subcutaneous glucose concentration.

4. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 1 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.

5. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 1 further comprising processing logic configured to determine an estimate of patient carbohydrate to insulin ratio.

7. The method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization of claim 5 wherein the subcutaneous glucose concentration data is noisy subcutaneous glucose concentration data and the insulin infusion data is noisy subcutaneous insulin infusion data, the meal information data is noisy meal information data and the initial condition data relevant to the glucose/insulin model of the patient is noisy initial condition data.

8. The method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization of claim 5 wherein the step of determining an estimated glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization further comprises determining a filtered subcutaneous glucose concentration.

9. The method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization of claim 5 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.

10. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 2 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.

11. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 3 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.

12. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of any one of claim 2 further comprising processing logic configured to determine an estimate of patient carbohydrate to insulin ratio.

13. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of claim 3 further comprising processing logic configured to determine an estimate of patient carbohydrate to insulin ratio.

14. The glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization measurement system of any one of claim 4 further comprising processing logic configured to determine an estimate of patient carbohydrate to insulin ratio.

16. The method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization of claim 7 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.

6. A method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization the method comprising:

receiving subcutaneous glucose concentration data from a continuous glucose sensor that is coupled to a subject;

receiving insulin infusion data from an insulin infusion device or from the user through an input device;

receiving meal information data from a user through an input device;

receiving initial condition data relevant to the glucose/insulin model of the patient;

determining a blood glucose and insulin concentration in the subject in response to a glucose disturbance and/or an insulin disturbance or a combination of both, a rate of glucose appearance from the intestine of the subject, a rate of endogenous glucose production and a rate of insulin dependent glucose utilization; and

determining an estimated glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization in response to received subcutaneous glucose concentration data, insulin infusion data and a determined blood glucose concentration in the subject in response to the glucose and/or insulin disturbance or a combination of both and the rate of glucose appearance from the intestine, rate of endogenous glucose production and rate of insulin dependent glucose utilization of the subject.

15. The method of estimating a glucose rate of appearance, endogenous glucose production and insulin dependent glucose utilization of claim 6 wherein the glucose disturbance is a meal, an infusion of insulin, or a combination thereof.