On Feb 11, 4:47 pm, Chris Malcolm > wrote:
> 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/]- Hide quoted text -
>
> - Show quoted text -
Good informative post, thanks.
Btw, it looks, in insulin resistance and glucotoxicity, body's natural
mechanism tries to lower insulin senstivity and quantity progressively
WHEREAS we try somewhat opposite. Why?
Can such more and continual insulin's exposure cause persisting
hyperglycemia insulin resistance, increased energy stores and their
decreased usage/breakdown?
Can such increased synthesis and decreased breakdown be pro-oxidation,
stimulate and promote oxidative stess orsystemic inflammatory
condition?