Timescale in which newbies should get control
Nicky
There was an interesting Medscape article today, talking in general terms
about how to improve diabetic control. Page 3 of it, however, was very
interesting wrt the discussion we've been having about the time it should
take for newbies to go to normal levels. They're not talking any specifics
about retinopathy here, but I wonder if it would kill 2 birds with one
stone! Incidentally, they recommend insulin for a newbie with an A1c>9%.
This is the bit that specifically caught my eye, though:
Recommendation 6: Treat patients intensively so as to achieve target HbA1c <
6.5%2within 6 months of diagnosis.
http://www.medscape.com/viewarticle/522344_1
Nicky.
--
A1c 10.5/5.4/<6 T2 DX 05/2004
1g Metformin, 100ug Thyroxine
95/74/72Kg
--
A1c 10.5/5.4/<6 T2 DX 05/2004
1g Metformin, 100ug Thyroxine
95/74/72Kg
Jenny
> As the ophthalmologist thread has been subverted : )
>
> There was an interesting Medscape article today, talking in general terms
> about how to improve diabetic control. Page 3 of it, however, was very
> interesting wrt the discussion we've been having about the time it should
> take for newbies to go to normal levels. They're not talking any specifics
> about retinopathy here, but I wonder if it would kill 2 birds with one
> stone! Incidentally, they recommend insulin for a newbie with an A1c>9%.
>
> This is the bit that specifically caught my eye, though:
>
> Recommendation 6: Treat patients intensively so as to achieve target HbA1c <
> 6.5%2within 6 months of diagnosis.
>
> http://www.medscape.com/viewarticle/522344_1
>
Interesting.
But it doesn't sound like the 6 month time period suggested here was
chosen with any thought as to the safety or non-safety of lowering blood
sugars too swiftly or a fear of causing retinopathy.
The authors are mainly arguing against the common practice which is to
leave patients with blood sugars in the danger zone for a few years
while putting them on this and that drug that don't work very well.
Suggesting control be attained in six months is meant to be a "hurry up!"
Looking at the references, the only reference to retinopathy is an
article explaining the DCCT discovery that lowering the A1c cuts down
significantly on the risk of retinopathy, which is cited in the article.
Indeed, I doubt you will find any serious discussion of the question of
whether retinopathy worsens in type 2s who get tight control quickly in
any practice guideline like this one.
With hundreds of thousands of people with Type 2 going blind because
their doctors never get them below 8%, the rare people with type 2 who
have mild worsening while getting better control does not seem to be
something doctors are worrying about or discussing.
The reports of worsening with gaining of tight control all came from the
big Type 1 study (DCCT) not the type 2 study (UKPDS) where no Type 2s
developed worsening when going for tight control. The few other studies
that look at the connection between better control for Type 2s and
worsening retinopathy are small, inconclusive, and have serious design
flaws. None of them comes up with a recommendation of a "safe" time period.
And it is worth reminding ourselves that the DCCT data did not show any
difference in worsening between those who gained quick control and those
who gained slow control. Indeed, the DCCT statistics suggest that the
worsening comes from getting control after being very high, period,
regardless of the time involved.
Beyond the analysis of the DCCT data, where they did look at speed of
gaining control, there is NO study that looks at different speeds of
gaining control and plots that speed against retinal worsening. Period.
The studies only show, incontrovertibly, that in a very small percentage
of people, worsening occurs when control improves.
I feel really bad that Chris has to go through what he is going through,
but nothing he has posted goes beyond the anecdotal and it is likely
that it may, when all is said and done, relate to people with blood
sugars near 600 and massive infections with long histories of drug and
allergic reactions who have some really, really bad luck.
If you really are interested in this question, you might email the
doctor who published the journal article (there always is an email
address included in the actual article) and ask whether he'd advise
against getting control more swiftly because of the retinal issue.
--Jenny
http:www.phlaunt.com/diabetes Diabetes Info
http://www.alt-support-diabetes.org/newlydiagnosed.htm Get Your Blood
Sugar Under Control
Quentin Grady
>As the ophthalmologist thread has been subverted : )
>
>There was an interesting Medscape article today, talking in general terms
>about how to improve diabetic control. Page 3 of it, however, was very
>interesting wrt the discussion we've been having about the time it should
>take for newbies to go to normal levels. They're not talking any specifics
>about retinopathy here, but I wonder if it would kill 2 birds with one
>stone! Incidentally, they recommend insulin for a newbie with an A1c>9%.
>
>This is the bit that specifically caught my eye, though:
>
>Recommendation 6: Treat patients intensively so as to achieve target HbA1c <
>6.5%2within 6 months of diagnosis.
>
>http://www.medscape.com/viewarticle/522344_1
>
>Nicky.
G'day G'day Nicky,
Thank you.
A couple of things have troubled me over the situation Chris found
himself in.
Firstly since the specialist he visited most recently has stated there
is a risk associated with rapidly dropping blood glucose, why wasn't
he provided with this information on a discharge sheet?
Secondly although the latest specialist has identified a risk
associated with reducing blood glucose rapidly he doesn't have given
the relative risk of not doing so. Put simply monstrously high blood
glucose is a risk in itself. There is a risk if one reduces them
rapidly and a risk associated with leaving them high. It could be
that there is risk associated with rapid decreasing them of
2% ie 1 in 50. What is the risk associated with leaving them high for
1 month, 2 months, 3 months etc? There must be some break even point
unless the risk of leaving them high is always higher than 2%.
Best wishes,
--
Quentin Grady ^ ^ /
New Zealand, >#,#< [
/ \ /\
"... and the blind dog was leading."
Nicky
"Quentin Grady" <que...@paradise.net.nz> wrote in message
news:bklvv1lr12glk3akc...@4ax.com...
> Put simply monstrously high blood
> glucose is a risk in itself.
Yes indeed. I don't think anyone's cavilling about knocking down bgs like
Chris had ASAP. Another variable here is, what's a monstrously high bg? The
link I posted suggested an A1c of 9.5, which must be a, what, 250-300 ave
bg?
> There is a risk if one reduces them
> rapidly and a risk associated with leaving them high.
Without knowing the damage mechanism, I'm worried that there may be an
increased potential to damage at having bgs running around the 140 mark too,
or whatever an individual's retinal threshold might be, as pressure is
reduced... and increased... reduced... increased...
> It could be
> that there is risk associated with rapid decreasing them of
> 2% ie 1 in 50. What is the risk associated with leaving them high for
> 1 month, 2 months, 3 months etc? There must be some break even point
> unless the risk of leaving them high is always higher than 2%.
Yup. And how do we trade that off against the known risks of micro and macro
damage from a >6 A1c.
The problem we have is that Chris is going through a deeply bad experience,
and has a duty to tell his story to newbies. As he's articulate and
persuasive (and a moral person) it's important for him, newbies, and us that
he is able to recommend a path that's as healthful as possible - or (quite
apart from confused newbies!) we're going to have endless paths where Chris
says "watch out!" and we say "But that's a small comparative risk!". We need
to find out as close to a mutually agreed path as possible - preferably via
Chris' eye doc.
Jenny
>
> Yes indeed. I don't think anyone's cavilling about knocking down bgs like
> Chris had ASAP. Another variable here is, what's a monstrously high bg? The
> link I posted suggested an A1c of 9.5, which must be a, what, 250-300 ave
> bg?
Using the formula that came out of DCCT, a 9.5% A1c relates to an
Average Plasma glucose of 261 mg/dl or 14.5 mmol/l. Since it is an
average, it could easily represent swings from 100 to 400 mg/dl.
Chris reported that his blood sugar in the hospital was 600 mg/dl 33
mmol/l which is more than twice as high. That sounds pretty "monstrous"
to me.
>>There is a risk if one reduces them
>>rapidly and a risk associated with leaving them high.
>
>
> Without knowing the damage mechanism, I'm worried that there may be an
> increased potential to damage at having bgs running around the 140 mark too,
> or whatever an individual's retinal threshold might be, as pressure is
> reduced... and increased... reduced... increased...
The "retinal threshold" for glucose is a speculation advanced in
discussions here, but has no basis in fact. A threshold is, by
definition, a sharp cutoff. With the renal threshold, for example, there
is no glucose spilling in urine and then at the threshold, the glucose
spills.
But from what I can see scanning research on retinal thresholds, glucose
in the eye does not appear to have a threshold, but rises in a straight
line relationship with the concentration of glucose in the blood.
The 140 mg/dl number is a GTT number that correlates with a threshold
increase in nerve damage, not retinopathy.
There is NO number that has a clearcut relationship to the increase in
retinopathy, a point that was emphasized by the recent discovery that
there is a significant percentage of people with blood sugars in the
pre-diabetic range who have already developed "diabetic" retinopathy.
What little research there is online suggests that the glucose level in
the eye rises in a straight line, which is why there is some research on
using visual tests to non-invasively measure blood sugars.
> The problem we have is that Chris is going through a deeply bad experience,
> and has a duty to tell his story to newbies. As he's articulate and
> persuasive (and a moral person) it's important for him, newbies, and us that
> he is able to recommend a path that's as healthful as possible - or (quite
> apart from confused newbies!) we're going to have endless paths where Chris
> says "watch out!" and we say "But that's a small comparative risk!". We need
> to find out as close to a mutually agreed path as possible - preferably via
> Chris' eye doc.
But we have to remember, also that Chris' eye doctor is a retinal
specialist who sees only a population of people after they have
developed retinopathy. He is also a hands-on technician whose focus is
on eye surgery, not a specialist in the treatment of diabetes as a whole.
This means that his statement while worthy of consideration is not the
last word on the subject, any more than your cardiologist's might be, no
matter how busy his practice, unless backed up with some kind of
evidence beyond "this is what it seems to me I'm seeing in my office."
W. Baker
: "Quentin Grady" <que...@paradise.net.nz> wrote in message
: Nicky.
I am not referring to the studies, but do want to reiterater what my
macula specilaist, who deals with man diabetis as well as non0dibetics
with AMD(Adult Macula Degeneration{wet}). Whe I describred Chris's
situaltion t him and asked, specifically, about what advice we should
think about giving on asd which he respects, (at lest a a concept) He sid
whe should not advise slower stivign for control, or slower lowering of
bgs, dispite the rare problem like Chris's of some retinopathy and
macular edema with fast reduction, as the long term benefits of rapidly
lowered bg's is so great.
I do not know if he is speking form knowledge gained form research or from
a long expeience with diabetics as well resaerch.
This doctor is delighted with my A1c's as well as my fsting glucose
readings and sees no canges in my slight background retinopathy which has
been stable for , at lest, the last 10 years. He wishes all his diabetics
had similar readings. (A1c-varyig between 5.2 and 5.9-fbgs between high
70's to low 90's)
Wendy
Jefferson
>> Yes indeed. I don't think anyone's cavilling about knocking down bgs
>> like Chris had ASAP. Another variable here is, what's a monstrously
>> high bg? The link I posted suggested an A1c of 9.5, which must be a,
>> what, 250-300 ave bg?
>
> Using the formula that came out of DCCT, a 9.5% A1c relates to an
> Average Plasma glucose of 261 mg/dl or 14.5 mmol/l. Since it is an
> average, it could easily represent swings from 100 to 400 mg/dl.
>
> Chris reported that his blood sugar in the hospital was 600 mg/dl 33
> mmol/l which is more than twice as high. That sounds pretty "monstrous"
> to me.
>
>>> There is a risk if one reduces them
>>> rapidly and a risk associated with leaving them high.
I posted the following in another thread but no one commented on it.
Progression of Retinopathy During Pregnancy in Type 1 Diabetic Women
Treated With Insulin Lispro -
http://care.diabetesjournals.org/cgi/content/full/26/4/1193
found on page 874 in a 1999 Diabetes Care article -
http://care.diabetesjournals.org/cgi/reprint/22/5/874
The thresholds have both upper and lower aspects (involved is rapid BG
change that results in retinopathy problems). The kind of insulin used
may also be a factor.
There are some aspects of diabetic complications that do involve
genetics as Nicky has mentioned. [retinopathy+edema+genetics+diabetes -
http://tinyurl.com/mx39u or retinopathy+edema+genetics+diabetic -
http://tinyurl.com/q4sqc.] The case with Chris may seem extreme but
upper thresholds much lower than his high might also be involved.
A growth factor termed "VEGF is involved in normal angiogenic processes
in adults such as cardiac collateral circulation, wound healing and
menstrual cycle." Angiogenisis (growth of new blood vessels)is also
necessary for a cancer turmor to grow larger than a pencil dot.
"Apparently clinical trials of lispro insulin in nonpregnant diabetic
women did not show unexpected development of PDR. Lispro is a homolog of
IGF-1. The role of the growth hormone–IGF-1 system in the development of
PDR is under increasing scrutiny. Insulin is known to enhance IGF-1
production, but the effect of insulin lispro on the IGF-1
system is not well described." From the second citation above.
The articles I have cited pertain to diabetes and pregnancy which
involve other factors involved in pregnancy.
Frank
Alan S
<croo...@netscape.net> wrote:
>I posted the following in another thread but no one commented on it.
Frank, I'm brave enough to be honest. Sometimes we need you
to also provide your synopsis, translated from medicspeak to
something laypeople can understand. I know it may not be
always possible to dumb it down and remain valid, but it
would help if you added some sort of personal analysis on
what a study means to you - the significance of it's
findings or the validity of it's recommendations.
What is obvious to you is sometimes a little obscure to me.
Cheers, Alan, T2, Australia.
d&e, metformin 2x500mg
--
Everything in Moderation - Except Laughter.
Jenny
I did scan your posting, but it wasn't clear to me how it would fit in
as pregnant type 1s are a whole different thing from obese type 2s
metabolically, and so much weird stuff happens during pregnancy that it
is hard to tease out what anything might mean in that context. And the
edema issues alone fill many books.
It's a good point that the kind of insulin might be related, except that
the one major study documenting the worsening was DCCT done long enough
ago that they may very well have been using nothing but animal insulins.
OTOH, there's a mention of Lantus possibly being associated with
worsening of retinopathy mentioned in the Lantus prescribing
information but rather brushed off as with some wording about how one
tiny study found it and another didn't and it isn't clear what the
relationship is to the insulin. Interestingly, worsening is NOT cited
as a side effect in the Levemir Prescribing Information that came with
my starter kit.
--Jenny
http://www.phlaunt.com/diabetes Diabetes Info
W. Baker
: Jenny, Nicky, Others:
: IGF-1. The role of the growth hormone?IGF-1 system in the development of
: PDR is under increasing scrutiny. Insulin is known to enhance IGF-1
: production, but the effect of insulin lispro on the IGF-1
: system is not well described." From the second citation above.
: The articles I have cited pertain to diabetes and pregnancy which
: involve other factors involved in pregnancy.
: Frank
Frank,
I have been slogging through a couple of articles you posted, and thanks.
From what I can gather (plese correct me if I am wrong) Lispro seems to
be the particular insulin to avoid in order to prevent neovascularization.
Is this just tht this iw what they happened to use in the test or could we
assume other insulins might be better on this score?
Wendy-just trying to make sense of it all.
Quentin Grady
wrote:
>The problem is that there doesn't seem to be, so far, a definition of
>what "too fast" is, or what the starting number danger zone is. Then
>there's the question of whether it's the method or the speed of lowering
>that causes the problem?
>
>Susan
G'day G'day Susan,
This is all too reminiscent of the issue of exercise with newly
diagnosed T2 diabetics. We all know exercise is so important that it
comes first.
Here is a rough guide to dealing with T2 diabetics.
1. Exercise.
2. Exercise and diet.
3. Exercise, diet and take oral medications.
4. Exercise, diet, take insulin.
It is tempting to think everyone should exercise if they are T2
diabetics. Forget for the moment those who are crippled and consider
just those who have high blood pressure. Sometimes it is vital to get
the high blood pressure in check before engaging in vigorous exercise.
It can be fatal not to do so. Other people write about these matters
of high blood pressure and exercise so much more elegantly than me,
I'd rather leave the details to them.
The point I'm driving at here is that for MOST people getting rapid
tight control is not problematic at all. If they get cracking they'll
simply get healthier and reduce a multitude of risks. Then there are
those who start out with enormously elevated blood glucose. Let's say
for arguments sake that we probably recognise people likely to be that
group. They are most likely a subgroup of those who need insulin
immediately to overcome glucose toxicity.
At least we now have a name we can use for searching for information
on the issue.
Quentin Grady
<wba...@panix.com> wrote:
>I am not referring to the studies, but do want to reiterater what my
>macula specilaist, who deals with man diabetis as well as non0dibetics
>with AMD(Adult Macula Degeneration{wet}). Whe I describred Chris's
>situaltion t him and asked, specifically, about what advice we should
>think about giving on asd which he respects, (at lest a a concept) He sid
>whe should not advise slower stivign for control, or slower lowering of
>bgs, dispite the rare problem like Chris's of some retinopathy and
>macular edema with fast reduction, as the long term benefits of rapidly
>lowered bg's is so great.
>
>I do not know if he is speking form knowledge gained form research or from
>a long expeience with diabetics as well resaerch.
>
>This doctor is delighted with my A1c's as well as my fsting glucose
>readings and sees no canges in my slight background retinopathy which has
>been stable for , at lest, the last 10 years. He wishes all his diabetics
>had similar readings. (A1c-varyig between 5.2 and 5.9-fbgs between high
>70's to low 90's)
>
>Wendy
G'day G'day Wendy,
You're a gem. You asked THE most important question needing to be
asked of someone qualified to answer it. Special thanks for being up
front with what you wanted the answer for. I'm sure it makes one heck
of a difference to a specialist to know how the answer they give will
be used. For instance if they thought the patient wanted the
information for a court case their answers might be very different.
Quentin Grady
wrote:
>On Sat, 25 Feb 2006 10:29:32 -0000, "Nicky"
><ukc802...@btconnect.com> wrote:
>
>
>>The problem we have is that Chris is going through a deeply bad experience,
>>and has a duty to tell his story to newbies. As he's articulate and
>>persuasive (and a moral person) it's important for him, newbies, and us that
>>he is able to recommend a path that's as healthful as possible - or (quite
>>apart from confused newbies!) we're going to have endless paths where Chris
>>says "watch out!" and we say "But that's a small comparative risk!". We need
>>to find out as close to a mutually agreed path as possible - preferably via
>>Chris' eye doc.
>
>This explains my dilemma very well. At the moment there are too many
>unknowns for me to know what the heck to say to a newbie about this.
>I've decided to have a consultation conference with both the
>specialist and ophthalmologist about this issue (what to say to
>newbies). It's going to cost me, but it's sure worth it.
G'day G'day Chris,
WOW. You are one impressive bloke. It's a privilege to be able to
call you are friend even if we have never met. In New Zealand much of
the specialist care come care of the state if recommended by doctors
and one doesn't mind waiting. Not so in some places elsewhere. I'm
deeply impressed that someone would dig deep into their pockets to
find out information which can't materially change their own situation
but could be a benefit to countless others.
>The biggest unknown: what rate of reduction is optimum? The big
>problems here seem to be that the underlining mechanism for
>normoglycemic re-entry retinopathy is not known. So, without knowing
>the mechanism, it's hard to even theorize a good strategy.
>
>My biggest fear at this point: that I'll end up with conflicting or
>non-definitive answers, and then be faced with a newbie, and have no
>clue as to what to say. And yes, that one *IS* keeping me up at night.
Why do we care so much?
It's not an easy question to find an answer to.
Jenny
>
>
>
>>There was an interesting Medscape article today, talking in general terms
>>about how to improve diabetic control. Page 3 of it, however, was very
>>interesting wrt the discussion we've been having about the time it should
>>take for newbies to go to normal levels. They're not talking any specifics
>>about retinopathy here, but I wonder if it would kill 2 birds with one
>>stone! Incidentally, they recommend insulin for a newbie with an A1c>9%.
>>
>>This is the bit that specifically caught my eye, though:
>>
>>Recommendation 6: Treat patients intensively so as to achieve target HbA1c <
>>6.5%2within 6 months of diagnosis.
>>
>>http://www.medscape.com/viewarticle/522344_1
>
>
> However, I do wish someone would do a study to examine the increased
> incidence and severity of normoglycemic re-entry retinopathy (the name
> for what happened to me) when temporary insulin intervention is used.
Chris,
The ONLY increases in retinopathy reported in the literature are found
in a small percentage of people (almost all type 1s) using insulin.
It is not an issue in people NOT using insulin, which is very important
to keep in mind before telling newbies with type 2 that they will go
blind if they bring down their blood sugar with dietary control.
Jenny
>
>>Beyond the analysis of the DCCT data, where they did look at speed of
>>gaining control, there is NO study that looks at different speeds of
>>gaining control and plots that speed against retinal worsening.
>
> How can you say that conclusively? I haven't been able to find one,
> but that's not proof it doesn't exist. I intend to keep looking.
>
>
Because when the ophthalmologists who have published the most on the
topic of diabetic ophthalmology published a comprehensive review of the
literature on the subject in 2004 in Diabetes Care, the premier journal
covering treatment for diabetes (an article citing 134 research papers)
they cited no such study.
The authors on this review are researchers with a huge presence in the
field. Do a Google Scholar search on authors Donald Fong or Ronald Klein
and you'll see what I mean.
Diabetic Retinopathy
Diabetes Care 27:2540-2553, 2004
http://care.diabetesjournals.org/cgi/content/full/27/10/2540
They did say, discussing the DCCT data (the only major study to come up
with data on this topic:
"Analysis for early worsening was conducted and noted to be present at
the 6- and/or 12-month visit in 13.1% of 711 patients assigned to
intensive treatment and in 7.6% of 728 patients assigned to conventional
treatment (P < 0.001). By the 18-month visit, there was recovery in 51%
of the intensive and 55% of the conventional groups (P = 0.39). The risk
of three-step or greater progression from the retinopathy level present
18 months after entry into the trial was greater in patients who had
previously had early worsening than in those who had not, but there was
a large long-term risk reduction with intensive treatment. Patients who
developed early worsening as a result of the intensive treatment were
similar to or had more favorable outcomes than those in the conventional
group who did not have early worsening. Analysis did not suggest
reduction of early worsening with more gradual reduction of glycemia."
PLEASE NOTE THE LAST TWO SENTENCES
>
> Would that include my retinal specialist stating, explicitly, that
> slower lowering is better? I don't see how that is at all anecdotal in
> this context.
Yes. This is anecdotal, as is Wendy's distinguished retinologist telling
her the exact opposite.
In scientific terms "anecdotal" means "what I am concluding based on the
stuff I've personally seen, as opposed to what large, well conducted
studies have been able to document in ways that hold up to subsequent
analysis of study design and which can be validated by reproducing
results."
These retinal specialists are in the field doing the laser coagulation
and treatments. They aren't researchers setting up experiments or
analyzing data. So their opinions are formed by what they see in their
office which is only a small segment of the patient population. And if
they are anything like the retinal specialist I worked for many years
ago, most of their very sparse spare time is spent reading up on new
surgical techniques and practicing them on sheep's eyeballs in the lab
not reading up on the causes of the conditions they treat.
> And BTW, so far both my retinologist and opthamologist have said
> "slower would be better", and I'll try and get them to specify a
> timeframe.
>
When you do, be sure you ask them what they base their recommendations
on. Have they seen research that supports that conclusion or is it an
educated guess?
I have found with my doctors, that they don't like to admit they don't
know the answer to something. So If you ask them a question, they often
will state things with great certainty which upon further examination
turn out to be opinions not fact. (And in my case, turn out to be
completely different than what labs turn out to show.) That's why it is
always a good idea to ask what the basis is for a statement that has
great importance to you.
--Jenny
http://www.phlaunt.com/diabetes Diabetes Info
Jenny
t's hard to even theorize a good strategy.
>
> My biggest fear at this point: that I'll end up with conflicting or
> non-definitive answers, and then be faced with a newbie, and have no
> clue as to what to say. And yes, that one *IS* keeping me up at night.
>
It should. I have already gotten hate mail telling me that following the
advice on my web page has caused someone to go blind.
Jenny
> I have been slogging through a couple of articles you posted, and thanks.
> From what I can gather (plese correct me if I am wrong) Lispro seems to
> be the particular insulin to avoid in order to prevent neovascularization.
> Is this just tht this iw what they happened to use in the test or could we
> assume other insulins might be better on this score?
>
> Wendy-just trying to make sense of it all.
>
Unfortunately, since this study takes place in the context of pregnancy,
the growth hormone environment is already altered, making the
application of results to non-pregnancy questionable.
Lantus is the insulin I have seen implicated in worsening, but the DCCT
retinopathy worsening results were gotten years ago in a population
using the older insulins.
--Jenny
http://www.phlaunt.com/diabetes Diabetes Info
Jenny
> The point I'm driving at here is that for MOST people getting rapid
> tight control is not problematic at all. If they get cracking they'll
> simply get healthier and reduce a multitude of risks. Then there are
> those who start out with enormously elevated blood glucose. Let's say
> for arguments sake that we probably recognise people likely to be that
> group. They are most likely a subgroup of those who need insulin
> immediately to overcome glucose toxicity.
>
And it must not be forgotten that the problem is documented ONLY found
in people who lower glucose using insulin, almost all of them Type 1s.
Another point to remember: The danger of a blood sugar of 600 in a
person who still produces their own insulin is death from something
called hyperosmolar Coma. This condition occurs in people who do not
develop ketoacidosis because unlike type 1s, their bodies don't consume
their own tissue with extremely high blood sugars. But the dehydration
this condition causes can be fatal or can cause permanent brain damage.
That probably is why doctors would administer large doses of insulin
immediately to anyone with a fasting blood sugar of 600 mg/dl.
Andrea
>And BTW, so far both my retinologist and opthamologist have said
>"slower would be better", and I'll try and get them to specify a
>timeframe.
But the real question is how slow.
I understand the problem you've had and that you want to prevent it in others.
Definitely a worthy goal!
But I can imagine the newbie coming along -- just diagnosed, doctor said "take
this pill, stay away from sugar, and test your blood sugar in the morning."
The guy is scared, wondering if his whole life is going to change, wondering
if he's going to end up on dialysis, and then he reads "don't get your blood
sugar down too quickly." And he thinks "hey, my doctor wasn't too excited
about this and now this guy says be careful about going down too fast. So
I'll just keep taking that pill every day and I'll be fine."
What's really needed is a number. You should aim to lower your BG by X points
a week or Y points a month. Or maybe by a percentage. I don't know if such
guidelines exist, but they would be helpful.
--
Lord, make me an instrument of your peace...
where there is hatred, let me sow love.
remove "spamtrap" for e-mail
Jenny
>
>>which is very important
>>to keep in mind before telling newbies with type 2 that they will go
>>blind if they bring down their blood sugar with dietary control.
>
>
> Jenny, I hope that's hyperbole on you part, as I'd NEVER make such a
> blanket statement to a newbie or anyone else!
I know that and I've been impressed with the way you've handled your
postings. My comment is in regard to what some other people have posted
since you told your story, where it seems that they have oversimplified
the message and now are writing that it might be dangerous to suggest
to the newly diagnosed type 2 that they should make dietary changes (as
per Jennifer's Advice) to bring down blood sugars to the AACE target
(140 mg/dl at 2 hours).
>So far as I can tell, that's true. I think however (just theorizing
>here) that it could be due to the fact that without insulin, their
>lowering is slower. THIS is one thing I would really like to see
>studied.
Cutting carbs can make a massive change in blood sugars very quickly.
Many people besides yourself have posted here of bringing their blood
sugars down 4% or more on the A1c within three months using diet and
metformin or another oral and no insulin.
I myself brought my postprandial blood sugars down from the 240s to
around 100 within two weeks just by cutting out all but 30 grams a day
of carbohydrate, 7 years ago. I've seen other people accomplish even
steeper drops.
So with that in mind, you can see that the question of whether speedy
lowering is dangerous segues into the question of whether low carbing is
dangerous, a question that any casual reader of this newsgroup knows can
bring out the worse in some unbalanced posters.
Theories have also been proposed here, and then treated as if they were
fact--like the idea that going up and down over some threshold at 140
mg/dl might be more dangerous than staying over it This kind of idea,
followed to its logical conclusion, would result in people going out of
their way to keep their blood sugars OVER 140 mg/dl--the level that the
AACE says is where the problems start, and which is well-documented to
be the level at which nerve damage gets significant.
That is why I keep harping on how important it is to keep in mind the
details involved in your situation and what the research shows. No one
would be happier than I would be if we could come up with the answer to
the question of what causes this kind of retinopathy and whether there
are steps we can take to avoid it. (Well, I'd be even happier if we
could find out what you can do to restore your vision to where it is no
longer a matter of concern.) But let's be careful to keep the message
straight so that the 20 years of research showing that for blood sugars
"Lower is better" and that lowering blood sugar to as near normal as
possible _is_ the only way to prevent diabetic blindness doesn't get
mangled.
> At most, and *ONLY* if supported by hard data, I'll be telling what
> happened to me, posting links to whatever I find about normoglycemic
> re-entry, and strongly suggesting that they see an ophthalmologist
> immediately if they are lowering very high BG's with insulin.
That's an excellent suggestion. I'd agree that everyone with diabetes
should see an ophthalmologist as soon as possible after diagnosis
because quite a lot of people by the time of diagnosis do have early
retinopathy and they need to be aware of that if they are to keep it
under control.
Alan S
<lott...@hotmail.com> wrote:
>> My biggest fear at this point: that I'll end up with conflicting or
>> non-definitive answers, and then be faced with a newbie, and have no
>> clue as to what to say. And yes, that one *IS* keeping me up at night.
>>
>
>It should. I have already gotten hate mail telling me that following the
>advice on my web page has caused someone to go blind.
>
>--Jenny
I'm terribly sorry to hear that Jenny. I presume from the
context that you believe it was triggered by this
discussion?
Keep doing what you're doing. I doubt you'll ever know how
many lives your web-site has improved.
Including mine.
Cheers, Alan, T2, Australia.
d&e, metformin 2x500mg
--
Everything in Moderation - Except Laughter.
Jenny
>>>My biggest fear at this point: that I'll end up with conflicting or
>>>non-definitive answers, and then be faced with a newbie, and have no
>>>clue as to what to say. And yes, that one *IS* keeping me up at night.
>>>
>>
>>It should. I have already gotten hate mail telling me that following the
>>advice on my web page has caused someone to go blind.
>>
>>--Jenny
>
>
> I'm terribly sorry to hear that Jenny. I presume from the
> context that you believe it was triggered by this
> discussion?
Given who signed one of the emails and the content, the conclusion is
inescapable.
This isn't the first time if I've wondered whether bad temper and
paranoia might also be diabetic complications.
> Keep doing what you're doing. I doubt you'll ever know how
> many lives your web-site has improved.
>
> Including mine.
Thanks!
Nicky
"Jenny" <lott...@hotmail.com> wrote in message
news:3MCdneG2uqfgXJzZ...@rcn.net...
> It should. I have already gotten hate mail telling me that following the
> advice on my web page has caused someone to go blind.
That's disgusting. Apart from being an outright lie! Your research is like a
wake-up call - "Hey! You need to know this, and the starting point is right
here - in English, not medicalese!" That's how I felt/feel, anyway! Please
don't let the nutters make you feel bad!
Nicky.
--
A1c 10.5/5.4/<6 T2 DX 05/2004
1g Metformin, 100ug Thyroxine
95/74/72Kg
Jenny
>
> I'm slightly leery of the DCCT data, as it's a T1 study. The
> circumstances for a T1 at DX are quite different in this regard:
> mainly, they are quite unlikely to have had sustained high BG's for as
> long as a T2. There are also seem to be (not sure yet) differences in
> the IGF-1 profile.
The reason that DCCT data is cited is that it is the only large scale,
long term study that found worsening and analyzed enough data to come to
conclusions. The UKPDS is the other corresponding study of Type 2s, but
it did NOT find evidence of retinal worsening in it's population though
they made the same dramatic decrease in blood sugar levels.
There are a few, much smaller studies of worsening in Type 2s put on
insulin (your cite might be one of them.) Bbut one of the articles I
cited for you back when you first posted (and don't have at hand, though
the message is still out there and should be able to be found via
Google) included a review of several small studies that found worsening
in Type 2s put on insulin.
If I recall correctly, that review explained that the problem with these
studies was that the patients put on insulin in these studies were
typically those who had been out of control for many years who were only
put on insulin, very late, as a last resort. So there was a huge
question as to whether their retinopathy was already pre-existent due to
the decades of high blood sugar exposure. These after all, were patients
whose A1cs had been over 10% for many years.
Here's another relevant article for you from Medscape where the question
is asked of experts from Joslin & Harvard Med School. They pretty much
say the same thing as the Fong article, but they said it in 5/03. I've
included most of the text for your convenience. Follow the link to see
the references.
http://www.medscape.com/viewarticle/452955
Does Initiating Intensive Glucose Control Worsen Existing Diabetic
Retinopathy?
Question
Some endocrinologists in Japan state that controlling blood glucose
levels too quickly in patients with severe diabetic retinopathy can
worsen retinal lesions. Is there any evidence to support this statement?
Response from Lloyd Paul Aiello, MD, PhD
Assistant Director, Beetham Eye Institute, Joslin Diabetes Center;
Associate Professor of Ophthalmology, Harvard Medical School, Boston,
Massachusetts
Jerry Cavallerano, OD, PhD
Assistant to the Director, Beetham Eye Institute, Joslin Diabetes
Center, Boston, Massachusetts
The Diabetes Control and Complications Trial (DCCT) definitively
demonstrated that intensive control of blood glucose levels in patients
with type 1 diabetes mellitus substantially reduces the risk of onset
and progression of diabetic retinopathy.[1,2] In addition, the reduced
risks of onset and progression of retinopathy associated with intensive
therapy persisted at least 4 years beyond the conclusion of the DCCT,
despite near convergence of hemoglobin A1c levels in the
intensive-therapy and conventional-therapy groups.[3]
The United Kingdom Prospective Diabetes Study (UKPDS) found similar
benefits of intensive blood glucose control for patients with newly
diagnosed type 2 diabetes.[4] In the Kumamoto study in Japan of patients
with type 2 diabetes who were taking insulin, the benefits of intensive
control of blood glucose levels were likewise demonstrated.[5]
The DCCT documented "early worsening" of diabetic retinopathy in the
study population.[6] Early worsening of retinopathy was defined as a
3-step or more progression of retinopathy on the severity scale, the
development of cotton wool spots and/or intraretinal microvascular
abnormalities, and "clinically important retinopathy" if it occurred
between baseline and the 12-month follow-up visit. Early worsening of
retinopathy occurred in 13.1% of 711 patients assigned to intensive
treatment and in 7.6% of 728 patients assigned to conventional
treatment. Nevertheless, after 18 months this early worsening in
retinopathy reversed, and patients in the intensive-treatment group
fared better than those on conventional therapy. Risk factors for early
worsening were higher hemoglobin A1c level at baseline and reduction of
this level during the first 6 months following randomization. There was
no evidence that a gradual reduction in A1c levels reduced the risk of
early worsening.
In the DCCT, the long-term benefits of intensive control clearly
outweighed the risk of early worsening of retinopathy, and no case of
early worsening resulted in serious visual loss. Based on these
findings, it is recommended that persons with type 1 or type 2 diabetes
initiate intensive therapy as early as possible, and maintain intensive
therapy for as long as possible, with the expectation that intensive
control of blood glucose levels will reduce the risk of onset and
progression of diabetic retinopathy. For patients with elevated
hemoglobin A1c levels, careful retinal evaluation, close retinal
follow-up, and laser photocoagulation as indicated are important
components of care as intensive therapy is initiated.
--
Jenny
>
> I sincerely hope that is not the case! Jenny, if so, I'm deeply sorry
> for my inadvertent role in this.
The only thing I'm deeply sorry about is that you have to go through
this nightmare with your eyes!
The only reason I brought this distasteful issue up was to make sure you
understood that not everyone reads critically and with the kind of
intelligence you bring to a topic. And when a topic as emotional as
blindness comes up among people with diabetes, emotion really enters the
picture. Stir in a pinch of the usual newsgroup conflicts, and the
result is pretty predictable, if sad.
Hopefully when you have dug around and asked your questions, we'll all
end up knowing a lot more about how to protect our eyes. Or if nothing
else, we'll know this is another area where there's a lot we need to
know that no one has gotten around to figuring out--which seems to be
where all too much related to diabetes sits right now.
>>Keep doing what you're doing. I doubt you'll ever know how
>>many lives your web-site has improved.
>
>
>>Including mine.
>
>
> I second that!
>
You guys are sweet, and I am feeling a lot better about this whole
imbroglio.
Jefferson
> Let me be clear on this aspect: *EVERY* bit of data I've found, and
> also the opinions of both my specialists, all say the same thing:
> lowering the A1C is THE BEST thing you can do regarding retinopathy
> (and other complications).
This seems to be the consensus.
"The first is blood pressure control. It is clear that blood pressure
control slows the progression of diabetic retinopathy.2 There are now
provocative data to suggest that angiotensin-converting enzyme (ACE)
inhibitors may independently protect against the development or slow the
progression of retinopathy,3,4 perhaps through reductions in retinal
vascular endothelial growth factor levels.5
It also needs to be appreciated that rapid improvement of glycemic
control may cause a worsening of preexisting retinopathy in both type 1
and type 2 diabetes.6,7 Patients at highest risk for this are those with
longstanding poor control with some degree of preexisting retinopathy.8
Absence of any retinopathy at the initiation of improved control does
not result in any acute problems.
Patients at high risk of early worsening should have more frequent
ophthalmologic evaluations. Although not yet formally studied, a common
recommendation is a slower improvement in glycemic control for these
patients." Solurce: "Seeing" Between the Lines -
http://clinical.diabetesjournals.org/cgi/content/full/19/1/28
"Acute reduction of chronic hyperglycaemia can accelerate early diabetic
retinopathy. In adolescent patients with Mauriac's syndrome, this
phenomenon is related to an upregulation of subnormal serum IGF-1
levels." Evidence that upregulation of serum IGF-1 concentration can
trigger acceleration of diabetic retinopathy (link below)
My note: You are not likely to know your baseline serum IGF-1 levels. I
know that I have never been tested. While the patients were type 1, the
rapid big shift in glycemia with the associated changes in IGF-1 is the
issue. I don't see any reason for you to wait to get your IGF-1 level
measured. IGF-1, ng/ml, normal range 71-290 (>55 yr). I know you are
much younger than this, but this is a starting point for a reference range.
"RESULTS---Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA1c
>11%) to <10 mmol/l (HbA1c <8%) within 5 months increased serum IGF-1
levels by 70-220%. ... CONCLUSION---Upregulation of serum IGF-1
preceding retinal deterioration in these patients suggests a
cause-effect relation, consistent with earlier experimental and clinical
data. ... (Initially) Serum IGF-1 was low with levels ranging from 78 to
167 ng/ml ... IGF-1 levels increased by 70-220% immediately after
improving insulin therapy, while retinopathy progressed ..." Source:
Evidence that upregulation of serum IGF-1 concentration can trigger
acceleration of diabetic retinopathy -
http://bjo.bmjjournals.com/cgi/content/full/82/7/725
(snipped)
Frank
Jenny
--
mrslang
> > This isn't the first time if I've wondered whether bad temper and
> > paranoia might also be diabetic complications.
>
so susan since you brag about having such a good diet then what do you
blame your paranoia and being an a-hole on? hmmm?
TO ALL NEWBIES: please keep in mind when reading advice from susan and
other shere that you should first find out what the state of their
health is, how much they exercise, what medical problems they have, and
what kind of medications they are taking. this has a direct impact on
what advice they are giving to others. you'd be surprised to find out
the loudest voices in here are usally the ones with the most medical
problems. don't be bullied into being like them!
Sally
Chris J.
wrote:
>Chris J. wrote:
> >
>> I'm slightly leery of the DCCT data, as it's a T1 study. The
>> circumstances for a T1 at DX are quite different in this regard:
>> mainly, they are quite unlikely to have had sustained high BG's for as
>> long as a T2. There are also seem to be (not sure yet) differences in
>> the IGF-1 profile.
>
>The reason that DCCT data is cited is that it is the only large scale,
>long term study that found worsening and analyzed enough data to come to
>conclusions.
And those conclusions are slightly questionable for T2's under these
circumstances. I'm not saying they are wrong, only that I can't see
them as being definitive or proven.
>The UKPDS is the other corresponding study of Type 2s, but
>it did NOT find evidence of retinal worsening in it's population though
>they made the same dramatic decrease in blood sugar levels.
That I think depends on one's definition of dramatic. The studies
involved A1c changes of 2 to 4 %, and made little reference for actual
timeframe. Mine went down over 7 in three months, with the vast
majority of the decline taking place in a week.
>There are a few, much smaller studies of worsening in Type 2s put on
>insulin (your cite might be one of them.) Bbut one of the articles I
>cited for you back when you first posted (and don't have at hand, though
>the message is still out there and should be able to be found via
>Google)
I still have the links. I've been saving everything.
>If I recall correctly, that review explained that the problem with these
>studies was that the patients put on insulin in these studies were
>typically those who had been out of control for many years who were only
>put on insulin, very late, as a last resort. So there was a huge
>question as to whether their retinopathy was already pre-existent due to
>the decades of high blood sugar exposure. These after all, were patients
>whose A1cs had been over 10% for many years.
My A1c at Dx was 12.5, but my BG's at Dx were far higher than that
would indicate, probably due to my infection. However, a couple of
months before I was Dx'd, I had a full retinal exam, and no signs of
retinopathy were seen.
>Here's another relevant article for you from Medscape where the question
>is asked of experts from Joslin & Harvard Med School. They pretty much
>say the same thing as the Fong article, but they said it in 5/03. I've
>included most of the text for your convenience. Follow the link to see
>the references.
>
>http://www.medscape.com/viewarticle/452955
I've seen this one, but I missed some critical items (one very
critical to me personally), so I'll comment on those below and THANK
YOU!
>The Diabetes Control and Complications Trial (DCCT) definitively
>demonstrated that intensive control of blood glucose levels in patients
>with type 1 diabetes mellitus substantially reduces the risk of onset
>and progression of diabetic retinopathy.[1,2] In addition, the reduced
>risks of onset and progression of retinopathy associated with intensive
>therapy persisted at least 4 years beyond the conclusion of the DCCT,
>despite near convergence of hemoglobin A1c levels in the
>intensive-therapy and conventional-therapy groups.[3]
>The United Kingdom Prospective Diabetes Study (UKPDS) found similar
>benefits of intensive blood glucose control for patients with newly
>diagnosed type 2 diabetes.[4] In the Kumamoto study in Japan of patients
>with type 2 diabetes who were taking insulin, the benefits of intensive
>control of blood glucose levels were likewise demonstrated.[5]
>The DCCT documented "early worsening" of diabetic retinopathy in the
>study population.[6] Early worsening of retinopathy was defined as a
>3-step or more progression of retinopathy on the severity scale, the
>development of cotton wool spots and/or intraretinal microvascular
>abnormalities, and "clinically important retinopathy" if it occurred
>between baseline and the 12-month follow-up visit.
Mine certainly qualifies for that.
>Early worsening of
>retinopathy occurred in 13.1% of 711 patients assigned to intensive
>treatment and in 7.6% of 728 patients assigned to conventional
>treatment. Nevertheless, after 18 months this early worsening in
>retinopathy reversed,
THIS is something I missed: It *REVERSED*!!! I had seen some other
reports of it doing so in up to 50% of cases, but this seems to state
it as an absolute.
>There was
>no evidence that a gradual reduction in A1c levels reduced the risk of
>early worsening.
I still say I would like to see a study done on this, as I suspect
there never has been one. Even the mechanisms for early worsening
(normoglycemic re-entry) is only theoretical at this point.
>For patients with elevated
>hemoglobin A1c levels, careful retinal evaluation, close retinal
>follow-up, and laser photocoagulation as indicated are important
>components of care as intensive therapy is initiated.
This part I missed too: Get an exam as intensive therapy is
*INITIATED*
OK, I'm going to SHOUT here, to draw attention to this, for anyone
reading: For anyone with high A1C's at Dx, and going on insulin, GET A
RETINAL EXAM FROM AN OPTHAMOLOGISTS ASAP!!!!!
Chris J.
wrote:
>Chris J. wrote:
>>
>> I sincerely hope that is not the case! Jenny, if so, I'm deeply sorry
>> for my inadvertent role in this.
>
>The only thing I'm deeply sorry about is that you have to go through
>this nightmare with your eyes!
Thanks, but I'm dealing with it OK. The waiting is the hard part, but
I'll know a lot more in about a week.
Weirdly, I don't tend to stress out over major stuff. I have for
example stressed out a lot more over a single blood sugar spike than I
did over an arguably more serious aviation emergency: On my long
cross-country solo as a student pilot, I had a massive fuel leak which
required me to shut down both the engine and electrical system. It was
a low wing single engine (Piper Cherokee) that had very poor glide
characteristics, and also electric flaps (which I couldn't use). I had
to dead-stick that flying bomb into an emergency landing, no flaps (so
a much higher than normal touchdown speed, something I'd never done
before.) and make darn sure there were no sparks. Couldn't use the
brakes as I suspected fuel in them, too. I ended the rollout at an
airport restaurant, with several feet to spare. I had only one injury
from that: while walking away from the plane after the landing, my
knees went weak and I fell down and skinned my elbow. (go ahead and
laugh, I sure did!) But, I wasn't nervous or stressed until I was
safe.
>The only reason I brought this distasteful issue up was to make sure you
>understood that not everyone reads critically and with the kind of
>intelligence you bring to a topic. And when a topic as emotional as
>blindness comes up among people with diabetes, emotion really enters the
>picture. Stir in a pinch of the usual newsgroup conflicts, and the
>result is pretty predictable, if sad.
Thanks... I've been expecting trouble over this, and that doesn't
bother me (I have a very thick skin when needed). What does bother me
is anyone else (you in this case) being caught in the crossfire.
>Hopefully when you have dug around and asked your questions, we'll all
>end up knowing a lot more about how to protect our eyes. Or if nothing
>else, we'll know this is another area where there's a lot we need to
>know that no one has gotten around to figuring out--which seems to be
>where all too much related to diabetes sits right now.
That's my sole interest in keeping this topic going so long.
>You guys are sweet, and I am feeling a lot better about this whole
>imbroglio.
Not that anything on your site is capable of leading to blindness, but
I feel it would be a good idea to mention that I was already off of
insulin (and thus the damage probably done) *BEFORE* I read Jenny's
site.
Jenny
Chris,
The difficulty with the study of Type 2s is that for a definitive study
you need a very large group because in most studies Type 2s don't
develop this problem, so only a tiny number might even develop the
problem in your study. Then you need to have subjects broken into groups
and very well matched with controls and you need to have a protocol
where the speed is controlled at different speeds and the insulin types
controlled and the diet controlled. All this would be very expensive to
do, if it is even possible, and will not enrich any drug company--and in
fact might end up putting the insulin companies into a Vioxx-type
condition. So the chances of it being funded are zilch.
The other problem is that all the data shows that this is only a problem
for people with existing retinopathy. You would not even have fallen
into that group given your recent retinal exam showing no problem.
Every study I've seen shows that people with the tight control end up in
no worse shape and mostly in much better shape than those who don't
control tightly no matter what the initial worsening is. That is
probably why Wendy's doctor says go for the control.
And I still think your own situation may be complicated by a drug
reaction or something to do with the infection itself, which doctors
wouldn't be aware of. I have never yet found a doctor who was aware
that the drug I took causes permanent tinnitus, though I have found two
other people online who have suffered the same injury from the same
class of drugs.
Jenny
> Weirdly, I don't tend to stress out over major stuff. I have for
> example stressed out a lot more over a single blood sugar spike than I
> did over an arguably more serious aviation emergency: On my long
> cross-country solo as a student pilot, I had a massive fuel leak which
> required me to shut down both the engine and electrical system.
This is how the human mind works, When my Sweetie was taken to the
hospital in a state of near-shock, bleeding out, and went into
convulsions in the ER, I remember how strangely calm I felt. In the back
of my mind was the thought, "How odd. He might die, and I don't feel
anything." Same when my 11 year old daughter underwent two dreadful
surgeries on her jaw. Only when they were both clearly out of danger did
the emotions kick in. When my daughter was finally safe I ended up
getting extremely sick, probably from the stored up terror.
OTOH, maybe your story is also a pilot thing. My brother is a small
plane pilot and on his last trip across the country in a plane built in
1966 he'd call me every night with cheery reports on how his radio had
broken or how some piece had fallen off the plane requiring the
emergency landing in Nebraska where a guy at a gas station had tied
something together till he could get to an airport, etc. etc. I'd stay
up all night worrying, but he was having the time of his life. He did
end up losing his plane, eventually--it was turned over and smashed by a
downdraft when it was tethered at its home airport.
>
> Not that anything on your site is capable of leading to blindness, but
> I feel it would be a good idea to mention that I was already off of
> insulin (and thus the damage probably done) *BEFORE* I read Jenny's
> site.
>
And don't forget that Jennifer's advice which is what most newbies here
read first is NOT mine (though, of course, I would have been proud to
have written something that life-changing!)
Jefferson
> "RESULTS---Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA1c
> >11%) to <10 mmol/l (HbA1c <8%) within 5 months increased serum IGF-1
> levels by 70-220%. ... CONCLUSION---Upregulation of serum IGF-1
> preceding retinal deterioration in these patients suggests a
> cause-effect relation, consistent with earlier experimental and clinical
> data. ... (Initially) Serum IGF-1 was low with levels ranging from 78 to
> 167 ng/ml ... IGF-1 levels increased by 70-220% immediately after
> improving insulin therapy, while retinopathy progressed ..." Source:
> Evidence that upregulation of serum IGF-1 concentration can trigger
> acceleration of diabetic retinopathy -
> http://bjo.bmjjournals.com/cgi/content/full/82/7/725
Coming back to this same article.
For the one patient "CH" in this small study, a time course of both
IGF-1 and retinopathy progression was shown. Beginning intensive
therapy, serum IGF-1 concentration 167 ng/ml; 1 month, Retinopathy level
1, serum IGF-1 concentration 282 ng/ml; 5 months, Retinopathy level 2,
serum IGF-1 level 284 ng/ml; and 9 months, Retinopathy level 5, serum
IGF-1 level 307 ng/ml.
Inflate figure 7 "Dynamics of retinopathy level (A), serum IGF-1 (B),
HbA1c (C), before and after initiation of improved diabetes control
(time 0)..." in order to see the details. "Changes in IGF-1, HbA1c, and
retinopathy over time are depicted in Figure 7. All patients required
laser coagulation because of sight threatening macular oedema (according
to fluorescein angiography). Initially, serum IGF-1 levels increased in
all patients from low normal to high normal levels.10 After some months
with the HbA1c level around 8%-10% (corresponding to an average
glycaemia of 10-14 mmol/l), serum IGF-1 levels declined in three
patients (Fig 7). In patient CH IGF-1 levels did not decline, while
macular oedema persisted with reduction in visual acuity to 0.4. Laser
coagulation treatment was suspended. Only after the insulin dosage was
reduced in order to lower her IGF-1 level to 160 ng/ml, did macular
oedema resolve, and she regained full visual acuity. Laser treatment was
continued.
In all four cases, the institution of sufficient insulin substitution
induced an overshooting upregulation of serum IGF-1 within some weeks,
which 2-8 weeks later was followed by a significant progression of early
diabetic retinopathy to a sight threatening stage with macular oedema.
One patient with severe macular oedema was re-exposed to insulin
deficiency; while glycaemia and HbA1c levels increased serum IGF-1
decreased and the macular oedema improved. Paradoxical worsening of
pre-existing diabetic retinopathy after improved diabetes control (by
intensive insulin therapy) had been noted repeatedly, and termed
"normoglycaemic re-entry phenomenon".15-20"
Points of interest: It did not take very long to induce retinopathy
progression after upregulating serum IGF-1 (See the steep slope between
0 and 3 months for figure 7B). Even in the worst case presented, the
retinopathy was significantly reversed, including edema and visual acuity.
Frank
Jenny
>> Source: Evidence that upregulation of serum IGF-1 concentration can
>> trigger acceleration of diabetic retinopathy -
>> http://bjo.bmjjournals.com/cgi/content/full/82/7/725
>
This is an extremely interesting article, but it seems to me unclear
whether the cause of the IGF-1 upregulation in these 4 patients with
Type 1 who had been in extremely poor control "for extended periods of
time" is the lowering of blood sugar or the higher amounts of insulin
used. And to what extent the lowered IGF-1 levels were due to these Type
1s having no insulin production for years.
I looked up the normal range for IGF-1 and it looks like three of the
people in this study were still in that normal range when their IGF-1
was raised, which raises more questions. Do all people with diabetes
have lowered IGF-1 or just those who do NOT produce insulin any more
(the type 1s in this study.)
And what is a typical IR type 2's IGF-status? Since a lot of injected
insulin raises IGF-1, does a lot of self-produced insulin do the same
thing? In which case, IR Type 2s might have elevated IGF-1 to start with
and decreasing blood sugar, which often decreases the secretion of
insulin, might actually LOWER IGF-1.
Since this seems to be a type 1 problem in most cases, and the few Type
2s documented with it appear to be those who have burnt out their beta
cells completely, that would be a significant piece of information.
And one that would rule this out as a cause for Chris's retinopathy as
he still produces insulin. And he only was on injected insulin for a
very brief period. But then, to make it more complicated (again <g>)
Chris is wondering if he is an IR Type 2 or is more insulin sensitive.
On casual search, I can't find anything that answers the question of the
relationship between IGF-1 levels and one's own insulin production.
This is getting more and more interesting, given the relationship of
IGF-1 and other problems, like cancer. But at the same time, it also
may relate to why so many people who go on insulin report a huge
improvement in their energy levels. I certainly have gone from
narcoleptic to energetic over the past two months though my fasting
blood sugars have only dropped about 25 mg/dl.
bj
news:2b85025paev26mcua...@4ax.com...
>
>Weirdly, I don't tend to stress out over major stuff. I have for
> example stressed out a lot more over a single blood sugar spike than I
> did over an arguably more serious aviation emergency: On my long
> cross-country solo as a student pilot, I had a massive fuel leak which
> required me to shut down both the engine and electrical system. It was
> a low wing single engine (Piper Cherokee) that had very poor glide
> characteristics, and also electric flaps (which I couldn't use). I had
> to dead-stick that flying bomb into an emergency landing, no flaps (so
> a much higher than normal touchdown speed, something I'd never done
> before.) and make darn sure there were no sparks. Couldn't use the
> brakes as I suspected fuel in them, too. I ended the rollout at an
> airport restaurant, with several feet to spare. I had only one injury
> from that: while walking away from the plane after the landing, my
> knees went weak and I fell down and skinned my elbow. (go ahead and
> laugh, I sure did!) But, I wasn't nervous or stressed until I was
> safe.
>
Some people will do *anything* to park close to the door.
:)
bj
(your landing sounds even more exciting than the ones in dark & stormy
weather that I've endured (as an airline passenger) at Boston's
Logan....wondering if we'd stop before we hit the water....)
Jefferson
> This is an extremely interesting article, but it seems to me unclear
> whether the cause of the IGF-1 upregulation in these 4 patients with
> Type 1 who had been in extremely poor control "for extended periods of
> time" is the lowering of blood sugar or the higher amounts of insulin
> used. And to what extent the lowered IGF-1 levels were due to these Type
> 1s having no insulin production for years.
>
> I looked up the normal range for IGF-1 and it looks like three of the
> people in this study were still in that normal range when their IGF-1
> was raised, which raises more questions. Do all people with diabetes
> have lowered IGF-1 or just those who do NOT produce insulin any more
> (the type 1s in this study.)
Looking at figure 7B, 3 these people moved from lower normal IGF-1
levels to higher normal IGF-1 levels. The forth person went above normal
levels.
>
> And what is a typical IR type 2's IGF-status? Since a lot of injected
> insulin raises IGF-1, does a lot of self-produced insulin do the same
> thing? In which case, IR Type 2s might have elevated IGF-1 to start with
> and decreasing blood sugar, which often decreases the secretion of
> insulin, might actually LOWER IGF-1.
While earlier type 2s have hyperinsulinaemia, their insulin as measured
under the curve is typically less than a normalglycemic .
>
> Since this seems to be a type 1 problem in most cases, and the few Type
> 2s documented with it appear to be those who have burnt out their beta
> cells completely, that would be a significant piece of information.
> And one that would rule this out as a cause for Chris's retinopathy as
> he still produces insulin. And he only was on injected insulin for a
> very brief period. But then, to make it more complicated (again <g>)
> Chris is wondering if he is an IR Type 2 or is more insulin sensitive.
I don't know how rare Chris's case is, but the short time frame for
IGF-1 to jack up retinopathy progression suggest that type of diabetes
may not be that significant. Plus "Beta cells do appear to contain IGF-1
receptors, and IGF-1 has been shown to negatively regulate insulin
secretion."
http://www.mstp.northwestern.edu/M2JC_2003/Papers/Kulkarni_Holmgren.pd
(Note the IGF-1 was scarcely mentioned in this article.)
"... insulin-like growth factor (IGF)-I is classified primarily as a
mitogenic hormone and insulin as a metabolic hormone. Nevertheless,
increasing evidence suggests that IGF-I plays a role in glucose
homeostasis, lipolysis, proteolysis, and protein oxidation (14). It is
important to note that two of the insulin-sensitive tissues, namely
liver and adipose tissue, express little if any IGF-I receptors. Thus,
any direct effect of IGF-I on glucose metabolism would primarily be
mediated by its effects on either pancreatic insulin secretion or on
glucose uptake by muscle. ... IGFBPs. In the circulation, IGF-I is bound
to IGFBPs, six of which have been well characterized. IGFBPs increase
the half-life of IGF-I in circulation and regulate its action."
http://diabetes.diabetesjournals.org/cgi/content/full/50/5/1110
> On casual search, I can't find anything that answers the question of the
> relationship between IGF-1 levels and one's own insulin production.
I haven't looked at any of the following finds, but it isn't always easy
to frame a meaningful search criteria that limits to a specific topic.
IGF-1+"type 2"+diabetes+"insulin secretion" - 1,130 finds -
http://tinyurl.com/rkq8f. Articles seem to be extensively cited by
other publications. IGFBP-3 and IGFBP-1 relate to this topic as well.
I will leave it to the retina specialists and endocrinology experts.
> This is getting more and more interesting, given the relationship of
> IGF-1 and other problems, like cancer. (snipped)
Agreed. The IGF-1 topic has been discussed extensively in the
sci.life-extension newsgroup. Generally speaking the people on that
group are much more knowledgeable in physiology and biochemistry than
those in the diabetic newsgroups - http://tinyurl.com/s6wzc. On the
other hand some of them think humans are nothing but big rodents. ;)
Aging in men seems to relate to testosterone, DHEA, and IGF-1. DHEA
peaks in the 20s and declines significantly thereafter.
Frank
W. Baker
: > which is very important
: >to keep in mind before telling newbies with type 2 that they will go
: Jenny, I hope that's hyperbole on you part, as I'd NEVER make such a
: blanket statement to a newbie or anyone else!
: At most, and *ONLY* if supported by hard data, I'll be telling what
: happened to me, posting links to whatever I find about normoglycemic
: re-entry, and strongly suggesting that they see an ophthalmologist
: immediately if they are lowering very high BG's with insulin.
What worries me, Chris, is not that you would say such a stupid thing, but
that others might falsely accuse you of saying that when you didn't ,
perhaps because of not close redin or perhaps for some persoal adgenda, as
we have been seeing around here alot lately.
Wendy
Jenny
>
> Looking at figure 7B, 3 these people moved from lower normal IGF-1
> levels to higher normal IGF-1 levels. The forth person went above normal
> levels.
Yes, I noticed that. But I wondered whether type 2s would start out with
the low IGF-1, or if that low value had something to do with having no
insulin production at all.
>
> While earlier type 2s have hyperinsulinaemia, their insulin as measured
> under the curve is typically less than a normalglycemic .
But since the retinal worsening is documented as occurring in type 1s
with no insulin and type 2s of long duration with extremely high A1cs
who probably have lost their beta cells, it would be nice to know if
people who still make insulin have very low IGF-1 levels like these Type
1s.
> I don't know how rare Chris's case is, but the short time frame for
> IGF-1 to jack up retinopathy progression suggest that type of diabetes
> may not be that significant.
Chris was on insulin for less than a week. And before that he'd never
been told he was diabetic and had just had a retinal exam that showed
nothing. That's why one really would want to know more about the
relationship of IGF-1 levels to homemade insulin. If Chris had diabetes
before the infection, it was probably mild. For that matter, after the
infection went away, his diabetes was mild, too, and still is. A more
severe Type 2 would probably not be able to attain the levels he got
with diet alone, and certainly not within a couple days.
> Agreed. The IGF-1 topic has been discussed extensively in the
> sci.life-extension newsgroup. Generally speaking the people on that
> group are much more knowledgeable in physiology and biochemistry than
> those in the diabetic newsgroups - http://tinyurl.com/s6wzc. On the
> other hand some of them think humans are nothing but big rodents. ;)
>
> Aging in men seems to relate to testosterone, DHEA, and IGF-1. DHEA
> peaks in the 20s and declines significantly thereafter.
>
I think it is also safe to say that hanging out on Life Extension
newsgroups is right up there with the purchase of a red convertible for
signaling that a man has reached a Certain Age. <g>
Sleepyman
wrote:
Logan is the pit of the pits.
Sleepy
------------------------------------------------------------------
It is easier to make a saint out of a libertine than out of a prig.
-George Santayana (1863-1952)
------------------------------------------------------------------
Chris J.
wrote:
>Chris J. wrote:
>
>> Let me be clear on this aspect: *EVERY* bit of data I've found, and
>> also the opinions of both my specialists, all say the same thing:
>> lowering the A1C is THE BEST thing you can do regarding retinopathy
>> (and other complications).
>
>This seems to be the consensus.
>
>"The first is blood pressure control. It is clear that blood pressure
>control slows the progression of diabetic retinopathy.2 There are now
>provocative data to suggest that angiotensin-converting enzyme (ACE)
>inhibitors may independently protect against the development or slow the
>progression of retinopathy,3,4 perhaps through reductions in retinal
>vascular endothelial growth factor levels.5
I'll ask about getting back on an ACE. Lisinopril did not agree with
me, but others might.
I often wonder, though, if the benefits of ACe are truly independent
from lowered BP?
>It also needs to be appreciated that rapid improvement of glycemic
>control may cause a worsening of preexisting retinopathy in both type 1
>and type 2 diabetes.6,7 Patients at highest risk for this are those with
>longstanding poor control with some degree of preexisting retinopathy.8
>Absence of any retinopathy at the initiation of improved control does
>not result in any acute problems.
That wasn't true in my case: A couple of months pre Dx, I had a
retinal exam, and was fine, no retinopathy.
>Patients at high risk of early worsening should have more frequent
>ophthalmologic evaluations. Although not yet formally studied, a common
>recommendation is a slower improvement in glycemic control for these
>patients." Solurce: "Seeing" Between the Lines -
>http://clinical.diabetesjournals.org/cgi/content/full/19/1/28
This seems to be the big issue: is slower better, and if so how slow?
I've seen cites both ways on this one, and it's the issue I most need
to resolve.
>My note: You are not likely to know your baseline serum IGF-1 levels.
I don't; it's never been on my blood tests.
>I
>know that I have never been tested. While the patients were type 1, the
>rapid big shift in glycemia with the associated changes in IGF-1 is the
>issue. I don't see any reason for you to wait to get your IGF-1 level
>measured. IGF-1, ng/ml, normal range 71-290 (>55 yr). I know you are
>much younger than this, but this is a starting point for a reference range.
I'm still waiting to find out if my lab can test IGF-1. I should know
tomorrow. However, I am going to have a full blood test done if I do
this (might as well) and include thyroid, lipids, and A1c.
Thanks, Frank!!!!!
Chris J.
wrote:
>Chris was on insulin for less than a week.
Minor nit-pick, in case it's relevant: I was on insulin for 9 days,
although the last few days was just one shot per day, two to three
units.
>And before that he'd never
>been told he was diabetic and had just had a retinal exam that showed
>nothing. That's why one really would want to know more about the
>relationship of IGF-1 levels to homemade insulin. If Chris had diabetes
>before the infection, it was probably mild. For that matter, after the
>infection went away, his diabetes was mild, too, and still is.
I'm not sure if I'd classify my present diabetes as mild or not (I'm
not arguing, I just don't know), but my diabetic progress did seem to
match the battle against the infection. The infection was only
slightly active (perhaps an ounce of discharge per day) by the time I
got off of insulin. And, once it had cleared up completely a week
later, my BG's (and carb tolerance) were much more stable.
Hmmmm, now that I think about it, given my Bg profile and carb ratio,
I guess I might fit into the "mild" category, and that would explain
why I'm having an easier time (regarding BG's) than many.
>A more
>severe Type 2 would probably not be able to attain the levels he got
>with diet alone, and certainly not within a couple days.
I should mention here (as it might be relevant) that I have never been
on D&E alone. I've been on Metformin since Dx. I have no idea what my
BG's would be like without it (and I sure as heck don't want to find
out the hard way!).
Chris J.
<wba...@panix.com> wrote:
>Chris J. <ch...@noadress.com> wrote:
>: > which is very important
>: >to keep in mind before telling newbies with type 2 that they will go
>: >blind if they bring down their blood sugar with dietary control.
>
>: Jenny, I hope that's hyperbole on you part, as I'd NEVER make such a
>: blanket statement to a newbie or anyone else!
>
>: At most, and *ONLY* if supported by hard data, I'll be telling what
>: happened to me, posting links to whatever I find about normoglycemic
>: re-entry, and strongly suggesting that they see an ophthalmologist
>: immediately if they are lowering very high BG's with insulin.
>
>What worries me, Chris, is not that you would say such a stupid thing,
Wendy, I am quite capable of saying stupid things. I'm quite good at
it, actually. <Grin>
>but
>that others might falsely accuse you of saying that when you didn't ,
>perhaps because of not close redin or perhaps for some persoal adgenda, as
>we have been seeing around here alot lately.
I reluctantly agree with this analysis. But, I can't think of much i
can do about it.
Chris J.
wrote:
>"Chris J." <ch...@noadress.com> wrote in message
>news:2b85025paev26mcua...@4ax.com...
>>
>>Weirdly, I don't tend to stress out over major stuff. I have for
>> example stressed out a lot more over a single blood sugar spike than I
>> did over an arguably more serious aviation emergency: On my long
>> cross-country solo as a student pilot, I had a massive fuel leak which
>> required me to shut down both the engine and electrical system. It was
>> a low wing single engine (Piper Cherokee) that had very poor glide
>> characteristics, and also electric flaps (which I couldn't use). I had
>> to dead-stick that flying bomb into an emergency landing, no flaps (so
>> a much higher than normal touchdown speed, something I'd never done
>> before.) and make darn sure there were no sparks. Couldn't use the
>> brakes as I suspected fuel in them, too. I ended the rollout at an
>> airport restaurant, with several feet to spare. I had only one injury
>> from that: while walking away from the plane after the landing, my
>> knees went weak and I fell down and skinned my elbow. (go ahead and
>> laugh, I sure did!) But, I wasn't nervous or stressed until I was
>> safe.
>>
>
>Some people will do *anything* to park close to the door.
>:)
ROFL!!!!!!!!!!!!!!!!!!
>bj
>(your landing sounds even more exciting than the ones in dark & stormy
>weather that I've endured (as an airline passenger) at Boston's
>Logan....wondering if we'd stop before we hit the water....)
I've been in a few anxious moments on commercial airliners, including
severe turbulence (enough to cause a loss of several thousand feet of
altitude), a near mid-air collision over Dallas, and a partial stall
due to avoiding a mid-air near NY. I've had a few minor airline scares
such as a blown tire on landing, and an engine failure on takeoff,
too. Actually, all those bothered me more that my emergency as a
pilot, because as a passenger I was helpless. I've heard quite a few
people comment on logan approaches. I've never been there, so I can't
say. I do remember flying into Hong Kong (the old airport in Kowloon,
not the new one on the island) and you literally thread the tall
buildings on final.
The approach to the airport (when i had my fuel leak) was fun. I had
shut off the master electrical switch, so had no radio (or anything
else electrical, including transponder). I also didn't know if I had
enough altitude to make it to the airport. For a while, I thought I'd
have to set it down on a dirt road (which would have been fun with a
landing speed of over 100mph). Fortunately for me, I picked up a bit
of a tailwind, and stretched it out enough. But, I was a new pilot,
and had never done a dead-stick before in the type of aircraft, so I
darn near blew the landing. I had also never flown a straight in
approach before, nor landed without flaps, and I found I was coming in
hot on final (would have touched down too far down the runway). Being
dead stick, I couldn't go around, and I had to crab the thing at full
rudder, then keep reversing it, to increase my rate of decent. I
overdid it and barely cleared the airport fence. I held it off the
ground as long as I could, and set the wheels down on the threshold.
weirdly, it was probably the smoothest landing I ever made, didn't
even feel a bump.
I probably wasn't in too much danger at that point, as I'd have used
the breaks if I absolutely had to. I later learned that I'd have been
unlikely to set myself on fire by doing so, but I didn't know that
then.
Half an hour later, I'd fixed the leak and was in the air again, no
worse for wear (except for my skinned elbow).
Chris J.
wrote:
>Jefferson wrote:
>>> Source: Evidence that upregulation of serum IGF-1 concentration can
>>> trigger acceleration of diabetic retinopathy -
>>> http://bjo.bmjjournals.com/cgi/content/full/82/7/725
><details snipped>
>>
>
>This is an extremely interesting article, but it seems to me unclear
>whether the cause of the IGF-1 upregulation in these 4 patients with
>Type 1 who had been in extremely poor control "for extended periods of
>time" is the lowering of blood sugar or the higher amounts of insulin
>used. And to what extent the lowered IGF-1 levels were due to these Type
>1s having no insulin production for years.
>
>I looked up the normal range for IGF-1 and it looks like three of the
>people in this study were still in that normal range when their IGF-1
>was raised, which raises more questions. Do all people with diabetes
>have lowered IGF-1 or just those who do NOT produce insulin any more
>(the type 1s in this study.)
>
>And what is a typical IR type 2's IGF-status? Since a lot of injected
>insulin raises IGF-1, does a lot of self-produced insulin do the same
>thing?
This is one thing I've been trying to find out. Nothing so far.
>Since this seems to be a type 1 problem in most cases, and the few Type
>2s documented with it appear to be those who have burnt out their beta
>cells completely, that would be a significant piece of information.
>And one that would rule this out as a cause for Chris's retinopathy as
>he still produces insulin.
This is why I suspect (but don't know) that there *might* be a link
between speed of BG reduction and normoglycemic re-entry phenomenon.
My rate of BG decrease (and initial high BG's) were much more normal
for a T1 than a T2. So, too, was my probable pre-Dx BG profile: I had
most likely been high for a long time, but then went much higher for a
few weeks due to the infection.
>And he only was on injected insulin for a
>very brief period. But then, to make it more complicated (again <g>)
>Chris is wondering if he is an IR Type 2 or is more insulin sensitive.
If my HOMA analysis of my C-peptide/FBG ratio is accurate, I only have
60% insulin sensitivity, so have a 40% deficiency (as of 3 months
after Dx). On the other hand, my BG profile and carb response lately
is more similar to IGT: brief spikes, more of a delayed rather than a
deficient pancreatic response.
>On casual search, I can't find anything that answers the question of the
>relationship between IGF-1 levels and one's own insulin production.
Neither can I, but I'm going to keep looking.
Chris J.
wrote:
>Jefferson wrote:
>
>> "RESULTS---Reducing hyperglycaemia from >16 mmol/l (equivalent to HbA1c
>> >11%) to <10 mmol/l (HbA1c <8%) within 5 months increased serum IGF-1
>> levels by 70-220%. ... CONCLUSION---Upregulation of serum IGF-1
>> preceding retinal deterioration in these patients suggests a
>> cause-effect relation, consistent with earlier experimental and clinical
>> data. ... (Initially) Serum IGF-1 was low with levels ranging from 78 to
>> 167 ng/ml ... IGF-1 levels increased by 70-220% immediately after
>> improving insulin therapy, while retinopathy progressed ..." Source:
>> Evidence that upregulation of serum IGF-1 concentration can trigger
>> acceleration of diabetic retinopathy -
>> http://bjo.bmjjournals.com/cgi/content/full/82/7/725
>
>Coming back to this same article.
>
>For the one patient "CH" in this small study, a time course of both
>IGF-1 and retinopathy progression was shown. Beginning intensive
>therapy, serum IGF-1 concentration 167 ng/ml; 1 month, Retinopathy level
>1, serum IGF-1 concentration 282 ng/ml; 5 months, Retinopathy level 2,
>serum IGF-1 level 284 ng/ml; and 9 months, Retinopathy level 5, serum
>IGF-1 level 307 ng/ml.
IMHO, one big problem here is the use of A1c's: They are near useless
for documenting rapid changes in BG's.
>Inflate figure 7 "Dynamics of retinopathy level (A), serum IGF-1 (B),
>HbA1c (C), before and after initiation of improved diabetes control
>(time 0)..." in order to see the details. "Changes in IGF-1, HbA1c, and
>retinopathy over time are depicted in Figure 7. All patients required
>laser coagulation because of sight threatening macular oedema (according
>to fluorescein angiography). Initially, serum IGF-1 levels increased in
>all patients from low normal to high normal levels.10 After some months
>with the HbA1c level around 8%-10% (corresponding to an average
>glycaemia of 10-14 mmol/l), serum IGF-1 levels declined in three
>patients (Fig 7). In patient CH IGF-1 levels did not decline, while
>macular oedema persisted with reduction in visual acuity to 0.4. Laser
>coagulation treatment was suspended. Only after the insulin dosage was
>reduced in order to lower her IGF-1 level to 160 ng/ml, did macular
>oedema resolve, and she regained full visual acuity. Laser treatment was
>continued.
I've been studying this, and I find it very interesting, and the
reversal seen to be very encouraging. One thing it has convinced me
of, though, is that it's critical that I get an IGF-1 test ASAP. If my
IGF-1 is still high, even after months of stable BG's, I'll have to do
something to bring it down.
Hopefully, either time or meds can do this. I have no intention of
cranking up my BG's to what they were at my DX unless everything else
fails and the retinologist tells me it's hopeless and my sight will
soon be gone. At that point I would try absolutely anything as I'd
have nothing else to lose, but I'm a long way from that now. Actually,
I'm feeling more upbeat about all this.
>In all four cases, the institution of sufficient insulin substitution
>induced an overshooting upregulation of serum IGF-1 within some weeks,
>which 2-8 weeks later was followed by a significant progression of early
>diabetic retinopathy to a sight threatening stage with macular oedema.
>One patient with severe macular oedema was re-exposed to insulin
>deficiency;
That might be difficult in a T2. However, I do recall that the IGF-1
inhibitor you mentioned had some nasty pancreatic inhibitory effects,
and I now wonder if that's how it lowers IGF-1?
>while glycaemia and HbA1c levels increased serum IGF-1
>decreased and the macular oedema improved. Paradoxical worsening of
>pre-existing diabetic retinopathy after improved diabetes control (by
>intensive insulin therapy) had been noted repeatedly, and termed
>"normoglycaemic re-entry phenomenon".15-20"
>Points of interest: It did not take very long to induce retinopathy
>progression after upregulating serum IGF-1 (See the steep slope between
>0 and 3 months for figure 7B). Even in the worst case presented, the
>retinopathy was significantly reversed, including edema and visual acuity.
What worries me is that the BG changes in the subjects were minor
compared to mine, in both timescale and magnitude. Perhaps that's why
I have this problem in spite of no pre-existing retinopathy? I shudder
to think what would have happened if I'd already had retinopathy.
Chris J.
wrote:
>Chris J. wrote:
>> Weirdly, I don't tend to stress out over major stuff. I have for
>> example stressed out a lot more over a single blood sugar spike than I
>> did over an arguably more serious aviation emergency: On my long
>> cross-country solo as a student pilot, I had a massive fuel leak which
>> required me to shut down both the engine and electrical system.
>
>This is how the human mind works, When my Sweetie was taken to the
>hospital in a state of near-shock, bleeding out, and went into
>convulsions in the ER, I remember how strangely calm I felt. In the back
>of my mind was the thought, "How odd. He might die, and I don't feel
>anything." Same when my 11 year old daughter underwent two dreadful
>surgeries on her jaw. Only when they were both clearly out of danger did
>the emotions kick in. When my daughter was finally safe I ended up
>getting extremely sick, probably from the stored up terror.
Those kind of stresses are about the worst imaginable IMHO. I'm glad
you all made it ok.
>OTOH, maybe your story is also a pilot thing. My brother is a small
>plane pilot and on his last trip across the country in a plane built in
>1966 he'd call me every night with cheery reports on how his radio had
>broken or how some piece had fallen off the plane requiring the
>emergency landing in Nebraska where a guy at a gas station had tied
>something together till he could get to an airport, etc. etc.
ROFL!!!!!!!! Yep, he's a pilot. I never did understand the look of
horror on a friend's face when I mentioned that I needed to borrow a
pencil for my flight, so I could plug up a broken vacuum line so the
vacuum driven instruments would work.
>> Not that anything on your site is capable of leading to blindness, but
>> I feel it would be a good idea to mention that I was already off of
>> insulin (and thus the damage probably done) *BEFORE* I read Jenny's
>> site.
>>
>And don't forget that Jennifer's advice which is what most newbies here
>read first is NOT mine (though, of course, I would have been proud to
>have written something that life-changing!)
[Usenet logic]
You both have names beginning with Jenn, so therefor you must be the
same person, or close enough that you are each to blame for the other.
[/Usenet logic]
:-)
Jenny
>> A more
>> severe Type 2 would probably not be able to attain the levels he got
>> with diet alone, and certainly not within a couple days.
>
> I should mention here (as it might be relevant) that I have never been
> on D&E alone. I've been on Metformin since Dx. I have no idea what my
> BG's would be like without it (and I sure as heck don't want to find
> out the hard way!).
>
You're still mild. I could not attain the numbers you are getting even
with the low carb diet and metformin--and I'm still considered to have a
"mild" form.
I was never been able to get my fasting blood sugar into the 80s with
D&E & orals. Since my fasting blood sugar only used to go into the
95-100 range, doctors considered it normal, but they did not understand
how much dietary restriction I was using. Had I been eating anything
approaching the diet most doctors recommend to their Type 2s, I would
have quickly been identified as moderate, rather than mild.
It was only when I saw how many people here with type 2 were able to get
their fastings into the 80s with the same diet I use--or one that was
much less restrictive, and how many had A1cs under 5.5% when I was not
able to achieve that, I realized my control was not as good as I'd thought.
Jenny
> I'll ask about getting back on an ACE. Lisinopril did not agree with
> me, but others might.
>
> I often wonder, though, if the benefits of ACe are truly independent
> from lowered BP?
This month I learned, first-hand, about another effect of Diovan, the
ARB I was taking. My blood pressure went up some after I started the
insulin, so I took one 40 mg Diovan (the smallest dose they sell.) My
blood pressure plummeted (which is why I had to stop taking it last
spring.) But far more interesting, I spent the whole day having to eat
extra carbs as my blood sugar kept dropping-though my insulin dose was
the one that I usually have no problem with even if I postpone lunch.
The Diovan was pushing my blood sugar down another 10-15 mg/dl when it
was at its lowest.
I'd always wondered why I'd suddenly been able to lose weight without
changing my reducing diet when I started Diovan, after years of being
stalled on that same diet. Now I have my answer: for me, Diovan makes a
significant difference in my insulin resistance--way past what metformin
does.
Diovan is being used in a study, NAVIGATOR, to see if it reduces IR.
However, the anecdotal evidence from everyone who has ever tried Diovan
after hearing my experience is that it doesn't make a significant
difference for seriously IR type 2s. That it has such an effect on me,
probably has to do with the fact that I have some form of MODY
characterized by near-normal insulin sensitivity and defective insulin,
rather than Type 2.
This also explains why my blood sugar "suddenly deteriorated" last
spring. It isn't, as my doctors told me, the normal progression of type
2. It was losing the blood sugar lowering effect of the Diovan I'd been
on for years when the fainting attacks made me have to quit it. This
was quite cheering to me, as I had been depressed to think I was
deteriorating. In fact, I'm just back to where I used to be, though in
the old days my blood-calibrated meter (which reads 12% lower) made that
level seem closer to normal than looks now on my plasma-calibrated meter
. The fasting 120 mg/dl on the plasma-calibrated meter is only a 106 on
the blood-calibrated meter and at the time 110 mg/dl was considered
"normal".
>> My note: You are not likely to know your baseline serum IGF-1 levels.
>
> I don't; it's never been on my blood tests.
This is not a normally performed lab test. It looks like it's usually
only done in conjunction with growth hormone testing to identify rare
hormonal problems kids have that interfere with normal growth. This
means it is going to be very expensive. Be sure you check out the price
if you are paying for this yourself. You might get a nasty shock.
Since you don't have a baseline with which to compare it the results
might not be all that meaningful. In the study Frank pointed us to, 3 of
the 4 patients were still within the normal range when their IGF-1 had
surged. The significant finding was that it was much higher than the
previously low baseline. <sigh>
Jenny
>
> If my HOMA analysis of my C-peptide/FBG ratio is accurate, I only have
> 60% insulin sensitivity, so have a 40% deficiency (as of 3 months
> after Dx). On the other hand, my BG profile and carb response lately
> is more similar to IGT: brief spikes, more of a delayed rather than a
> deficient pancreatic response.
I would not give that C-peptide/FBG ratio much credence. In my case, the
result it gave did not correspond at all to the measure of insulin
sensitivity provided by how my body responds to 1 unit of R insulin.
Your brief bout of severe diabetes seems very likely to have been a
response to the infection. Is it possible that a bunch of your beta
cells shut down for a couple days due to some chemical imbalance caused
by the severe infection?
If that is the case, it may have turned out that even without the
insulin your blood sugars would d have dropped down swiftly from
extremely high back to near normal on their own (possibly permanently a
bit worse due to glucose toxicity wiping out beta cells), once the
infection resolved and the betas woke up. That might also have left you
with the same problem if it was caused by the blood sugar drop, rather
than some effect of the insulin, which is still unknown.
You might also want to take a look into the research on the effects of
temporary but very high blood sugars caused by severe infection or
cortisone which resolve after the crisis and whether they too have been
associated with your kind of problem.
Jenny
Laser
>> coagulation treatment was suspended. Only after the insulin dosage was
>> reduced in order to lower her IGF-1 level to 160 ng/ml, did macular
>> oedema resolve, and she regained full visual acuity. Laser treatment was
>> continued.
>
perilously close to levels of neuropathy leading to amputation--one had
"ulcers" and the others sensory defects and a skin problem that occurs
in people with neuropathy. So inducing "insulin deficiency" to prevent
blindness might have also made their chances of amputation go up.
What I really got from this article, is that if you are a Type 1,
letting your blood sugar go completely uncontrolled for 3 years is a
great way to guarantee an ugly outcome, no matter what interventions are
made later on.
>
> What worries me is that the BG changes in the subjects were minor
> compared to mine, in both timescale and magnitude. Perhaps that's why
> I have this problem in spite of no pre-existing retinopathy? I shudder
> to think what would have happened if I'd already had retinopathy.
Well, you are still making the assumption (understandable, but not
proven) that the retinopathy was caused by swiftly lowering the blood
sugar and was not a byproduct of the severe infection itself, the
lisinopril, or something else.
So many people with Type 2 report having their blood sugars as high as
yours--often for much longer than you had them, bringing them down very
quickly, and NOT having any problems, that you can't rule out the
possibility that something else is involved. Like me, you seem to have a
body with a long history of weird and uncommon reactions. <sigh>
Jefferson
>>"The first is blood pressure control. It is clear that blood pressure
>>control slows the progression of diabetic retinopathy.2 There are now
>>provocative data to suggest that angiotensin-converting enzyme (ACE)
>>inhibitors may independently protect against the development or slow the
>>progression of retinopathy,3,4 perhaps through reductions in retinal
>>vascular endothelial growth factor levels.5
>
>
> I'll ask about getting back on an ACE. Lisinopril did not agree with
> me, but others might.
>
> I often wonder, though, if the benefits of ACe are truly independent
> from lowered BP?
I believe that there is some association with insulin resistance/insulin
sensitivity. ACE inhibitors may lower IGF-1. IGF-1 may also be
associated with insulin resistance. So much of this endocrinology stuff
is relative. Consider the small volume of exogeneous insulin that it
takes to alter the blood glucose balance. The volume of IGF-1 is even
smaller. Relatively speaking a ship without a rudder might be an
analogy to a insulin dependent diabetic, but the rudder doesn't have to
be very large to control the ship. Weird stuff.
I hope that the various posts that you have received will assist you in
asking the appropriate questions on your upcoming visits with different
doctors. Much of this has been new to me as well as over my head, but I
tried to give it a shot. I don't want to get into bull jiving for the
sake of bull jiving. I haven't admitted this to many people who are my
acquaintance, but in the last 5 years my favorite phrase has become
"bull shit." ;)
Frank Roy
Jefferson, Md.
W. Baker
: On Mon, 27 Feb 2006 23:08:48 +0000 (UTC), "W. Baker"
: <wba...@panix.com> wrote:
Not much on your part, but you have built up quite a large fan club here
who, I believe, would be willing to come out swinging in support of you:-)
I don't know what causes peole to strt folloing people around the
vewsgroup just to make unkin sttements, but it certainly makes things less
hapy around here when it happens.
Wendy
Chris J.
wrote:
>> I often wonder, though, if the benefits of ACe are truly independent
>> from lowered BP?
>
>I believe that there is some association with insulin resistance/insulin
>sensitivity. ACE inhibitors may lower IGF-1. IGF-1 may also be
>associated with insulin resistance. So much of this endocrinology stuff
>is relative. Consider the small volume of exogeneous insulin that it
>takes to alter the blood glucose balance. The volume of IGF-1 is even
>smaller. Relatively speaking a ship without a rudder might be an
>analogy to a insulin dependent diabetic, but the rudder doesn't have to
>be very large to control the ship. Weird stuff.
Oh, how true. It's certainly a complex and confusing interplay of
things.
I'm going to look into Diovan, but I'm going to wait and see how
things go with my eyes next week, and what my IGF-1 results are. .
>> I'm still waiting to find out if my lab can test IGF-1. I should know
>> tomorrow. However, I am going to have a full blood test done if I do
>> this (might as well) and include thyroid, lipids, and A1c.
>
>I hope that the various posts that you have received will assist you in
>asking the appropriate questions on your upcoming visits with different
>doctors. Much of this has been new to me as well as over my head, but I
>tried to give it a shot.
Your input has been *EXTREEMLY* helpful to me in many ways. I often
take a day to reply to your posts, due to needing to study them, and
get a better understanding of the info.
Thank you so much for all your input on this and other issues!
> I don't want to get into bull jiving for the
>sake of bull jiving. I haven't admitted this to many people who are my
>acquaintance, but in the last 5 years my favorite phrase has become
>"bull shit." ;)
ROFL!!!!!!
Yes, of that, there is a never a shortage. :-)
Thanks again, Frank, for all you have done. I really appreciate it.
Chris J.
wrote:
>Chris J. wrote:
> Laser
>>> coagulation treatment was suspended. Only after the insulin dosage was
>>> reduced in order to lower her IGF-1 level to 160 ng/ml, did macular
>>> oedema resolve, and she regained full visual acuity. Laser treatment was
>>> continued.
>>
>It's worth noting that the patients in this study already were
>perilously close to levels of neuropathy leading to amputation--one had
>"ulcers" and the others sensory defects and a skin problem that occurs
>in people with neuropathy. So inducing "insulin deficiency" to prevent
>blindness might have also made their chances of amputation go up.
Worth noting, but IMHO very much worth doing anyway! This is IMHO one
of those cases where it's a value judgement and must be left up to the
patient: "What would you rather risk, your sight or your legs?". For
me personally, it would not be much of a decision: I'd risk absolutely
anything to save my sight.
>> What worries me is that the BG changes in the subjects were minor
>> compared to mine, in both timescale and magnitude. Perhaps that's why
>> I have this problem in spite of no pre-existing retinopathy? I shudder
>> to think what would have happened if I'd already had retinopathy.
>
>Well, you are still making the assumption (understandable, but not
>proven) that the retinopathy was caused by swiftly lowering the blood
>sugar and was not a byproduct of the severe infection itself, the
>lisinopril, or something else.
OK, I should be more clear on that: I am using the rapidly lowering BG
as my strongest candidate hypothesis, but I'm not trying to claim it's
factual. I do also agree that the other factors you mention could have
been either independently, or in combination with others, causal.
>So many people with Type 2 report having their blood sugars as high as
>yours--often for much longer than you had them, bringing them down very
>quickly, and NOT having any problems, that you can't rule out the
>possibility that something else is involved.
Very true.
>Like me, you seem to have a
>body with a long history of weird and uncommon reactions. <sigh>
Aren't we lucky? <G>
Chris J.
wrote:
>Chris J. wrote:
>>
>> If my HOMA analysis of my C-peptide/FBG ratio is accurate, I only have
>> 60% insulin sensitivity, so have a 40% deficiency (as of 3 months
>> after Dx). On the other hand, my BG profile and carb response lately
>> is more similar to IGT: brief spikes, more of a delayed rather than a
>> deficient pancreatic response.
>
>I would not give that C-peptide/FBG ratio much credence. In my case, the
>result it gave did not correspond at all to the measure of insulin
>sensitivity provided by how my body responds to 1 unit of R insulin.
Mine is suspect for another reason: one side of the equation gave
preposterous results. It claimed I had 137% pancreatic capacity!
I've been thinking of trying the one unit of R test, but not while
this IGF-1 issue is still unresolved. Also, how would I do it? I'm
assuming that I'd want to try it on stable between meal BG's, but
those run in the upper 70's if I'm not eating, and I wouldn't want to
lower them below that (and my liver might interfere if I tried).
My problem here is that my BG's, when not at their stability range
(80, plus or minus 5) are exceedingly volatile; they change very
quickly.
>Your brief bout of severe diabetes seems very likely to have been a
>response to the infection. Is it possible that a bunch of your beta
>cells shut down for a couple days due to some chemical imbalance caused
>by the severe infection?
That's quite possible. Or, the infection sent my IR through the roof
(as infections are well known to do).
This brings up another interesting theory: If insulin is to blame,
including that I produce myself, then still having most of my
pancreatic function could have been causal for my normoglycemic
re-entry phenomenon.
>If that is the case, it may have turned out that even without the
>insulin your blood sugars would d have dropped down swiftly from
>extremely high back to near normal on their own (possibly permanently a
>bit worse due to glucose toxicity wiping out beta cells),
I am not sure on that. I did have symptoms of diabetes (tiredness,
etc.) for over a year pre Dx, and I suspect that I had high BG's long
before the infection (and they could have caused the infection). I
also have one test showing sugar in my urine from 20 years ago.
One interesting coincidence: some forms of rice (mainly, when rice is
used as an ingredient) spike me far more than anything else, vastly
more than pure sugar. This is interesting because I made some dietary
changes a year before Dx: I went from being a very rare rice eater to
being a frequent one.
>You might also want to take a look into the research on the effects of
>temporary but very high blood sugars caused by severe infection or
>cortisone which resolve after the crisis and whether they too have been
>associated with your kind of problem.
That's a good idea! I'll do that. Thanks!
Chris J.
wrote:
>Chris J. wrote:
>> I'll ask about getting back on an ACE. Lisinopril did not agree with
>> me, but others might.
>>
>> I often wonder, though, if the benefits of ACe are truly independent
>> from lowered BP?
>
>This month I learned, first-hand, about another effect of Diovan, the
>ARB I was taking. My blood pressure went up some after I started the
>insulin, so I took one 40 mg Diovan (the smallest dose they sell.) My
>blood pressure plummeted (which is why I had to stop taking it last
>spring.) But far more interesting, I spent the whole day having to eat
>extra carbs as my blood sugar kept dropping-though my insulin dose was
>the one that I usually have no problem with even if I postpone lunch.
>The Diovan was pushing my blood sugar down another 10-15 mg/dl when it
>was at its lowest.
That is a very interesting result! I'm definitely considering Diovan.
If you can't tolerate the smallest dose, what about using a pill
cutter?
>I'd always wondered why I'd suddenly been able to lose weight without
>changing my reducing diet when I started Diovan, after years of being
>stalled on that same diet. Now I have my answer: for me, Diovan makes a
>significant difference in my insulin resistance--way past what metformin
>does.
That is interesting! I wonder if reducing the need for insulin also
reduces IGF-1 levels?
>Diovan is being used in a study, NAVIGATOR, to see if it reduces IR.
>However, the anecdotal evidence from everyone who has ever tried Diovan
>after hearing my experience is that it doesn't make a significant
>difference for seriously IR type 2s. That it has such an effect on me,
>probably has to do with the fact that I have some form of MODY
>characterized by near-normal insulin sensitivity and defective insulin,
>rather than Type 2.
>This also explains why my blood sugar "suddenly deteriorated" last
>spring. It isn't, as my doctors told me, the normal progression of type
>2. It was losing the blood sugar lowering effect of the Diovan I'd been
>on for years when the fainting attacks made me have to quit it. This
>was quite cheering to me, as I had been depressed to think I was
>deteriorating. In fact, I'm just back to where I used to be, though in
>the old days my blood-calibrated meter (which reads 12% lower) made that
>level seem closer to normal than looks now on my plasma-calibrated meter
>. The fasting 120 mg/dl on the plasma-calibrated meter is only a 106 on
>the blood-calibrated meter and at the time 110 mg/dl was considered
>"normal".
Ahhh. That does make sense.
I guess you are in the same boat as me: you would be better off with
high BP, so you could tolerate the ACE...
>>> My note: You are not likely to know your baseline serum IGF-1 levels.
>>
>> I don't; it's never been on my blood tests.
>
>This is not a normally performed lab test. It looks like it's usually
>only done in conjunction with growth hormone testing to identify rare
>hormonal problems kids have that interfere with normal growth. This
>means it is going to be very expensive. Be sure you check out the price
>if you are paying for this yourself. You might get a nasty shock.
Thanks, and it appears that my insurance sure won't cover this, nor
can my local lab do it, but frankly, right now I don't much care
regarding price. Money in the bank isn't going to be much use to me if
I'm not around to spend it.
>Since you don't have a baseline with which to compare it the results
>might not be all that meaningful. In the study Frank pointed us to, 3 of
>the 4 patients were still within the normal range when their IGF-1 had
>surged. The significant finding was that it was much higher than the
>previously low baseline. <sigh>
Now that is troubling, and it's been nagging at me, too. It looks to
me as if IGF-1 levels are more relational than absolute, so are very
individual. .
On the other hand, it might be very helpful to get an IGF-1 now, and
compare it to one later. If my IFG-1 does not decline and my
retinopathy continues to advance, it might be time to try medical
means of inhibiting my insulin production (basically, do what the T-1
in the study did).
Chris J.
wrote:
>Chris J. wrote:
>>> A more
>>> severe Type 2 would probably not be able to attain the levels he got
>>> with diet alone, and certainly not within a couple days.
>>
>> I should mention here (as it might be relevant) that I have never been
>> on D&E alone. I've been on Metformin since Dx. I have no idea what my
>> BG's would be like without it (and I sure as heck don't want to find
>> out the hard way!).
>>
>
>You're still mild. I could not attain the numbers you are getting even
>with the low carb diet and metformin--and I'm still considered to have a
>"mild" form.
I don't want to misrepresent, so I should clarify: Depending on how
you define fasting, my FBG's are either in the upper 70's-low 80's
range, or in the 90's. The reason is that I've got "Dawn phenomenon".
My Bg's crank up about an hour before I wake up, and then decline
about half an hour later. So, if you consider FBG to be my BG on
waking, then it's in the 90's. But, if I don't eat between meals, it's
usually in the upper 70's (sometimes low 80's) shortly thereafter and
between meals.
>I was never been able to get my fasting blood sugar into the 80s with
>D&E & orals. Since my fasting blood sugar only used to go into the
>95-100 range, doctors considered it normal, but they did not understand
>how much dietary restriction I was using. Had I been eating anything
>approaching the diet most doctors recommend to their Type 2s, I would
>have quickly been identified as moderate, rather than mild.
I can see how that would be a big problem.
>It was only when I saw how many people here with type 2 were able to get
>their fastings into the 80s with the same diet I use--or one that was
>much less restrictive, and how many had A1cs under 5.5% when I was not
>able to achieve that, I realized my control was not as good as I'd thought.
One thing to keep in mind about A1c is it's individually variable by
up to 1%. So, two people with identical BG's could have A1C's at 5.5%
and 6.5%. Personally, I trust my meter averages as a better indicator,
but that's just an opinion.
Chris J.
wrote:
>Chris,
>
>The difficulty with the study of Type 2s is that for a definitive study
>you need a very large group because in most studies Type 2s don't
>develop this problem, so only a tiny number might even develop the
>problem in your study. Then you need to have subjects broken into groups
>and very well matched with controls and you need to have a protocol
>where the speed is controlled at different speeds and the insulin types
>controlled and the diet controlled. All this would be very expensive to
>do,
Not to mention perhaps exposing some groups to increased risks.
>if it is even possible, and will not enrich any drug company--and in
>fact might end up putting the insulin companies into a Vioxx-type
>condition. So the chances of it being funded are zilch.
Yep...
>The other problem is that all the data shows that this is only a problem
>for people with existing retinopathy.
Not exactly. I've seen at least one report of it occurring in 2% of
people without retinopathy, and I'm one of them.
>Every study I've seen shows that people with the tight control end up in
>no worse shape and mostly in much better shape than those who don't
>control tightly no matter what the initial worsening is. That is
>probably why Wendy's doctor says go for the control.
OK, we might be discussing tangential issues here: Tight Control Vs.
Speed of tight control. I'm absolutely not questioning tight control.
Everything I've seen indicates tight control is the best defense. The
only thing I'm questioning is the SPEED of attaining tight control. I
think it might be that excessive speed is an aggravating factor in
normoglycemic re-entry phenomenon, but I don't know if that's true or
not.
>And I still think your own situation may be complicated by a drug
>reaction or something to do with the infection itself, which doctors
>wouldn't be aware of.
I think that's possible, too.
>I have never yet found a doctor who was aware
>that the drug I took causes permanent tinnitus, though I have found two
>other people online who have suffered the same injury from the same
>class of drugs.
Same with me and lisinopril: my Doc was unaware that it can cause
tingling in the fingers and toes.