Using increasingly sophisticated measuring tools, a Massachusetts General Hospital researcher is finding innovative ways to predict heart disease and diabetes years before their symptoms become apparent. With support from Agilent Technologies, Robert Gerszten, MD, has done so by tracking previously undetectable chemical changes in the blood.
“We need better predictors of who’s going to get these diseases so we can intervene earlier.”
The health risks driving his research are enormous. Heart disease is the leading cause of death in the United States, killing more than 600,000 people annually. Meanwhile, an estimated 29 million Americans have diabetes, which is itself a major risk factor for heart disease and contributes to hundreds of thousands deaths as well.
“We need better predictors of who’s going to get these diseases so we can intervene earlier,” says Dr. Gerszten, MD, director of Clinical and Translational Research at Mass General’s Corrigan Minehan Heart Center.
Tracking Stealthy Conditions
Often occurring together, heart disease and diabetes can be stealthy conditions, damaging blood vessels and organs many years before they are typically diagnosed using current methods. High cholesterol and high blood pressure are major risk factors for heart disease.Type 2 diabetes is diagnosed by high levels of glucose in blood. “But the truth of the matter is that the majority of people who develop heart disease have only one or no risk factors,” Dr. Gerszten explains, “and by the time it or diabetes is diagnosed, damage has already occurred.
Tracking changes in the blood is not a new idea. But currently, only about 10 to 20 indicators of health can be measured from the vials of blood typically drawn during annual physicals. These include cholesterols, blood glucose and calcium. However, lurking undetected by current analysis are several thousand more chemicals involved in the processes that keep the body alive. Dr. Gerszten believes they may better foretell who is going to have heart disease and diabetes.
Darlene Solomon, PhD, Agilent’s senior vice president and chief technology officer, says thousands of different metabolites can be measured with Agilent´s existing technology.
As a Mass General physician-researcher, Dr. Gerszten has access to the kind of patient blood samples needed to track changes over decades of a lifetime. He uses samples kept as part of the Framingham Heart Study, which has followed three generations of men and women from Framingham, Massachusetts, since 1948. Because some developed diseases like diabetes and cardiovascular disease, he can trace changes in blood chemicals suspected of being part of the disease process.
Diabetes and Heart Disease Predictors
About four years ago, Dr. Gerszten and his team used first-generation analytical techniques to identify and measure more than 300 chemicals involved in the body’s metabolism. That research allowed Dr. Gerszten and his colleagues to pinpoint several chemicals that become elevated up to 12 years before symptoms of diabetes and heart disease become apparent.
Dr. Gerszten’s identification of those new chemical predictors was a breakthrough in the emerging field of metabolomics, the study of these chemicals called metabolites and how they reflect health and disease. Metabolic disorders, which include heart disease and diabetes, are diseases that involve imbalances in the proteins, amino acids, carbohydrates and vitamins circulating in our bloodstream as a result of the chemical reactions that keep us alive.
His work brought him to the attention of Agilent Technologies, a research, development and manufacturing company headquartered in Santa Clara, California. In 2012, Dr. Gerszten received a Thought Leader Award from Agilent, which included financial support and access to the company’s state of the art analytical instrumentation and software solutions. Of particular interest to Dr. Gerszten were Agilent’s sophisticated mass spectrometry tools, which are used to identify and measure chemicals in a sample. With them, “I have been able to cast a much wider net,” he says.
Indeed, Darlene Solomon, PhD, Agilent’s senior vice president and chief technology officer, says thousands of different metabolites can be measured with Agilent´s existing technology. The key for Dr. Gerszten is determining which ones are most relevant to the prevention and treatment of disease. “Our capabilities have enabled him to ask and answer these questions,” Dr. Solomon says. “With our leading edge tools and his leading edge questions and patient samples, we’re doing great work together.”
The Mass General researcher also foresees a time when all that is known about the genes, proteins and chemical interactions will be integrated into one comprehensive blueprint.
Dr. Gerszten agrees, describing the collaboration as “a very real example of the value of industry and academia partnerships.”
Personalizing Patient Care
Dr. Gerszten believes the measure of an individual’s metabolites may someday be used to create personalized recommendations about diet, exercise and medical therapies. His research on diabetes, which doubles the risk for heart disease, is already headed in this direction.
The Mass General researcher also foresees a time when all that is known about the genes, proteins and chemical interactions will be integrated into one comprehensive blueprint. “Metabolites are very important,” Dr. Gerszten says, “but when combined with other information, we will get a more complete picture of what’s going right and wrong.”
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