a very important article

November 26, 2011

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Study: Insulin Resistance is Associated with Inflammatory Processes

that Lead to Cortical Atrophy and Brain Dysfunction

9-Nov-2011

November 2011 - Many complications of diabetes, including kidney

disease, foot problems and vision problems are generally well

recognized. But the disease's impact on the brain is often overlooked.

For the past five years, a team led by Beth Israel Deaconess Medical

Center (BIDMC) neurophysiologist Vera Novak, MD, PhD, has been studying

the effects of diabetes on cognitive health in older individuals and has

determined that memory loss, depression and other types of cognitive

impairment are a serious consequence of this widespread disease.

Now, Novak's team has identified a key mechanism behind this course of

events. In a study published in the November 2011 issue of the journal

Diabetes Care, they report that in older patients with diabetes, two

adhesion molecules -- sVCAM and sICAM -- cause inflammation in the

brain, triggering a series of events that affect blood vessels and,

eventually, cause brain tissue to atrophy. Importantly, they found that

the gray matter in the brain's frontal and temporal regions --

responsible for such critical functions as decision-making, language,

verbal memory and complex tasks -- is the area most affected by these

events.

" In our previous work, we had found that patients with diabetes had

significantly more brain atrophy than did a control group, " explains

Novak, Director of the Syncope and Falls in the Elderly (SAFE) Program

in the Division of Gerontology at BIDMC and Associate Professor of

Medicine at Harvard Medical School. " In fact, at the age of 65, the

average person's brain shrinks about one percent a year, but in a

diabetic patient, brain volume can be lowered by as much as 15 percent. "

Diabetes develops when glucose builds up in the blood instead of

entering the body's cells to be used as energy. Known as hyperglycemia,

this condition often goes hand-in-hand with inflammation. Novak wanted

to determine if chronic inflammation of the blood vessels was causing

altered blood flow to the brain in patients with diabetes.

To test this hypothesis, Novak's team recruited 147 study subjects,

averaging 65 years of age. Seventy one of the subjects had type 2

diabetes and had been taking medication to manage their conditions for

at least five years. The other 76 were age and sex-matched non-diabetic

controls.

Study subjects underwent a series of cognitive tests, balance tests and

standard blood-pressure and blood-glucose tests. Serum samples were also

collected to measure adhesion molecules and several other markers of

systemic inflammation. To determine perfusion (blood flow) measures in

the brain, patients also underwent functional MRI testing, in which a

specialized imaging technique known as arterial spin labeling (developed

by BIDMC MR physicist Alsop, PhD) was used in conjunction with a

standard MRI to measure vascular reactivity in several brain regions and

to show changes in blood flow.

As predicted, the scans showed that the diabetic patients not only had

greater blood vessel constriction than the control subjects, but they

also had more atrophied brain tissue, particularly gray matter. The

results also showed that, in the patients with diabetes, the frontal,

temporal and parietal regions of the brain were most affected.

Similarly, the team's measurements of serum markers confirmed that high

glucose levels were strongly correlated with higher levels of

inflammatory cytokines.

" It appears that chronic hyperglycemia and insulin resistance -- the

hallmarks of diabetes -- trigger the release of adhesion molecules

[sVCAM and sICAM] and set off a cascade of events leading to the

development of chronic inflammation, " says Novak. " Once chronic

inflammation sets in, blood vessels constrict, blood flow is reduced,

and brain tissue is damaged. "

This discovery now provides two biomarkers of altered vascular

reactivity in the brain. " If these markers can be identified before the

brain is damaged, we can take steps to try and intervene, " says Novak,

explaining that some data indicates that medications may improve

vascoreactivity.

But more important, she says, the new findings provide still more reason

for doctors and patients to focus greater attention on the management --

and prevention -- of diabetes.

" Cognitive decline affects a person's ability to successfully complete

even the simplest of everyday tasks, such as walking, talking or

writing, " says Novak. " There are currently 25.8 million cases of type 2

diabetes in the United States alone, which is more than eight percent of

our total population. The effects of diabetes on the brain have been

grossly neglected, and, as our findings confirm, are issues that need to

be addressed. "

This study was supported, in part, by grants from the National Institute

of Aging, the National Institute of Diabetes, Digestive and Kidney

Diseases, the American Diabetes Association, and the National Center for

Research Resources. Study coauthors include BIDMC investigators Peng

Zhao, PhD, Brad Manor, PhD, Ervin Sejdic, PhD, Alsop, PhD, and

Medha Munshi, MD; Amir Abduljalil, PhD, of Ohio State University; a

Roberson, PhD, of the University of Arkansas for Medical Sciences; and

Novak, MD, PhD, of the University of Massachusetts Medical School.

Source: Beth Israel Deaconess Medical Center

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November 26, 2011

very good article,, thanks,, larry

________________________________

To: Blind Diabetics <blind-diabetics >

Sent: Friday, November 25, 2011 9:15 PM

Subject: a very important article

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