Impaired Glucose Tolerance Makes the Heart Grow Fatter

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<0.01). Overweight/obese normoglycemic participants had elevated triglycerides compared with the lean participants, but this, difference was not significant.
The differences in cardiac steatosis between the lean, impaired glucose tolerance and type 2 diabetes groups remained significant after adjustment for differences in serum triglycerides, body mass index, age, and gender (P for trend <0.05).
The participants in the type 2 diabetes group had significantly higher (P <0.01) systolic blood pressure, heart rate, and left ventricular mass index than those in the other three groups, all of whom had normal values.
Diastolic blood pressure and left ventricular ejection fraction were normal and similar across all groups.
"The major new findings from the present 1H-MRS study are two-fold," the investigators wrote. "First, in humans, impaired glucose tolerance and type 2 diabetes are accompanied by excessive myocardial triglyceride accumulation in vivo. Second, cardiac steatosis precedes the onset of diabetes mellitus and left ventricular systolic dysfunction."
They noted that potential limitations of their study included confounding by age, the known lipogenic effects of insulin in patients with type 2 diabetes, and the cross-sectional design of the study, which precludes establishment of a causal link between cardiac steatosis and cardiomyopathy.
in an accompanying editorial, Frederick L. Ruberg, M.D., of Boston University wrote, "The principal finding of myocardial triglyceride accumulation in humans with insulin resistance … is of significant importance because it provides strong evidence linking observations from animal models of cardiac lipotoxicity to humans with diabetes mellitus."
"With future simplification of spectroscopic techniques, it is foreseeable that myocardial lipid content may one day be used as a biomarker to predict the development of cardiac dysfunction in patients with insulin-resistant states and may serve as a measurable target for intervention before the development of diabetic cardiomyopathy," Dr. Ruberg added.
Support for the study came from grants to investigators from the Heart and Stroke Foundation of Canada, Canadian Institutes for Health Research, Canadian Diabetes Association, National Institutes of Health, American Diabetes Association, Donald W. Reynolds Foundation, and Takeda Pharmaceuticals. The authors had no conflict of interest disclosures. Primary source: CirculationSource reference: McGavock JM et al. "Cardiac Steatosis in Diabetes Mellitus A 1H-Magnetic Resonance Spectroscopy Study." Circulation. 2007;116