Re: HbA1C

[Guest guest]

The below is a pretty long and pretty technical explanation of HbA1C and how

it works from Ron. Thought at least a few people here might be interested in

reading it. Vicki

>

> What is: HbA1c?

>

> Thanks in Advance,

> Marsha

Your blood contains a host of different protein molecules. Different

chemically, I

mean. The different molecules are called fractions. One of those fractions is

named

A1c. There is also an A1a, and A1b, for example. The Hb is shorthand for

Hemoglobin. So HbA1c is simply saying this is a test of a property of the A1c

fraction in hemoglobin. That fraction happens to have an affinity for

glucose. What

they do is determine how much of that fraction is chemically bonded to

glucose.

That test is revealing because once bonded the bond persists. Red cells tend

to die

in about a month so the A1c (list shorthand for HbA1c) represents an average

of

what has been going on for several weeks. The way the A1c test reacts to a

sudden

change in average sugar level is very much like the behavior of a capacitor

being

charged through a resistor. For those who understand that, the time constant

is 10

days. For the rest it means that well over 90% of the ultimate response to a

change

in BG average is seen in one month and at 45 days it exceeds 99%. That is why

it is

pointless to schedule A1c tests closer than a month apart, regardless of what

you

think is happening.

In addition to being useful as a means of diagnosis, A1c is an excellent

predictor

of your status with respect to risk of complications. That A1c was a risk

predictor

was established with essentially the same findings in studies done in the US,

the

UK, and Japan. Taken together those tests covered both type ones and type

twos. I

have a one meg Power Point file of the British findings that I can send to

anyone

who wants to suffer a large download to see what they said in detail.

The table below shows how those risks vary over time for various A1c

categories.

While the specific table is for retinopathy severe enough to require

treatment,

there is a strong parallel with the risk of other diabetic complications. In

all,

the A1c is one of the best tests for assessment of control and of risk. It is

the

rigorous way of answering this important question about control. How good is

good

enough?

The A1c is presumed constant over the 9

years addressed in the original data and the 15 years addressed by

extrapolating along the curves that were fitted to the original data.

Each A1c trace in the family of curves was determined to be of the form

LN(Y)= a + bX where Y is the incidence of 3 step retinopathy progression

(on a 9 step evaluation scale) in a particular year and X is the year

itself. Seen on a semi log graph, each of the curves in the family is a

straight line. Rather surprisingly, the <a> coefficient in the a + bX is

a straight line, though a change in sign is needed for low A1c values.

The coefficient is described by a constant plus K*LN(A1c)/A1c, where

K is also a constant. Thus, it was possible to arrive at an expression

for A1c of 6 and of 12, even though they were not contained in the

original data. The original charts made no distinction between 1st time

occurrence and repeat occurrence. To answer the question about 1st time

risk, I had to assume that in each year, those with a history of

retinopathy were all going to have a repeat of the prior years

progression. While that is unlikely to be literally true, it is probably

close enough to true to put the calculation of 1st time risk in the ball

park. Of those with no history, it was assumed that occurrence in any

given year was random. That allowed an occurrence of 1st time problems

to be calculated for each year by subtracting the occurrence of problems

in the prior year. The growth in occurrence year to year, therefore, is

all from the group having no prior retinopathy history. The probability

of no 1st time retinopathy through a given year is the product of

(1 minus the 1st time probability in year one) times (1 minus the 1st

time probability in year two) times (1 - probability of 1st time in year

three), etc. through the year in question. That figure is then

multiplied by (1 - prior year incidence) and the result subtracted from

one.

The table contains the cumulative

probability that, at a particular A1c, there will be a sudden appearance

of retinopathy progression of three steps on the official 9 step scale

for the first time. As time

passes, that becomes ever more probable and, at the higher A1c levels,

that increase in likelihood grows more rapidly even to the point of

becoming a near certainty. In the real world, such data are not nearly

as well behaved as the family of curves that were used as the source for

this analysis. The actual data points lie above and below each line in

the curve family and the curves only represent a least squares fit to

the real data points. Since the true data is rather noisy, consider the

curves and the tables derived from them to be approximate. That will

account for exceptions to the table seen in the real world.

Nevertheless, it is undoubtedly true that for A1c, lower is better. That

for A1c of 8 or above, the long term risk is entirely unacceptable

because it becomes too high after 15 years and by my yardstick is too

high even after 8 years. A one in ten chance of having those

complications is more of a chance than I care to risk. I am a bit

biased when it comes to such matters because I once had a paralytic

disease that had one in four million odds in my favor. If you are in the

ten percent waiting for your laser eye surgery appointment, it is scant

comfort to know that the other 90% of your friends have a few years to

go yet.

I feel that an A1c of 6 is as high as I would care to carry and lower is

better. It should also be noted that there is reason to believe that

these numbers can be considerably improved by chronic use of a spectrum

of powerful antioxidants and ACE inhibitor.

In the table the top row is A1c and the left column is passage of time in

years.

The entries are

probabilities expressed in percent. Thus 100 means a 100 percent probability

and

1.25 means

that the chance of an occurrence is only 1.25 in 100, and so on.

Cumulative risk of 1st time 3 step progression of

retinopathy as a percentage

Yr/

A1c 6 7 8 9 10 11 12

2 1.25 1.28 1.72 2.58 3.16 4.54 6.22

3 1.33 1.69 3.15 4.70 7.18 11.52 16.54

4 1.41 2.09 4.11 6.69 11.26 18.14 26.82

5 1.49 2.52 5.25 9.19 16.37 27.03 40.57

6 1.58 3.05 6.64 12.30 22.68 38.53 57.67

7 1.66 3.64 8.47 16.19 30.80 52.87 76.48

8 1.76 4.14 10.42 21.22 41.07 69.14 91.33

9 1.85 4.61 12.87 27.98 53.36 85.26 100

10 1.95 5.33 15.99 35.79 67.08 96.50

11 2.04 6.24 19.37 44.57 81.10 100

12 2.15 7.14 23.44 54.86 92.6

13 2.25 8.15 28.17 66.12 100

14 2.36 9.28 33.63 77.73

15 2.47 10.53 39.85 88.69

Ron

[Guest guest]

> The A1c is presumed constant over the 9

> years addressed in the original data and

> the 15 years addressed by extrapolating

> along the curves that were fitted to the

> original data.

Not a very practical presumption, Vicki. Isn't it rather unlikely

that patients being followed would have a constant and high HbA1c

over 9 - 15 years and not do anything about it? You can't get an

HbA1c without going to a physician and there is no point in making

the test for 9 - 15 years if he/she doesn't act on it by changing the

treatment to minimize it. The long-term constant HbA1c appears to me

to be a hard nut to swallow.

> The growth in occurrence year to year, therefore,

> is all from the group having no prior retinopathy

> history.

I am not sure that I understand all that. Why is there no distinction

made between retinopathy patients that receive laser treatment and

those that don't? And between patients that have only peripheral

damage (good prognosis) and those that have both peripheral and

macula damage (not such good prognosis). No distinction made between

young and old patients, either (there are other eye problems!).

> Nevertheless, it is undoubtedly true that

> for A1c, lower is better. That for A1c of 8

> or above, the long term risk is entirely

> unacceptable because it becomes too high after

> 15 years and by my yardstick is too high even

> after 8 years. .... If you are in the

> ten percent waiting for your laser eye surgery

> appointment, it is scant comfort to know that

> the other 90% of your friends have a few years

> to go yet.

I can't believe that this kind of calculation is intended for

individual patients to make an assessment of their personal risk of

having retinopathy! Who walks about assessing the statistical risks

of something unpleasant happening, the risk of crossing the road and

getting hit by a runaway horse, the risk of having a leg amputated

and the surgeon cutting off the wrong leg, the risk of having

retinopathy if you maintain a constant HbA1c of 9% for 15 years?

Nobody does that! And no diabetic that I ever met is going to

conclude that if the risk is going to be improved from 89% to 40% by

reducing their HbA1c from 9% to 8% then it might be worth the hassle!

If people did that kind of a calculation then there wouldn't be any

overweight people in the world.

Wouldn't this kind of calculation only be used by such organizations

as health care administrations so that they can predict, for example,

how many thousand blind people they are going to have to care for in

15 years time compared with how much money they might have available

to budget for preventive care of diabetics over that period?

> I feel that an A1c of 6 is as high as I

> would care to carry and lower is better.

Surely, everybody aims for the lowest they can get, don't they? Is

there a real problem with diabetics deciding that once they have got

down to 8%, they are going to stop there and not bother going any

lower?

All the table tells you, for example, is that out of a group of 1000

diabetics with a constant HbA1c of 9%, 890 of them will have

retinopathy at the end of 15 years whereas out of another group of

1000 with constant 8%, only 400 of them will have retinopathy at the

end of that period - but unfortunately there is no way of knowing in

advance which particular individuals it will be.

So individual diabetics have really only one option: they just have

to assume that they are going to be amongst those that get

retinopathy whatever their HbA1c might be and that they therefore

have to do whatever they can to reduce their HbA1c as far as it will

safely go, regardless of the mathematical probability that the effort

might not be really necessary! In other words, you as an individual

will never know whether you are one of those that will get it before

15 years until you have actually got it, or the 15 years are up,

whichever is the sooner (if you live so long, that is).

The implied concept of diabetics backing off in their efforts to

reduce their HbA1c just because the odds that they will get

retinopathy anyway after a particular number of years are not high

enough to be worth the hassle seems rather bizarre to me.

Or have I misunderstood the whole thing?

[Guest guest]

> It wasn't me that wrote this post, ,

> it was merely a copy from another.

It was quite clear to me that you didn't write all that technical

stuff, Vicki (no offense meant)! But by reposting it here, you are

opening the subject up for discussion here, aren't you? And who are

we to address the discussion to here if not to you?

> Don't remember now, it may have been from

> Ron. Why don't you join the new list and read

> his posts yourself?

I really don't see the point of you trying so hard to get discussion

moved from this list to some other list, Vicki. If we can't discuss

the subject here then the repostings become not much more than spam,

do they?

To be fair, you would have to repost the entire discussion, not just

Ron Sebold's share of it and that would end up in chaos sooner or

later, I predict.

I am not trying to be critical but I am puzzled by this new

development. Of course we can all go and join other diabetes lists,

there are dozens of them, but I can't see the point of encouraging

cross-list postings like that nor of prompting members of this list

to migrate, sorry.

[Guest guest]

Hi, , no, I'm not trying to get people to move from this list to the new

list. There's no law that you can't be on more than one list, is there?. The

only reason is that if you have some questions for Ron it would seem more

expedient for you to address them to him directly instead of thru me. I only

post his relevant stuff here as some people asked that I do this. And of

course any time there's something interesting elsewhere it would behoove all

of us to post it here. Vicki

In a message dated 01-01-17 03:24:22 EST, you write:

<<

I really don't see the point of you trying so hard to get discussion

moved from this list to some other list, Vicki. If we can't discuss

the subject here then the repostings become not much more than spam,

do they?

To be fair, you would have to repost the entire discussion, not just

Ron Sebold's share of it and that would end up in chaos sooner or

later, I predict.

I am not trying to be critical but I am puzzled by this new

development. Of course we can all go and join other diabetes lists,

there are dozens of them, but I can't see the point of encouraging

cross-list postings like that nor of prompting members of this list

to migrate, sorry.

>>

[Guest guest]

In a message dated 01/17/2001 3:24:23 AM Eastern Standard Time,

lists@... writes:

<< I am not trying to be critical but I am puzzled by this new

development. Of course we can all go and join other diabetes lists,

there are dozens of them, but I can't see the point of encouraging

cross-list postings like that nor of prompting members of this list

to migrate, sorry. >>

The point was to be able to have the privilege of the counseling from Ron

Sebol, I believe.

He didn't want to come to this list, guess we're not technical enough for him

:-)

carol

[Guest guest]

> The only reason is that if you have some

> questions for Ron it would seem more

> expedient for you to address them to him

> directly instead of thru me.

Oh, I see, Vicki. No, I don't have any questions for him, I was just

making a comment on the content in case anybody on THIS list wanted

to discuss the subject right here!

> And of course any time there's something

> interesting elsewhere it would behoove all

> of us to post it here

Wow, I hope that doesn't get out of hand! " Elsewhere " is a big place,

Vicki. It could make the Digest Version somewhat longer!

[Guest guest]

> He didn't want to come to this list, guess

> we're not technical enough for him

Well, Carol, judging by his " technical " effort in answer to the

simple question: " What is HbA1c? " it might be better if we stay that

way! If the rest of the members of that list ask him such profound

questions, he is still going to feel out of water, even there.

[Guest guest]

Thornton wrote:

<snip>

> I am not trying to be critical but I am puzzled by this new

> development. Of course we can all go and join other diabetes lists,

> there are dozens of them, but I can't see the point of encouraging

> cross-list postings like that nor of prompting members of this list

> to migrate, sorry.

>

>

I agree! I've been a bit concerned about all the talk of cross-postings,

and promoting other lists here. I don't feel that it's prudent to do

that at all.

--

Dave - 1:05:13 PM

T2 - 8/98 Glucophage, Precose

-

Davors Daily Aphorism:

I may not be perfect, but parts of me are excellent.

--

Visit my HomePage:

http://dorcutt.homepage.com