Hi Quentin ,
nice article

I found the institute :
http://www.baker.edu.au/bakernet/external/index2.asp

Diabetic Complications Group:
http://www.baker.edu.au/bakernet/external/research/vascular.asp

The Glycation and Diabetic Complications group
http://www.baker.edu.au/bakernet/external/research/glycdiabcomp.asp

Kidney disease, blindness, heart attacks and atherosclerosis are
complications of diabetes they are the major cause of death and disability
in the western world.Some pathways lead to irreversible interactions between
the excess sugar found in diabetes and proteins such as haemoglobin,
collagen and albumin (advanced glycation). The process of advanced glycation
alters the ability of the human body to renew these proteins and they
accumulate at many sites causing disruption of the normal tissue structure
especially in the blood vessels, heart and kidney.

No this I found very interesting .I did not know something can be done about
the bad effect of high blood glucose , the advanced glycation end products ,
even without lowering the bg:

Our group is researching the pathways of damage related to advanced
glycation in diabetic complications. This approach involves the integration
of many areas of research including oxidative stress and interactions with
angiotensin II.

I looked up this groups publications in 2005 . I found these :

Ann N Y Acad Sci. 2005 Jun;1043:644-54.
Low-molecular weight advanced glycation end products: markers of tissue AGE
accumulation and more?
Thomas MC, Forbes JM, MacIsaac R, Jerums G, Cooper ME.
The Baker Heart Research Institute, P.O. Box 6492, St. Kilda Rd. Central,
Melbourne, Victoria, Australia. mthomas@baker.edu.au

Incomplete digestion of advanced glycation end product (AGE)-modified
protein results in the formation of low-molecular weight degradation
products incorporating AGE modifications (LMW-AGEs). In addition to being
biomarkers of AGE modification, LMW-AGEs may have a high toxic potential,
being free to interact with AGE receptors at distant sites via the
circulation.

Did not know that there were AGE receptors . Afterall these incomplete
breakdown products of glycosilated proteins do not normally occur in our
body (?)

Several free AGEs have been identified, including pentosidine,
N(epsilon)-(carboxymethyl)lysine (CML), and free-imidazole AGEs. In
addition, fluorescence (370 nm [excitation]/440 nm [emission]) in the LMW
phase of serum correlates with tissue fluorescence, an established marker
for AGE modification. In experimental diabetes, LMW fluorescence increases
with duration of disease and is normalized with the AGE inhibitor
aminoguanidine. LMW fluorescence is also higher in patients with diabetes,
in whom it is associated with glomerular filtration rate and hemoglobin.
Patients with hyperfiltration have lower LMW fluorescence than those with
normal renal function, which may protect them from AGE accumulation in the
short term. These findings provide clinical support for the association
between AGEs and progressive renal injury in diabetes.

So this proves that the LMW-AGE can be used as markers for the diabetic
damage.

PMID: 16037288 [PubMed - indexed for MEDLINE]

The other articles are even more interesting :

J Am Soc Nephrol. 2005 Aug;16(8):2363-72. Epub 2005 Jun 1.
Modulation of soluble receptor for advanced glycation end products by
angiotensin-converting enzyme-1 inhibition in diabetic nephropathy.
Forbes JM, Thorpe SR, Thallas-Bonke V, Pete J, Thomas MC, Deemer ER, Bassal
S, El-Osta A, Long DM, Panagiotopoulos S, Jerums G, Osicka TM, Cooper ME.
Address correspondence to: Dr. Josephine Forbes, Danielle Alberti Memorial
Centre for Diabetes Complications, Baker Heart Research Institute, P.O. Box
6492, St. Kilda Road, Melbourne, Victoria, 8008, Australia.
josephine.forbes@baker.edu.au.

Recent studies have identified that first-line renoprotective agents that
interrupt the renin-angiotensin system not only reduce BP but also can
attenuate advanced glycation end product (AGE) accumulation. This study used
in vitro, preclinical, and human approaches to explore the potential effects
of these agents on the modulation of the receptor for AGE (RAGE). Bovine
aortic endothelial cells that were exposed to the angiotensin-converting
enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose
demonstrated a significant increase in soluble RAGE (sRAGE) secreted into
the medium. In streptozotocin-induced diabetic rats, ramipril treatment
(ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked
carboxymethyllysine and pentosidine, as well as circulating and renal AGE.
Renal gene upregulation of total RAGE (all three splice variants) was
observed in ACEi-treated animals. There was a specific increase in the gene
expression of the splice variant C-truncated RAGE (sRAGE). There were also
increases in sRAGE protein identified within renal cells with ACEi
treatment, which showed AGE-binding ability. This was associated with
decreases in renal full-length RAGE protein from ACEi-treated rats.
Decreases in plasma soluble RAGE that were significantly increased by ACEi
treatment were also identified in diabetic rats. Similarly, there was a
significant increase in plasma sRAGE in patients who had type 1 diabetes and
were treated with the ACEi perindopril. Complexes between sRAGE and
carboxymethyllysine were identified in human and rodent diabetic plasma. It
is postulated that ACE inhibition reduces the accumulation of AGE in
diabetes partly by increasing the production and secretion of sRAGE into
plasma.

PMID: 15930093 [PubMed - in process]

So here , even in the presence of high glucose , the Angio Tensine
Converting Enzyme inhibitor reverses the glycation , which is demonstrated
by the fact that there was a significant increase in soluble form of the
receptor for Advanced Glycation End products secreted into the medium : the
partial break down products of the Advanced Glycation End products bound to
their receptor , the receptor together with the ligand was internalized by
the cells , broken down and excluded in the medium (Blood stream). But ACE
inhibitors are already given for preventing hearth attack's (?) So now they
also seem to do something to the  _already existing damage_  (?)

Am J Ther. 2005 Nov-Dec;12(6):562-72.
Advanced glycation end products and diabetic nephropathy.
Thomas MC, Forbes JM, Cooper ME.
Danielle Alberti Memorial Centre for Diabetes Complications, Baker Medical
Research Institute, Melbourne, Victoria, Australia.

Chronic hyperglycemia and oxidative stress in diabetes results in the
formation and accumulation advanced glycation end products (AGEs). AGEs have
a wide range of chemical, cellular, and tissue effects that contribute to
the development of microvascular complications.

So here again are the micro vascular complications mentioned.Causing the
peripheral artery desease and the cold feet . I thought this damage was
permanent. For reading this I get the impression that it might be reversible
(?)

In particular, AGEs appear to have a key role in the diabetic nephropathy.
Their importance as downstream mediators of tissue injury in diabetic kidney
disease is demonstrated by animal studies using inhibitors of advanced
glycation to retard the development of nephropathy without directly
influencing glycemic control.

So here is the method for lowering your A1c ,  _WITHOUT_  controling your bg
. I would not even dream of doing that , but keeping my bg under strickt
control  _AND_ taking ACE inhibitor might be very usefull (??)

AGE modification of proteins may produce in changes charge, solubility, and
conformation leading to molecular dysfunction as well as disrupting
interactions with other proteins. AGEs also interact with specific receptors
and binding proteins to influence the renal expression of growth factors and
cytokines, implicated in the progression of diabetic renal disease. The
effects of AGEs appears to be synergistic with other pathogenic pathways in
diabetes including oxidative stress, hypertension, and activation of the
renin-angiotensin system. Each of these pathways may be activated by AGEs,
and each may promote the formation of AGEs in the vicious cycle associated
with progressive renal damage. It is likely that therapies that inhibit the
formation of AGEs or remove established AGE modifications will form an
important component part of future therapy in patients with diabetes, acting
in concert with conventional approaches to prevent diabetic renal injury.

PMID: 16280650 [PubMed - in process]

hth
Gys