Hba1C - does average apply?

[Scardoc]

I've read a couple of comments lately about how the Hba1C is an average only, ie, 7% may indicate that blood sugars have been higher but the figure is pulled down by low blood sugar levels. This is certainly a view I have always subscribed to and is the main reason I like to keep my reading in the mid 6's as opposed to lower. Believing, as I do, that 6.1% may indicate frequent episodes of low blood sugar.

However, I read recently that Hba1c is a measurement of glycated haemoglobin in red blood cells and that once glycated, haemoglobin stays glycated. Which to me indicates that episodes of low blood sugar would not reduce the amount of glycated haemoglobin in the red blood cells. So, my last Hba1c at 6.8% indicates that within the life cycle of the red blood cells tested there was sufficient glycated haemoglobin to produce a result of 6.8%.

Can anyone shed anymore light on this?

 

[zand]

Not really. Like you, I was always told it was an average but last time I saw my GP he gave me the explanation about the glycated haemoglobin. I had so many other questions on my mind I didn't think to ask him your question, I wish I had. I will next time.

 

[sally and james]

It's silly to call HbA1c an average, (although it is an easy explanation, which serves a purpose in some circumstances) because it isn't strictly that. It is a measure of the amount of glycation at the time of the test and, because blood cells live for 8 to 12 weeks, it reflects the amount of sugars which have entered the blood stream over this period. A blood cell will not un-glycate, but, if you have a period of low sugar levels, no blood cells (or very, very few) will become glycated and some glycated ones will die off, so your total level of glycation will become lower.

If this seems a bit confusing, try imagining pouring occasional and varied size jugs of water into a leaky bucket. The water level is the bucket's Hba1c!

Sally

 

[zand]

It's silly to call HbA1c an average, (although it is an easy explanation, which serves a purpose in some circumstances) because it isn't strictly that. It is a measure of the amount of glycation at the time of the test and, because blood cells live for 8 to 12 weeks, it reflects the amount of sugars which have entered the blood stream over this period. A blood cell will not un-glycate, but, if you have a period of low sugar levels, no blood cells (or very, very few) will become glycated and some glycated ones will die off, so your total level of glycation will become lower.

If this seems a bit confusing, try imagining pouring occasional and varied size jugs of water into a leaky bucket. The water level is the bucket's Hba1c!

Sally

Now that makes sense and you're right that's not an average at all is it?! Thank you.

 

[Bluetit1802]

So how low is low in this respect? If a period of low blood sugars means very few blood cells become glycated, at what level are we talking?

 

[Squire Fulwood]

I was told that the red blood cell took on an amount of glucose relative to the blood sugar level at the time of its creation and a measurement of the average amount of all red blood cells is what is used as the Hba1c.

I have also read that red blood cells have a lifetime of three months and so the average is of the sugar level for the last three months with a bias towards the last month. This brings on a problem as to how the red blood cells can read my diary to find out the date of my blood test so I decided to think about how else this bias might occur.

The only logical explanation I came up with is that the premise that red blood cells live for three months is false. I believe it likely that a spectrum of life spans exists and three months might be a very long lived blood cell. If this is true then the the total red blood cells in the body at one time probably contains a high proportion of one month old cells, a lesser proportion of two month old cells and a lowest proportion of three month old cells.

 

[Bluetit1802]

I was told that the red blood cell took on an amount of glucose relative to the blood sugar level at the time of its creation and a measurement of the average amount of all red blood cells is what is used as the Hba1c.

I have also read that red blood cells have a lifetime of three months and so the average is of the sugar level for the last three months with a bias towards the last month. This brings on a problem as to how the red blood cells can read my diary to find out the date of my blood test so I decided to think about how else this bias might occur.

The only logical explanation I came up with is that the premise that red blood cells live for three months is false. I believe it likely that a spectrum of life spans exists and three months might be a very long lived blood cell. If this is true then the the total red blood cells in the body at one time probably contains a high proportion of one month old cells, a lesser proportion of two month old cells and a lowest proportion of three month old cells.

Yes, your logical explanation is correct. Some blood cells die quicker than others, 3 months is the maximum in normal folk, and people with anaemia cannot rely on the HbA1c being accurate.

 

[SamJB]

I work in pharmacology and HbA1c is, in fact, a measure of the exposure your red blood cells have had to glucose. In the industry we shorten the word "exposure" to AUC, which stands for Area Under the Curve. It's called this because if you were to draw a line graph of blood glucose levels on the y (side) axis and time on the x (bottom) axis, then the area under that line is the Area Under the Curve and it is this that is directly related to the HbA1c measurement. Some health care professionals will tell you that it is related to your average BG, when, in fact, it's got nothing to do with it.

You are correct that once a blood cell is glycated, it cannot become un-glycated. So no matter how many lows you get, you cannot reduce the hitherto exposure of glucose. Saying that, because the HbA1c is a measure of exposure over the course of 120 days, a reduction in BGs half way through would affect the HbA1c because new red blood cells would have a reduced exposure to glucose (compared to the older cells), hence giving you a lower HbA1c.

Some countries give out an average BG, calculated from your HbA1c, when they give you the results of your HbA1c. Thankfully, we don't do that in the UK, because mathematically, an average BG and your exposure to glucose is only very loosely related.

 

[Scardoc]

I work in pharmacology and HbA1c is, in fact, a measure of the exposure your red blood cells have had to glucose. In the industry we shorten the word "exposure" to AUC, which stands for Area Under the Curve. It's called this because if you were to draw a line graph of blood glucose levels on the y (side) axis and time on the x (bottom) axis, then the area under that line is the Area Under the Curve and it is this that is directly related to the HbA1c measurement. Some health care professionals will tell you that it is related to your average BG, when, in fact, it's got nothing to do with it.

You are correct that once a blood cell is glycated, it cannot become un-glycated. So no matter how many lows you get, you cannot reduce the hitherto exposure of glucose. Saying that, because the HbA1c is a measure of exposure over the course of 120 days, a reduction in BGs half way through would affect the HbA1c because new red blood cells would have a reduced exposure to glucose (compared to the older cells), hence giving you a lower HbA1c.

Some countries give out an average BG, calculated from your HbA1c, when they give you the results of your HbA1c. Thankfully, we don't do that in the UK, because mathematically, an average BG and your exposure to glucose is only very loosely related.

Now, to the second point. If we take your Hba1c at 6.1% as an example: my Doc would say "that's too low, it indicates frequent periods of low blood sugar and hypo's". However, could that not be translated into - it indicates that in the last 3 months, and especially the last 4-6 weeks, your haemoglobin has not been exposed to prolonged periods of high BG levels? With no suggestion of BG levels ever being too low?

I am in a potentially good position at present in that I only attend the hospital for a check up once a year - but I only agreed to this as long as I got to submit blood for an Hba1c every 3mths. I should, therefor, get a pretty good picture of how variable my BG levels really are. I will most definitely quiz a Doc on this at the next opportunity.

 

[sally and james]

@Scardoc wrote, "If we take your Hba1c at 6.1% as an example: my Doc would say "that's too low,"
I think doctors say this because it is assumed that a diabetics blood sugar will be up and down like a yo-yo, so to get an overall glucose exposure of 6.1%, must mean lots of periods when sugar exposure is very low, ie. hypos, or very close to hypo. As many of us know, by eating an appropriate diet, it's possible to keep sugar levels much more steady, unfortunately, only some HCP's seem to know this.
Sally

 

[Scardoc]

Scientific question - what constitutes a prolonged period of exposure to high BG levels? You could say that a Hba1c of 6.1% represents a consistently low, almost normal BG level with some prolonged periods of exposure to high BG levels which you would expect in a diabetic.

So what kind of exposure to high BG levels would cause glycated haemoglobin? 2 hours? 6 hours?

I am coming from this at a completely ignorant angle so genuinely have no idea. Let's say my Hba1c was running nicely at 6.0% and three days before the blood test I had high bloods, struggling to keep them under 8. I've got 8 weeks worth of "good" red blood cells in there but what impact would 3 days "bad" cells have? 6.2%? 6.6%? Or virtually none at all?

Interesting.

 

[phoenix]

This is a model of a haemoglobin molecule that may help visualise it The blue blobs represent glucose bonded to it and the light blue blobs floating around represent glucose in the plasma. Once the glucose has attached then, as has been said it ,stays there for cell's lifetime.

Picture from youtube Glycated Haemoglobin A1c Protein Model Casey Steffen
The one thing I am not sure about is the rate of glycation. There is an article here that suggests it happens slowly so short term variations may not effect it. http://www.diabetesincontrol.com/articles/64-feature-writer-article/1695-
We are also individual in the rate that we glycate haemoglobin so two people with the same HbA1c can have had very different average glucose levels. The age of the average blood cell in the blood varies between individuals ( the range has been found to be 38-59 days in non diabetics and 39-56 days in people with diabetes. This range alone accounts for a variation in HbA1c for any given average glucose level. Apparently if someone with a typical red blood cell life had a HbA1c of 8%, someone with the same average glucose level who had short lived(but still normal) red blood cells would have an HbA1c of only 6.4%. The person who had very long lived blood cells could have an HbA1c of 9.6%.
http://dst.sagepub.com/content/3/4/635.full.pdf html
(one reason why it is important to look at the trends in our own HbA1cs but not always right to compare it with another persons.)

 

[Squire Fulwood]

So what kind of exposure to high BG levels would cause glycated haemoglobin? 2 hours? 6 hours?.

According to my limited understanding haemoglobin is not only glycated during periods of high blood sugar but every red cell takes on glucose in proportion to the blood glucose level at the time of its creation.

All red blood cells will contribute to the Hba1c reading but the three month old cells will be under-represented due to the fact that lots of them (more than one third) have already died off on the day of your blood test. Any high of a more recent nature will contribute more since there is a higher proportion of young cells than of old cells.

It is not a good idea to have a "bad" bout within the period running up to your test.

 

[lessci]

Going off at a slight tangent, is this how Forgixa works, by stopping the Glycation?

 

[sally and james]

Er, no.
Quoting from this site, http://www.ema.europa.eu/ema/index....2/human_med_001546.jsp&mid=WC0b01ac058001d124
It works by,
The active substance in Forxiga, dapagliflozin, works by blocking a protein in the kidneys called sodium‑glucose co‑transporter 2 (SGLT2). SGLT2 is a protein that absorbs glucose from the urine into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, Forxiga causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood.
Any the wiser? Not me!
Sally

 

[phoenix]

Transporters are used for some molecules to pass through a cell membrane into and out of a cell. Sodium glucose transporters are co transporters. The glucose 'piggybacks' with the sodium . (don't know if this helps explain what is happening
http://en.wikipedia.org/wiki/Active_transport#Symport
These particular co transporters occur in the kidney (and in the intestine) In the kidneys, they are there to reabsorb glucose enabling it to be returned to the circulation and be used rather than being excreted out into the urine ie it is an energy saving mechanism stopping the loss of glucose.
If you have too much glucose in the system then you may not want to reabsorb it.
. If the transporter is blocked then some of the excess glucose will excreted rather than put to reuse. ( ?? presumably some sodium will also be excreted which should be beneficial if you have high blood pressure)

 

[phoenix]

According to this increased life (p16) http://www.who.int/diabetes/publications/report-hba1c_2011.pdf

 

[Squire Fulwood]

Er, no.
Quoting from this site, http://www.ema.europa.eu/ema/index....2/human_med_001546.jsp&mid=WC0b01ac058001d124
It works by,
The active substance in Forxiga, dapagliflozin, works by blocking a protein in the kidneys called sodium‑glucose co‑transporter 2 (SGLT2). SGLT2 is a protein that absorbs glucose from the urine into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, Forxiga causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood.
Any the wiser? Not me!
Sally

You see, you learn something new every day. I got used to the liver contributing sugar and now I have kidneys taking the pee. No wonder my sugar levels go up.

 

[Kat100]

So I would love some simple for me feedback ...

My last two hba1c numbers were 5.7 % old money ...over 18 % 18 months ago ....
Is this ok ....

My dietitein wishes her hba1c numbers were as low as mine ....am I doing something right ....it all gets very confusing ....Thank you ...Kat

 

[noblehead]

So I would love some simple for me feedback ...

My last two hba1c numbers were 5.7 % old money ...over 18 % 18 months ago ....
Is this ok ....

My dietitein wishes her hba1c numbers were as low as mine ....am I doing something right ....it all gets very confusing ....Thank you ...Kat

They look great Hba1c's Kat, what's do you mean by ''18% 18 months.''

TBH I think that everyday bg control is more important than the Hba1c figure, that is why having access to a bg meter and strips is crucial for all diabetics.