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Re: [IP] hypoglycemic seizures

OK Celia, let me give it a try.

<Some questions for you Wayne (or any other physiologically knowledgeable
<1. Couldn't the seizure result from the speed or acceleration of the bg
drop in
<the brain itself rather than just the instantaneous bg level in the brain?
<Or, 2. Does the body have protections in place that tend to make brain bg
<more static than blood bg levels? (Maybe even some storage system such as

	I don't know of any reason why the speed of the drop by itself
would be the problem.  It  certainly might be possible, but unless the
simpler explanations fail,  it might not be necessary to get so complex.
The level of G in the brain cells is what leads to seizures.  I don't know
what that level is exactly, but there may be some information in the
literature.  It is sort a classic problem in system dynamics.  You've got
brain cells happily munching away on sugar.  This would tend to make the
glucose in thefluid around them decrease.  This decrease causes more
glucose to diffuse from the capillaries to the space around the cells. So
there are two reasons why the G in the brain extracellular space can fall:
1. if  the brain cells start to chew more G or 2. if the blood glucose
falls, i.e., either more out or less in.  At any instant of time, the
diffusion to the brain is only a function of the difference between the BG
in the capillaries and that in  the extracellular space.  The brain has no
storage  as glycogen like muscles and thus no protection--the only
"protection" is the reservoir of glucose in the blood; and the brain
doesn't need insulin to use the glucose

<3. Is there really a single brain bg level (or do the working brain cells
take in
<and use glucose on a more independent basis?).

	Well as summarized above, the local level depends on how quickly
glucose is being used.  So yes there may be wide local variations in G in
different parts of the brain.  Exactly which parts with low G would cause
you to have seizures and which just make you feel stupid (actually be
stupid) I don't know.

<4. How much time might it take to have glucose diffuse from the blood
stream into
<the brain cells? What sorts of things might slow or speed up this rate?

	Glucose moves passively  in proportion to the difference in
concentrations.   The diffusion distance is also a factor, and in some
tissues edema might slow this down.  But in the brain if you've got enough
edema to do this, you've got worse problems than diabetes to worry about.

<5. Might really rapid drops in blood bg level be the result of the brain
<up some much needed glucose?

	I don't know if the brain by itself could do this.  But as I've
said above, if the brain cells start sucking glucose very rapidly (like
when you are trying to figure out whether there's enough relevant evidence
to force Clinton out of office :-), then the local concentration could get
lower than the BG for a period of time.   Regarding the regulation of BG,
its similar to that in the brain.  Here the output is the whole body's use
of insulin and the input is whatever is coming from the GI tract, liver,and
protein metabolism.  It's more complicated than for the brain.

<I don't think that I have ever had a full-blown seizure, but I certainly
have had
<many instances of "leg jerks" and other neurological symptoms (I still
have this
<problem unless I am very careful concerning exercising soon after a bolus).  I
<have sometimes had these fairly extreme symptoms occur at reasonable blood bg
<levels such as in the 4's (mmol/l) which are in the process of dropping
into the
<2's within 10 minutes (I think that this is fast).
<What I find to be as interesting as it is scary, is that though my brain
<control my muscles very well at these times, it is functioning well in
terms of
<abstract and practical thought.

	I've never had a knockout seizure either, and like you I have had
some low BG associated "twitches."  I think that the main reason for those
very rapid drops in BG (yes 4 to 2 in 10 min is fast), is related to the
absorption and delivery of stored subcutaneous insulin.  This is clearly a
much much greater problem with injections, especially with those long
acting insulins.   We had a recent discussion about Lily's recent
experience, and sometimes others see it with the pump, but I'm sure this is
a much rarer event with a pump than with that old archaic methods of
treating diabetes with MDI and leeches (blood letting will in fact decrease
the BG temporarily :-)

<One more question:
	Why not.  When I'm done, I'll let one of my students use this for
their thesis :-)

<Is it possible that humalog/insulin (when peaking) actually prevents the
body from
<using fat or muscle glycogen stores for energy? A number of people on this
<have mentioned having problems with exercising after humalog boluses.
Certainly I
<do - and I am well trained physically - with lots of endurance (which I would
,think would mean that I am naturally good at converting fat or muscle glycogen
<into fuel...) . Yet after a meal with a bolus, my system seems to work
	Celia, now you're really asking tough questions.  We've moved from
Masters work to the Ph.D. level :-)  The interaction between insulin, BG,
and exercise is so variable that no one has a consistent theory.  You've
got so many dynamic changes going on that many outcomes are possible.
There are a few knowns here though.  1. The muscle glycogen breakdown
occurs within the muscle cells directly and doesn't require any insulin.
However, you do need insulin to get glucose in to the muscle cells to make
new glycogen.   Conversion of fats or free fatty acids (FFA) to energy does
not require insulin either.   So the simple answer to your question at the
start of this last paragraph is no.
      BUT there are so many exercise induced dynamics we haven't even
touched on--as just one example there is protein in the muscle cells called
GLUT4, which is a glucose transporter that facilitates glusose uptake and
utilization during and after exercise.   If you have enough of this, you
can get by without much insulin.  Sometimes when I have a very hard day of
physical work/exercise I can completely disconnect from the pump
overnight--and my BGs stay stable (once they even decreased!!!)  So, with
exercise, its the ultimate YMMV.
	If you have any more questions, I may have to start charging
tuition *S*


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