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[IP] Fwd: JDRF Research E-Newsletter #26



In a message dated 11/22/2002 12:25:58 PM Pacific Standard Time,
email @ redacted writes:


> JDRF was recently notified of an error in the transmition of Research
> E-Newsletter #26.  Please accept our apologies.
>
> JDRF RESEARCH E-NEWSLETTER #26
> October 4, 2002
>
> The Juvenile Diabetes Research Foundationbs Research E-Newsletter provides
> all those interested with the latest information about research on type 1
> diabetes and its complications.  Please forward this report to others who
> may be interested.  To add your name to the distribution list, send an
> e-mail to email @ redacted <mailto:email @ redacted> with bSubscribe to Research
> E-Newsletterb in the subject line and your full name and postal address in
> the message portion of the e-mail.  If you do not wish to receive future
> mailings of this newsletter, please send an e-mail to email @ redacted <
> mailto:email @ redacted> with bUnsubscribe to Research E-Newsletterb in the
> subject line.
>
> IN THIS ISSUE:
>
> 1. Nighttime Blood Pressure Gives Clue to Kidney Risk
> 2. Changes In Diabetic Foot Clarified-May Allow Better Prevention
> 3. Compound Shows Potential in Preventing Retinopathy
> 4. ENDIT Prevention Trial Delivers Clear Answer
> 5. New Evidence Raises Doubt About Diabetes Hypothesis
>
> 1. Nighttime Blood Pressure Gives Clue to Kidney Risk
> Researchers have discovered an early warning sign for diabetic nephropathy
> or kidney disease, the dangerous complication of diabetes that can progress
> to kidney failure, requiring dialysis or kidney transplant for survival.
> Normally, a personbs systolic blood pressure dips slightly overnight
before
> rising again in the morning hours. However, many patients with type 1
> diabetes do not show this overnight drop. Based on a study monitoring 75
> adolescents and young adults with type 1 diabetes, scientists at the
> University of Valencia in Spain and Northwestern University report in the
> September 12 New England Journal of Medicine that the study subjects whose
> blood pressure did not dip during nighttime are more likely to develop a
> condition called microalbuminuria-accumulation of the blood protein albumin
> in the urine, which is an early indicator of nephropathy. They suggest that
> the higher level of nighttime blood pressure may play an important role in
> the development of diabetic nephropathy and may serve as the earliest
> indicator that someone with type 1 diabetes is at high risk for the
> condition. Currently, urine microalbumin tests can detect early kidney
> disease, but at a point when substantial damage to the organ has already
> occurred. Julie Ingelfinger, an editor of the journal, wrote in an
> accompanying editorial that these findings, if confirmed, could argue for
> giving blood pressure drugs to type 1 diabetes patients who donbt show a
> relative nighttime decrease-even if overall blood pressure is at normal
> levels during other periods. She added, bAdditional studies with long-term
> follow-up will be needed to learn whether these observations can be
> generalized to a larger group of patients.b
>
> To read the abstract of this study, click below:
> <http://content.nejm.org/cgi/content/abstract/347/11/797>
>
>
> 2. Changes In Diabetic Foot Clarified-May Allow Better Prevention
> People with diabetes are at increased risk of serious foot problems,
> especially ulcers or sores that can lead to hospitalization or even
> ultimately to amputation. Current treatments, while useful, have limited
> success, as shown by high rates of ulcer recurrence. Now researchers at
> Washington University School of Medicine in St. Louis, in an NIH-funded
> study, report they have identified changes that occur in the tissue and
> bone structure of the feet of people with diabetes that may contribute to
> foot ulcers. The study group of 32 individuals included 16 with diabetes
> and a prior foot ulcer, and 16 matched controls. The scientists used
> computed tomography imagery to display a three-dimensional picture,
> allowing the researchers to identify and measure internal and external soft
> tissue, bone structure and joint disease. The images revealed that the
> people with diabetes had much lower muscle density on the soles of their
> feet than the control group.  The people with diabetes also had more joint
> deformity (joint extension) and joint disease (arthropathy). Findings from
> this study were published in the August issue of the Journal of Bone and
> Joint Surgery. JDRF is currently funding a study at Cleveland Clinic that
> images foot tissue via MRI, thereby seeking ways to non-invasively predict
> ulcer development. Findings from studies  such as those in St. Louis and
> Cleveland will help guide new interventions to prevent or treat foot
> ulcerations in people with diabetes.
>
> To read the abstract of this study, click below:
> <http://www.ejbjs.org/cgi/content/abstract/84/8/1395>
>
>
> 3. Compound Shows Potential in Preventing Retinopathy
> Among the several biological mechanisms by which high blood glucose may
> contribute to diabetic retinopathy is the conversion of proteins into
> harmful advanced glycation endproducts (AGEs), which cause havoc in the
> walls of vulnerable small blood vessels. One strategy for preventing
> complications such as retinopathy in people with diabetes involves blocking
> AGE formation. Researchers at Queenbs University of Belfast in Northern
> Ireland and the University of South Carolina investigated whether a
> compound known to inhibit AGE formation, pyridoxamine (PM), would protect
> retinal blood vessels from AGE-related damage. In particular, they wanted
> to see if PM was more effective at preventing damage than vitamin E (VE)
> and R-C-lipoic acid (LA), both of which have shown some protective effect
> against the harm caused by high blood glucose. The researchers examined the
> effects of each compound in separate groups of animals that were induced to
> develop diabetes and have the disease for 29 weeks. The researchers report
> that PM appears to protect the capillaries better than VE or LA, partly
> because it inhibits a range of changes in the retinal blood vessels-some of
> which VE and LA are not capable of blocking. This finding, funded partly by
> JDRF and reported in the September issue of the journal Diabetes, suggests
> that PM could become a unique component of any treatment developed to block
> retinopathy in people with diabetes.
>
> To read the abstract of this study, click below:
> <http://diabetes.diabetesjournals.org/cgi/content/abstract/51/9/2826>
>
> To read about some of JDRFbs initiatives in diabetic retinopathy, click
> below:
> <http://www.jdrf.org/research/retinopathy_bkg.php>
>
>
> 4. ENDIT Prevention Trial Delivers Clear Answer
> Results are in from a large-scale clinical trial investigating the
> possibility of preventing or delaying the onset of type 1 diabetes by
> treating at-risk patients with nicotinamide, a vitamin present in small
> amounts in a normal diet. The study, called European Nicotinamide Diabetes
> Intervention Trial (ENDIT), was initiated to see whether promising results
> from animal studies and preliminary human studies would hold up in a
> large-scale clinical study. ENDIT, which incorporated participants from
> countries in Europe, plus Canada and the U.S., was in danger of ending
> without providing any results when funding was unexpectedly withdrawn in
> its third year. JDRF stepped in and provided the money to complete the
> study. At the 38th Annual Meeting of the European Association for the Study
> of Diabetes (EASD) in early September, Dr. Edwin Gale, a professor of
> Diabetic Medicine in Bristol, U.K., announced that nicotinamide does not
> work any better than a placebo. Despite the disappointing outcome, there
> was considerable positive value in having conducted a well-designed,
> carefully controlled clinical trial to conclusively evaluate a specific
> preventative approach.
>
> To read background about the ENDIT trial, click below:
> <http://www.bris.ac.uk/Depts/DivMed/endit.html>
>
>
> 5. New Evidence Raises Doubts About Diabetes Hypothesis
> New investigations frequently call established theories into question.
> Since the early 90s, researchers have hypothesized that defects in certain
> protective immune T cells, called NKT cells, play an important role in the
> onset of autoimmune diseases like type 1 diabetes. These cells normally
> hold destructive immune cells in check to keep them from attacking the
bodyb
> s own tissue. Scientists developed the defect theory after observing that
> NKT cells appear to be low in number in nonobese diabetic (NOD) mice, an
> animal model for the disease, and in people with type 1 diabetes. In
> addition, the NKT cells that are present in type 1 diabetes seem to
> function less well than NKT cells in mice and humans without the disease.
> The connection between NKT function or deficiency and type 1 diabetes has
> been hard to establish, however, because actual identification of NKT cells
> was based on indirect methods. Now a team of researchers at Princeton
> University, University of Colorado Health Sciences Center, and the Scripps
> Research Institute, headed by Dr. Albert Bendelac, report they have
> developed a direct way to count NKT cells and measure their effectiveness.
> Using this new method, they compared the number and functioning of NKT
> cells in people with type 1 diabetes, people at high risk for developing
> the disease, and people without the disease. To their surprise, the
> researchers found that the number and functioning of NKT cells did not seem
> to be affected by the onset of type 1 diabetes.  People with type 1
> diabetes or pre-diabetes did not show any difference in NKT cells compared
> with those in the control (non-diabetes) group.  These results seem to
> refute the hypothesis that NKT deficiency and defects underlie autoimmune
> diseases. In an accompanying commentary, JDRF-funded researcher, Lucienne
> Chatenoud, of France, writes that it is difficult to compare the new data
> with that of previous research, because of differences in assays. bThus
the
> role of NKT cells in autoimmunity is still unsettled and will only be
> resolved by the consistent use of techniques and reagents [substances used
> to detect or measure]b The research, funded partly by JDRF, was reported
in
> the September issue of the Journal of Clinical Investigation.
>
> To read the full text of this study, click below:
> <http://www.jci.org/cgi/content/full/110/6/793>
>
> To read the commentary on this study by Dr. Chatenoud, click below:
> <http://www.jci.org/cgi/content/full/110/6/747>
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Date: Fri, 22 Nov 2002 14:21:37 -0500
From: email @ redacted
Subject: JDRF Research E-Newsletter #26
To: email @ redacted
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JDRF was recently notified of an error in the transmition of Research E-Newsletter #26.  Please accept our apologies.

JDRF RESEARCH E-NEWSLETTER #26
October 4, 2002

The Juvenile Diabetes Research Foundations Research E-Newsletter provides all those interested with the latest information about research on type 1 diabetes and its complications.  Please forward this report to others who may be interested.  To add your name to the distribution list, send an e-mail to email @ redacted <mailto:email @ redacted> with Subscribe to Research E-Newsletter in the subject line and your full name and postal address in the message portion of the e-mail.  If you do not wish to receive future mailings of this newsletter, please send an e-mail to email @ redacted <mailto:email @ redacted> with Unsubscribe to Research E-Newsletter in the subject line.

IN THIS ISSUE: 

1. Nighttime Blood Pressure Gives Clue to Kidney Risk 
2. Changes In Diabetic Foot Clarified-May Allow Better Prevention 
3. Compound Shows Potential in Preventing Retinopathy
4. ENDIT Prevention Trial Delivers Clear Answer
5. New Evidence Raises Doubt About Diabetes Hypothesis

1. Nighttime Blood Pressure Gives Clue to Kidney Risk
Researchers have discovered an early warning sign for diabetic nephropathy or kidney disease, the dangerous complication of diabetes that can progress to kidney failure, requiring dialysis or kidney transplant for survival. Normally, a persons systolic blood pressure dips slightly overnight before rising again in the morning hours. However, many patients with type 1 diabetes do not show this overnight drop. Based on a study monitoring 75 adolescents and young adults with type 1 diabetes, scientists at the University of Valencia in Spain and Northwestern University report in the September 12 New England Journal of Medicine that the study subjects whose blood pressure did not dip during nighttime are more likely to develop a condition called microalbuminuria-accumulation of the blood protein albumin in the urine, which is an early indicator of nephropathy. They suggest that the higher level of nighttime blood pressure may play an important role in the development of diabetic !
nephropathy and may serve as the earliest indicator that someone with type 1 diabetes is at high risk for the condition. Currently, urine microalbumin tests can detect early kidney disease, but at a point when substantial damage to the organ has already occurred. Julie Ingelfinger, an editor of the journal, wrote in an accompanying editorial that these findings, if confirmed, could argue for giving blood pressure drugs to type 1 diabetes patients who dont show a relative nighttime decrease-even if overall blood pressure is at normal levels during other periods. She added, Additional studies with long-term follow-up will be needed to learn whether these observations can be generalized to a larger group of patients.

To read the abstract of this study, click below:
<http://content.nejm.org/cgi/content/abstract/347/11/797>


2. Changes In Diabetic Foot Clarified-May Allow Better Prevention
People with diabetes are at increased risk of serious foot problems, especially ulcers or sores that can lead to hospitalization or even ultimately to amputation. Current treatments, while useful, have limited success, as shown by high rates of ulcer recurrence. Now researchers at Washington University School of Medicine in St. Louis, in an NIH-funded study, report they have identified changes that occur in the tissue and bone structure of the feet of people with diabetes that may contribute to foot ulcers. The study group of 32 individuals included 16 with diabetes and a prior foot ulcer, and 16 matched controls. The scientists used computed tomography imagery to display a three-dimensional picture, allowing the researchers to identify and measure internal and external soft tissue, bone structure and joint disease. The images revealed that the people with diabetes had much lower muscle density on the soles of their feet than the control group.  The people with diabetes also!
 had more joint deformity (joint extension) and joint disease (arthropathy). Findings from this study were published in the August issue of the Journal of Bone and Joint Surgery. JDRF is currently funding a study at Cleveland Clinic that images foot tissue via MRI, thereby seeking ways to non-invasively predict ulcer development. Findings from studies  such as those in St. Louis and Cleveland will help guide new interventions to prevent or treat foot ulcerations in people with diabetes.

To read the abstract of this study, click below:
<http://www.ejbjs.org/cgi/content/abstract/84/8/1395>


3. Compound Shows Potential in Preventing Retinopathy
Among the several biological mechanisms by which high blood glucose may contribute to diabetic retinopathy is the conversion of proteins into harmful advanced glycation endproducts (AGEs), which cause havoc in the walls of vulnerable small blood vessels. One strategy for preventing complications such as retinopathy in people with diabetes involves blocking AGE formation. Researchers at Queens University of Belfast in Northern Ireland and the University of South Carolina investigated whether a compound known to inhibit AGE formation, pyridoxamine (PM), would protect retinal blood vessels from AGE-related damage. In particular, they wanted to see if PM was more effective at preventing damage than vitamin E (VE) and R-\-lipoic acid (LA), both of which have shown some protective effect against the harm caused by high blood glucose. The researchers examined the effects of each compound in separate groups of animals that were induced to develop diabetes and have the disease for 2!
9 weeks. The researchers report that PM appears to protect the capillaries better than VE or LA, partly because it inhibits a range of changes in the retinal blood vessels-some of which VE and LA are not capable of blocking. This finding, funded partly by JDRF and reported in the September issue of the journal Diabetes, suggests that PM could become a unique component of any treatment developed to block retinopathy in people with diabetes. 

To read the abstract of this study, click below:
<http://diabetes.diabetesjournals.org/cgi/content/abstract/51/9/2826>

To read about some of JDRFs initiatives in diabetic retinopathy, click below:
<http://www.jdrf.org/research/retinopathy_bkg.php>


4. ENDIT Prevention Trial Delivers Clear Answer
Results are in from a large-scale clinical trial investigating the possibility of preventing or delaying the onset of type 1 diabetes by treating at-risk patients with nicotinamide, a vitamin present in small amounts in a normal diet. The study, called European Nicotinamide Diabetes Intervention Trial (ENDIT), was initiated to see whether promising results from animal studies and preliminary human studies would hold up in a large-scale clinical study. ENDIT, which incorporated participants from countries in Europe, plus Canada and the U.S., was in danger of ending without providing any results when funding was unexpectedly withdrawn in its third year. JDRF stepped in and provided the money to complete the study. At the 38th Annual Meeting of the European Association for the Study of Diabetes (EASD) in early September, Dr. Edwin Gale, a professor of Diabetic Medicine in Bristol, U.K., announced that nicotinamide does not work any better than a placebo. Despite the disappointi!
ng outcome, there was considerable positive value in having conducted a well-designed, carefully controlled clinical trial to conclusively evaluate a specific preventative approach. 

To read background about the ENDIT trial, click below:
<http://www.bris.ac.uk/Depts/DivMed/endit.html>


5. New Evidence Raises Doubts About Diabetes Hypothesis
New investigations frequently call established theories into question.  Since the early 90s, researchers have hypothesized that defects in certain protective immune T cells, called NKT cells, play an important role in the onset of autoimmune diseases like type 1 diabetes. These cells normally hold destructive immune cells in check to keep them from attacking the bodys own tissue. Scientists developed the defect theory after observing that NKT cells appear to be low in number in nonobese diabetic (NOD) mice, an animal model for the disease, and in people with type 1 diabetes. In addition, the NKT cells that are present in type 1 diabetes seem to function less well than NKT cells in mice and humans without the disease. The connection between NKT function or deficiency and type 1 diabetes has been hard to establish, however, because actual identification of NKT cells was based on indirect methods. Now a team of researchers at Princeton University, University of Colorado Health!
 Sciences Center, and the Scripps Research Institute, headed by Dr. Albert Bendelac, report they have developed a direct way to count NKT cells and measure their effectiveness. Using this new method, they compared the number and functioning of NKT cells in people with type 1 diabetes, people at high risk for developing the disease, and people without the disease. To their surprise, the researchers found that the number and functioning of NKT cells did not seem to be affected by the onset of type 1 diabetes.  People with type 1 diabetes or pre-diabetes did not show any difference in NKT cells compared with those in the control (non-diabetes) group.  These results seem to refute the hypothesis that NKT deficiency and defects underlie autoimmune diseases. In an accompanying commentary, JDRF-funded researcher, Lucienne Chatenoud, of France, writes that it is difficult to compare the new data with that of previous research, because of differences in assays. Thus the role of NKT !
cells in autoimmunity is still unsettled and will only be resolved by the consistent use of techniques and reagents [substances used to detect or measure] The research, funded partly by JDRF, was reported in the September issue of the Journal of Clinical Investigation.

To read the full text of this study, click below:
<http://www.jci.org/cgi/content/full/110/6/793>

To read the commentary on this study by Dr. Chatenoud, click below:
<http://www.jci.org/cgi/content/full/110/6/747>


            
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