Lab Tests

This useful link was posted on the ADA forum by a member who
is also a lab tech:

http://www.ascls.org/labtesting/

She notede that it is the web-site for the American Society
for Clinical Laboratory Science(ASCLS). At the bottom of the
page there is a link to submit questions to a laboratory
professional.


Cheers, Alan, T2, Australia.
d&e, metformin 1500mg, ezetrol 10mg
Everything in Moderation - Except Laughter.
--
http://loraldiabetes.blogspot.com/
http://loraltravel.blogspot.com/
latest: Athens and The Adriatic

On Fri, 04 May 2007 03:54:37 GMT, Alan S
<loralgtweightandcarbs@gmail.com> wrote:

>This useful link was posted on the ADA forum by a member who
>is also a lab tech:
>
>http://www.ascls.org/labtesting/
>

This part is intriguing:

"WHAT ARE NORMAL VALUES?

Reference ranges used to be called normal ranges. They reflect the
results expected for 95% of your neighbors. These cannot be national
in scope or even by state but must be developed by the clinical
laboratory scientists in your local laboratory. This is due to the
fact that they are affected by the type of instrument and reagents
used, the principle or method for the test that is being performed and
the type of population being served."

!!!

I had heard before that each lab's reference range was different due
to different testing methods. I had never heard that it varied with
local populations.

So, say there is a lab located the part of Arizona which is populated
by Pima Indians. 95% of the Pima population there is obese, and more
than half have T2 diabetes. Since the "normal" or reference range is
based on "the results expected for 95% of your neighbors" (more than
half of whom would be diabetic if your neighbors are all Pima), does
that mean that you could get an A1c of, say, 10 -- but the "reference
range" could be something like "8-12", so you'd think you were
perfectly normal?

Or am I missing something really basic here? Sorry for being dim, if
that's the case.

--bittersweet

"bittersweet" <bittersweet@spamless.invalid> wrote in message
news:t0im33dnt6596gc0rtajicjpgim86d7l25@4ax.com...
> On Fri, 04 May 2007 03:54:37 GMT, Alan S
> <loralgtweightandcarbs@gmail.com> wrote:
>
>>This useful link was posted on the ADA forum by a member who
>>is also a lab tech:
>>
>>http://www.ascls.org/labtesting/
>>
>
> This part is intriguing:
>
> "WHAT ARE NORMAL VALUES?
>
> Reference ranges used to be called normal ranges. They reflect the
> results expected for 95% of your neighbors. These cannot be national
> in scope or even by state but must be developed by the clinical
> laboratory scientists in your local laboratory. This is due to the
> fact that they are affected by the type of instrument and reagents
> used, the principle or method for the test that is being performed and
> the type of population being served."
>
> !!!
>
> I had heard before that each lab's reference range was different due
> to different testing methods. I had never heard that it varied with
> local populations.
>
> So, say there is a lab located the part of Arizona which is populated
> by Pima Indians. 95% of the Pima population there is obese, and more
> than half have T2 diabetes. Since the "normal" or reference range is
> based on "the results expected for 95% of your neighbors" (more than
> half of whom would be diabetic if your neighbors are all Pima), does
> that mean that you could get an A1c of, say, 10 -- but the "reference
> range" could be something like "8-12", so you'd think you were
> perfectly normal?
>
> Or am I missing something really basic here? Sorry for being dim, if
> that's the case.
>
Does seem strange. Could be useful though. If you want some tests done -
say for insurance purposes - go and have them done in a retirement village
rather than in a town full of healthy young things.

It can't be that easy though. I bet the insurance companies use national
standard reference values. Anyone know?

bittersweet <bittersweet@spamless.invalid> wrote in part:

>On Fri, 04 May 2007 03:54:37 GMT, Alan S
><loralgtweightandcarbs@gmail.com> wrote:
>
>>This useful link was posted on the ADA forum by a member who
>>is also a lab tech:
>>
>>http://www.ascls.org/labtesting/
>>
>
>This part is intriguing:
>
>"WHAT ARE NORMAL VALUES?
>
>Reference ranges used to be called normal ranges. They reflect the
>results expected for 95% of your neighbors. These cannot be national
>in scope or even by state but must be developed by the clinical
>laboratory scientists in your local laboratory. This is due to the
>fact that they are affected by the type of instrument and reagents
>used, the principle or method for the test that is being performed and
>the type of population being served."
>
>!!!
>
>I had heard before that each lab's reference range was different due
>to different testing methods. I had never heard that it varied with
>local populations.
>
>So, say there is a lab located the part of Arizona which is populated
>by Pima Indians. 95% of the Pima population there is obese, and more
>than half have T2 diabetes. Since the "normal" or reference range is
>based on "the results expected for 95% of your neighbors" (more than
>half of whom would be diabetic if your neighbors are all Pima), does
>that mean that you could get an A1c of, say, 10 -- but the "reference
>range" could be something like "8-12", so you'd think you were
>perfectly normal?
>
>Or am I missing something really basic here? Sorry for being dim, if
>that's the case.
>
>--bittersweet

Most labs use the data they obtain from very large populations over the
large geographical areas in which they operate.

Nevertheless, when a large part of the population is affected by some sort
of change, that changed result will come to be considered within the
reference range. There is some ongoing discussion about this sort of thing
re children's weights in the US. Children who are even well within the
reference range for BMI may be obese by other measures based on less recent
historical data.
--
Jim Chinnis Warrenton, Virginia, USA

On May 4, 7:58 am, bittersweet <bittersw...@spamless.invalid> wrote:
> On Fri, 04 May 2007 03:54:37 GMT, Alan S
>
> <loralgtweightandca...@gmail.com> wrote:
> >This useful link was posted on the ADA forum by a member who
> >is also a lab tech:
>
> >http://www.ascls.org/labtesting/
>
> This part is intriguing:
>
> "WHAT ARE NORMAL VALUES?
>
> Reference ranges used to be called normal ranges. They reflect the
> results expected for 95% of your neighbors. These cannot be national
> in scope or even by state but must be developed by the clinical
> laboratory scientists in your local laboratory. This is due to the
> fact that they are affected by the type of instrument and reagents
> used, the principle or method for the test that is being performed and
> the type of population being served."
>
> !!!
>
> I had heard before that each lab's reference range was different due
> to different testing methods. I had never heard that it varied with
> local populations.
>
> So, say there is a lab located the part of Arizona which is populated
> by Pima Indians. 95% of the Pima population there is obese, and more
> than half have T2 diabetes. Since the "normal" or reference range is
> based on "the results expected for 95% of your neighbors" (more than
> half of whom would be diabetic if your neighbors are all Pima), does
> that mean that you could get an A1c of, say, 10 -- but the "reference
> range" could be something like "8-12", so you'd think you were
> perfectly normal?
>
> Or am I missing something really basic here? Sorry for being dim, if
> that's the case.
>
> --bittersweet

While historically the reference ranges were determined by running
tests on thousands of apparently healthy individuals and using all of
the values that fell within 2 standard deviations of the mean--95% of
the values--today instrumentation and science plays a much larger
role. Science has found that "apparently healthy" individuals are not
always that healthy. Take cholesterol for example. When I was a new
lab tech back in 1985, normal ranges for cholesterol were based on
populations of "apparently healthy individuals". The normal ranges
were defined by age and gender. There were actually three groups,
divided by age, of normal ranges for cholesterol for each gender.
Higher total cholesterol was considered "normal" in older
individuals. While I no longer remember these "normal values", I do
remember that among them was a reference range for a woman over 65
that said her total cholesterol would be considered normal at 300 mg/
dl. (However, I'm not sure those ranges were entirely incorrect given
what we know now about HDL, and the fact that many older women have
HDLs in the 70+ mg/dl range--but that's a topic for another day). So
our scientific knowledge now plays a role in determining normal range
as well.

Best regards,
Michelle C., T2
diet & exercise

In article <2kim33h3ffse2drafnckpoq0kpoarf9c7r@4ax.com>, bittersweet
<bittersweet@spamless.invalid> wrote:

> On Fri, 04 May 2007 03:54:37 GMT, Alan S
> <loralgtweightandcarbs@gmail.com> wrote:
>
> >This useful link was posted on the ADA forum by a member who
> >is also a lab tech:
> >
> >http://www.ascls.org/labtesting/
> >
>
> This part is intriguing:
>
> "WHAT ARE NORMAL VALUES?
>
> Reference ranges used to be called normal ranges. They reflect the
> results expected for 95% of your neighbors. These cannot be national
> in scope or even by state but must be developed by the clinical
> laboratory scientists in your local laboratory. This is due to the
> fact that they are affected by the type of instrument and reagents
> used, the principle or method for the test that is being performed and
> the type of population being served."
>
> !!!
>
> I had heard before that each lab's reference range was different due
> to different testing methods. I had never heard that it varied with
> local populations.
>
> So, say there is a lab located the part of Arizona which is populated
> by Pima Indians. 95% of the Pima population there is obese, and more
> than half have T2 diabetes. Since the "normal" or reference range is
> based on "the results expected for 95% of your neighbors" (more than
> half of whom would be diabetic if your neighbors are all Pima), does
> that mean that you could get an A1c of, say, 10 -- but the "reference
> range" could be something like "8-12", so you'd think you were
> perfectly normal?
>
> Or am I missing something really basic here? Sorry for being dim, if
> that's the case.
>
> --bittersweet

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Some labs use the reference ranges from this famous book:
"Tietz Textbook of Clinical Chemistry"
It's my guess that insurance companies use the reference ranges from that
book and ignore any reference ranges from labs.
I once compared the reference ranges from one of my blood tests to the
reference ranges mentioned in a "Laboratory Test Handbook." The reference
ranges on my blood test were identical to the reference ranges in that
handbook.
Some labs do establish their own special reference ranges.
jason
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

Bittersweet,

The lab normals are generated by using patients who are free of any disease.

So you don't use people with DM to create a normal range for your HbA1c
assay, and you don't use people with hepatitis to determine the normal range
for liver tests.

The normal range does vary from instrument to instrument, and to a lesser
extent from place to place. All labs in the US participate in proficiency
surveys, even the smaller doctors office labs. We are graded against all the
other labs using the same make and model equipment for each test.

One test that shows significant variation according to which manufacturer is
the TSH. We use a DPC (now Siemens) Immulite 2000. The results from the
Immulite are typically higher than the same sample run on an Abbott
Architect for instance.

http://www.clinchem.org/cgi/content/full/50/12/2338

Most patients will have no ability to know that the Immulite runs higher,
but they will be able to see how their result compares against our lab
normals because they are set to match our particular instrument. If we
decide in the future to run TSH tests on an Abbott Architect instead, we
will change the lab normal range to accomodate that fact.

BTW, the HbA1c test has been transformed from one of the most poorly
standardized tests to one of the most well standardized tests in only a
matter of years. The NGSP people have done a great service to us all in
getting most of the manufacturers to be calibrated to the same standards.

Most of the other lab assays are NOT as well standardized, thus you need to
know the local normal range.

William C Biggs MD FACE




"bittersweet" <bittersweet@spamless.invalid> wrote in message
news:2kim33h3ffse2drafnckpoq0kpoarf9c7r@4ax.com...
> On Fri, 04 May 2007 03:54:37 GMT, Alan S
> <loralgtweightandcarbs@gmail.com> wrote:
>
>>This useful link was posted on the ADA forum by a member who
>>is also a lab tech:
>>
>>http://www.ascls.org/labtesting/
>>
>
> This part is intriguing:
>
> "WHAT ARE NORMAL VALUES?
>
> Reference ranges used to be called normal ranges. They reflect the
> results expected for 95% of your neighbors. These cannot be national
> in scope or even by state but must be developed by the clinical
> laboratory scientists in your local laboratory. This is due to the
> fact that they are affected by the type of instrument and reagents
> used, the principle or method for the test that is being performed and
> the type of population being served."
>
> !!!
>
> I had heard before that each lab's reference range was different due
> to different testing methods. I had never heard that it varied with
> local populations.
>
> So, say there is a lab located the part of Arizona which is populated
> by Pima Indians. 95% of the Pima population there is obese, and more
> than half have T2 diabetes. Since the "normal" or reference range is
> based on "the results expected for 95% of your neighbors" (more than
> half of whom would be diabetic if your neighbors are all Pima), does
> that mean that you could get an A1c of, say, 10 -- but the "reference
> range" could be something like "8-12", so you'd think you were
> perfectly normal?
>
> Or am I missing something really basic here? Sorry for being dim, if
> that's the case.
>
> --bittersweet

"William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in message
news:IWR0i.153729$2Q1.8689@newsfe16.lga...
> Bittersweet,
>
> The lab normals are generated by using patients who are free of any
> disease.
>
> So you don't use people with DM to create a normal range for your HbA1c
> assay, and you don't use people with hepatitis to determine the normal
> range for liver tests.
>

This still seems a bit circular. I assume that when calibrating lab
normals for HbA1c you exclude anyone who's already carrying a DM diagnosis,
but your sample must/may include a few who are diabetic but who haven't been
diagnosed and whose results go into the determination of the upper limit.
Because they're likely to have much higher readings than most others even if
they're few in number they may have a disproportionate effect on the upper
limit of normal. I imagine/hope there are statisticians who've thought
that through and compensated for it.

x-no-archive: yes

Peter wrote:

> This still seems a bit circular. I assume that when calibrating lab
> normals for HbA1c you exclude anyone who's already carrying a DM diagnosis,
> but your sample must/may include a few who are diabetic but who haven't been
> diagnosed and whose results go into the determination of the upper limit.
> Because they're likely to have much higher readings than most others even if
> they're few in number they may have a disproportionate effect on the upper
> limit of normal. I imagine/hope there are statisticians who've thought
> that through and compensated for it.
>
>


I don't think they do or have.

If they use fbg as the screening measure, we already know that it misses
at *least* 70% of women over 50 and 48% of men over 50 compared to a two
hour pp. Wonder how many more are missed who would be over 200 at one hour?

Susan

In alt.support.diabetes William C Biggs MD <MIQMRBIKFCMU@spammotel.com> wrote:
> Bittersweet,

> The lab normals are generated by using patients who are free of any disease.

Are you sure about that? I thought what they did was to exclude people
who had been diagnosed with a disease, which is not the same thing,
especially in the case of diabetes (and hence BG control) where there
are known to be significant numbers of undiagnosed victims in the
general population.

One doesn't want to fall into the "Normal For Norfolk" trap :-)

--
Chris Malcolm cam@infirmatics.ed.ac.uk DoD #205
IPAB, Informatics, JCMB, King's Buildings, Edinburgh, EH9 3JZ, UK
[http://www.dai.ed.ac.uk/homes/cam/]

On Fri, 11 May 2007 13:10:46 GMT, "Peter"
<peternorthlondon0001@lycos.co.uk> wrote:

>
>"William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in message
>news:IWR0i.153729$2Q1.8689@newsfe16.lga...
>> Bittersweet,
>>
>> The lab normals are generated by using patients who are free of any
>> disease.
>>
>> So you don't use people with DM to create a normal range for your HbA1c
>> assay, and you don't use people with hepatitis to determine the normal
>> range for liver tests.
>>
>
>This still seems a bit circular. I assume that when calibrating lab
>normals for HbA1c you exclude anyone who's already carrying a DM diagnosis,
>but your sample must/may include a few who are diabetic but who haven't been
>diagnosed and whose results go into the determination of the upper limit.
>Because they're likely to have much higher readings than most others even if
>they're few in number they may have a disproportionate effect on the upper
>limit of normal. I imagine/hope there are statisticians who've thought
>that through and compensated for it.
>

That's a very important point, not just for lab range
setting but for all scientific research that looks at blood
glucose and A1c levels. We are repeatedly told that there is
a high "undiagnosed" section of the population varying
anywhere from 5-10% and UKPDS suggested that we as T2 had
been suffering beta cell loss for years by the time of
diagnosis. There is probably an equal proportion of
undiagnosed IGT and IFG.

Some research studies exclude subjects who exceed set A1c
levels - but many don't. So the "normal" population sample
is skewed by those undiagnosed pre-diabetics and diabetics.


Cheers, Alan, T2, Australia.
d&e, metformin 1500mg, ezetrol 10mg
Everything in Moderation - Except Laughter.
--
http://loraldiabetes.blogspot.com/
http://loraltravel.blogspot.com/
latest: Slovenia

Chris,

My reply was intended to be for "Lab 101" readers.

If we use the TSH example again, if you graph the results with the number of
patients on the y-axis and the TSH result on the x-axis you will see a
bimodal distribution. There are TWO humps in the graph, not a simple bell
shaped curve.

If we choose the highest and lowest 2.5% curve, the high 2.5% mark is in
the middle of the second hump.

So what does this mean? These are healthy people, without KNOWN thyroid
disease. They have no symptoms.

If you follow the people in the second hump, with TSH levels in the 3.5 - 10
range, over time they get progressively higher. And many of them also have
positive thyroid antibodies. So what the second hump represents is people
who are in the process of developing thyroid disease.

Similarly, I can tell you that a normal person doesn't have a 5.9 HbA1c.
Most people with 5.9's are in either diabetics who have good treatment, or a
person in the midst of developing diabetes.

The numbers for AST and ALT are skewed by people who unknowingly have fatty
liver, take too much Tylenol, drink too much, or all three!

So you are right, that people who have unrecognized diseases will could skew
the results. Thats why you get as large of a 'normal' population as possible
to create your lab normals.

Many of the tests have data available to create Bayesian equations for
sensitivity and specificity for a particular disease state. You can then
estimate the 'pre-test probability' and decide how helpful a particular test
is for you in a specific situation.

Cheers,
WCB






"Chris Malcolm" <cam@holyrood.ed.ac.uk> wrote in message
news:5ajr30F2olf1pU1@mid.individual.net...
> In alt.support.diabetes William C Biggs MD <MIQMRBIKFCMU@spammotel.com>
> wrote:
>> Bittersweet,
>
>> The lab normals are generated by using patients who are free of any
>> disease.
>
> Are you sure about that? I thought what they did was to exclude people
> who had been diagnosed with a disease, which is not the same thing,
> especially in the case of diabetes (and hence BG control) where there
> are known to be significant numbers of undiagnosed victims in the
> general population.
>
> One doesn't want to fall into the "Normal For Norfolk" trap :-)
>
> --
> Chris Malcolm cam@infirmatics.ed.ac.uk DoD #205
> IPAB, Informatics, JCMB, King's Buildings, Edinburgh, EH9 3JZ, UK
> [http://www.dai.ed.ac.uk/homes/cam/]
>

Peter wrote:
> "William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in message

>> The lab normals are generated by using patients who are free of any
>> disease.
>>
>> So you don't use people with DM to create a normal range for your HbA1c
>> assay, and you don't use people with hepatitis to determine the normal
>> range for liver tests.
>
> This still seems a bit circular. I assume that when calibrating lab
> normals for HbA1c you exclude anyone who's already carrying a DM diagnosis,

It's still circular because how can you diagnose DM
as "so much above normal" and then define "normal"
as the average of people without that diagnosis?

On the other hand, with A1c, you can show that the rate of
certain complications is the same at 4.0 or at 5.4, but that
above 5.4 it goes up. From THAT, you could _assume_ 5.4 is
"normal" and pick a range centered on that. But perhaps it
would be easier to swallow if you just call the range "ideal"
as opposed to "normal"--subtle semantics, but .....

Maybe that's why they don't call it "normal," they call it
"reference"

--
Wes Groleau

Trying to be happy is like trying to build a machine for which
the only specification is that it should run noiselessly.
-- unknown

On Fri, 11 May 2007 18:47:53 -0500, "William C Biggs MD"
<MIQMRBIKFCMU@spammotel.com> wrote:

>If we use the TSH example again, if you graph the results with the number of
>patients on the y-axis and the TSH result on the x-axis you will see a
>bimodal distribution. There are TWO humps in the graph, not a simple bell
>shaped curve.
>
>If we choose the highest and lowest 2.5% curve, the high 2.5% mark is in
>the middle of the second hump.

Oh, very cool - thanks, Dr Biggs!

Nicky (off to do some reading...)
T2 dx 05/04 + underactive thyroid
D&E, 100ug thyroxine
Last A1c 5.5% BMI 25

William C Biggs MD wrote:
> If we use the TSH example again, if you graph the results with the number of
> patients on the y-axis and the TSH result on the x-axis you will see a
> bimodal distribution. There are TWO humps in the graph, not a simple bell
> shaped curve.

Wow, I didn't know that. I read a thing by some Australian group
complaining that the (at the time) TSH reference of 0.5 to 4.5 was
based on the entire population and claiming that it was skewed by the
inclusion of asymptomatic hypothyroid people.

Their claim was that removing those people would make the reference
range 0.5 to 1.5 and so they wanted treatment to aim for 1.0.
I wondered how they could determine the effects on the range of
removing a group when that group's definition is based on the range.

--
Wes Groleau
"To know what you prefer, instead of humbly saying
Amen to what the world tells you you should prefer,
is to have kept your soul alive."
-- Robert Louis Stevenson

Wes,

I haven't seen anyone advocating a reference range of 1.5, but I have seen
2.5 used frequently.

In my own practice, once I treat someone, I shoot for 0.5 - 2.0 . Even
though the published range is 0.3 - 5.0 in a lot of labs, IMHO if we are
already going to the trouble of treating someone we should get below 2.0.

As far as the arguments for and against redefining the 'normal' range of
TSH, here is a European opinion
http://www.eje-online.org/cgi/content/full/154/5/633 .

To quote:
"The definition of a 'normal' TSH level is not trivial. 'Normal', 'reference'
and/or 'discrimination' values are commonly used to define the interval with
which a measured TSH level is then compared. However, defining 'normal' as
absolute health in a population free of disease has been heavily criticized
as being far too simplistic because it implies that everything not being
normal ought to be corrected (3). "

Here is an American opinion:
"The Thyrotropin Reference Range Should Remain Unchanged" from Harvard
http://jcem.endojournals.org/cgi/content/full/90/9/5489

And a differing opinion from Boston University
http://www.thyroidtoday.com/TTLibrar...Newsletter.pdf
Bottom line: The laboratory TSH reference range needs to be reevaluated and
reset to 0.5 to 2.5 mIU/L in order to reflect TSH levels of the normal
reference population.

(FYI: The primary endo quoted here is Dr Stephanie Lee. Dr Lee & I worked
together when she was a medical student and intern at UC San Diego. She is
now at Boston University.)

Cheers,
WCB



"Wes Groleau" <groleau+news@freeshell.org> wrote in message
news:WMi1i.107$Gm.90@trnddc04...

> Their claim was that removing those people would make the reference
> range 0.5 to 1.5 and so they wanted treatment to aim for 1.0.
> I wondered how they could determine the effects on the range of
> removing a group when that group's definition is based on the range.
>
> --
> Wes Groleau

On Sat, 12 May 2007 10:52:42 -0500, "William C Biggs MD"
<MIQMRBIKFCMU@spammotel.com> wrote:

>I haven't seen anyone advocating a reference range of 1.5, but I have seen
>2.5 used frequently.

Dr Biggs, how important do you consider it to keep within the upper
limit of free T4? Would you think it better to medicate to keep the
TSH under 2-ish even if the T4 was above the lab normal, or are the T4
levels more important here? Would you consider supplementation with
T3?

Nicky.
T2 dx 05/04 + underactive thyroid
D&E, 100ug thyroxine
Last A1c 5.5% BMI 25

William C Biggs MD wrote:
> I haven't seen anyone advocating a reference range of 1.5, but I have seen
> 2.5 used frequently.

I cannot remember the group's name, but it was in Australia.
I read their argument about the time I was diagnosed with
Hashimoto's. I am not certain they said 1.5 but I am certain
they wanted the target for treatment to be 1.0.

If I remember right, this was about the time the AACE lowered
one of their numbers to 3.0

> In my own practice, once I treat someone, I shoot for 0.5 - 2.0 . Even
> though the published range is 0.3 - 5.0 in a lot of labs, IMHO if we are
> already going to the trouble of treating someone we should get below 2.0.

My current doctor aims for 1.0 but also takes T3 and T4 into account.
It seems I am also somewhat slow on the T4->T3 conversion.

Interestingly, I have had almost every kind of heart exam
that exists due to recurrent chest pain, with never any
cardiovascular trouble found. The chest pain stopped when
we got my TSH to 1.0. It started again when a V.A. doc
insisted the target is 4.5 and cut my T4 dose.
Stopped again when I went back to the civilian doctor
and got it back to 1.0


--
Wes Groleau

After the christening of his baby brother in church, Jason sobbed
all the way home in the back seat of the car. His father asked him
three times what was wrong. Finally, the boy replied, "That preacher
said he wanted us brought up in a Christian home, and I wanted to
stay with you guys."

While you are with us still, what has been your experience with the
incretin related meds byetta/januvia? I have read and kept up with the
relevant literature.


Do you use it as monotherapy and if so at which point in a1c do you
start? For someone well controlled for several years now, in the 5 or
less a1c range, have you any experience?

I ask the latter based on the additional potential for it to arrest and
prhapse improve usual beta cell loss.

This is well established in our rodent friends but docs aren't eagar to
have a direct look at their patients beta cells. At best some indirrect
evidence with long time byetta users suggests they are no longer on the
usual progression curve for diabetes even though they started usually in
the 8 a1c range in the trials.

This obviously brings one to consider the well controlled folk and doing
more then just arressting progression.

Gigs,

> While you are with us still, what has been your experience with the
> incretin related meds byetta/januvia? I have read and kept up with the
> relevant literature.

Byetta has been very impressive in what it does. Initially we were using it
for people that were just short of needing insulin. The majority of patients
are seeing a substantial benefit from it. Recently we have been using it at
earlier stages, particularly when weight loss is needed. Monotherapy is
off-label (i.e. not FDA approved), however several of our patients have done
so well we were able to wean them off all their oral drugs. I have used it
as monotherapy for special situations. Because of the cost, Byetta is
typically not my first line drug. In addition, many insurance companies are
requiring pre-certification for Byetta, and won't cover it if it used
outside FDA approved uses.

I battled one Medicare Part D plan last month (Sierra Rx) over their
reluctance to cover Byetta. The patient had contraindications to oral meds
due to heart disease, and he had an absolutely fabulous response to Byetta.
He lost 26#, his A1c fell to about 6.5, and he felt great. After he was
taking Byetta for 2 years, I received a letter from disapproving his Byetta
coverage, and asking if he had tried insulin. I was in the process of
reporting them to every possible regulatory agency when they reversed course
and approved his Byetta.

There isn't good data on when to use Byetta as monotherapy, and which A1c to
start at. I agree that it looks very promising as far as retarding
progression of disease. Avandia also has good data for that now.

One other non-FDA approved indictaion is fatty liver. I have seen some
patients with non-alcoholic fatty liver have almost miraculous improvement
on Byetta. One of my patients was getting worse on Avandia; after about 6
months on Byetta her liver tests went from 4x normal to about 1.5x normal.

Januvia has a much shorter track record. It has worked well for our patients
who are intolerant of TZD drugs (Actos & Avandia), and has been better
tolerated than the TZDs or metformin. I have seen zero data on human beta
cell preservation with Januvia, but I don't doubt that this is seriously
being looked at.

Obviously the biggest factor in use of these meds is cost. You can get
metformin or generic Amaryl at Target or WalMart for $4 a month.

Last I checked, Byetta was about $230 a month, and Januvia about $170.

If the data showed we could halt the onset of diabetes with Byetta, it would
be worth it. However it may be a challenge to get people to take injections
for a disease they don't have yet. We have occasional Byetta failures
because people who ALREADY have the disease won't stick with the injections.

Which of course, brings up the prospect of the once a week version of
Byetta, which I'll have to save for another day....

Cheers,
WCB




>
>
> Do you use it as monotherapy and if so at which point in a1c do you
> start? For someone well controlled for several years now, in the 5 or
> less a1c range, have you any experience?
>
> I ask the latter based on the additional potential for it to arrest and
> prhapse improve usual beta cell loss.
>
> This is well established in our rodent friends but docs aren't eagar to
> have a direct look at their patients beta cells. At best some indirrect
> evidence with long time byetta users suggests they are no longer on the
> usual progression curve for diabetes even though they started usually in
> the 8 a1c range in the trials.
>
> This obviously brings one to consider the well controlled folk and doing
> more then just arressting progression.

"William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in
news:IWR0i.153729$2Q1.8689@newsfe16.lga:

> BTW, the HbA1c test has been transformed from one of the most poorly
> standardized tests to one of the most well standardized tests in
> only a matter of years. The NGSP people have done a great service to
> us all in getting most of the manufacturers to be calibrated to the
> same standards.
>
> Most of the other lab assays are NOT as well standardized, thus you
> need to know the local normal range.
>
>

I have seen this said in many places. It does not, however, seem to mesh
with the, admittedly non-random, surveys I have taken on m.h.d. over the
years. In the first survey, the percentage of respondents reporting a
reference range on their last A1c of 4-6% was in the single digits. The
percentage has grown slowly with each survey. In the last survey in May
it was around 25%. Comments?

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

In article <Xns993164E4B60A8ccoughranucsdedu@132.239.1.220> ,
Charly Coughran <ccoughran@REMOVE-TO-DELETE-UCSD.EDU> wrote:
>"William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in
>news:IWR0i.153729$2Q1.8689@newsfe16.lga:

>> BTW, the HbA1c test has been transformed from one of the most poorly
>> standardized tests to one of the most well standardized tests in
>> only a matter of years. The NGSP people have done a great service to
>> us all in getting most of the manufacturers to be calibrated to the
>> same standards.

>> Most of the other lab assays are NOT as well standardized, thus you
>> need to know the local normal range.



>I have seen this said in many places. It does not, however, seem to mesh
>with the, admittedly non-random, surveys I have taken on m.h.d. over the
>years. In the first survey, the percentage of respondents reporting a
>reference range on their last A1c of 4-6% was in the single digits. The
>percentage has grown slowly with each survey. In the last survey in May
>it was around 25%. Comments?

You have the responses of voluntary or selected responders.
No matter how large the sample, it is unreliable.

The most famous example of this is the Literary Digest poll
in 1936. Its readers were polled about their preference in
the presidential race, and Landon was predicted to win by
60%-40%. The proportion as about right, but the other way.

When there are voluntary responders, the situation is similar.
This applies to demonstrations as well. There are demonstrations
for almost anything, attended by many, but these are usually
only a small proportion of the people who are concerned about
the subject, either way.
--
This address is for information only. I do not claim that these views
are those of the Statistics Department or of Purdue University.
Herman Rubin, Department of Statistics, Purdue University
hrubin@stat.purdue.edu Phone: (765)494-6054 FAX: (765)494-0558

hrubin@odds.stat.purdue.edu (Herman Rubin) wrote in
news:f2cptv$3mj6@odds.stat.purdue.edu:

> In article <Xns993164E4B60A8ccoughranucsdedu@132.239.1.220> ,
> Charly Coughran <ccoughran@REMOVE-TO-DELETE-UCSD.EDU> wrote:
>>"William C Biggs MD" <MIQMRBIKFCMU@spammotel.com> wrote in
>>news:IWR0i.153729$2Q1.8689@newsfe16.lga:
>
>>> BTW, the HbA1c test has been transformed from one of the most
>>> poorly standardized tests to one of the most well standardized
>>> tests in only a matter of years. The NGSP people have done a great
>>> service to us all in getting most of the manufacturers to be
>>> calibrated to the same standards.
>
>>> Most of the other lab assays are NOT as well standardized, thus
>>> you need to know the local normal range.
>
>
>
>>I have seen this said in many places. It does not, however, seem to
>>mesh with the, admittedly non-random, surveys I have taken on m.h.d.
>>over the years. In the first survey, the percentage of respondents
>>reporting a reference range on their last A1c of 4-6% was in the
>>single digits. The percentage has grown slowly with each survey.
>>In the last survey in May it was around 25%. Comments?
>
> You have the responses of voluntary or selected responders.
> No matter how large the sample, it is unreliable.
>
> The most famous example of this is the Literary Digest poll
> in 1936. Its readers were polled about their preference in
> the presidential race, and Landon was predicted to win by
> 60%-40%. The proportion as about right, but the other way.
>
> When there are voluntary responders, the situation is similar.
> This applies to demonstrations as well. There are demonstrations
> for almost anything, attended by many, but these are usually
> only a small proportion of the people who are concerned about
> the subject, either way.

A perfectly valid criticism. Even the requirement that the respondents
actually know the reference range for their A1c tests must additionally
bias the respondent pool.* None-the-less, it is the only tool I have.

The poll results have had an evolution, a relatively constant increase in
the percentage of those reporting DCCT standardized reference ranges.
The kind of result you might expect. And they have been consistent with a
couple other sample groups I have polled. Since I'm primarily interested
in the differences over time, I am ok with what looks like consistent
biases.



* I would have thought this would bias the responses high rather than
low.

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