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[IP] Glycosylation, Vitamin E -Scientific, Long, Great- Wayne?

A great Email, which I received from IP member Kevin Hass.  Lots of 
excellent stuff that you science buffs and other DMers will love.  Wayne are 
you reading?

>From: Kevin Hass <email @ redacted>
>To: email @ redacted (Dianne De Mink)
>Subject: Re: Vitamin E & Bumping basals
>Date: Sun, 14 May 2000 20:51:10 -0600 (MDT)
>And now, the glycosylation notes.....
>Glycosylation is a nasty chemical reaction, that is thought to be
>at the heart of most cardiovascular DM complications.  Nearly all
>of the common complications can be linked to the blood vessels.
>Retinopathy, nephropathy, heart disease, neuropathy, and amputation.
>All have the underlying cause of poor circulation.
>Glycosylation is where glucose reacts with proteins in the body.  It
>is a two step process.  First glucose attaches to a protein.  This is
>where the hemoglobin A1c test came from.  It measures how much of the
>hemoglobin's protein has attached to glucose.  It is sorta linear:
>where if you have twice the Bg level, you will have more "glycosylated
>hemoglobin" (HbA1c).  It happens to everyone that is alive, because we
>all have glucose in our bodies, but it happens much more rapidly in
>diabetics.  The old age diseases that non-DMers get, are uaually
>the same kind of thing - but we face them sooner because we usually
>have higher average glucose levels.
>Going on, after the glucose has attached itself to a protein, it
>can later rearrange, and attach to another protein, forming a
>permanent crosslink.  This is especially bad in proteins that
>last a lifetime - like the collagen in our blood vessels, and connective
>tissues.  The flexibility/elasticity is reduced, and "hardening of
>the ateries" is the end result (fat & lipids are not the only "bad
>guy" that brings about it).  For us DMers, we tend to have our
>capillaries screwed up from this as well.  This second stage glycosylation
>has a fitting name: Advanced Glycosylation Endproducts - or AGE.
>While HbA1c shows the average glucose level for the last couple
>months, it is not necessarily a predictor of how much AGE is
>formed.  This is because there are some things that prevent the
>crosslinking - or slow it down.   In most cases, it IS a predictor
>of AGE formation, but not always.  Some people's body's do something
>to slow this down, as well as other things, such as vitamin E,
>bioflavnoids, lipoic acid, and even alcohol in moderation.
>Back in 1987, an article was published in Scientific American, that
>described this glycosylation.  It was written by a fellow type-I
>DMer: Dr. Michael Brownlee.  Since that was published, there has
>been great volumes of research on this process.  In that article,
>they describe their discovery of a drug that inhibits this process
>in mice, and was found in other studies to prevent or slow down
>the various common complications in diabetic mice - usually retinopathy.
It is being tested
>in type-I DMers who are in renal failure - to see if it can extend their
>lives, and slow down the rate of renal failure.   That drug is
>aminoguanidine, now being tested under the name Pimagedine.
>One of the universities that are the birthplace of much of this research,
>is the picower institute (www.picower.edu), but much of this has made
>it's way to commercial pharmacuetical research.  There is one company
>that is running with most of this work:  Alteon (www.alteonpharma.com).
>Take a look at those two sites, for some inspiring information!
>As for various published articles, and web sites on this, here are
>some.  I would encourage you to visit your local library, and at
>least look at the Scientific American article below.  The other ones
>may be in journals that are too obscure for most libraries to carry,
>but you can always order copies thru libraries - usually for about
>$3-$8 each.  I have a folder with MANY such articles.  I am only
>listing a few of the more easily understood ones here...  Those that
>have "**" next to it, I have copies that I can send via email to you,
>if you can't find them yourself.
>http://www.diabetesnet.com/ada98.html  (**)
>This is the summary of the 1998 ADA convention.  Look closely at the
>information about retinopathy, vit E, and lipoic acid.  They even found
>that they help nephropathy too, by slowing down the progession of
>"vitamin E reduction of protein glycosylation in diabetes", Antonio
>Ceriello.  Diabetes Care, Vol 14, No 1, Page 68.  January 1991
>Here they study 600 units/day, and 1200 units/day, and find a dose
>related reduction in AGE formation.
>"prevention of diabetes-increased aging effect on rat collagen-linked
>flourescence by aminoguanidine and rutin".  Diabetes July 1990,
>39 (7) p796-801.
>This article shows that rutin and aminoguanidine are equally effective in
>slowing glycosylation.  RUTIN IS A CHEAP BIOFLAVANOID, available in most
>health food stores!!!  I've been taking this for longer than the vitamin
>E - probably started it about 1992, and now my endo is keeping notes on
>whether I'm still taking it....  (GRIN :) )
>"Glucose and Aging", Anthony Cerami, Helen Vlassara, and Michael Brownlee.
>Scientific American, May 1987, vol 256, no 5, p90-96
>This was the first article that was published for the general public
>on glycosylation, AGE, and aminoguanidine.  The first two authors are
>now part of the team at Alteon.
>No name, but I found this at the www.picower.edu web site.  It tells how
>they discovered the "French Paradox" - where the french have just as bad
>of diets as most Europeans, but they also drink wine at all meals usually.
>It was found that one of alcohol's metabolites (acetaldehyde) reacts
>with the first stage glycosylation products, and prevents them from
>crosslinking.   If they have a search engine, look for the keywords
>French, and acetaldehyde to find it.  This is in ADDITION to the
>benefits of the grape polyphenols!
>Finally, look at www.alteonpharma.com.  They now are begining studying
>a new breakthrough drug, that BREAKS the AGE crosslinks!  It has been
>PROVEN to break the links, and permanently lower the blood pressure of
>diabetic apes - due to the reduction of the hardened arteries.  This is
>great news!!!  The ADA mentions it in the 1998 convention news, that
>I first listed.   BTW, this new drug is VERY CLOSELY related to
>thiamine.... Hmmmmm!!!???  Also, it turns out that these crosslink
>breakers are also inhibitors of AGE.
>You can also read detailed info about this new drug, from their
>patent on it:  US patent number 6,007,865  You can look it up
>at www.uspto.gov (the US patent office's web site).  Go do a
>patent search by number, to find it.  I can also send you a copy.
>It may just be a bunch of gobble-dee-gook, but if you can follow it,
>the patent reveals that they have patented a whole class of related
>compounds - many of which are almost identical to thiamine.  The
>relationship to thiamine is NOT stated unless you understand
>organic chemistry, and then it becomes very clear!  Whether
>high doses of thiamine can actually reverse crosslinks is
>not mentioned, and may not actually work (I would think someone
>would have correlated high thiamine diets with better circulatory
>systems if it did).
>Another noteworthy observation....  I had been reading much about
>glycosylation, how to slow it down, and even reverse it.  Many sulfur
>based compounds are known to inhibit this reaction - and many are used
>outside of our bodies, to prevent the "browning reaction" of foods,
>which is a close close parallel, if not identical, to the AGE process.
>Sulfites are added to foods, to prevent this.  The new crosslink
>breaker is a sulfur based compound, etc.  My wife occasionally brings
>home junk magazines like National Enquirer, for entertainment.  I looked
>thru one recently, that had a story about the "oldest lady alive".
>She's 114 years old, and credits drinking Scotch, and eating boiled
>onions for her longevity.  Well..... It turns out that both of those
>have been kinda linked to reducing AGE:  alcohol (www.picower.edu)
>inhibits AGE, and onions contain great amounts of sulfur compounds.
>Just a curious observation that may have something to it!
>If you do search engine searches for these keywords, not necessarily
>all at the same time, you'll find lots of stuff:
>glycosylation, maillard, "browning reaction", AGE, diabetes
>Glycosylation reaction, browning reaction, maillard reaction are all
>synonyms of the same process.
>Kevin Hass WB0DPN      		Transportation Technology Center, Inc
>Senior Systems Programmer	P.O. Box 11130
>(719)-584-0596			Pueblo, CO 81001, USA
>email @ redacted

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