Dead in Bed IGF-I hypothesis

[Jim Dumas]

With my recent paralysis while sleeping events (6 to date), I'm starting
to think the liver must be producing excess IGF-I that has no control
system to lower output (maybe neurological via hypothalamus, will have to
check for IGF-I Release Hormone, etc.), as the beta cells do. In any
case, my control system is oblivious to my NPH bedtime dosing, and
suggests a different mechanism for glucose disposal.

My hypothesis is the Insulin-like Growth Factor I hormone, produced by
the liver, is causing my nocturnal hypoglycemia/paralysis. My guess is
I've dodged the Dead in Bed bullet 6 times in the last 8 months. Since
the "Dead in Bed" syndrome predates these new designer analogue insulins,
then maybe this syndrome is just the normal progression of T1 DM under
special growth hormone stimulated conditions. (TBD of course.)

The "Dead in Bed" syndrome usually happens in youngsters, suggesting it
is related to growth hormones like IGF-I.

And needless to say, I have BG tablets throughout the house these days.
--
Jim
Still kick'n! Low tech T1 4/86, no complications.
Email mangled: change SeeSig2Fix to mindspring for utopia. (Who?!)

[willbill]

Sun, 11 Mar 2012 15:16:26 -0500, Jim Dumas wrote:

> With my recent paralysis while sleeping events (6 to date), I'm starting
> to think the liver must be producing excess IGF-I that has no control
> system to lower output (maybe neurological via hypothalamus, will have to
> check for IGF-I Release Hormone, etc.), as the beta cells do. In any
> case, my control system is oblivious to my NPH bedtime dosing, and
> suggests a different mechanism for glucose disposal.

Many t1s on m.h.d. have spoken out against t1 use of human-NPH.

> My hypothesis is the Insulin-like Growth Factor I hormone, produced by
> the liver, is causing my nocturnal hypoglycemia/paralysis. My guess is
> I've dodged the Dead in Bed bullet 6 times in the last 8 months. Since
> the "Dead in Bed" syndrome predates these new designer analogue insulins,
> then maybe this syndrome is just the normal progression of T1 DM under
> special growth hormone stimulated conditions. (TBD of course.)

Wow Jim, you take the cake! (see: negative idiom definition)

I've met several high degreed people in aerospace
and they couldn't fight their way out of a paper bag,
and I'm starting to think that this may be true of you.

Just keep doing what you're doing and maybe you won't
be so lucky when the 7th really bad hypo happens.

AFAICT, you still don't know how variable your sleeptime/morning
dawn phenomena is. Do you?

Quit fooling around! Get an insulin pump and find out!

> The "Dead in Bed" syndrome usually happens in youngsters, suggesting it
> is related to growth hormones like IGF-I.

AFAIK, you're not a youngster.

> And needless to say, I have BG tablets throughout the house these days.

Far better to use real food for lows, when possible.

Since you used to help Groves with his computers...

... I bet $10 to a doughnut (figuratively) that
when Groves found out that you'd gone to the trouble
to order the very very new lispro analog (aka Humalog)
from Switzerland (in 1996?) he thought you were
out of your mind.

Bill t1 since '57

[Jim Dumas]

On Sun, 11 Mar 2012 19:26:23 -0500, willbill wrote:

> ... I bet $10 to a doughnut (figuratively) that when Groves found out
> that you'd gone to the trouble to order the very very new lispro analog
> (aka Humalog) from Switzerland (in 1996?) he thought you were out of
> your mind.

Well, Groves was quite the pistol, and I did use Humalog in front of
him. But he was too distracted with some issue at the time to give me
much trouble. The group went to Washington DC about 9/2000 to push the
beef insulin importation issue and I was this only non-bovine user that
went (so caught some flack from others but not Groves over my Human
use). So they all saw me use Humalog while there. But it was in a Novo
Pen so not obvious.

I see you're in rare form today, Dude. So I'll pass on the jabs.

[willbill]

Sun, 11 Mar 2012 20:22:43 -0500, Jim Dumas wrote:

> On Sun, 11 Mar 2012 19:26:23 -0500, willbill wrote:

>> ... I bet $10 to a doughnut (figuratively) that when Groves found out
>> that you'd gone to the trouble to order the very very new lispro analog
>> (aka Humalog) from Switzerland (in 1996?) he thought you were out of
>> your mind.

> Well, Groves was quite the pistol, ...

> I see you're in rare form today, Dude. So I'll pass on the jabs.

Two other t1s I remember are ennis, who supported groves
with a new site, and then changed his mind. Is he still alive?

And Mike Gray, an adult onset t1 who preferred human-NPH.
Haven't seen any sight of him for some time. I wonder if
the NPH got to him?

While we're both being polite (I didn't think my last post
merited "rare form"), and talking about "pistol" - another
was/is Mr. Gray the quintessential curmudgeon on m.h.d.

I remember once posting something like this
either to him or someone else:

... Look up in the sky!
It's a bird!
No!
It's a plane!
No!
It's superman!
NO!
It's Mr. Gray!!

:)

Bill t1 since '57

[Jim Dumas]

On Sun, 11 Mar 2012 21:22:54 -0500, willbill wrote:

> Two other t1s I remember are ennis, who supported groves with a new
> site, and then changed his mind. Is he still alive?
>
> And Mike Gray, an adult onset t1 who preferred human-NPH. Haven't seen
> any sight of him for some time. I wonder if the NPH got to him?

I remember having some argument with Gary Ennis. But why and what have
been lost.

I don't think I ever interacted with Mike Gray, but the cupboards are
dusty.

It looks like my trouble with IGF-I starts with growth hormone releasing
factor (released in the brain) that stimulates the liver to produce IGF-
I. IGF-I does have direct effects on glucose uptake and is independent
of insulin (but evolved away from insulin).

My initial paralysis last July were before I began my exercise regimen.
In September with 2 more paralysis events, I cut the NPH dose in half:
from 16U to 8U at bedtime. Then a few weeks ago, 2 days post exercise, I
had another paralysis event. So dropped NPH from my regimen.

I began the exercise experiments to see if I could achieve similar
success in no exogenous insulin requirements, as I did in the honeymoon
phase of T1. This would allow to to estimate endogenous insulin
production (have test data from Joslin research on me from 1986,
insulinemia assays that showed I was not producting much insulin under IV
glucose load). It looks like I am doing better today, 26 years later,
than back in 1986. Suggesting that some new glucose disposal mechanism
has kicked in.

Last night I was freaked out and chose not to dose at bedtime. Fasting BG
was 340 mg/dl but this was ~3 days post training last Friday morning
(rained yesterday). But will train today and see what happens.

But GRF (growth hormone releasing factor) is my culprit. Or perhaps the
lack of the inhibiting hormone somatostatin.

So will using training to push the GRF envelope.

[Jim Dumas]

On Sun, 11 Mar 2012 15:16:26 -0500, Jim Dumas wrote:

> My hypothesis is the Insulin-like Growth Factor I hormone, produced by
> the liver, is causing my nocturnal hypoglycemia/paralysis. My guess is
> I've dodged the Dead in Bed bullet 6 times in the last 8 months. Since
> the "Dead in Bed" syndrome predates these new designer analogue
> insulins, then maybe this syndrome is just the normal progression of T1
> DM under special growth hormone stimulated conditions. (TBD of course.)
>
> The "Dead in Bed" syndrome usually happens in youngsters, suggesting it
> is related to growth hormones like IGF-I.

One article I've read suggests there is a 6% lifetime risk of Dead-in-Bed
for all T1s. So it happens in elder T1s too.

In my case, all it would take to cancel my subscription is seizure of my
diaphragm from hypoglycemia. So I think the cause of death for the Dead
in Bed T1s is suffocation. This abstract captured CGMS data for a 23 yo
male in 2010:

http://www.ncbi.nlm.nih.gov/pubmed/19833577

Cause of death was unknown.

So all T1s are at risk for Dead in Bed.

[Alan Mackenzie]

Hi, Jim,

Jim Dumas <j-d...@seesig2fix.com> wrote:
> On Sun, 11 Mar 2012 15:16:26 -0500, Jim Dumas wrote:

>> My hypothesis is the Insulin-like Growth Factor I hormone, produced by
>> the liver, is causing my nocturnal hypoglycemia/paralysis. My guess is
>> I've dodged the Dead in Bed bullet 6 times in the last 8 months. Since
>> the "Dead in Bed" syndrome predates these new designer analogue
>> insulins, then maybe this syndrome is just the normal progression of T1
>> DM under special growth hormone stimulated conditions. (TBD of course.)

>> The "Dead in Bed" syndrome usually happens in youngsters, suggesting it
>> is related to growth hormones like IGF-I.

> One article I've read suggests there is a 6% lifetime risk of Dead-in-Bed
> for all T1s. So it happens in elder T1s too.

> In my case, all it would take to cancel my subscription is seizure of my
> diaphragm from hypoglycemia. So I think the cause of death for the Dead
> in Bed T1s is suffocation. This abstract captured CGMS data for a 23 yo
> male in 2010:

> http://www.ncbi.nlm.nih.gov/pubmed/19833577

> Cause of death was unknown.

> So all T1s are at risk for Dead in Bed.

Even those using natural insulin? I always thought that it was the
introduction of GE insulin which gave rise to the Dead In Bed Syndrome.

--
Alan Mackenzie (Nuremberg, Germany).

[Charly Coughran]

Jim Dumas <j-d...@SeeSig2Fix.com> wrote in
news:pan.2012.03...@seesig2fix.com:

> With my recent paralysis while sleeping events (6 to date),
> I'm starting to think the liver must be producing excess
> IGF-I that has no control system to lower output (maybe
> neurological via hypothalamus, will have to check for IGF-I
> Release Hormone, etc.), as the beta cells do. In any case,
> my control system is oblivious to my NPH bedtime dosing,
> and suggests a different mechanism for glucose disposal.
>
> My hypothesis is the Insulin-like Growth Factor I hormone,
> produced by the liver, is causing my nocturnal
> hypoglycemia/paralysis. My guess is I've dodged the Dead
> in Bed bullet 6 times in the last 8 months. Since the
> "Dead in Bed" syndrome predates these new designer analogue
> insulins, then maybe this syndrome is just the normal
> progression of T1 DM under special growth hormone
> stimulated conditions. (TBD of course.)
>
> The "Dead in Bed" syndrome usually happens in youngsters,
> suggesting it is related to growth hormones like IGF-I.
>
> And needless to say, I have BG tablets throughout the house
> these days.

The papers that I have encountered on the corelation between
hypoglycemia or severe hypoglycemia and diabetic mortality have
been very mixed. I have not made a sytematic review, but my
impression is weak correlations with some likely counfounding
variables or no correlations. One paper, based on ACCORD, had
the interesting conclusion that, "A significantly lower
[mortality] risk was observed in the intensive arm compared
with the standard arm in participants who had experienced at
least one hypoglycaemic episode requiring medical assistance
(adjusted HR 0.55, 95% CI 0.31 to 0.99)." I would have
expected the opposite that intensive treatment tends to result
in more hypoglycemia.

Article at:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803744/?
tool=pubmed

--
______________________
ccou...@DELETE-TO-RESPOND-UCSD.EDU

[Jim Dumas]

On Tue, 13 Mar 2012 19:29:45 +0000, Alan Mackenzie wrote:

>> So all T1s are at risk for Dead in Bed.
>
> Even those using natural insulin? I always thought that it was the
> introduction of GE insulin which gave rise to the Dead In Bed Syndrome.

Hi Alan,

Based on my observations of hypoglycemic events by/in Dave Groves on
bovine insulin, it seemed he lost cognizance when hypoglycemic just like
the rest of us long-term T1s on an intensive insulin therapy. So with my
n=1 sample, I would anticipate similar results for animal source insulins
with regards to Dead-in-Bed.

One of the recent articles demonstrated 6 of 16 normals in the control
group failed to wake up when hypoglycemic. So it follows, IMO, that
animal source insulins would only provide a small level of protection
from hypoglycemic induced seizures.

This Dead-in-Bed syndrome is something I ignored for years, thinking it
could never happen to me. After a few shocking WTFs, I decided to take
action. I thought I was having a stroke the first time it happened.

In any case, the trick is to have a strong enough, hypoglycemic-induced,
adrenaline response to wake up before a seizure occurs. The literature
shows death from Dead-in-Bed happens around a BG of 25-30 mg/dl for 2-4
hours. Nocturnal hypoglycemic-induced adrenaline response has a lower BG
value than an adrenaline response in the waking hours. So you can not
use the diurnal response data to infer nocturnal protection.

So everybody should be careful about nocturnal hypoglycemia.

[Jim Dumas]

Hi Charlie,

This study was for/with only T2s:

Participants: Patients were eligible for the ACCORD study if they had
type 2 diabetes, a glycated haemoglobin (haemoglobin A1C) concentration
of 7.5% or more during screening, and were aged 40-79 years with
established cardiovascular disease or 55-79 years with evidence of
subclinical disease or two additional cardiovascular risk factors.


So I think the better outcome for intensive therapy with T2s could be
very different than that of T1s. Moreover, if endogenous human growth
hormone is a cofactor in the hypoglycemic-induced, Dead-in-Bed event,
then older T2s are not the correct group to be testing for "a link
between hypoglycaemia and mortality."

My personal exercise-induced hGH hypoglycemia provided a 30 mg/dl this
Monday before bedtime. I corrected the hypoglycemia with a very large
amount of glucose which surprised me. I tried to duplicate this event
with the same exercise the next day, but it did not happen this time
(last night). No nocturnal basal insulin was taken each time. But a
different dinner with different respective insulin dosing was taken.

So still working on this mechanism of action.

[Jim Dumas]

On Wed, 14 Mar 2012 08:21:35 -0500, Jim Dumas wrote:

> My personal exercise-induced hGH hypoglycemia provided a 30 mg/dl this
> Monday before bedtime. I corrected the hypoglycemia with a very large
> amount of glucose which surprised me. I tried to duplicate this event
> with the same exercise the next day, but it did not happen this time
> (last night). No nocturnal basal insulin was taken each time. But a
> different dinner with different respective insulin dosing was taken.

I should provide more information on the differences. The hypoglycemic
event on Monday used a 15U dose (@ 7:52pm when euglycemic) of Humalog
with a carbo-loading large meal (two servings) of mostly rice. Dinner on
Tuesday was the 405 FBG mostly protein, (but 4 slices of bread as
carbohydrate with a banana for potassium/muscle cramping), with two Human
Regular 5U doses for fast subcutaneous absorption. I did not suffer
hypoglycemia last night, but did not collect much data. FBG was 394 mg/
dl. So will try it again, maybe today, muscle glycogen stores permitting.

But R seems better than Humalog for training effects, IMO.

[Charly Coughran]

I did not mean to indicate the reference to be suitable to your
particular circumstances. I added it as an example of the
mixed and odd conclusions found in some of papers I have read
over. Sorry for not being clear.

--
______________________
ccou...@DELETE-TO-RESPOND-UCSD.EDU

[Jim Dumas]

On Wed, 14 Mar 2012 18:01:36 +0000, Charly Coughran wrote:

> I did not mean to indicate the reference to be suitable to your
> particular circumstances. I added it as an example of the mixed and odd
> conclusions found in some of papers I have read over. Sorry for not
> being clear.

Hi Charly,

I did another 22 miles for the third consecutive day. Actually training
harder now than in the past: college and time of DM Dx. Muscle glycogen
stores low as I couldn't sprint much, but averaged 16.7 mph with 4 red
light stops and 8 mph headwind going home. Average heart rate was 145 HB/
min giving an intensity of 145 * 60 / 16.7 = 521 avg HB/mile. This
compares to the lowest intensity to date of 511 avg HB/mi yesterday.

So today is another GRF -> hGH -> IGF-I axis test. But will only use
Human R tonight, as Humalog seems to lockup hepatic BG homeostasis
function for my metabolism with training effects.

Certainly tired, so will under-dose as well.

[Jim Dumas]

On Wed, 14 Mar 2012 15:42:14 -0500, Jim Dumas wrote:

> Humalog seems to lockup hepatic BG homeostasis function for my
> metabolism with training effects.

I guess I should explain this observation in more detail. My 30 mg/dl
hypoglycemia for a carbo-heavy, two serving meal, used the same dose that
I typically do with Human Regular (15U) for this type of carbo-loading
meal. 4.5 hours post Humalog dose was this 30 mg/dl BG assay. This was
at 12:15am at the start of the usual hGH spike that lasts for 2+ hours.
So I knew I was in trouble and was very surprised at how slow BG rose
when Humalog action should be almost finished.

So Humalog has such a strong pulse, the liver fails to keep BG normalized
properly. Humalog, at least for me while training, seems to lock-up the
liver.

I'm cooking dinner now with potatoes to carbo-load. So different meal.

[Jim Dumas]

On Wed, 14 Mar 2012 17:12:41 -0500, Jim Dumas wrote:

> On Wed, 14 Mar 2012 15:42:14 -0500, Jim Dumas wrote:
>
>> Humalog seems to lockup hepatic BG homeostasis function for my
>> metabolism with training effects.
>
> I guess I should explain this observation in more detail. My 30 mg/dl
> hypoglycemia for a carbo-heavy, two serving meal, used the same dose
> that I typically do with Human Regular (15U) for this type of
> carbo-loading meal. 4.5 hours post Humalog dose was this 30 mg/dl BG
> assay. This was at 12:15am at the start of the usual hGH spike that
> lasts for 2+ hours. So I knew I was in trouble and was very surprised at
> how slow BG rose when Humalog action should be almost finished.
>
> So Humalog has such a strong pulse, the liver fails to keep BG
> normalized properly. Humalog, at least for me while training, seems to
> lock-up the liver.
>
> I'm cooking dinner now with potatoes to carbo-load. So different meal.

I decided to add an extra potato to the meal last night and take the
usual Human R 15U dose for comparison to the Humalog effects. I did wake
up about 3am wet (on the couch) with an epinephrine induced hypoglycemic
event. The Human R dose was taken at 6:37pm the previous day. So 8.5
hours later I received a wake up signal. It was so mild that I changed
PJs and went to bed. Fasting BG 13 hours post R dose and 23 hours post
Human Ultralente dose (14U), was 70 mg/dl.

The computer model gives a fasting insulin basal rate of 0.36 U/hour
insulin-receptor binding at the time of the FBG assay. In the past, I
have tried to keep this fasting basal rate near 0.7U/hour. The 3am
hypoglycemia (IGF-I peak) and the significantly lower basal rate suggest
I was hammered by IGF-I induced glucose disposal this morning. These
effects continue for hours from the plasma binding protein that keeps IGF-
I in circulation. IGF-I is stimulated by the growth hormone spike from
midnight to 2am on a 4 hour "duty cycle" in engineering terms.

My math model for exercise does not model the accumulative training
effects for back-to-back consecutive training days. I should have
lowered the R dose by 1-2U for these accumulative effects. So will try
to add this to the math today, a day off to let a pulled muscle heal.
This left quad started to bother me this morning.

I might also be interesting to add the glucose disposal effects for IGF-I
to my current computer model, as the Intensity and Duration parameters
for the exercise session could be used to estimate the impact of IGF-I
release. Will have to think about it.

So the triple-session hypo was very mild.

[Jim Dumas]

On Thu, 15 Mar 2012 07:08:14 -0500, Jim Dumas wrote:

> It might also be interesting to add the glucose disposal effects for

> IGF-I to my current computer model, as the Intensity and Duration
> parameters for the exercise session could be used to estimate the impact
> of IGF-I release. Will have to think about it.

This leads to adding exercise effects as a fictitious insulin preparation
that is only in the last compartment (interstitial fluid compartment), so
a fictitious bolus (simple exponential decay) is delivered to the
interstitial fluid compartment for calculation of insulin doses with
exercise effects.

IGF-I, on the other hand requires 3 biological compartments: plasma
binding protein, plasma and interstitial fluid compartments. The IGF-I
bolus will be "launched" at 1am with an interstitial fluid peak at
2-3am. The exercise Intensity and Duration parameters with set the bolus
size.

So exercise has two major effects that lower insulin requirements.

[Jim Dumas]

On Thu, 15 Mar 2012 10:49:34 -0500, Jim Dumas wrote:

> This leads to adding exercise effects as a fictitious insulin
> preparation that is only in the last compartment (interstitial fluid
> compartment), so a fictitious bolus (simple exponential decay) is
> delivered to the interstitial fluid compartment for calculation of
> insulin doses with exercise effects.

I take that back. The Bergman "remote compartment" that I use, has a set
decay rate that is different from the exercise decay rate. So an
exercise remote compartment must be added to the Bergman minimal model
and the results of insulin-receptor binding summed for these two
different exponential decays.

So more work mathematically than I initially thought.

[Jim Dumas]

On Thu, 15 Mar 2012 11:16:52 -0500, Jim Dumas wrote:

> On Thu, 15 Mar 2012 10:49:34 -0500, Jim Dumas wrote:
>
>> This leads to adding exercise effects as a fictitious insulin
>> preparation that is only in the last compartment (interstitial fluid
>> compartment), so a fictitious bolus (simple exponential decay) is
>> delivered to the interstitial fluid compartment for calculation of
>> insulin doses with exercise effects.
>
> I take that back. The Bergman "remote compartment" that I use, has a
> set decay rate that is different from the exercise decay rate. So an
> exercise remote compartment must be added to the Bergman minimal model
> and the results of insulin-receptor binding summed for these two
> different exponential decays.
>
> So more work mathematically than I initially thought.

Just to say that the model for exercise effects on insulin dosing is
independent of the exogenous insulin transport model, like the Bergman
Minimal Model. So it can be added as an "exercise space" subsystem to
any insulin transport model. It includes hepatic/muscle glycogen store
rebuilding as well as IGF-I induced glucose uptake from 1am to about 7am
with a simple 3 equal compartment biological model for IGF-I release.
The IGF-I peak "insulin action" time is set to 2:30am from personal data.

Any physiologist will state that n=1 is all that is required to set up
the mathematical model. Since the model is only for personal use, n=me
is all that I need (or want).

It is also helpful to see these effects as an insulin equivalent.

[Jim Dumas]

On Fri, 16 Mar 2012 08:19:35 -0500, Jim Dumas wrote:

> IGF-I induced glucose uptake from 1am to about 7am with a simple 3 equal
> compartment biological model for IGF-I release. The IGF-I peak "insulin
> action" time is set to 2:30am from personal data.

This is primarily for Bill. My nocturnal basal requirements will try to
use this IGF-I caused glucose uptake. Hopefully, this exercise effect
can be used therapeutically. If I can, then I will probably be the first
to incorporate this endogenous capability quantitatively into my insulin
therapy. (Today is another 22 mile test and broke my records so lowest
average heart beats/mile of 504 vs. 511 on Tuesday.)

But I think this is also active without exercise and caused the initial
four of my seizures last year. So how to determine what triggered this
without exercise. (Wondering if NPH's protamine triggers something in
the hGH axis, as strange as that seems, like preventing the inhibitor for
hGH, somatostatin.)

So it's interesting if it works. But may identify a tumor so scary too.

[willbill]

Fri, 16 Mar 2012 19:24:35 -0500, Jim Dumas wrote:

> This is primarily for Bill. My nocturnal basal requirements will try to
> use this IGF-I caused glucose uptake. Hopefully, this exercise effect
> can be used therapeutically. If I can, then I will probably be the first
> to incorporate this endogenous capability quantitatively into my insulin
> therapy. (Today is another 22 mile test and broke my records so lowest
> average heart beats/mile of 504 vs. 511 on Tuesday.)

With regard to you being "first" I rather doubt it.

I remember when I saw a t1 on m.h.d. post that he
was only using human-R as his only insulin, with multiple
injections through the day.

Wow! I thought he was unique!

Then another t1 turned up doing that, then another...

So not unique at all.

I myself sometimes move to using only beef-R
for up to 5 days without any background insulin.
Surely an easier thing to do, given that beef-R
has residual that is slightly past 12 hours.

> But I think this is also active without exercise and caused the initial
> four of my seizures last year. So how to determine what triggered this
> without exercise. (Wondering if NPH's protamine triggers something in
> the hGH axis, as strange as that seems, like preventing the inhibitor for
> hGH, somatostatin.)
>
> So it's interesting if it works. But may identify a tumor so scary too.

Other than the nasty nighttime hypos, is ther any
real reason to think that you have a brain tumor?

Coz I doubt that you do.

Odds are your nighttime hypos are due to your
use of human-NPH, which is not uncommon with
t1 use of *peaky* human-NPH at bedtime.

Bill t1 since '57

[willbill]

Tue, 13 Mar 2012 19:29:45 +0000 (UTC), Alan Mackenzie wrote:

> Jim Dumas wrote:

>> So all T1s are at risk for Dead in Bed.

> Even those using natural insulin? I always thought that it was the
> introduction of GE insulin which gave rise to the Dead In Bed Syndrome.

IMO odds are HUGE that more t1 diabetics are at risk
*now* of Dead in Bed given that human-NPH is way
peakier than the best selling beef-NPH of the past.

AFAIK Dead in Bed has existed for t1 diabetics
since the early days of commercial insulin (1923?)

When Doc Biggs posted on m.h.d. one of his more interesting
posts (of many) was that the American "cause of death"
certificate was generally highly inaccurate.

You really don't think that the whole Dead in Bed thing
is going to have accurate data at it's disposal?

Bill t1 since '57

[Jim Dumas]

On Fri, 16 Mar 2012 19:24:35 -0500, Jim Dumas wrote:

> Hopefully, this exercise effect can
> be used therapeutically. If I can, then I will probably be the first to
> incorporate this endogenous capability quantitatively into my insulin
> therapy.

An initial estimate from basal requirements suggests the IGF-I glucose
uptake from exercise is equivalent to a 5U Human R bolus at 1am. Still
analyzing the data, so have yet to settle on a number. But 5U is more
than enough "equivalent" insulin to cause seizure when already
hypoglycemic from the strong pulse of Humalog for dinner following an
intense exercise session.

Next, in reviewing my 1990 vintage insulin therapy, I used 40U Human R
and 32U NPH daily. The bedtime bolus was 22U NPH. The last seizure
event used 8U NPH. So clearly I am producing endogenous insulin that I
have estimated as 6.5U nocturnally alone. My body weight is about 5 lbs
lower today at 160 lbs.

So on days w/o exercise, a 5U R dose may be necessary at bedtime.

[Jim Dumas]

On Sat, 17 Mar 2012 12:40:38 -0500, willbill wrote:

> Fri, 16 Mar 2012 19:24:35 -0500, Jim Dumas wrote:
>
>> This is primarily for Bill. My nocturnal basal requirements will try
>> to use this IGF-I caused glucose uptake. Hopefully, this exercise
>> effect can be used therapeutically. If I can, then I will probably be
>> the first to incorporate this endogenous capability quantitatively into
>> my insulin therapy. (Today is another 22 mile test and broke my
>> records so lowest average heart beats/mile of 504 vs. 511 on Tuesday.)
>
> With regard to you being "first" I rather doubt it.

The key word was "quantitatively" as I have a dose equivalent value in
the neighborhood of 5U for the IGF-I glucose uptake effect from exercise.

So yes, I think I'm the first to use numbers for this effect.

> I myself sometimes move to using only beef-R for up to 5 days without
> any background insulin. Surely an easier thing to do, given that beef-R
> has residual that is slightly past 12 hours.

Well, I added my anti-Human R antibody binding delay to the model a few
years ago. Human R has about a 1 hour delay in insulin action, from
published graphs by Lilly and Novo, for my metabolism. So this is close
to beef insulin action already. This is why I think I can use Human R at
bedtime for a small basal requirement without hypoglycemia.

>> But I think this is also active without exercise and caused the initial
>> four of my seizures last year. So how to determine what triggered this
>> without exercise. (Wondering if NPH's protamine triggers something in
>> the hGH axis, as strange as that seems, like preventing the inhibitor
>> for hGH, somatostatin.)
>>
>> So it's interesting if it works. But may identify a tumor so scary
>> too.
>
> Other than the nasty nighttime hypos, is ther any real reason to think
> that you have a brain tumor?
>
> Coz I doubt that you do.

Well, the more I look at old therapy data, the more I doubt I have a
tumor too. The test will be hypoglycemia/seizures when I haven't taken
any insulin. But I doubt this will happen.

> Odds are your nighttime hypos are due to your use of human-NPH, which is
> not uncommon with t1 use of *peaky* human-NPH at bedtime.

You must have missed my post where I was hypoglycemic at 3am without
taking NPH at bedtime. The cause of this nocturnal paradox is what this
thread is working on. Yes, Human NPH is peaky, but it wasn't used and
hypoglycemia occurred. So there is another mechanism for hypoglycemia.

In effect, the body has at least two independent systems that cause
glucose disposal. The human growth hormone system that causes the
release of IGF-I doesn't have BG feedback to shut it down when already
hypoglycemic from an insulin dose like NPH at bedtime.

That's what nailed me, but without using exercise last year.

[Jim Dumas]

On Sat, 17 Mar 2012 12:57:55 -0500, willbill wrote:

> AFAIK Dead in Bed has existed for t1 diabetics since the early days of
> commercial insulin (1923?)
>
> When Doc Biggs posted on m.h.d. one of his more interesting posts (of
> many) was that the American "cause of death" certificate was generally
> highly inaccurate.
>
> You really don't think that the whole Dead in Bed thing is going to have
> accurate data at it's disposal?

I remember Doc Biggs, now that you mention him. I suspect the Dead in
Bed deaths are caused by exercise induced IGF-I release. It is probably
more of an issue today with the rapid-acting insulins: Humalog and
Novolog. But it probably has been an issue since 1923 or so.

Accurate data? Well, now that I use a heart rate monitor to estimate my
exercise session intensity, it has me thinking about one of those
wristwatch heart monitors to record daily intensity values for use in
insulin therapy. So you download the daily data at bedtime, look for
excess exercise and lower the bedtime basal dose in anticipation of IGF-I
release. This is possible today.

So accurate data could be around the corner.

[Jim Dumas]

On Fri, 16 Mar 2012 08:19:35 -0500, Jim Dumas wrote:

> So it can be added as an "exercise space" subsystem to any insulin
> transport model. It includes hepatic/muscle glycogen store rebuilding
> as well as IGF-I induced glucose uptake from 1am to about 7am with a
> simple 3 equal compartment biological model for IGF-I release.

Just a minor observation about the time of the day when strenuous
exercise is taken. This "exercise space" model suggests morning
strenuous exercise is better than evening strenuous exercise. The idea
is to move the single compartment exponential decay equivalent insulin
bolus (end of exercise session) as far away from the hGH -> IGF-I 5U
bolus event at 1am. The closer these two components are, the more chance
of severe hypoglycemia.

So my new goal is to have two half-lives == 13.3 hours away from 1am,
i.e., try to exercise at or before 11am in the morning. So the heavy
exponential decay of glycogen rebuilding has dropped to 25% of max when
IGF-I kicks in.

And yes, I trained today, but did not follow this rule.

[Jim Dumas]

On Sat, 17 Mar 2012 12:40:38 -0500, willbill wrote:

> Odds are your nighttime hypos are due to your use of human-NPH, which is
> not uncommon with t1 use of *peaky* human-NPH at bedtime.

Hi Bill,

This morning was another normal FBG when I took no insulin at bedtime.
My last dose was 8U Humalog at 6:35pm for a 375 mg/dl BG. The intent was
to normalize BG before dinner. I had a salad while waiting for BG to
normalize. But fell asleep instead. So my only active dose this morning
was a 14U Ultralente from 8:33am yesterday. My fasting BG was 86 mg/dl
just now.

I clearly have endogenous insulin production and probably a small IGF-I
pulse from exercise two days ago (still repairing soft tissue). My last
training session was Sunday afternoon. Had I dosed NPH at bedtime, I
would have been severely hypoglycemic while sleeping.

Interestingly, I was tossing-and-turning all night. So did not get a
good sleep but FBG was normal. This is part of the training effect where
I can not wait to get back out and train. Saw this same "can't sleep and
get out of my way" adrenaline effect while running years ago. So this is
normal.

But this no NPH required is another example my changing therapy.

[willbill]

Tue, 20 Mar 2012 05:45:57 -0500, Jim Dumas wrote:

> I clearly have endogenous insulin production

Maybe.

> and probably a small IGF-I
> pulse from exercise two days ago (still repairing soft tissue). My last
> training session was Sunday afternoon. Had I dosed NPH at bedtime,
> I would have been severely hypoglycemic while sleeping.

Why don't you rent a continuous blood glucose monitor?

MiniMed used to make them. But after Medtronic took
them over, I'm not sure if they went out of business?

Coughran would know. e-mail him and ask.

Bill t1 since '57

[Jim Dumas]

On Tue, 20 Mar 2012 08:08:30 -0500, willbill wrote:

>> I clearly have endogenous insulin production
>
> Maybe.

Hi Bill,

No "maybe" about it. FBG was 106 mg/dl today with a 10U Human R bolus at
10:19pm last night for a frozen dinner. So this morning only a 14U Human
Ultralente bolus over 24h old is working. So my estimate is 10U
endogenous insulin production as half of basal requirements on a daily
basis. Looking back on personal records, it looks like this was a slow
decline in exogenous insulin requirements. I just didn't believe the
data so ignored it.

>> and probably a small IGF-I
>> pulse from exercise two days ago (still repairing soft tissue). My
>> last training session was Sunday afternoon. Had I dosed NPH at
>> bedtime, I would have been severely hypoglycemic while sleeping.
>
> Why don't you rent a continuous blood glucose monitor?

I have been spot checking BG and most of the time it is normal. So I
don't think I will learn much from CGMS data.

Yesterday was the first time I tried to separate the training session end
point from the IGF-I release point. This worked well last night with no
hypoglycemia. The time delay from the exercise glycogen rebuilding start
time to the 1am IGF-I release point was 12h. So the heavy surge of
glycogen rebuilding was yesterday afternoon and well away from the IGF-I
tissue repair surge while sleeping.

Current training goal is to break through the 500 average heart beats/
mile floor. I am close at 504 avg HB/mi now for this 22 mile course. I
hit 29 mph yesterday on the way home. I sprint on the last few miles if
I feel good. There was a strong variable 13 mph easterly wind yesterday
that was annoying. The intensity level yesterday was 520 avg HB/mile.

So far, so good with second guessing my nocturnal insulin requirements.

[willbill]

Wed, 21 Mar 2012 08:07:28 -0500, Jim Dumas wrote:

> On Tue, 20 Mar 2012 08:08:30 -0500, willbill wrote:

>> Why don't you rent a continuous blood glucose monitor?

> I have been spot checking BG and most of the time it is normal.
> So I don't think I will learn much from CGMS data.

Every t1 that I've seen that's commented on using a continuous
blood glucose monitor expressed surprise at the unexpected
useful info that turned up from actually using one.

As a t1 who's currently experiencing occasional extreme
nighttime lows (hypos) i.e. you, I fail to understand your
"I don't think I will learn much" attitude.

Bill t1 since '57

[Jim Dumas]

On Wed, 21 Mar 2012 12:51:44 -0500, willbill wrote:

> As a t1 who's currently experiencing occasional extreme nighttime lows
> (hypos) i.e. you, I fail to understand your "I don't think I will learn
> much" attitude.

Well, now that I have a model for the exercise-induced IGF-I equivalent
insulin bolus, I will experiment with its therapeutic use, as in push
residual beta cell growth with endogenous IGF-I versus Humalog, as an
example. So I am planning to only use Humalog first thing in the morning
to shock the liver insulinase enzyme to get with it (break the fast).
Then use Human R for prandial requirements.

Admittedly, I am amazed that Growth Hormone is so strong at my age. So
exercise is now a permanent requirement for my insulin therapy. In my
case, it is starting to look like nocturnal insulin requirements can be
left on autopilot. This certainly begs the question "What happened to my
dawn phenomenon?" I suspect it's still there, just handled by endogenous
insulin. This could be why I still need the 14U Human Ultralente in the
morning along with a small Humalog bumper dose to push the liver.

My math model basal rate today is 50% of what it used to be in 1990. So
I must have a residual beta cell mass that my immune system left alone.
Now that I know they exist, I will try to stimulate them to grow without
pushing them too hard for insulin production. The test will be to stop
exercising and see how much they can handle. I might try this every 6
months. But I plan to hit them with endogenous IGF-I from exercise for a
while at the present.

And BG moves slow in my case, so CGMS data has no new information.
--
Jim
Still kick'n! Low tech T1 4/86, no complications. T.75? 7/2011
Email mangled: change SeeSig2Fix to mindspring for utopia. (Where?)

[Jim Dumas]

On Wed, 21 Mar 2012 14:25:23 -0500, Jim Dumas wrote:

> My math model basal rate today is 50% of what it used to be in 1990.

Just to say today FBG was 109 mg/dl for a dinner 16U Human R bolus at
9:30pm last night. The antibody binding delay of Human R shows as a
basal rate of 0.8U/h at the time BG was measured. Without this last dose
the basal rate would have been 0.2U/h from the Ultralente doses (2 spaced
24h apart so oldest is 48h). So the math model has dinner R from 9:30pm
still active now (7:44am).

The math model has a dose size dependence from Lilly published dose
ranging data for subcutaneous delivery. The dose size dependence shows
an oscillatory behavior of peak action time where the peak action is the
latest around 14U bolus size and the earliest around 6-7U size. This
same behavior can be seen in all U100 insulin preparations. So it is a
function of capillary bed geometry absorption in the subcutaneous tissue.

In short, I used a single 16U Human R bolus for dinner to get it to cover
nocturnal basal requirements as well as dinner. But yesterday morning I
took four small 4U Human R boluses at the same time to cover a bowl of
cereal (still carbo-loading) thereby using the fast tail of these small
doses to simulate a 16U Humalog bolus. My total insulin requirements
yesterday, without exercise, were 8U Humalog, 32U Human R and 14U Human
Ultralente for two large meals. No hypoglycemia and no NPH.

So I'm using physiological tools to fine-tune insulin therapy.

[willbill]

Wed, 21 Mar 2012 14:25:23 -0500, Jim Dumas wrote:

> On Wed, 21 Mar 2012 12:51:44 -0500, willbill wrote:
>
>> As a t1 who's currently experiencing occasional extreme nighttime lows
>> (hypos) i.e. you, I fail to understand your "I don't think I will learn
>> much" attitude.

> Well, now that I have a model for the exercise-induced IGF-I equivalent

> insulin bolus, I will experiment with ...

Jim,

It's like you're on a distant system
other than Sun and earth/planets!

So I'm done with talking with you
on an open forum, and for certain
not via e-mail!.

What's worse is that I honestly
don't think that you could find
your way out of a paper bag!

I offered a couple of good ideas
in this and prior threads. You ran
over them like a bulldozer.

If you kill yourself via an extreme
hypo (which I think has some chance)
I really don't want to get sued for it.

Bill

[Jim Dumas]

On Fri, 23 Mar 2012 20:56:30 -0500, willbill wrote:

> If you kill yourself via an extreme
> hypo (which I think has some chance)
> I really don't want to get sued for it.

Dear Bill,

Don't worry Dude. Interestingly, FBG today was 65 mg/dl with my last
Humalog dose of 17U at 1:47pm yesterday for a carbo-loading meal.

I did not train yesterday but did minor physical work. So it looks like
the Growth Hormone induced by exercise still has an effect two days later.

I did visualize last night, my death as insulin/IGF-I induced while
sleeping. So not a bad way to go when your number is up. My brother and
sister-in-law know of my troubles and are checking on me. Have a niece
that's an RN and she is trying to help as well. But this is uncharted
water for everybody. (Yes, my Doc as well.)

Perplexingly (this ain't a real word but I'm gonna use it), it seems as
though I inhibit insulin production while awake and neurologically
stimulate glucose disposal while sleeping.

But no seizures from hypoglycemia. Time to train!

[Jim Dumas]

On Sat, 24 Mar 2012 08:04:25 -0500, Jim Dumas wrote:

> Don't worry Dude. Interestingly, FBG today was 65 mg/dl with my last
> Humalog dose of 17U at 1:47pm yesterday for a carbo-loading meal.

Just to say that this 1:47pm dose was the last insulin dose for about 19
hours when I took 14U Ultralente to start the day.

Trained today and picked up an A1cNow kit at the Walmart pharmacy drive
through. This gave a 6.2% A1c just now. The only problem I had with it
was excess bleeding from the finger stick. The training should force a
faster turnover of red blood cells with increased blood flow through the
spleen. The kit has two assays so will try again in a few months.
Expiration is 14 months out. The cost was $34.46 at the window.

Interestingly, I added a 2U Humalog bolus after the 14U Ultralente. This
2U was in preparation for training so was lower than when no exercise.
Measured BG an hour later, just before training and BG was falling fast
so had to take a BG tab before riding the 22 mile course. I expected
more inertia from the liver in switching from fasting to the daily
routine. This suggests endogenous insulin is working.

Never a dull DM moment.

[Jim Dumas]

On Sat, 24 Mar 2012 15:17:24 -0500, Jim Dumas wrote:

> I expected more
> inertia from the liver in switching from fasting to the daily routine.
> This suggests endogenous insulin is working.

Just to say that my role in DM management seems to be transforming into
nudging endogenous to take over. So yesterday evening I had dinner at my
brother and sister-in-law's and deliberately under-dosed Human R,
(trained yesterday so only use R that day after training), for the drive
home with some Walmart food shopping on the way home.

Measured BG at 1am and it was 308 mg/dl and now how to dose without over-
dosing for the training Growth Hormone -> IGF-I glucose disposal. I
decided to use only the day time (no insulin resistance from dawn
phenomenon) Human R recovery bolus of 5U and hit the hay.

Fasting BG was 77 mg/dl. So far so good. The new found betas seem to be
controlling BG properly with a small nudge at bedtime.

The intent is to keep raising the bar for the betas.

[Jim Dumas]

On Sun, 18 Mar 2012 18:55:15 -0500, Jim Dumas wrote:

> On Fri, 16 Mar 2012 08:19:35 -0500, Jim Dumas wrote:
>
>> So it can be added as an "exercise space" subsystem to any insulin
>> transport model. It includes hepatic/muscle glycogen store rebuilding
>> as well as IGF-I induced glucose uptake from 1am to about 7am with a
>> simple 3 equal compartment biological model for IGF-I release.
>
> Just a minor observation about the time of the day when strenuous
> exercise is taken. This "exercise space" model suggests morning
> strenuous exercise is better than evening strenuous exercise. The idea
> is to move the single compartment exponential decay equivalent insulin
> bolus (end of exercise session) as far away from the hGH -> IGF-I 5U
> bolus event at 1am. The closer these two components are, the more
> chance of severe hypoglycemia.
>
> So my new goal is to have two half-lives == 13.3 hours away from 1am,
> i.e., try to exercise at or before 11am in the morning. So the heavy
> exponential decay of glycogen rebuilding has dropped to 25% of max when
> IGF-I kicks in.

Just to say that I triggered a nocturnal hypoglycemic seizure event about
3am this morning. I trained on a longer 33 mile course yesterday morning
for the first time. The duration multiplier is 33 / 22 = 1.5 so this is
the longest exercise induced hGH -> IGF-I training session to date of
almost 2 hours in the morning. The session ended at 11:50 am. The
intensity was 496.4 average heart beats per mile. The average speed for
the 33 mile course was 16.8 mph with an average heart rate of 139 HB/min.

I tried to carbo-load with potatoes for dinner and decided to ignore the
exercise model 1.5 multiplier to lower a dinner Human Regular dose. So I
over-dosed Human R of 16U at 9:55pm. This event had no NPH component.

In combination with the 1.5 multiplier for endogenous IGF-I at about 1am,
I had a minor seizure event that took about 12 glucose tablets at the
bedside. Dexterity was fair and breathing was not shallow, so I changed
PJs (minor struggle) and went back to sleep. Fasting BG was 169 mg/dl
this morning.

In any case, I did follow the new rule to exercise in the morning but I
ignored the impact of growth hormone for the much longer training
session. Yesterday's insulin requirements were 14U Ultralente, 2U Humalog
before the training session; 12U Human R in two 6U doses at 2pm for the
405 mg/dl high protein+carbo meal and 16U Human R for dinner. This last
dose should have been 12U in expectation of the IGF-I contribution.

Another interesting point is the neuroendocrine contribution that may
play a role via the cholinergic pathways. I take 100 mg of DMAE daily, a
precursor to acetylcholine. This probably stimulates insulin and glucagon
production, per Baulieu and Kelly's textbook "Hormones" p. 499. This may
be why nocturnal insulin production seems to work for me.

I'll ride the 33 mile course again tomorrow and try this again w/12U.
--
Jim
Still kick'n! Low tech T1 4/86, no complications. T.75? 7/2011
Email mangled: change SeeSig2Fix to mindspring for utopia. (Where?)

[Jim Dumas]

On Sat, 31 Mar 2012 10:23:45 -0500, Jim Dumas wrote:

> I'll ride the 33 mile course again tomorrow and try this again w/12U.

I was invited to a birthday dinner for the niece RN yesterday. So only
did the "known" workout of 22 miles to avoid hypoglycemic trouble for
driving the car. My intensity parameter was 490 average heart beats per
mile yesterday for a 10 mph NNW wind that was an issue the second half.
The average heart beats were 139 HB/min with average speed of 17.0 mph
with 4 red light stops in this average.

And naturally, the exercise model was a topic of discussion with the
niece RN. I also emailed her the March 2012 Diabetes Care article on C-
peptide in long-term T1s so that was discussed as well. The IGF-I
contribution to glucose disposal is surprisingly high nocturnally and
seems to scale directly with the exercise duration.

Too much dessert and too tired to check bedtime BG. So quite the blow
out this morning.

Will do the 33 mile experiment tomorrow.

[Jim Dumas]

On Mon, 02 Apr 2012 08:53:35 -0500, Jim Dumas wrote:

> Will do the 33 mile experiment tomorrow.

I did a 30.7 mile course yesterday with an intensity of 487 average heart
beats per mile. I had two large (two servings) carbo-loading meals that
each used 14U Human Regular. Insulin requirements yesterday were 14U
Ultralente, 4U Humalog (before exercise) and 28U Human R. The last R
dose was at 10:22pm to carbo-load and fasting BG was a 77 mg/dl without
nocturnal hypoglycemia (or without any hypoglycemia yesterday).

BG was 184 mg/dl before exercise and 310 mg/dl at the end of exercise
with the 4U Humalog dose active. 2U R was in the first 14U R dose (two
7U boluses for short tail) to normalize BG with the large meal.

The last R dose (one 14U bolus for long tail) is peaking when endogenous
IGF-I is active from the exercise session. The meal was carbo rich with
cooked carrots and potatoes that would usually require 20U R to cover
without exercise.

So learning to use nocturnal endogenous production w/o HG.

[willbill]

Sat, 31 Mar 2012 10:23:45 -0500, Jim Dumas wrote:

> Just to say that I triggered a nocturnal hypoglycemic seizure event
> about 3am this morning.

I personally do not like playing with fire.

But you seem to?

Can't help with any else at this point,
other than to again say that my own
extreme hypos in the 1980's were due
to the peakiness of pork-NPH.

Human-NPH (which I gather that you're
no longer using?) is slightly more peaky
than pork-NPH.

Bill t1 since '57

[Jim Dumas]

Hi Bill,

Today's HG event will knock your socks off. Yesterday, I had Easter
dinner at my brother and sister-in-law's and I brought a nice Merlot that
was split with the sister-in-law, as my brother is on the wagon these
days. My last insulin dose was 14U Humalog at about 8pm last night. I
had a fasting BG of 76 mg/dl with only my 14U Ultralente working from
yesterday morning.

This morning was busy so I didn't get the bicycle ride in until 1pm and
decided to go the 30.7 mile distance (not the 22 mile course). BG was
126 mg/dl at 12:30pm without any breakfast, so still in the high insulin
resistance fasting state. I thought BG would rise during the exercise
session so I dosed 1U Humalog at 12:31pm. BG was 31 mg/dl at 3:37pm.

So 14U Ultralente at 8:59am and 1U Humalog at 12:31pm + 30 miles on a
bicycle gives hypoglycemia at 3:30pm today.

So I ate a banana for calf cramping and BG. But did not expect HG.

[Jim Dumas]

On Mon, 09 Apr 2012 15:14:31 -0500, Jim Dumas wrote:

> So 14U Ultralente at 8:59am and 1U Humalog at 12:31pm + 30 miles on a
> bicycle gives hypoglycemia at 3:30pm today.

I should also state that my last exercise session was two days ago on
Saturday for the 22 mile course. So the training effect from this
session was over.

Felt strong today and met two bicyclists (one a male flight RN).

[Jim Dumas]

On Mon, 09 Apr 2012 15:24:31 -0500, Jim Dumas wrote:

>> So 14U Ultralente at 8:59am and 1U Humalog at 12:31pm + 30 miles on a
>> bicycle gives hypoglycemia at 3:30pm today.
>
> I should also state that my last exercise session was two days ago on
> Saturday for the 22 mile course. So the training effect from this
> session was over.

This will be an interesting day for the Growth Hormone pulse and IGF-I
1am pulse. I ate my high protein high carbohydrate dinner that caused
the 405 mg/dl fasting BG reference. My usual dose for this meal is 12U
Human R in 2 boluses of 6U. I decided to drop this to 8U R in two
boluses at 6pm this evening. BG 3 hours post-dose was 39 mg/dl. So I
ate another banana with some dried fruit to increase BG.

But I am concerned about nocturnal hypoglycemia from the IGF-I pulse from
today's exercise. I will probably not dose further today. So my current
daily insulin requirements are 14U Ultralente, 1U Humalog and 8U Human R.

Will have to drop R and Humalog next if this keeps up.

[willbill]

Mon, 09 Apr 2012 20:37:45 -0500, Jim Dumas wrote:

> Will have to drop R and Humalog next if this keeps up.

Drop one or the other, not both.

I'd drop Humalog but that's personal experience speaking.

Meaning odds are LARGE that human-R insulin
is generally safer to use than Humalog insulin.

Both my own negative experience with Humalog
(the 1st of the questionable analog insulins;
Lantus a much more worrisome analog insulin
given it's clear increased risk of cancer with use)

One thing at a time.

BTW, that doesn't give a clear ticket to use
of human-R, which I happen to think caused
my own breast cancer incident in '94.

There's nothing simple about long term insulin use.

Bill t1 since '57

[Jim Dumas]

Hi Bill,

Current BG is 91 mg/dl so pulled out of the hypoglycemia. I've decided
to do nothing more in expectation that nocturnal endogenous insulin will
be on autopilot to lower production when IGF-I kicks in at 1am or so.

Should be interesting. Hitting the hay now.

[Jim Dumas]

On Mon, 09 Apr 2012 22:41:43 -0500, Jim Dumas wrote:

> Current BG is 91 mg/dl so pulled out of the hypoglycemia. I've decided
> to do nothing more in expectation that nocturnal endogenous insulin will
> be on autopilot to lower production when IGF-I kicks in at 1am or so.

Here we go! Fasting BG was 57 mg/dl without any nocturnal wake-up call
for hypoglycemia. But clearly some other insulin producing without
hypoglycemic cut-off event happened. This suggests IGF-I or a tumor
producing insulin. I feel fine so I'll ignore the tumor hypothesis.

The computer model basal rate is 0.2 U/hour at the time fasting BG was
taken.

Daily vitamin therapy includes 81mg Aspirin for the CV and anticancer
effects, B-complex for muscle cramping/mitochondria energy burning, 100mg
Zinc gluconate (about 11 days now) to assist enzyme activity, 1gm C for
Linus Pauling (sp?) and others that are not as important. Also use
Morton's light salt in cooking (50% NaCl + 50% KCl) for muscle cramping
and to replace electrolytes.

So not too bad on autopilot.

[Jim Dumas]

On Mon, 09 Apr 2012 22:41:43 -0500, Jim Dumas wrote:

> production when IGF-I kicks in at 1am or so.

I rode the 22 mile course yesterday in the afternoon, as the morning
phone calls by recruiters never stopped. BG before was 228 mg/dl and BG
at the end was 123 mg/dl with only 1U Humalog just before the session. I
finally go around to dinner at 6:45pm and BG was 55 mg/dl then. All this
from 1U Humalog plus 22 miles on a bicycle. I ate a banana for cramping
and BG, along with dried fruit for an extra BG kick.

Dinner was a massive two serving carbo-load with extra potatoes and a 14U
Human R dose that is 1U lower than usual for this in the past. I woke up
in a sweat on the couch at 11:45pm with a 25 mg/dl BG. So had another
banana and a massive amount of dried fruit that usually pushes BG high
very quickly. Fasting BG this morning was 181 mg/dl. But had a great
sleep with no nocturnal cramping.

In effect, IGF-I kicked in early with my falling asleep on the couch.
The intent was to stay awake to check BG at midnight before the typical
IGF-I pulse would hit at 1am. The late exercise session glycogen
rebuilding also contributed to hypoglycemia too.

What shocks me is the quantity of glucose necessary to recover.

[Jim Dumas]

On Thu, 12 Apr 2012 08:40:27 -0500, Jim Dumas wrote:

> What shocks me is the quantity of glucose necessary to recover.

Today was more typical with a 338 mg/dl with only a 4U Humalog dose at
7pm last night. But I'm starting to think I have a positive feedback
loop with IGF-I at the liver. So the liver generates IGF-I under growth
hormone control and also uses this IGF-I to cause glucose uptake while I
am sleeping. This means the liver has 3 sources of glucose uptake
stimulation, the IGF-I just mentioned, then my insulin dose and finally,
the glycogen rebuilding from the exercise session. This assumes
endogenous insulin production from beta cells has been throttled back
from hypoglycemia. But endogenous could be a fourth source.

This would explain why my trouble is only while sleeping. It also
suggests the Humalog IGF-I homology may be a co-factor in this IGF-I
positive feedback hypothesis.

My focus is how to control it or at least predict it.

[willbill]

Fri, 13 Apr 2012 07:22:42 -0500, Jim Dumas wrote:

> This would explain why my trouble is only while sleeping. It also
> suggests the Humalog IGF-I homology may be a co-factor in
> this IGF-I positive feedback hypothesis.

"Dead in bed" suggests to me that the most serious
of all hypos are during nighttime sleep.hours.

So why does your above 1st sentence include

"why my trouble is only while sleeping"

Ditch your use of Humalog and only use the
slower synthetic human-R as your meal insulin
and see where you get to with that.

Bill t1 since 57

[Jim Dumas]

On Fri, 13 Apr 2012 12:26:59 -0500, willbill wrote:

> Fri, 13 Apr 2012 07:22:42 -0500, Jim Dumas wrote:
>
>> This would explain why my trouble is only while sleeping. It also
>> suggests the Humalog IGF-I homology may be a co-factor in this IGF-I
>> positive feedback hypothesis.
>
> "Dead in bed" suggests to me that the most serious of all hypos are
> during nighttime sleep.hours.
>
> So why does your above 1st sentence include "why my trouble is only
> while sleeping"

Because BG rises after I get up in the morning. This rise is varibale
but averages 30mg/dl/hour. So if I do nothing, BG is 250 mg/dl at noon.
So no chance of hypoglycemia once I get up in the morning.

> Ditch your use of Humalog and only use the slower synthetic human-R as
> your meal insulin and see where you get to with that.

I still use the fast pulse of Humalog for special needs, like a 12U
Humalog dose to clobber the 338 mg/dl fasting BG this morning. So not
ready to toss it yet.

And I did workout on the 22 mile course this afternoon. So will only use
Human R for the rest of the day. BG before the ride was 214 mg/dl so
dosed 1U Humalog for the short tail. BG after the ride was 144 mg/dl.
But is probably still falling from the training effect in combination
with residual liver enzyme activity from the 12U bolus 5+ hours earlier.

So I still have special requirements for Humalog use.

And looking for a consistent pattern that I can use therapeutically.