February 2006 - The high-fat "diet" that diabetic heart muscle consumes helps make cardiovascular disease the most common killer of diabetic patients, according to a study done at Washington University School of Medicine in St. Louis. The study will appear in the February 7 issue of the Journal of the American College of Cardiology and is now available online.
Sixty-five percent of people with diabetes die from heart attack or stroke. When the researchers investigated fuel consumption in heart muscle, they found that heart muscle of type 1 diabetic patients relies heavily on fat and very little on sugar for its energy needs. In contrast, heart muscle in non-diabetics doesn't have this strong preference for fat and can use either sugar (glucose) or fat for energy, depending on blood composition, hormone levels or how hard the heart is working.
"The diabetic heart's overdependence on fat could partly explain why diabetic patients suffer more pronounced manifestations of coronary artery disease," says senior author Robert J. Gropler, M.D., professor of radiology, medicine and biomedical engineering and director of the Cardiovascular Imaging Laboratory at the Mallinckrodt Institute of Radiology at the School of Medicine. "The heart needs to use much more oxygen to metabolize fats than glucose, making the diabetic heart more sensitive to drops in oxygen levels that occur with coronary artery blockage."
Compared to non-diabetics, diabetic patients often have larger infarctions and suffer more heart failure and sudden death when the heart experiences an ischemic (low-oxygen) event.
In addition, when the diabetic heart burns fat, it accumulates reactive oxygen molecules that interfere with the fuel consumption mechanism and encourage the accumulation of fats in the muscle cells. This can lead to increased inflammation, cell death and heart dysfunction.
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The diabetic heart's reliance on fat molecules for energy was previously observed in experiments using diabetic animals. But this is the first time researchers have confirmed that burning of fatty acids in the heart muscle is increased in humans with diabetes. In this study, 11 healthy, non-diabetic people were compared to 11 otherwise healthy people with type 1 diabetes. The researchers found that the diabetic patients had much higher levels of fats in their blood and had an increased uptake of fatty acids into heart muscle cells.
The cells of diabetic hearts not only absorbed more fat, they also burned a higher percentage of the fats they took in. As a result, diabetic heart muscle used about half as much glucose and four times more fat for energy than the hearts of non-diabetics.
The researchers are now engaged in a larger study of heart muscle metabolism in type 2 diabetics. Patients in the study are divided into two groups with one group receiving standard therapies to normalize blood glucose levels and the other group receiving additional therapies designed to decrease the amount of fat in the blood. The study is still accruing patients, and people with type 2 diabetes who would like to participate can call 314-362-8608.
If the increased blood-fat levels are confirmed to be responsible for the dysfunctional metabolism of diabetic heart muscle, reducing fat levels may become an important way to decrease illness and death from cardiovascular disease in diabetics, according to the authors.
"We believe it's not enough to control blood glucose in diabetes," Gropler says. "You also have to target fat delivery to the heart. If you decrease the fat delivery through a combination of diet, exercise and drugs, you'll improve the heart's ability to use other energy sources, which will improve heart health."
Herrero P, Peterson LR, McGill JB, Matthew S, Lesniak D, Dence C, Gropler RJ. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. Journal of the American College of Cardiology February 7, 2006. Funding from the National Institutes of Health supported this research.
Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.
Source: Washington University School of Medicine
