January/February 2006 - Although people with diabetes are twice as likely as the general population to develop depression, the cause of this increased risk is not well understood. Now, a Joslin Diabetes Center-led collaboration has documented for the first time subtle changes in the gray matter of the brain of type 1 diabetes patients compared to control subjects who did not have diabetes. They made these observations using voxel-based morphometry (VBM), a relatively new magnetic resonance imaging (MRI) technology that allows researchers to take very sensitive measurements of small regions in the brain. For the first time, doctors have reason to ask if the increased risk of depression could in fact be due to changes in brain.
"We have known for a long time that diabetes can damage the nerves that control the extremities and those that control internal organs like the heart and the intestine," says the study's principal investigator, Alan M. Jacobson, M.D., head of Behavioral and Mental Health Research at Joslin Diabetes Center. "This research helps document diabetes-related changes to the central nervous system. People tended to assume that the stress of dealing with a severe chronic illness and its complications was the sole source of depression. That still is an important issue, but now we have evidence that something else might be at work."
Equally important, by showing the effectiveness of VBM for observing and evaluating changes in brain structure that appear to be related to diabetes, the study opens up whole new approaches to understanding the central nervous system in diabetes. This technology creates three-dimensional images of magnetic resonance imaging data, which researchers can then use to observe and evaluate structural changes, in this case, in the brain.
"We've used this technology to look at patients with bipolar disorder or with classic neurodegenerative disorders, but this is the first study to use VBM to investigate brain changes in patients with diabetes," says co-investigator Perry Renshaw, M.D., Ph.D., who directs the Brain Imaging Center at McLean Hospital in Belmont, Mass.
For the study, the researchers measured gray matter densities in areas of the brain responsible for memory, language processing and attention. When they compared the images of 82 patients who had type 1 diabetes for 15 to 25 years with minimal complications to those of 36 age-matched control subjects who did not have diabetes, they discovered lower levels of gray matter density in the group with diabetes. Among that group, they also found that these lower levels in density were associated with poorer glycemic control and higher frequency of hypoglycemic events that led to unconsciousness.
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"This study definitely does not mean that everyone who gets type 1 diabetes will suffer from clinically significant brain damage," Dr. Jacobson emphasizes. Indeed, he explains that in fact they observed little difference in cognitive function when patients with diabetes were compared to the participants in the control group. What is important, however, is the new tool researchers now have to examine what changes do occur, what drives them, and how they may affect brain functions, including those that lead to depression.
Understanding changes in brain structure becomes particularly critical as more and more people with type 1 diabetes are living longer lives, explains co-investigator Gail Musen, Ph.D., also of Joslin. "We want to be able to understand how the metabolic changes of diabetes affect the risks these patients face so we can find ways to minimize them as they go on to live 50 or more years with this disease."
Dr. Jacobson and his colleagues will continue now to follow the patients in the study to observe if and how the changes progress over time and whether high or low blood glucose influences that progression. Because they can also use MRI to measure the brain's response to stimuli like cognitive or emotional tests, they will also start looking at functional changes.
"Now that we've identified unexpected structural changes in the brains of people with diabetes, we need to understand more about how these relate to changes in brain function," says Dr. Renshaw. "The more we understand the problem, the better solutions we can find."
Other researchers participating in the study include Caitlin Sparks and Katie Weinger, Ed.D., R.N., of Joslin; In Kyoon Lyoo, M.D., Ph.D., and Jaeuk Hwang, M.D., of Seoul National University College of Medicine and Hospital in Korea; Christopher M. Ryan, Ph.D., of the University of Pittsburgh School of Medicine; David C. Jimerson, M.D., of Beth Israel Deaconess Medical Center in Boston; and the late John Hennen, Ph.D., M.P.H., who was a biostatistician at McLean Hospital. Funding for the study was provided by the National Institutes of Health.
Source: Joslin Diabetes Center
