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HbA1c represents a 4 week average?

R

reidpj

Well-Known Member
Hi

It would seem (from this study) that, contary to the normally state the 90-120 day average, the HbA1c test is 'an exponentially weighted average of blood glucose levels from the preceding 4 weeks, with the most recent 2 weeks being by far the most important'. And that conversion of hemoglobin A to HbA1c is actually reversible :eh:

http://www.faqs.org/faqs/diabetes/faq/p ... on-11.html

Anyone heard anything similar?
 
Red blood cells last on average 3 months, new cells are being added all the time. There will be more newer blood cells than the oldest ones so HbA1c is weighted towards more recent levels. 4 week average??? don't know
Initially glycation is reversible but this is a temporary state.
It does appear that some people are high glycators some lower glycators, This is why 2 people who have similar averages can have very different HbA1cs.

This study from 2009, found that low glycators,ie those with lower HbA1cs than their average glucose levels would suggest, had higher levels of labile A1c (ie glycated haemoglobin that is still reversible)
They say
http://care.diabetesjournals.org/content/33/2/273.full

No-one seems to know just what causes people to be high or low glycators (biological variation?) but it may influence outcomes.

edited, put in some punctuation!
.
 
As Phoenix says, HbA1c reaches a steady state in 4 to 12 weeks depending on if you are a high or low glycator.

This means that HbA1c is most useful when comparing against your own previous control, than other peoples (who might glycate differently than you).

I really like this review of the science behind HbA1c, its history and its practical use:
http://professional.diabetes.org/Content/Editorial.pdf
It's not too technical and very readable.
 
phoenix said:
Red blood cells last on average 3 months, new cells are being added all the time. There will be more newer blood cells than the oldest ones so HbA1c is weighted towards more recent levels.
Click to expand...

That was my understanding of an HbA1c result as well, made up of 70% preceding 4 weeks, 20% the 4 weeks prior to that and lastly 10% being the latter 4 weeks of a 12 week period.

Hope that added up to 100%
 
Annual HBA1Cs won't be a great deal of use then. Or 6monthly either. I have 3 monthly HBA!cs bu have always felt that monthly would make more sense.

It seems almos immoral to tell people that an annual HBA1C is sufficient and to discourage them or fail o inform them about self testing.
 
Hi All

"The longer estimate [3-4 months] is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured". See below:


Charly Coughran
ccoughran@DELETE-TO-RESPOND-UCSD.EDU

Subject: What's HbA1c and what's it mean?

Hb = hemoglobin, the compound in the red blood cells that transports oxygen. Hemoglobin occurs in several variants; the one which composes about 90% of the total is known as hemoglobin A. A1c is a specific subtype of hemoglobin A. The 1 is actually a subscript to the A, and the c is a subscript to the 1. "Hemoglobin" is also spelled "haemoglobin", depending on your geographic allegiance.

Glucose binds slowly to hemoglobin A, forming the A1c subtype. The reverse reaction, or decomposition, proceeds relatively slowly, so any buildup persists for roughly 4 weeks. Because of the reverse reaction, the actual HbA1c level is strongly weighted toward the present. Some of the HbA1c is also removed when erythrocytes (red blood cells) are recycled after their normal lifetime of about 90-120 days. These factors combine so that the HbA1c level represents the average bGlevel of approximately the past 4 weeks, strongly weighted toward the most recent 2 weeks. It is almost entirely insensitive to bG levels more than 4 weeks previous.

In non-diabetic persons, the formation, decomposition and destruction of HbA1c reach a steady state with about 3.0% to 6.5% of the hemoglobin being the A1c subtype. Most diabetic individuals have a higher average bG level than non-diabetics, resulting in a higher HbA1c level. The actual HbA1c level can be used as an indicator of the average recent bG level. This in turn indicates the possible level of glycation damage to tissues, and thus of diabetic complications, if continued for years.

Interpreting HbA1c values can be tricky for several reasons. See the
following section for more details.


Subject: Why is interpreting HbA1c values tricky?

Interpreting HbA1c values is tricky for several reasons: differing lab measurements, variation among individuals, and misapprehension of the relevant timeframe.

First trick: several different lab measurements have been introduced since 1980, measuring slightly different subtypes with different
limits for normal values and thus different interpretive scales.

A National Glycohemoglobin Standardization Program began in 1996, sponsored by the American Diabetes Association and others. See reference 1. This program certifies HbA1c assays which conform to the method used in the DCCT. However, as of 1998 other versions are still in use in many places, both in the US and elsewhere. When you get a lab result, be sure to look at what the lab considers to be the normal range. Most discussion of HbA1c values in m.h.d appears to be based on the DCCT, where the normal range is approximately 3.0-6.1%. Caveat lector. (See part 5, Research, of this FAQ for more information on the DCCT, the Diabetes Control and Complications Trial.)

Second trick: HbA1c levels appear to vary by up to 1.0% among individuals with the same average bG. See reference 2.

This is very recent research and its implications are not yet clear. The actual reaction rates governing the formation of HbA1c may vary among individuals. Some of the variation may be due to differences in erythrocyte (red blood cell) survival times -- the rough 90-120 day range noted earlier -- although other work limits this to a small part of the total variation (see reference 5). Variations in the HbA1c formation rate may or may not correlate with the rate of damage to other tissues.

While we await further research, we can only say that differences of 1.0% from one individual to another may not be meaningful.

Although HbA1c varies among individuals with the same average bG, it is very stable for any given individual. Thus a change of 1.0% in your own HbA1c is definitely meaningful.

Third and final trick: most medical professionals have been given incorrect information about the timeframe which HbA1c represents. Even textbooks normally state the 90-120 day average, as does the American Diabetes Association in its Position Statement on Tests of Glycemia in Diabetes (see reference 1).

The longer estimate is based on the assumption that the conversion of hemoglobin A to HbA1c is essentially irreversible. This was a reasonable assumption before the reaction rates were actually measured. See the following section for information about the research which measured the reaction rates and simulated the consequences.

See the following section for the references mentioned above.



Subject: Who determined the HbA1c reaction rates and the consequences?

In the early 1980s, Henrik Mortensen and colleagues at Glostrup University Hospital, in Denmark, measured the reaction rates in vitro. Their results showed the assumption of irreversibility to be untrue. In fact the reverse reaction (HbA1c to HbA and glucose) proceeds at about 1/8 the rate of the forward reaction, which is very far from irreversible. Mortensen et alia also built a biokinetic model based on the measurements, and validated the model by comparing its predictions to actual patients. See references 3-5.

Among other things, Mortensen's work shows that after a change in average bG level, the HbA1c level restabilizes after about 4 weeks. This has several consequences. Clinically, the most important are these:

First, the HbA1c is an exponentially weighted average of blood glucose levels from the preceding 4 weeks, with the most recent 2 weeks being by far the most important.

Second, measuring HbA1c less often than monthly results in unmonitored gaps between measurements. To use HbA1c as a continuous monitoring tool, you need to check it at least once a month.

Third, it is worthwhile checking the HbA1c of newly diagnosed patients as often as once a week to determine the effectiveness of the newly imposed treatment.

Reference 1: American Diabetes Association, Tests of Glycemia in Diabetes, Diabetes Care 23:S80-S82, January 2000 Supplement 1. This specific issue is no longer available online, but the most recent version is available at http://diabetes.org/cpr/.

Reference 2: Kilpatrick ES, Maylor PW, Keevil BG: Biological Variation of Glycated Hemoglobin. Diabetes Care 21:261-264, February 1998. Abstract available on the web at http://care.diabetesjournals.org/cgi...tract/21/2/261.

Reference 3: Mortensen HB, Christophersen C: Glucosylation of human haemoglobin a in red blood cells studied in vitro. Kinetics of the formation and dissociation of haemoglobin A1c. Clinica Chimica Acta 134:317-326, 15 November 1983.

Reference 4: Mortensen HB, Volund A, Christophersen C: Glucosylation of human haemoglobin A. Dynamic variation in HbA1c described by a biokinetic model. Clinica Chimica Acta 136:75-81, 16 January 1984.

Reference 5: Mortensen HB, Volund A: Application of a biokinetic model for prediction and assessment of glycated haemoglobins in diabetic patients. Scandinavian Journal of Clinical and Laboratory Investigation 48:595-602, October 1988.
 

Interesting and worrying. Who's going to tell this lot.

Diabetes UK:- The HbA1c test measures diabetes management over two to three months.

Diabetes.co.uk: - Because red blood cells in the human body survive for 8-12 weeks before renewal, measuring glycated haemoglobin (or HbA1c) can be used to reflect average blood glucose levels over that duration, providing a useful longer-term gauge of blood glucose control.

NHS:- The HbA1c test gives your average blood glucose levels over the previous two to three months.

Wikipedia:- This serves as a marker for average blood glucose levels over the previous 3 months prior to the measurement as this is the half life of red blood cells.

Abbot Diabetes Care:- This test is usually done on a sample of blood taken from a vein in your arm and the result shows your overall control of glucose levels over the last 2-3 months.

I try to get more than one opinion on anything that the net spews up, I wouldn't always trust Wikipedia, but enough people have the opportunity to edit it, so I've included them.

I've also noticed that Mortensen's findings were based on blood "in vitro", I wonder if it's the same in a person.
Also this work was done in the 1980s, I'm surprised that it's not better known.
The statement "To use HbA1c as a continuous monitoring tool, you need to check it at least once a month". is probably true if there is no other monitoring going on.
Innovations in Participatory Medicine: The Advent of Do-It-Yourself Blood Glucose Monitoring by Jeanna Frost PhD suggests that self monitoring was only really taken up in the 80's, although machines had been around for 20 years or so.
Maybe this bit of research is just a bit too out of date to worry about.
 
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I wouldn't worry about it. It's another slightly inaccurate measure that gives you some indication of how well you are managed your condition in the past.

The reality is that Hba1C is really a measuring stick for the clinical profession. As a T1 (and I can't speak to T2s here, but the same holds true) you know how your management is going by virtue of the fact that you measure (or should measure) multiple times everyday and have instant feedback on what your glucose is now.

If you are doing the recommended pre- and post-prandial measures + the occasional overnights, you'll also know whether you are spiking. It is your monitoring which really drives the indication of how well you are controlled and not the Hba1C.

If an Hba1C is really an assessment of the past month, it's likely to be a reflection of how every month before that has been handled too, i.e. a high Hba1C one month is unlikely to be different to one four months prior. As such it provides some level of insight.

Having said all that, the Hba1C being a month or three months is also a bit irrelevant. It shows how well a period prior to the test was managed. Just because it doesn't represent what we thought it did makes very little difference, and as the Hba1C tests are now dirt cheap and can be done within 15 mins, I see no reason to not do them more frequently if this is required.
 
so until we get a true weighted average of the damage high b.g. can cause over time it is merely an indicator.
it leads one to be sceptical of the hard and fast 42 and 48 thresholds!
It also commends R.H. and says nothing about the problems of low b.g.
 

I'd put it another way. We have a lot of evidence that an Hba1C below 40 results in little damage, and similarly that Hba1Cs above 50 result in damage. As a result, we know that elevated Hba1C is an inidcator of damage.

We also know that swinging highs and lows are the major cause of retinopathy and that any swinging high in a T2 is a cause of Hyperinsulinemia, which leads to other issues such as Atherosclerosis and non-alcoholic fatty liver disease.

Therefore, given what we do know, it seems to me that it is worth keeping your Hba1C and blood glucose levels within what is considered normal, given the very real issues that are already identified.
 

Hi Tim,
Yes its an indicator but use of one's own meter is an absolute necessity.
After dieting my HbA1c has been 45 consistently but I had hypos and my GGT is c.100.
I am screwing back on carbs and stopping the hypos but time will tell if my HbA1c comes down to 40 and better still my GGT goes back to 35, where it was three years ago before I went on Warfarin.
regards
 
Some very interesting reading on this thread. My last Hb test was done at the end of July and it was 34 but in August I found it really hard to stay on track and in the first 2 weeks of September I ate quite a lot of baked goods ect as my daughter was bringing them home from her course but for the last 2 weeks I have been religiously eating less than 20gr carbs per day. I had to go to my GP today and one of the blood tests done was an Hb test so it will be interesting to see what the result is in comparison to 2 months ago given the fact that for half of the month I ate **** and the other half I have eaten well.
 
I had read some stuff about the weighting of a1c's before and I will be interested to see what mine is next week, I started low carb around 6-8 weeks ago (was a gradual start) and my 90 day average on libre is 8.2 but my 30 day average is 6.7, so it will be interesting to see what my actual a1c comes out at! I'm kind of hoping it is more the last month of so as I have a chance then of a personal best!
 
I think HbAc1 is a poor way to measure other blood sugar abnormalities. Infact it may miss diabetics and almost all those that have acute hyperglycemia i.e above 11.1mmol/L and acute hypoglycemia i.e 3.5mmol/L.

It is essential that the extended OGTT remains as the gold standard for the diagnosis of diabetes and blood sugar disregulation. See comment under reactive hypoglycemia.

Sent from the Diabetes Forum App

Edited by a moderator to remove medical opinions.
 
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They sound like a horrific shock to the system. Couldn't one just test levels before and at regular levels after eating?
 
LucySW said:
They sound like a horrific shock to the system. Couldn't one just test levels before and at regular levels after eating?
Click to expand...

I've restarted my testing regime (after a rather long lapse) and I'm looking at the average BG readings I'm getting. It'll be interesting to see how the results of my next blood test compare to the HbA1c from using the calculator at: http://www.diabetes.co.uk/hba1c-to-blood-sugar-level-converter.html

I appreciate that the average of my tests aren't going to be a truly accurate measure of my average BG leveIs, but I used them in 2014 and they corresponded quite well to the results from the GP.
 
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