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Diabetic Cardiomyopathy Drugs In Pipeline Will Boost Identification


 

WASHINGTON — Diabetic cardiomyopathy is likely to become a more common problem in diabetic patients, but several new therapies in the pipeline look promising, Dr. Francisco Villarreal said at a meeting sponsored by the National Hispanic Medical Association.

“This is something we will have to watch for in our young people developing diabetes, and it takes a long time to evolve,” said Dr. Villarreal of the division of cardiology at the University of California, San Diego.

The term “diabetic cardiomyopathy” will become much better known in the near future, Dr. Villarreal predicted. The term “refers to pathological changes in the hearts of certain diabetics in the absence of an underlying identifiable cause.”

“Very frequently we associate diabetes with atherosclerosis, but in these patients we could not identify problems with blood vessels or the presence of hypertension. But we could document changes that occurred at the cellular level—be it muscle cells or cells that produce fibrous tissue—and also at the tissue level. These structural changes are characterized by myocardial hypertrophy and also by the presence of excess fibrotic tissue—in particular, collagens,” he explained.

Diabetic cardiomyopathy appears to play a role in the increased rate of heart failure in diabetic patients, according to Dr. Villarreal. The Strong Heart Study concluded that the extent and frequency of diastolic dysfunction was directly proportional to level of hemoglobin A1c (Circulation 2000;101:2271–6). The Framingham heart study led to similar conclusions (Prog. Cardiovasc. Dis. 1985;27:255–70).

“When they looked at the risk of heart failure in diabetics and nondiabetics, in adult diabetic males, the risk was about two times that of [nondiabetic males], and in females, it was about five times,” he said. “But even worse, these risks multiplied about twice when observing young individuals—in young males, it was a four times higher risk, and in young females, eight times higher. It was also noted that each 1% elevation in HbA1c levels led to an increase of about 50% in the risk of heart failure.”

In one study, Doppler echocardiography documented the presence of diastolic dysfunction in up to 60% of well-controlled type 2 diabetic patients, Dr. Villarreal noted (Diabetes Care 2001;24:5–10).

Two compounds in the therapeutic pipeline appear promising, he noted. Early studies of ruboxistaurin, a novel highly selective inhibitor of protein kinase C-β, suggest that it may curb diabetes-related blindness, nephropathy, and neuropathy. None of these trials involved cardiac diseases, but “it is likely that these drugs probably will also benefit the heart,” he said. Another compound, alagebrium (ALT-711), may help collagen become more compliant, Dr. Villarreal said.

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