William Schrage, PhD
Occupation: Associate Professor, University of Wisconsin-Madison
ADA Research Funding: Innovation Grant
The human brain contains more than 400 miles of blood vessels, ranging from major veins and arteries (the throbbing one running past your temple, for example) to microscopic capillaries. Their job is to keep blood and the oxygen it carries flowing to the billions of nerve cells in the brain. Without oxygen, the brain can't do its many jobs, from keeping your body working to remembering where you left your keys.
In people with prediabetes, a condition that includes insulin resistance and often leads to type 2 diabetes, these hundreds of miles of blood vessels may not expand and contract as well as they should. That means blood has a harder time flowing through the brain. Over time, the results can be damaging, or even deadly. "People in their 60s with prediabetes are twice as likely to have a stroke," says researcher William Schrage of the University of Wisconsin-Madison.
But is prediabetes alone enough to keep the brain's blood vessels from working properly, or does it take decades of prediabetes plus the accumulated effects of age to increase the risk of stroke and other damage? Doctors know, for example, that decision-making capability declines in older people with prediabetes, but not whether that's a result of age or prediabetes.
Part of the problem is that as people age, it's hard to separate the effects of prediabetes from the general toll of aging. "We know people who are older have cognitive impairment and an increased risk of stroke," Schrage says. "The question is: How soon do these things start? Where do the cracks in the foundation actually come in?"
To find out, Schrage is homing in on the flow of blood inside the brain, using a multi-million-dollar scanner called a magnetic resonance imager, or MRI, to create detailed, three-dimensional pictures of the brain's network of blood vessels. With the help of a grant from the American Diabetes Association, he has recruited people in their 30s with prediabetes to have their brains scanned under a variety of conditions.
While similar tests have been done in the past on people at rest, Schrage's study introduces a novel element: stress. Measuring a relaxed brain isn't enough, he says, to get a complete picture. Schrage compares such studies to evaluating a high-performance car without starting up the engine. "Your Ferrari looks fine in the parking lot. It's shiny and red," he says. "But does it drive well if you take it out on the road?"
To road test their brains, people participating in Schrage's study are put through stress tests that push the blood vessels to pump more blood. While lying in an MRI machine, they breathe air with lowered oxygen levels. Using the MRI, Schrage then monitors how well their brains respond to the stress.
It may sound extreme, but for many people such stressors are quite common in everyday life. "If you're overweight and prediabetic and have sleep apnea," a condition that causes people to briefly stop breathing in their sleep, "you probably give your brain low-oxygen stressors over and over and over again every night," Schrage says.
Schrage's early results suggest that prediabetes alone has a negative effect on the brain's ability to respond to stress. By looking at the MRI, "we know whether the size of the tubing is changing. More flow is better than less," he says. "In people with prediabetes, even if the brain is screaming for more oxygen, the blood vessels are not opening up as much."
As far as Schrage can tell, the problem may be that people with prediabetes have trouble producing a substance called prostacyclin that helps open up blood vessels. At the same time, they produce too much of another, thromboxane, that promotes blood clots and keeps blood vessels constricted. It could be a double whammy, he says: "You're not only limiting dilation; you're promoting clot formation."
By showing that prediabetes alone can negatively impact the brain, Schrage hopes to open up new areas for researchers. Eventually, his data might give doctors a better understanding of prediabetes's impact on the brain and how to design treatments to ward off some of the ill effects. "This might change the way physicians look at things," he says. "Now it seems we have dysfunction knowledge 30 years ahead of symptoms, and that gives us more time to prevent disaster."