System and method for deriving parameters for homeostatic feedback control of an individual

Patent metadata

Field	Value
Publication number	US-10204708-B2
Application number	US-201314443276-A
Country	US
Kind code	B2
Filing date	Dec 5, 2013
Priority date	Dec 5, 2012
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

Abstract

A method and system of deriving a physiological homeostatic operating set point of an individual comprising the steps of: obtaining a dataset of predetermined number of homeostatic measurements of the individual; fitting the dataset of predetermined number of homeostatic measurements according to a negative exponential decay function; identifying and setting the physiological homeostatic operating set point unique to the individual as the point corresponding to the point of maximum curvature on the fitted negative exponential decay function is disclosed. The method is especially suited for determining the [FT4]-[TSH] set point, which is unique for each individual.

First claim

The claims defining the invention are as follows:

1. A method of deriving a physiological homeostatic operating set point of an individual and adjusting the homeostatic measurements of the individual comprising:
a. obtaining a dataset of predetermined number of homeostatic measurements of the individual;
b. fitting the dataset of predetermined number of homeostatic measurements according to a negative exponential decay function in a manner so as to derive a multiplier parameter and a rotational parameter;
c. identifying and setting a physiological homeostatic operating set point unique to the individual as the point corresponding to the point of maximum curvature on the fitted negative exponential decay function; and
d. administering to the individual in need, a therapeutically effective amount of a compound to adjust the homeostatic measurements of the individual to the physiological homeostatic operating set point unique to the individual.

2. A method according to claim 1 , wherein each of the predetermined number of homeostatic measurements is a thyroid-stimulating hormone [TSH] level and a corresponding free thyroxin [FT4] level of the individual, the homeostatic measurements obtained under controlled predetermined measurement conditions.

3. A method according to claim 1 , wherein each of the predetermined number of homeostatic measurements is a thyroid-stimulating hormone [TSH] level and a corresponding free thyroxin [FT4] level of the individual, the homeostatic measurements obtained under controlled predetermined measurement conditions, and wherein the negative exponential decay function is mathematically expressed as the following formula:

[
TSH
]

=

S

exp
⁡

(

φ
⁡

[

FT
⁢

⁢
4

]

)

Wherein S is the multiplier parameter; φ is the rotational parameter; and exp denotes the exponential function.

4. A method according to claim 3 , wherein the parameters S and φ are calculated from a first and a second homeostatic measurements of the individual according to the following formula:
φ = ( 1 [ FT ⁢ ⁢ 4 ] 1 - [ FT ⁢ ⁢ 4 ] 2 ) ⁢ ln ⁡ ( [ TSH ] 2 [ TSH ] 1 ) S =[TSH] 1 exp(φ[FT4] 1 )=[TSH] 2 exp(φ[FT4] 2 )

where the subscript 1 and 2 denote the first and second homeostatic measurement respectively.

5. A method according to claim 4 , wherein for any measurement subsequent to the second homeostatic measurement, the parameters S and φ are iteratively fine-tuned by using each subsequent homeostatic measurement with a first and a second homeostatic measurements.

6. A method according to claim 3 , wherein the physiological homeostatic operating set point of the individual is determined according to the following formula:

[

FT
⁢

⁢
4

]

SP

=

ln
(

S
⁢

⁢
φ
⁢

2

)

φ

⁢

[
TSH
]

SP

=

1

φ
⁢

2

Where [FT4] SP and [TSH] SP denote the physiological homeostatic operating set point of the individual.

7. A method according to claim 1 , further comprising validating the physiological homeostatic operating set point of the individual based on a control system model.

8. A method according to claim 1 , the method comprises calculating a loop gain of the obtained physiological homeostatic operating set point mathematically expressed as:—

G
L

=

A
⁢

⁢
φ

e

Where G L is the calculated loop gain; e is the exponential constant e≈2.718;

A
=

[

FT
⁢

⁢
4

]

setpoint

0.632

;

and [FT4] setpoint is the obtained [FT4] level of the operating set point for the individual, and accepting the obtained physiological homeostatic operating set point if the calculated G L is greater than 1.

9. A method according to claim 1 , wherein the each of the predetermined number of homeostatic measurements comprises a thyroid-stimulating hormone (TSH) level and a corresponding triiodothyronine (T3) level.

10. A method according to claim 1 wherein each homeostatic measurement is obtained by measuring an amount of a homeostatic amino acid expression product with a detection reagent capable of hybridizing to the homeostatic amino acid expression product.

11. A method according to claim 10 , wherein the detection reagent comprises a detectable marker and an antibody capable of hybridizing to a thyroid-stimulating hormone.

12. A method according to claim 1 wherein t

Assignees

• Agency Science Tech & Res

Inventors

• Goede Sam L
• Dietrich Johannes W
• Leow Khee Shing Melvin

Classifications

• G16H50/30 Primary

  for calculating health indices; for individual health risk assessment · CPC title

• A61B5/145

  Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value {; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue} (non-radiation detecting or locating of foreign bodies in blood A61B5/06) · CPC title

• G01N33/76 Primary

  Human chorionic gonadotropin {including luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone or their receptors} · CPC title

• A61B5/7275

  Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor · CPC title

• G01N33/78

  Thyroid gland hormones {, e.g. T3, T4, TBH, TBG or their receptors} · CPC title