A Biodesign team of researchers, led by Randall Nelson, PhD, has received a new five-year, $3.1 million award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. Their goal is to discover and validate telltale molecular signs to learn how to predict who will develop the disease long before any symptoms of diabetes appear.
Diabetes is a serious disease that often leads to a host of maladies including heart disease, blindness, kidney failure, and limb amputations. One in every ten health care dollars is spent on diabetes management and treatment. And with the number of Americans afflicted with diabetes expected to double in the next generation, identifying those at risk has become a critical health care challenge.
"The disease itself is bad enough, but the outcomes are worse," said Nelson. "We wish to identify and validate the critical clinical correlates of diabetes."
Nelson's group, in collaboration with researchers at the University of Arizona and the Veterans Administration, will use cutting-edge technology to analyze blood samples from more than 700 patients with type 2 diabetes to uncover molecular clues to better identify those at risk for developing diabetes and a closely associated risk, heart disease. These clues, called biomarkers, are able to identify proteins circulating in the body to predict risk of disease.
Currently, doctors can only measure blood sugar levels from finger sticks and sugar-modified red blood cells. By verifying protein biomarkers along with accompanying assays and methods of data evaluation, the group hopes to move the monitoring and treatment of type 2 diabetes and cardiovascular disease beyond simple blood sugar measurements.
"We have now developed all of the technologies and tools to construct a finely detailed molecular portrait of diabetes," said Nelson, who directs Biodesign's Molecular Biomarkers Center, which strives to improve human health and contribute to the vision of personalized medicine by understanding protein differences in healthy and ill individuals. "By studying the changes in both the amounts and structures of proteins related to diabetes, we can determine their unique contribution to the disease process."
Nelson is an expert in the emerging field of proteomics, a scientific discipline that studies changes in the composition of proteins circulating in body fluids such as blood and urine and how these changes relate to disease.
"Dr. Nelson and co-workers have been using cutting-edge proteomic technologies to identify novel markers of type 2 diabetes and its cardiovascular complications. Diabetes is really a group of diseases with the common outcome of hyperglycemia. We hope that the identification of novel markers will help determine disease subsets and lead to treatments that are tailored, or personalized, for individual patients," said Dr. Salvatore Sechi, director of NIDDK's Proteomic Program.
The researchers use state-of-the-art technology including protein identification by mass spectrometer, an instrument used to determine the chemical makeup of a protein sample by generating a spectrum representing the masses of sample components. The team uses mass spectrometers not only to identify proteins and their functional states, but also to measure the quantity of particular proteins. For example, someone with a disease may be producing too much of a given protein that would normally be present in lower amounts in a healthy individual.
Nelson's group has observed that many proteins become "sugar-coated" in people with diabetes, the extent of which is dependent on disease severity. Simultaneously, many proteins known to be risk factors for heart disease become oxidized, affecting the formation of arterial plaques. "We've seen that diabetes and heart disease have a change in their protein signatures over time, which correlates very strongly with the progression of these diseases," said Nelson.
The Biodesign team hopes to identify and validate several new biomarkers before the end of the research study.
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