In alt.support.diabetes Jefferson > wrote:
> Alan S wrote:

>>>Catherine E. Gleason, Michael Gonzalez, Jamie S. Harmon, and R. Paul
>>>Robertson. Determinants of glucose toxicity and its reversibility in
>>>pancreatic islet Beta-cell line, HIT-T15. Am J Physiol Endocrinol Metab
>>>279: E997-E1002, 2000
>>>
>>>http://ajpendo.physiology.org/cgi/co...act/279/5/E997
>>>
>>
>>
>> That's a really interesting paper. It's specifically
>> interested in beta-cell damage and recovery, not other
>> damage that may occur to the body from spikes.
> (snipped)

>> "In summary, these findings indicate that glucose
>> toxicity of the b-cell is a continuous rather than a
>> threshold function of glucose concentration and that
>> the shorter the period of antecedent glucose toxicity,
>> the greater the degree of recovery.
> (snipped)
>> On the other hand, a spectrum of pathophysiological
>> changes may occur with more prolonged exposure of
>> the b-cell to supraphysiological glucose concentrations.
>>
> (snipped)
>>
>> In this context, it seems likely that early, effective
>> management by diet and drugs of hyperglycemia in type 2
>> diabetes is an important aspect of preserving residual
>> b-cell function. The same argument for meticulous glycemic
>> control can be made after pancreas or islet
>> transplantation."

If this is like many other cases of mild recoverable damage which if
too prolonged can become permanent, then it's not just the length of
exposure to high BGs which will matter, but the time interval between
episodes. What often seems to harden mild temporary recoverable damage
into permanent damage is if the interval between the damaging episodes
is not long enough for full recovery to take place. That's what would
make the episodes have a cumulatively damaging effect, even though
they may be brief and only very mildly damaging.

I have no idea how long it takes to recover from soft recoverable
glycation damage, but it wouldn't be too surprising if it was longer
than a day. In fact on first principles I would suspect that it would
follow the common half life logarithmic progression of recovering by
50% each fixed half-life interval of time (because that's the law of
chemical mass action in solution). If that were the case, then a big
long high spike once a week might be ok, but a brief little one every
day might lead to progressive permanent damage.

The A1C test is based on blood cell glycation damage. If there are
some important kinds of glycation damage which have different recovery
rates than blood cell glycation (which would hardly be surprising),
then all a low A1C will tell you is that you're protected from those
kinds of damage which recover at the same rate or more slowly than
blood cell glycation damage.

I note that at diagnosis I was already suffering from some typical
diabetic complications, such as some neuropathy in hands and feet,
despite having an A1C of 5.6%. My problem was that a few times a day I
was having brief (probably 30-45mins) BG spikes in excess of 200. When
I reduced the size and frequency of those spikes my neuropathy started
to improve.

My condition now seems to be close to the threshold of neuropathic
damage, because if I keep my BG spikes down my neuropathy continues
very slowly to improve, but one single brief BG spike over 150 will
produce mild tingling in the edges of my hands.

Other T2s posting here have reported the same kind of thing, even
though they too are in the 5% A1C club.

That suggests to me that there may be some merit in this idea that the
interval between brief BG spikes is a critical factor in certain kinds
of glycation damage. This idea does not seem to be a component in the
medical models of glycation damage I see in epidemiological diabetic
research reports, although I'd be surprised if it wasn't understood by
specialists who were trying to build mathematical models of very
specific kinds of glycation. One of the weaknesses of the current
medical fashion for "evidence-based medicine" is that the kind of
statistical attitude it encourages tends to devalue and distract
attention from such modelling work.

T1s please note that these observations are made in the context of the
entire possible T2 metabolism, including IR and failures in lipid
metabolism. They can't necessarily be generalised to T1s.

> TABLE 1 Literature supporting chronic oxidative stress as a mechanism
> for glucose toxicity of the beta-cell -
> http://diabetes.diabetesjournals.org...ll/52/3/581/T1

> Treating Postprandial Hyperglycemia Does Not Appear to Delay Progression
> of Early Type 2 Diabetes -
> http://care.diabetesjournals.org/cgi...full/29/9/2095
>

Yebbut look at what they tested!

"OBJECTIVE: Postprandial hyperglycemia characterizes early type 2
diabetes. We investigated whether ameliorating postprandial
hyperglycemia with acarbose would prevent or delay progression of
diabetes, defined as progression to frank fasting hyperglycemia, in
subjects with early diabetes (fasting plasma glucose [FPG] <140 mg/dl
and 2-h plasma glucose .200 mg/dl)."

It puzzled them that this study contradicts other findings. They did
recognise that their definition of "early diabetes" may be a little
late, e.g.:

"Another possible explanation is that our subjects, like those in the
UKPDS and in clinical practice, were "too far gone" along the path of
-cell failure for the intervention to affect progression. This would
require us to believe that early diabetes is quite different from IGT,
a condition in which controlling postprandial hyperglycemia seems to
preserve -cell function or at least delay onset of diabetes (20). Our
post hoc analysis of subjects who entered with FPG <126 mg/dl
(presumably with even earlier diabetes) suggested that the rate of
progression to FPG .126 mg/dl may have been reduced by acarbose. This
would support the argument that once FPG exceeds 126 mg/dl, it may be
too late to significantly affect -cell function."

Note BTW that the current FPG diabetes diagnostic threshold is
126mg/dl...

Finally they say curiously, without explanation:

"It is unlikely that diabetes could be easily diagnosed in stages
earlier than that of our subjects, ..."

Why on earth is that unlikely? Medical politics?

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