HbA1c and Estimated Average Glucose (eAG)

Source of this information: ADA and http://www.ngsp.org/A1ceAG.asp


There is a very predictable relationship between HbA1c and AG. 
Understanding this relationship can help patients with diabetes and their health-care providers set day-to-day targets for AG based on HbA1c goals
Fasting glucose should be used with caution as a surrogate measure of AG. 
Finally, it is important to remember that HbA1c is a weighted average of glucose levels during the preceding 4 months. Unless the patient’s glucose levels are very stable month after month, quarterly measurement is needed to insure that a patient's glycemic control remains within the target range. 

How does HbA1c relate to average glucose (AG)?

In the Diabetes Control and Complications Trial or DCCT (New Engl J Med 1993;329:977-986) study of patients with Type 1 diabetes, quarterly HbA1c determinations were the principal measure of glycemic control; study subjects also performed quarterly 24-hour, 7-point capillary-blood glucose profiles. 

Blood specimens were obtained by subjects in the home setting, pre-meal, 90 minutes post-meal, and at bed-time. In an analysis of the DCCT glucose profile data (Diabetes Care 25:275-278, 2002), mean HbA1c and AG were calculated for each study subject (n= 1439). Results showed a linear relationship between HbA1c and AG 

(AG(mg/dL) = ( 35.6 x HbA1c ) - 77.3), with a Pearson correlation coefficient (r) of 0.82.

CALCULATOR: The following link will help to do the Estimated Average Glucose Calculation

http://professional.diabetes.org/GlucoseCalculator.aspx :

HbA1c (%)	eAG (mg/dL)	eAG (mmol/l)
5	97	5.4
6	126	7.0
7	154	8.6
8	183	10.2
9	212	11.8
10	240	13.4
11	269	14.9
12	298	16.5

HbA1C - The new way of measuring it - IN future!!

There have been multiple attempts in Global Standarizations and consensus statements have been issued, but very difficult to implement.
In the US we still follow HbA1c in % and eAG ( estimated average glucose) is just catching up.
US guidelines developed based on he National Glycohemoglobin Standardization Program (NGSP)
Two major measurement criteria:  International Federation of Clinical Chemistry (IFCC) units vs NGSP 

IFCC-HbA1c	DCCT- HbA1c	Mono S- HbA1c
(mmol/mol)	(%)	(%)
10	3.1	2.0
20	4.0	2.9
30	4.9	3.9
40	5.8	4.8
45	6.3	5.3
50	6.7	5.8
55	7.2	6.3
60	7.6	6.8
65	8.1	7.2
70	8.6	7.7
80	9.5	8.7
90	10.4	9.6
100	11.3	10.6

The International Diabetes Federation and American College of Endocrinology recommend HbA_1c values below 48 mmol/mol (6.5%), while American Diabetes Association recommends that the HbA_1c be below 53 mmol/mol (7.0%) for most patients.^[

2010 Consensus Statement on the Worldwide Standardization of HbA1c

The recommendations are:

1. HbA1c test results should be standardized worldwide, including the reference system and results reporting.
2. The IFCC reference system for HbA1c represents the only valid anchor to implement standardisation of the measurement.
3. HbA1c results are to be reported by clinical laboratories worldwide in SI (Système International) units (mmol/mol – no decimals) and derived NGSP units (% - one decimal), using the IFCC-NGSP master equation (DCCT units).
4. HbA1c conversion tables including both SI (IFCC) and NGSP units should be easily accessible to the diabetes community.
5. Editors of journals and other printed material are strongly recommended to require that submitted manuscripts report HbA1c in both SI (IFCC) and NGSP/DCCT units.
6. The reportable term for glycated hemoglobin is HbA1c, although other abbreviations may be used in guidelines and educational material (A1C).

History of HbA1c and what does it do?

History:
Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958.  It was first characterized as a glycoprotein by Bookchin and Gallop in 1968. Its increase in diabetes was first described in 1969 by Samuel Rahbar The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.

N-linked protein glycosylation (N-glycosylation of N-glycans) at Asn residues (Asn-x-Ser/Thr motifs) in glycoproteins.


What are Glycoproteins? 
They are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational orposttranslational modification. This process is known as glycosylation. In proteins that have segments extending extracellularly, the extracellular segments are often glycosylated. Glycoproteins are often important integral membrane proteins, where they play a role in cell–cell interactions. Glycoproteins are also formed in the cytosol, but their functions and the pathways producing these modifications in this compartment are less well understood


Why do we measure HbA1c every 3 months?

In the normal 120-day lifespan of the red blood cell, glucose molecules react with hemoglobin, forming glycosolated hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycosolated hemoglobins are much higher than in healthy people.

Once a hemoglobin molecule is glycosolated, it remains that way. A buildup of glycosolated hemoglobin within the red cell, therefore, reflects the average level of glucose to which the cell has been exposed during its life-cycle. Measuring glycosolated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA_1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather shorter period of two to four weeks.

Image source: http://adiscar-adiscar.blogspot.com

We will talk about measuring HbA1c tomorrow