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Copper Chelator Reverses Cardiac Damage in Diabetes


NEW YORK (Reuters Health) Sept 01 - The copper chelator trientine
reduces left ventricular hypertrophy in patients with type 2 diabetes,
according to a new study in the September issue of Diabetes.

"To date, no one has known the mechanism that underlies diabetic
cardiomyopathy," co-author Dr. Thomas K. Borg, at the University of
South Carolina at Columbia, told Reuters Health. "Scientists have been
looking at cardiomyopathy in diabetic dogs and rats for a long time,
and noted the increases in collagen, but no one has ever explained why
it is there, and no one has every explained how to make it go away."

The current research, headed up by Dr. Garth J. S. Cooper at the
University of Auckland, New Zealand, indicates that by removing copper
in the extracellular matrix of the heart, the increased collagen in
diabetes is ameliorated, and the cardiomyopathy is reversed.

Dr. Cooper's group first investigated the effects of trientine in rats
with diabetes induced by streptozotocin. Trientine is used to treat
ac***ulation of copper in the liver in Wilson's disease. When
administered intravenously in diabetic rats, trientine elicited prompt
increases in urinary copper.

After 6 weeks of diabetes, rats were fed trientine for 7 more weeks.
Increased cardiac mass observed in untreated diabetic rats was
partially reversed and attenuated cardiac output was normalized.

Microscopy revealed decreased myocyte volume, disorganization of actin
filaments, and swollen mitochondria in diabetic animals. These
abnormalities were significantly improved by treatment. Furthermore,
increased type I and III collagen was also normalized by chelation
therapy.

The investigators then turned their attention to humans. Twenty
diabetic men and 20 healthy men were randomly assigned treatment with
trientine 2.4 g/d or placebo. Active treatment resulted in increased
copper excretion in urine of diabetic and healthy men over a period of
10 hours. The increase was more pronounced in those with diabetes.

A second group of patients with type 2 diabetes and presymptomatic
left ventricular hypertrophy were randomly assigned to 6 months
treatment with trientine 600 mg b.i.d. or placebo. In the active
treatment group, mean left ventricular mass as assessed by MRI
decreased by 5%, while it increased by 3% in the placebo group (p <
0.01).

There was no evidence of copper deficiency after prolonged treatment,
and there were no significant drug-related adverse events. It had no
effect on systolic or diastolic blood pressure or HbA1c measurements.

It thus appears that ac***ulation of loosely bound copper may be
responsible for cardiac damage in diabetes, the authors conclude. They
propose selective copper chelation for treating left ventricular heart
disease in diabetes or other conditions in which hyperglycemia occurs.

Diabetes 2004;53:2501-2508.
http://www.medscape.com/viewarticle/488373?src=mp