High blood sugar interferes with blood flow to heart in diabetics
Normally, when the heart pumps harder, the blood vessels that feed it open wider to bring the heart more fuel. But in people with diabetes this function often is impaired.
In the heart muscle of type 1 diabetics, high blood glucose is a significant contributor to poorly opening vessels, or poor vasodilation, according a study by scientists at Washington University School of Medicine in St. Louis. Even administration of high levels of insulin, which commonly enhances vasodilation, can't counteract the negative effect of high glucose on the heart.
"It's known that diabetes can lead to a reduced capacity for dilation of blood vessels and that this contributes to increased plaque buildup and heart 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. "Since it is typical for type 1 diabetics to periodically experience insulin deficits or increased blood glucose, we systematically isolated the effect of insulin and glucose to see which had a greater effect on dilation of blood vessels in these patients.".
The scientists measured the capacity of heart blood vessels to dilate in 20 patients with type 1 diabetes using positron emission tomography (PET) imaging. Other than their diabetes, the patients had no physical conditions, such as coronary disease, hypertension or high cholesterol, that would contribute to impaired vasodilation. Eighty percent of the patients were women, and their average age was 44.
The team used the drug adenosine to encourage dilation of the blood vessels of the heart, and at the same time they maintained constant insulin and glucose levels in the patients using an intravenous system.
The scientists found that in response to adenosine, patients maintained at high insulin and normal glucose levels increased the rate of blood flow in the heart about four fold. But patients maintained at high insulin and high glucose increased their heart blood flow rate only about two fold.
"We know that insulin has beneficial effects on vasodilation," Gropler says. "But in the second group of patients, we saw that a high level of insulin could not overcome the inhibition of vasodilation caused by a high level of glucose.".
The study demonstrates the detrimental effect of high glucose levels on heart function and highlights the importance for diabetic patients of keeping their blood glucose within the normal range.
"It can be very challenging for diabetic patients to maintain normal blood sugar," says co-author Janet B. McGill, M.D., associate professor of medicine. "But this study provides yet another reason to push for tight control of glucose levels. If instituted early enough, tight glycemic control may potentially reduce heart problems in diabetic patients.".
The study's authors note that high blood glucose reduces production of nitrous oxide, a substance that contributes to vasodilation, and increases production of hormones that constrict blood vessels. It also increases oxidative stress in tissues of the body by altering cellular energy metabolism.
"The heart has become an organ of primary concern for endocrinologists and people with diabetes," McGill says. "And eventhough clinicians previously were concerned with the risk of coronary artery disease in diabetics, it appears we must also consider the impact of high blood glucose on energy metabolism in the heart.".
Gropler and colleagues are now conducting a study of metabolic changes that occur in type 2 diabetes. "We are focusing on blood fat levels in this next study," Gropler says. "We want to see if drugs that reduce blood fat levels and thus decrease fat delivery to the heart will have beneficial effects on the metabolism of heart muscle as well as blood flow and heart function.".
For this study, the research team is recruiting patients over the age of 18 with type 2 diabetes and without known coronary disease. Each volunteer will receive a full physical exam, including a battery of tests to assess cardiac function, and will be followed up for four to six months on a study medicine. Those interested in participating in the study should call 314-362-8604.
Srinivasan M, Herrero P, McGill JB, Bennik J, Heere B, Lesniak D, Davila-Roman VG, Gropler RJ. The effects of plasma insulin and glucose on myocardial blood flow in patients with type I diabetes mellitus. Journal of the American College of Cardiology 2005 July 5;46(1):42-48.
Funding from the National Institutes of Health and the Barnes-Jewish Hospital Foundation supported this research.
Washington University School of Medicine's full-time and volunteer faculty clinicians 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 and World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.