Method for determining glucose concentration in human blood

Abstract

Measuring the impedance of a human body region at a high frequency (Z HF ) and a low frequency (Z LF ). Z HF is used to obtain the value of the volume of fluid in the tissues of the region. Z LF is used to obtain the value of the volume of extracellular fluid in the tissues. The increase in the metabolic component in the volume of extracellular fluid is determined by the increase of the volume of all of the fluid in comparison with the previous measurement, determining the increase in the volume of extracellular fluid in comparison with the previous measurement and subsequently calculating the difference between the increases in the volume of all of the fluid and the volume of extracellular fluid. The glucose concentration G(t k ) is determined by adding the amount of increase in the glucose concentration and the value of the glucose concentration determined at the previous measuring stage.

What is claimed is: 
     
         1 . A method of measuring of a concentration of blood glucose in a human, the method comprising:
 using spaced apart electrodes attached to a region of a body of the human to successively measure values of high frequency impedance and low frequency impedance of the region at predetermined time intervals;   using a measured value of the high frequency impedance to determine an estimate of a volume of fluid in tissue of the region between the electrodes;   using a measured value of the low frequency impedance to determine an estimate of a volume of an extracellular fluid in the tissue in the region between the electrodes;   determining an increment of a metabolic component of the volume of the extracellular fluid by:
 determining an increment of the estimate of the volume of the fluid relative to a previously measured value of the volume of the fluid; 
 determining an increment of the estimate of the volume of the extracellular fluid relative to a previously measured value of the volume of the extracellular fluid; 
 determining a difference between the increment of the estimate of the volume of the fluid and the increment of the estimate of the volume of the extracellular fluid; 
   determining an increment of the concentration of the blood glucose by normalizing the increment of the metabolic component of the volume of the extracellular fluid; and   determining the concentration of the blood glucose by adding up the increment of the concentration of the blood glucose and a previously determined concentration of the blood;   wherein determining a concentration of the blood glucose at a first time interval comprises adding up an increment of the concentration at the first interval of time and an initial blood glucose concentration.   
     
     
         2 . The method according to  claim 1 , wherein the initial blood glucose concentration is determined invasively. 
     
     
         3 . The method according to  claim 1 , wherein at least two spaced apart electrodes attached to the region of the body of the human are used. 
     
     
         4 . The method according to  claim 3 , wherein the at least two spaced apart electrodes are attached to the peripheral body regions as an arm or a finger. 
     
     
         5 . The method according to  claim 1 , wherein the predetermined time intervals range from 1 s to 10 min. 
     
     
         6 . The method according to  claim 1 , wherein:
 W sum  (t k ) is the volume of fluid in tissue of the region between the electrodes, determined according to the following equation:
     W   sum ( t   k )= A·L   2   /Z   HF ( t   k ), 
 wherein: L—is a distance between the two electrodes;
 Z HF (t k ) is the high frequency HF impedance measured at time t k ; 
 A—is a calibration factor determined as A=V sum ·Z HF /L 2 ; 
 wherein V sum —is a preliminary determined value of the volume of fluid in the tissue in the region between the electrodes; 
 Z HF —preliminary determined high frequency HF impedance; 
 
   W out (t k ) is the volume of the extracellular fluid in the tissue of the region, between the electrodes determined according to the following equation:
     W   out (t k )= B·L   2   /Z   LF ( t   k ), wherein 
 Z LF (t k )—is the low frequency LF impedance measured at time t k ; 
 B—is a calibration factor, calculated as B=V out ·Z LF /L 2 ; 
 wherein V out —preliminary determined volume of the extracellular fluid in region; 
 Z LF —preliminary determined low-frequency LF impedance; 
   ΔW osm (t k ) is the increment of the metabolic component determined as:
   Δ W   osm ( t   k )=[ W   sum ( t   k-1 )− W   sum ( t   k )]− K   a   [W   out ( t   k-1 )− W   out ( t   k )], wherein
 
 W sum (t k-1 ) is the volume of the fluid in the tissue measured at time t k-1 ; 
 W out (t k-1 ) is the volume of the extracellular fluid measured at time t k-1 ; 
 K a  is a factor dependent on a human hematocrit volume selected from a range from 1.2 to 2.1; 
   ΔG(t k )is the increment of the concentration of the blood glucose determined as:
   Δ G ( t   k )=Δ W   osm ( t   k )· K   E   ·K   PR   /K   g , wherein
 
 K g  is a normalizing factor ranging from 0.005 l 2 millimole −1  to 0.006 l 2 millimole −1 ; 
 K E  is a factor selected from a range of 0.23 to 0.4 before a meal intake, and selected from a range of 0.6 to 1.0 after the meal; 
 K PR  is a factor corresponding to measuring the concentration of the glucose in blood from 20 min to 45 min after the meal intake and wherein: 
 K PR =1 if ΔW osm (t k )is more than 0; and 
 K PR =−1 if ΔW osm (t k ) is less than 0.