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Severe Glycemic Excursions Alters Brain Structure

In patients with long-standing type 1 diabetes, persistent hyperglycemia and episodes of severe hypoglycemia are associated with reductions in gray matter density in several brain regions, investigators report. Principal investigator Dr. Alan M. Jacobson, stated that, "We have a lot of data regarding peripheral autonomic neuropathy in diabetics." "The question remains, is there also a central neuropathy in diabetes that might translate into behavioral and functional changes?"

Dr. Jacobson, at the Joslin Diabetes Center in Boston, and colleagues used voxel-based morphometry (VBM) analysis of MRI images of the brain to compare patients with diabetes with age-matched healthy control subjects. VBM technology creates three-dimensional images of magnetic resonance imaging data, which can be used to evaluate structural changes in the brain.
VBM "is a tool increasingly being used in different types of neuroimaging, but has never been used in looking at patients with diabetes," Dr. Jacobson pointed out.

The patients were ages 25 to 40 years with diabetes duration of 15 to 25 years and minimal diabetes complications.
"We tried to limit certain factors that we knew would confound and causally complicate the analyses," the researcher noted, which is why they chose younger subjects who would be less likely to have major vascular disease. On the other hand, he added, "we tried to get a broad range of representation in terms of numbers of hypoglycemic events leading to coma or seizure, and a diverse range of blood sugar control, in order to see their effects on the gray matter."

VBM showed less dense gray matter in the left and right superior temporal gyri, left angular gyrus, left middle temporal and middle frontal gyri, and left thalamus among diabetic subjects compared with controls.

Chronically higher blood glucose levels, as measured by HbA1C, were associated with lower gray matter density in regions important for memory, language processing, and attention.

"It is possible that the observed structural changes predict future cognitive problems that are subclinical and may reflect early macrovascular damage," the authors suggest.

There was also a positive association between the occurrence of severe hypoglycemic events and reduced gray matter density in the left cerebellar posterior lobe.

The authors assessed subjects’ general intelligence, executive function, memory, and psychomotor speed with a battery of tests, to see how they were associated with the gray matter changes they observed. In 16 of 20 tests, the diabetic and control groups were similar. However, diabetic patients scored slightly lower on vocabulary, verbal paired associates, inhibition in the color-word task, and card sorting.

If alterations in gray matter density "could be detected at an early stage through use of VBM methods or other means, it might be possible to implement treatment regimens that minimize risks to the patient in terms of hypo- and hyperglycemia and its effects on the CNS," the authors conclude.
Diabetes 2006;55:326-333.