Originally created 04/28/04

Blood proteins might be early warning signs of diabetes

CHICAGO -- Blood proteins suggesting early artery damage might also be early warning signs of diabetes, researchers say.

Diabetics are known to face an increased risk of circulatory problems, artery disease and heart attacks. But this study found possible evidence of artery damage as much as eight years before diabetes was even diagnosed.

The study strengthens the evidence linking diabetes with silent inflammation, which also has been associated with heart disease.

The results stem from blood tests given to 32,826 women who participated in a study of U.S. nurses that began in 1976. Whether the findings apply to men, too, is uncertain, the researchers said.

The women provided blood samples in 1989 and 1990; during the next decade, 737 developed diabetes.

The researchers looked for three proteins that when elevated in the blood suggest the presence of irritation or damage to cells lining blood vessel walls: E-selectin, ICAM-1 and VCAM-1.

Women with the highest initial levels of E-selectin were about five times more likely to develop diabetes than women with the lowest levels. Those with the highest ICAM-1 levels faced more than triple the risk of women with the lowest ICAM-1 levels. Elevated VCAM-1 levels were associated with an increased risk in some but not all analyses.

E-selectin is produced by vessel-lining cells, sometimes in response to inflammation, while the two other proteins are produced by those cells and by white blood cells in response to inflammation, said lead author Dr. James Meigs of Harvard Medical School and Massachusetts General Hospital.

Blood vessel linings are supposed to be slippery to allow blood to flow smoothly. Meigs theorized that in "pre-diabetes," inflammation might hamper this process by irritating or roughening up vessel linings, ultimately leading to high blood sugar levels and diabetes.

The researchers said treatments that improve the functioning of blood vessel walls could prove helpful in slowing "the accelerating worldwide epidemic of type 2 diabetes."

An estimated 18 million Americans have diabetes, mostly adult-onset or Type 2, which increasingly is affecting children, too. In diabetes, the body does not produce or properly use insulin, a hormone that converts sugar and other foods into energy. High blood sugar levels result, which can lead to organ damage, heart disease and blindness.

Tests measuring the three proteins are not routinely available. Meigs said more studies are needed to determine if the substances are better predictors of diabetes than such factors as obesity, blood sugar levels and family history.

Dr. Nathaniel Clark of the American Diabetes Association said even if doctors could routinely measure these biomarkers, their recommendations for people at risk for diabetes probably would not change.

"We need to treat them aggressively, talk about weight reduction" and reducing other cardiovascular risk factors including smoking, he said.

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