David Saum
Fri, Jun-29-07, 17:16
http://www2.warwick.ac.uk/fac/med/newsfront/?newsItem=094d402-
513631e4601137249474419c5
New Warwick diabetes research published in New Scientist
Research led by Warwick Medical School's Dr Antonio Ceriello
into the effects of diabetes has been published in the June 30
edition of New Scientist magazine. His team has have uncovered
a process that locks the body’s metabolism in a diabetic state
after only relatively limited exposure to high glucose levels.
Researchers were already aware that there seems to be a point
of no return in the onset of diabetes. This was apparent in
the Diabetes Complications and Control Trial (DCCT) in the
1990s when Type 1 diabetic patients were either placed on
standard or intensive treatment regimens to normalize their
glucose levels. Because complications were so profoundly
reduced in patients with tight glucose control, all the
remaining DCCT patients were switched early onto intensive
therapy. However a follow-up study found that several years
after switching to intensive therapy the patients who started
the trial on only the standard treatment regimen continued to
have more complications than those who received intensive
therapy throughout the trial.
Research since has speculated that exposure to high glucose
levels quickly creates a metabolic memory in which diabetes
persists long after glucose levels have been corrected.
Research to date suggested that oxidation played a role but
the exact mechanism was unknown.
The Warwick research team, led by Dr Antonio Ceriello, have
now proven that the damage seems to be done in a process
called glycation when early on in a period of high glucose
levels glucose sugar molecules are able to bind to proteins in
the mitochondria of cells (the parts of cells governing the
production and regulation of energy). This persists even if
glucose levels later fall to normal. This inhibits and
distorts the mitochondria’s normal function and results in an
overabundance of the production of free radicals (or Reactive
Oxygen Species – ROS) which cause oxidation and thus continued
diabetic complications.
The researchers proved their hypothesis by taking tissue and
exposing it to 2 weeks of high levels of glucose, followed by
one week of normal glucose – however for half the tissue they
also applied several antioxidants at the end of the two weeks
of high glucose. The tissue without antioxidants levels of
glucose stress remained high but where antioxidants had been
applied there was a dramatic fall in the incidence of free
radicals and there was also a significant drop in 5 of the 6
key markers for high glucose stress.
The research confirms the need for very early tight control of
glucose levels to avoid diabetic complication and that that
control must be supplemented with the use of antioxidant
agents to mitigate the progression of complications.
However long term use of antioxidants can in itself produce
health problems so in a further research published this month
the team have tested the use of the AT-1 receptor blocker
Telmisartan and found it can be used in exactly the same way
to suppress the build up of free radicals without the side
affects that long term use of antioxidants would cause.
Dr Ceriello is now beginning to look at how to move beyond
simply suppressing the problematic production of free radicals
and actually finding ways of reversing the glycation process
itself thus erasing the harmful "metabolic memory".
------------------
http://www.newscientist.com/article/mg19426104.200-how-to-sto-
p-diabetes-wreaking-lasting-havoc.html
How to stop diabetes wreaking lasting havoc
29 June 2007 NewScientist.com news service Andy Coghlan
One of the nasty tricks that diabetes has up its sleeve is
the ability to carry on harming people long after they have
got the level of glucose in their blood under control. Now
researchers think they may be able to stop this, using cheap
available drugs.
The idea builds on the discovery that when cells are exposed
to the high levels of glucose typical of diabetes, proteins
within the cells' mitochondria suffer damaging changes. The
proteins become permanently attached to sugar-like molecules
called glycans, and this not only prevents them doing their
job properly but also makes them produce harmful molecules
called reactive oxygen species.
The reactive oxygen species circulate throughout the body,
attacking and damaging tissues, particularly in the limbs and
eyes. Because the changes to the cellular proteins are not
reversible, they continue to pump out these molecules even
when glucose levels have returned to normal. "This contributes
to the development of diabetic complications," says Antonio
Ceriello of the University of Warwick in Coventry, UK, whose
team now think there may be a way to stop this happening.
The clue came from lab experiments in which they took damaged
cells that had been previously exposed to high levels of
glucose, and showed that the reactive molecules could be
neutralised by exposing the cells to antioxidants such as
alpha-lipoic acid (Diabetologia, DOI:
10.1007/s00125-007-0684-2).
In a trial on 36 patients undergoing insulin treatment for
type 1 diabetes, they were then able to show that injections
of vitamin C could have the same effect in people, as did a
blood-pressure-lowering drug called telmisartan. "These
compounds can counteract the 'memory' because they work
inside cells to block free-radical production," says
Ceriello, who will publish the results of the trial in the
journal Diabetes Care.
“In a trial of 36 patients, injections of vitamin C
neutralised the reactive molecules that were responsible for
the damage”The researchers point out, however, that people
would have to take such antioxidants for life, to mop up the
continuous supply of reactive molecules being produced by the
damaged proteins. So they are now looking for other potential
drugs that might permanently reverse the chemical changes that
stopped the protein's normal function.
Ian Frame, research manager at the charity Diabetes UK,
cautions that the timescale of the experiments was relatively
short, so the proposed treatments might not work in people
with chronic diabetes. However, he does say the results are a
"step forward" in establishing how reactive oxygen species
contribute to long-term complications of diabetes.
From issue 2610 of New Scientist magazine, 29 June 2007, page
11
-------------
also see
http://www.sciencedaily.com/upi/index.php?feed=Science&articl-
e=UPI-1-20070628-16531900-bc-britain-diabetes.xml
513631e4601137249474419c5
New Warwick diabetes research published in New Scientist
Research led by Warwick Medical School's Dr Antonio Ceriello
into the effects of diabetes has been published in the June 30
edition of New Scientist magazine. His team has have uncovered
a process that locks the body’s metabolism in a diabetic state
after only relatively limited exposure to high glucose levels.
Researchers were already aware that there seems to be a point
of no return in the onset of diabetes. This was apparent in
the Diabetes Complications and Control Trial (DCCT) in the
1990s when Type 1 diabetic patients were either placed on
standard or intensive treatment regimens to normalize their
glucose levels. Because complications were so profoundly
reduced in patients with tight glucose control, all the
remaining DCCT patients were switched early onto intensive
therapy. However a follow-up study found that several years
after switching to intensive therapy the patients who started
the trial on only the standard treatment regimen continued to
have more complications than those who received intensive
therapy throughout the trial.
Research since has speculated that exposure to high glucose
levels quickly creates a metabolic memory in which diabetes
persists long after glucose levels have been corrected.
Research to date suggested that oxidation played a role but
the exact mechanism was unknown.
The Warwick research team, led by Dr Antonio Ceriello, have
now proven that the damage seems to be done in a process
called glycation when early on in a period of high glucose
levels glucose sugar molecules are able to bind to proteins in
the mitochondria of cells (the parts of cells governing the
production and regulation of energy). This persists even if
glucose levels later fall to normal. This inhibits and
distorts the mitochondria’s normal function and results in an
overabundance of the production of free radicals (or Reactive
Oxygen Species – ROS) which cause oxidation and thus continued
diabetic complications.
The researchers proved their hypothesis by taking tissue and
exposing it to 2 weeks of high levels of glucose, followed by
one week of normal glucose – however for half the tissue they
also applied several antioxidants at the end of the two weeks
of high glucose. The tissue without antioxidants levels of
glucose stress remained high but where antioxidants had been
applied there was a dramatic fall in the incidence of free
radicals and there was also a significant drop in 5 of the 6
key markers for high glucose stress.
The research confirms the need for very early tight control of
glucose levels to avoid diabetic complication and that that
control must be supplemented with the use of antioxidant
agents to mitigate the progression of complications.
However long term use of antioxidants can in itself produce
health problems so in a further research published this month
the team have tested the use of the AT-1 receptor blocker
Telmisartan and found it can be used in exactly the same way
to suppress the build up of free radicals without the side
affects that long term use of antioxidants would cause.
Dr Ceriello is now beginning to look at how to move beyond
simply suppressing the problematic production of free radicals
and actually finding ways of reversing the glycation process
itself thus erasing the harmful "metabolic memory".
------------------
http://www.newscientist.com/article/mg19426104.200-how-to-sto-
p-diabetes-wreaking-lasting-havoc.html
How to stop diabetes wreaking lasting havoc
29 June 2007 NewScientist.com news service Andy Coghlan
One of the nasty tricks that diabetes has up its sleeve is
the ability to carry on harming people long after they have
got the level of glucose in their blood under control. Now
researchers think they may be able to stop this, using cheap
available drugs.
The idea builds on the discovery that when cells are exposed
to the high levels of glucose typical of diabetes, proteins
within the cells' mitochondria suffer damaging changes. The
proteins become permanently attached to sugar-like molecules
called glycans, and this not only prevents them doing their
job properly but also makes them produce harmful molecules
called reactive oxygen species.
The reactive oxygen species circulate throughout the body,
attacking and damaging tissues, particularly in the limbs and
eyes. Because the changes to the cellular proteins are not
reversible, they continue to pump out these molecules even
when glucose levels have returned to normal. "This contributes
to the development of diabetic complications," says Antonio
Ceriello of the University of Warwick in Coventry, UK, whose
team now think there may be a way to stop this happening.
The clue came from lab experiments in which they took damaged
cells that had been previously exposed to high levels of
glucose, and showed that the reactive molecules could be
neutralised by exposing the cells to antioxidants such as
alpha-lipoic acid (Diabetologia, DOI:
10.1007/s00125-007-0684-2).
In a trial on 36 patients undergoing insulin treatment for
type 1 diabetes, they were then able to show that injections
of vitamin C could have the same effect in people, as did a
blood-pressure-lowering drug called telmisartan. "These
compounds can counteract the 'memory' because they work
inside cells to block free-radical production," says
Ceriello, who will publish the results of the trial in the
journal Diabetes Care.
“In a trial of 36 patients, injections of vitamin C
neutralised the reactive molecules that were responsible for
the damage”The researchers point out, however, that people
would have to take such antioxidants for life, to mop up the
continuous supply of reactive molecules being produced by the
damaged proteins. So they are now looking for other potential
drugs that might permanently reverse the chemical changes that
stopped the protein's normal function.
Ian Frame, research manager at the charity Diabetes UK,
cautions that the timescale of the experiments was relatively
short, so the proposed treatments might not work in people
with chronic diabetes. However, he does say the results are a
"step forward" in establishing how reactive oxygen species
contribute to long-term complications of diabetes.
From issue 2610 of New Scientist magazine, 29 June 2007, page
11
-------------
also see
http://www.sciencedaily.com/upi/index.php?feed=Science&articl-
e=UPI-1-20070628-16531900-bc-britain-diabetes.xml