Research may re-define management of heart failure in diabetes

Control of oxidised copper levels in the body may be as important as lowering blood glucose levels in preventing cardiovascular complications in diabetes mellitus, according to New Zealand researchers.

A study published in the international journal Diabetes shows that abnormal levels of oxidised copper accumulate in the bodies of people with type 2 diabetes mellitus and provides further support for the idea that treatment with drugs that eliminate this form of copper may reduce the incidence of heart disease. Trientine, developed by New Zealand biotechnology company, Protemix, as Laszarin extracts oxidised copper, which is then excreted in the patient's urine.

The research led by Professor Garth Cooper at the University of Auckland could help to redefine the management of type 2 diabetes worldwide. Professor Cooper explained: "The research is significant in pointing to a new direction for the management of heart failure and other cardiovascular complications in diabetes. Heart disease is the leading cause of death in people with diabetes. Those at risk tend to have high tissue levels of oxidised copper, [copper (II)], and by attending to this copper imbalance we believe the outcome is likely to improve. It is a fundamental change in our understanding of the disease process and its therapy. In addition to glucose-lowering agents, most people with type 2 diabetes might also benefit from copper regulation therapy. We may be able to turn back the heart disease and the wider vascular complications."

Mark Yeager, Professor in the Departments of Cell Biology and Molecular Biology at The Scripps Research Institute and Director of Cardiovascular Research at the Scripps Clinic, La Jolla, CA, USA commented: "This could have a tremendous impact on the treatment of diabetic heart disease and address an unmet clinical need. In addition to glucose regulation, it is becoming standard practice for patients diagnosed with diabetes mellitus to be treated with statin drugs to prevent coronary artery disease. However, it is a paradigm shift to address metal imbalance as a strategy to treat heart muscle disease in diabetes."

Kenneth Reid, Professor of Immunochemistry, the University of Oxford, added: "Last year Professor Cooper's team announced that trientine appears to reverse heart disease in people suffering from diabetes and may lead to a more effective intervention in a major cause of death worldwide. These clinical trials should be watched carefully by clinicians. The work to date clearly shows that it is beneficial."

Diabetes is often accompanied by heart enlargement, heart dysfunction and coronary heart disease and these are major causes of death. According to the World Health Organisation over 180 million people have type 2 diabetes. Previous work by the Auckland researchers (2) showed that six month's Treatment with trientine brought about a 25 per cent return to normal heart size people with diabetes that had enlarged hearts.

The new research showed that regulation of copper metabolism was abnormal in test subjects with diabetes and that Laszarin treatment increased elimination of oxidised copper. If successful in phase III trials, Laszarin has a potential worldwide market of over three million people with diabetic heart failure.