NEW YORK (Reuters Health) - 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 accumulation 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 accumulation 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.
Source: Diabetes 2004;53:2501-2508. [ Google search on this article ]
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