NEW YORK, Mar 19 (Reuters Health) - High blood levels of a naturally occurring compound involved in blood vessel function may be the "missing link" between insulin resistance, a precursor to type 2 diabetes, and heart disease.

The study findings also suggest drugs that improve insulin sensitivity may reduce levels of the compound, ADMA, and ultimately lower a person's heart disease risk.

ADMA is an enzyme that inhibits a compound involved in blood vessel dilation. Previous research has shown that elevated blood levels of ADMA reduce the ability of the blood vessels to widen, and are also linked to an increased risk of heart and blood vessel disease.

ADMA levels have been shown to rise in patients with high blood pressure, type 2 diabetes and kidney failure. While various risk factors for heart disease are associated with insulin resistance, the relationship between ADMA and insulin resistance has remained unclear. Insulin resistance is a condition in which the body loses its sensitivity to the blood sugar-regulating hormone insulin.

To investigate, Dr. Markus C. Stuhlinger and colleagues from Stanford University in California looked at 64 non-diabetic adults, including 16 with high blood pressure. Seven of the study volunteers had insulin resistance. Over the 9-month study, researchers measured patients' cholesterol, insulin, ADMA and other factors. Stuhlinger is now a researcher at the University of Innsbruck in Austria.

In addition, the insulin-resistant study participants took the diabetes drug rosiglitazone for 12 weeks.

The concentration of ADMA in patients' blood correlated with the degree of insulin resistance regardless of blood pressure.

However, treatment with the insulin-sensitizing drug rosiglitazone for 3 months significantly improved a person's ability to respond normally to insulin and also reduced ADMA levels in the blood, according to the report in the March 20th issue of The Journal of the American Medical Association.

The findings imply that elevated ADMA might be a marker of heart disease risk and point to a drug that could be used to lower this risk, the researchers report.

"A significant relationship exists between insulin resistance and (blood) concentrations of ADMA," they conclude.

In an accompanying editorial, Dr. David T. Nash from Syracuse Preventive Cardiology Center in New York notes that measuring patients' ADMA levels is currently "difficult," and it is not yet clear that high levels of the enzyme signal increased heart disease risk.

But, he adds, investigating links between ADMA, insulin resistance and blood vessel function offers promise for gaining understanding of cardiovascular disease risk and treatment.

SOURCE: The Journal of the American Medical Association 2002;287:1420-1426, 1451-1452.

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