Method and system for model-based tracking of changes in average glycemia in diabetes

• US 10,332,615 B2
• Filed: 02/21/2014
• Issued: 06/25/2019
• Est. Priority Date: 02/21/2013
• Status: Active Grant

• Current Assignee: Dow, Inc., University of Virginia Patent Foundation (University of Virginia)
• Original Assignee: University of Virginia Patent Foundation (University of Virginia)
• Inventors: Kovatchev, Boris P., Breton, Marc D.
• Primary Examiner(s): Riggs, II, Larry D
• Application Number:
  US14/769,638
• Publication Number:
  US 20160004813A1
• Time in Patent Office: 1,950 Days
• Field of Search: None
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• 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 5/7267 involving training the classification device
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 33/48707 by electrical means G01N33/49, G01N33/493 take precedence
• CPC Class Codes: G16B 5/00 ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
• CPC Class Codes: G16H 10/00 ICT specially adapted for the handling or processing of patient-related medical or healthcare data for medical reports G16H15/00; for therapies or health-improving plans G16H20/00; for the handling or processing of medical images G16H30/00
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders

Abstract

A method, system and computer readable medium for tracking changes in average glycemia in diabetes is based on a conceptually new approach to the retrieval of SMBG data. Using the understanding of HbA1c fluctuation as the measurable effect of the action of an underlying dynamical system, SMBG provides occasional glimpses at the state of this system and, using these measurements, the hidden underlying system trajectory can be reconstructed for individual diabetes patients. Using compartmental modeling a new two-step algorithm is provided that includes: (i) real-time estimate of HbA1c from fasting glucose readings, updated with any new incoming fasting SMBG data point(s), and (ii) initialization and calibration of the estimated HbA1c trace with daily SMBG profiles obtained periodically. The estimation of these profiles includes a factorial model capturing daily BG variability within two latent factors.

Claims

1. A computer-implemented method for providing a real-time estimate of glycosylated hemoglobin (HbA1c) of a patient from a self-monitoring blood glucose (SMBG) measurement, and tracking changes in average glycemia of said patient over time, said method comprising:

receiving, by a processor, a fasting SMBG measurement from said patient;

computing, by a processor, a glycation value using said fasting SMBG measurement in a predetermined glycation equation;

outputting, by a processor, said glycation value as an initial estimate of HbA1c upon initialization of tracking of said patient'"'"'s average glycemia;

updating, by a processor, said glycation value by using an updated SMBG value in said predetermined glycation equation, said updated SMBG value being based on a subsequent fasting SMBG measurement from said patient;

computing, by a processor, an updated estimate of HbA1c using said initial estimate of HbA1c and said updated glycation value in a predetermined HbA1c estimation equation; and

outputting, by a processor, said updated estimate of HbA1c to a user.

2. The computer-implemented method of claim 1, further comprising:

updating, by a processor, said updated estimate of HbA1c by;

using a subsequent updated SMBG value in said predetermined glycation equation based on a further subsequent fasting SMBG measurement from said patient to compute a further updated glycation value; and

computing, by a processor, a further updated estimate of HbA1c using a last updated estimate of HbA1c and said further updated glycation value in a predetermined HbA1c estimation equation; and

outputting, by a processor, said further updated estimate of HbA1c to a user.

3. The computer-implemented method of claim 2, wherein said predetermined glycation equation is given by:

4. The computer-implemented method of claim 3, wherein γ

is set so that the last updated estimate of HbA1c, eA1c(t), is set to correspond to a reference HbA1c measurement obtained from said patient.

5. The computer-implemented method of claim 3, wherein

6. The computer-implemented method of claim 5, wherein said SMBG profile is a multipoint peri-prandial profile.

7. The computer-implemented method of claim 6, wherein said multipoint peri-prandial profile is a seven point profile including the following SMBG measurements:

PG2;

first meal preprandial

PG3;

first meal postprandial

PG4;

second meal preprandial

PG5;

second meal postprandial

PG6;

third meal preprandial

PG7;

third meal postprandial

PG8;

before bedtime.

8. The computer-implemented method of claim 7, wherein

θ

₁=0.4006*PG2+0.4645*PG3+0.3753*PG4+0.2411*PG5−

0.1805*PG6−

0.2528*PG7+0.0481*PG8, and

θ

₂=−

0.1557*PG2−

0.2077*PG3.1177*PG4+0.0341*PG5+0.5255*PG6+0.6014*PG7+0.2543*PG8.

9. The computer-implemented method of claim 1, wherein said predetermined glycation equation is given by:

10. A system for providing a real-time estimate of glycosylated hemoglobin (HbA1c) of a patient from a self-monitoring blood glucose (SMBG) measurement, and tracking changes in average glycemia of said patient over time, comprising:

a processor; and

a processor-readable memory including processor-executable instructions for;

receiving a fasting SMBG measurement from said patient;

computing a glycation value using said fasting SMBG measurement in a predetermined glycation equation;

outputting said glycation value as an initial estimate of HbA1c upon initialization of tracking of said patient'"'"'s average glycemia;

updating said glycation value by using an updated SMBG value in said predetermined glycation equation, said updated SMBG value being based on a subsequent fasting SMBG measurement from said patient;

computing an updated estimate of HbA1c using said initial estimate of HbA1c and said updated glycation value in a predetermined HbA1c estimation equation; and

outputting said updated estimate of HbA1c to a user.

11. The system of claim 10, wherein said memory further includes processor-executable instructions for:

updating said updated estimate of HbA1c by;

using a subsequent updated SMBG value in said predetermined glycation equation based on a further subsequent fasting SMBG measurement from said patient to compute a further updated glycation value; and

computing a further updated estimate of HbA1c using a last updated estimate of HbA1c and said further updated glycation value in a predetermined HbA1c estimation equation; and

outputting said further updated estimate of HbA1c to a user.

12. The system of claim 11, wherein said predetermined glycation equation is given by:

13. The system of claim 12, wherein γ

is set so that the last updated estimate of HbA1c, eA1c(t), is set to correspond to a reference HbA1c measurement obtained from said patient.

14. The system of claim 12, wherein

15. The system of claim 14, wherein said SMBG profile is a multipoint peri-prandial profile.

16. The system of claim 15, wherein said multipoint peri-prandial profile is a seven point profile including the following SMBG measurements:

PG2;

first meal preprandial

PG3;

first meal postprandial

PG4;

second meal preprandial

PG5;

second meal postprandial

PG6;

third meal preprandial

PG7;

third meal postprandial

PG8;

before bedtime.

17. The system of claim 16, wherein

θ

₁=0.4006*PG2+0.4645*PG3+0.3753*PG4+0.2411*PG5−

0.1805*PG6−

0.2528*PG7+0.0481*PG8, and

θ

₂=−

0.1557*PG2−

0.2077*PG3.1177*PG4+0.0341*PG5+0.5255*PG6+0.6014*PG7+0.2543*PG8.

18. The system of claim 10, wherein said predetermined glycation equation is given by:

19. A non-transient computer-readable medium having stored therein computer-executable instructions for providing a real-time estimate of glycosylated hemoglobin (HbA1c) of a patient from a self-monitoring blood glucose (SMBG) measurement, and tracking changes in average glycemia of said patient over time, said instructions comprising instructions causing a computer to:

receive a fasting SMBG measurement from said patient;

compute a glycation value using said fasting SMBG measurement in a predetermined glycation equation;

output said glycation value as an initial estimate of HbA1c upon initialization of tracking of said patient'"'"'s average glycemia;

update said glycation value by using an updated SMBG value in said predetermined glycation equation, said updated SMBG value being based on a subsequent fasting SMBG measurement from said patient;

compute an updated estimate of HbA1c using said initial estimate of HbA1c and said updated glycation value in a predetermined HbA1c estimation equation; and

output said updated estimate of HbA1c to a user.

20. The computer-readable medium of claim 19, further including instructions for causing a computer to:

update said updated estimate of HbA1c by;

using a subsequent updated SMBG value in said predetermined glycation equation based on a further subsequent fasting SMBG measurement from said patient to compute a further updated glycation value; and

computing a further updated estimate of HbA1c using a last updated estimate of HbA1c and said further updated glycation value in a predetermined HbA1c estimation equation; and

output said further updated estimate of HbA1c to a user.

21. The computer-readable medium of claim 20, wherein said predetermined glycation equation is given by:

22. The computer-readable medium of claim 21, wherein γ

is set so that the last updated estimate of HbA1c, eA1c(t), is set to correspond to a reference HbA1c measurement obtained from said patient.

23. The computer-readable medium of claim 21, wherein

24. The computer-readable medium of claim 23, wherein

θ

₁=0.4006*PG2+0.4645*PG3+0.3753*PG4+0.2411*PG5−

0.1805*PG6−

0.2528*PG7+0.0481*PG8, and

θ

₂=−

0.1557*PG2−

0.2077*PG3.1177*PG4+0.0341*PG5+0.5255*PG6+0.6014*PG7+0.2543*PG8.

25. The computer-readable medium of claim 19, wherein said predetermined glycation equation is given by: