Method for analyzing the glycation of hemoglobin

• US 5,384,239 A
• Filed: 01/21/1993
• Issued: 01/24/1995
• Est. Priority Date: 04/08/1991
• Status: Expired due to Term

• Current Assignee: Chronomed Incorporated
• Original Assignee: Chronomed Incorporated
• Inventors: Saunders, Alexander
• Primary Examiner(s): Robinson, Douglas W.
• Assistant Examiner(s): SAUCIER, SANDRA E
• Application Number:
  US08/007,025
• Time in Patent Office: 733 Days
• Field of Search: 435/4, 435/14, 435/2, 436/67
• US Class Current: 435/2
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/723 Glycosylated haemoglobin

Abstract

As red blood cells age, their hemoglobin is progressively glycosylated. This invention relates to analyzing the history of blood sugar metabolism over a period of several months by taking a blood sample, separating the cells into age-ordered cohorts, determining glycohemoglobin levels in the cells of each cohort, and correlating glycohemoglobin levels with red blood cell age, while correcting for the reversibility of the Amadori rearrangement.

Claims

1. A method of determining an individual history of blood sugar control which comprises:

(a) taking a sample of red blood cells from the individual, wherein over the life of the red blood cells hemoglobin has been glycosylated to form a glycohemolobin, said reaction being an Amadori rearrangement, which is slowly reversible;

(b) separating the red blood cells according to age into a plurality of cohorts, and determining the average age of the red blood cells in each cohort, the average age differing from cohort-to-cohort;

(c) measuring the average glycohemoglobin levels of said red blood cells on a cohort-by-cohort basis, and correlating said average glycohemoglobin level with said average age for each cohort, while correcting for the reversibility of the Amadori rearrangement, so as to obtain a history of the individual'"'"'s blood sugar levels over the lifespan of said red blood cells; and

(d) examining said history for trends indicative of changes in blood sugar control;

wherein the correction is made by applying a transform of the form ##EQU2## where y is the untransformed mean glycohemoglobin level for the cohort, a and b are constants, e is the base of the natural logarithm and t is time.

2. The method of claim 1 wherein the sample is separated into between 8 and 20 age cohorts.

3. The method of claim 1 wherein the mean pyruvate kinase level is determined for each cohort.

4. The method of claim 1 wherein the Amadori rearrangement results in the formation of an adduct of hemoglobin with a sugar selected from the group consisting of fructosamine, 5-deoxy-xylulose-1-phosphate, galactulose and fructose-6-phosphate and the level of said adduct in the sampled red blood cells is determined on a cohort-by-cohort basis.