Impaired Glucose Tolerance Makes the Heart Grow Fatter

DALLAS -- A fatty heart, cardiac steatosis, can occur in patients on the road to type 2 diabetes and in the presence of normal left ventricular dysfunction, investigators here have determined.

DALLAS, Sept. 4 -- Just like a fatty liver, a fatty heart can be pathogenic, investigators here suggested.

Imaging studies of volunteers with various levels of glycemic control showed that those with impaired glucose tolerance or type 2 diabetes had twice the level of triglycerides in myocardial tissues as lean or obese volunteers with normal glycemic control, reported, reported Lidia S. Szczepaniak, Ph.D., of the University of Texas Southwestern, and colleagues.

"In humans, impaired glucose tolerance is accompanied by cardiac steatosis, which precedes the onset of type 2 diabetes and left ventricular systolic dysfunction, the investigators wrote in the Sept. 4 issue of Circulation, Journal of the American Heart Association. "Thus, lipid overstorage in human cardiac myocytes occurs early in the natural history of type 2 diabetes and is evident in the absence of overt clinical heart failure."

Evidence from animal studies suggests that in type 2 diabetes, lipid metabolism is altered, resulting in increased uptake and storage by cardiac myocytes of lipids, which in turn release lipotoxic products that cause apoptosis, eventually leading to heart failure, the authors said.

To determine whether cardiac steatosis might precede the development of type 2 diabetes in humans, they used proton magnetic spectroscopy (MRS) to study four groups who together would represent the natural course of type 2 diabetes.

They enrolled 134 men and women, mean age 45, into one of four groups on the basis of body mass index and glycemic control, as defined by a two-hour oral glucose tolerance test. The groups were as follows:

  • Lean, normoglycemic-BMI less than 25 kg/m2 and two-hour glucose less than140 mg/dL
  • Overweight and obese, normoglycemic-BMI 25 kg/m2 or greater, and two-hour glucose less than 140 mg/dL
  • Impaired glucose tolerance-two-hour glucose 140 to 199 mg/dL
  • Type 2 diabetes-a history of diabetes mellitus or two-hour glucose of at least 200 mg/dL.

They used localized proton MRS to image the hearts. The technique is capable of distinguishing between triglycerides stored in myocytes and those stored in adipocytes. They also evaluated left-ventricular function in the participants.

"There is currently no way to clinically evaluate the fatty heart," Dr. Szczepaniak said. "Using this technique, which analyzes magnetic signals, we might be able to determine if people are prone to heart disease very early before the disease progresses. This method might also allow us to measure the effectiveness of medical treatments targeted toward lowering fat in the heart."

They found that compared with the lean participants, those with impaired glucose tolerance had myocardial triglyceride levels 2.3 times higher, and those with type 2 diabetes had 2.1-fold higher levels (P