In patients with pre-diabetes (metabolic syndrome), the risk of stroke increases. This proposal will study the blood vessel network (structure) and the response to daily stressors like exercise (function) in blood vessels that provide blood flow to the brain. The overall concept is that patients with pre-diabetes have smaller or fewer brain blood vessels, and that those vessels have lost the ability to produce healthy substances (such as prostaglandins) that increase blood flow and prevent blood clots in the brain. The preliminary data support this research idea. Pre-diabetes patients will be compared to age-matched healthy controls using a blinded study design. Key techniques include state-of-the-art magnetic resonance imaging (MRI), and a common, readily available drug intervention to try to change brain blood flow. If results support the concept, this approach can be applied to 1) track vascular disease progression in many organs besides brain, 2) to track the effectiveness of drug interventions, and 3) developing new treatments to prevent or reverse the negative vascular effects of similar medical conditions like obesity, diabetes, and sleep apnea.
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?
This ADA grant is focused on the brain circulation. Our laboratory focuses on determining mechanisms of blood flow regulation, and how this regulation is altered by pre-diabetes. Our newest data seem to tell us that patients with pre-diabetes cannot respond to a need for increased brain blood flow. Vascular dysfunction is typically not diagnosed until middle-age or later; and is the culmination of decades of complex interactions between genetic, lifestyle, and environmental inputs. Our research tests pre-diabetes in young adults without the complicating factors of aging or other cardiovascular disease. In some ways, this research echoes the phrase "an ounce of prevention is worth a pound of cure". In other words, it's easier to keep the brain circulation healthy than to try to fix what's broken. We believe this area is critical to study as young "healthy" people transition from health to disease. Earlier detection of vascular problems may open a treatment window where vascular disease is more likely to be reversible. My research program is designed to fill this scientific gap in knowledge specifically on the brain circulation.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
Stroke is a big problem in pre-diabetes, aging, and diabetes. Often, as patients, we first see a physician when we have a problem with brain blood flow-after a lot of damage has been done. We are trying to understand the earliest changes in your body's ability to maintain proper blood flow to the brain-twenty years before you might detect a problem and see a doctor. We use state-of-the-art imaging (eg MRI scans) to measure whether your brain blood vessels are getting smaller or disappearing. An important study is to test whether your brain can respond to stressors of everyday life in order to increase blood flow when your brain needs it. Thus, we will stress your body to see if it maintains the ability to respond to stress. If it doesn't, as our early data suggest, then we can use these findings to develop strategies or treatments to improve your brain blood flow.
Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?
Scientifically, pre-diabetes is fascinating as it presents in so many ways across different patients. Personally, some of my family members are struggling with diabetes and related problems, which takes its toll emotionally, medically, and financially. It is important to me that I feel our research program is a vital cog in the international team of care-givers, scientists, and doctors who try every day to make the lives of diabetics better.
In what direction do you see the future of diabetes research going?
Since diabetes is such a complex disease, I envision the most fruitful approach will be multifaceted. We need people who understand the psychology of having diabetes, the medical aspects, the new treatments, the prevention, as well as national health care policy. It will take grass roots efforts like church based diet and exercise community programs, to visionary leadership from the world's experts on the medical front of diabetes research.