Protein Points to Significantly Higher Stroke Risk

Nov. 30, 2000 -- People who have increased levels of a protein linked to diabetes may be at increased risk for stroke, even if they have no other stroke risk factors and no diabetes, a Swedish study suggests. And women with high levels of the protein, known as proinsulin, appear to be at twice the risk of men.

Lindahl describes proinsulin as a "not fully matured" form of insulin, the substance produced by the pancreas to control the amount of sugar -- or glucose -- in the blood.

When study participants had other stroke risk factors, the effect of increased proinsulin levels increased dramatically. The risk of stroke in women with high proinsulin levels and high diastolic blood pressure -- the bottom number in a blood pressure reading -- was almost 20 times that of women who had the lowest levels of both.

"We know from earlier studies that diabetic patients often have high proinsulin ... and we also know that diabetic patients have a three- to sixfold increased risk of having a stroke compared with nondiabetics," lead researcher Bernt Lindahl, MD, PhD, tells WebMD. "In this study, we excluded all diabetics ... Yet, we found an association between proinsulin and stroke, indicating that these individuals, without having diabetes, had an imbalance ... between glucose and insulin, which increased the risk for stroke."

"Many times this imbalance between glucose and insulin starts a decade before diabetes develops, and is due to a lowered [response] to insulin in the muscles, fat, and liver cells," Lindahl says. To compensate, the cells that produce insulin must speed up, leading to an increase of proinsulin in the blood stream. Lindahl explains that if doctors can use proinsulin levels to identify people at high risk -- before they get diabetes -- they may be able to prevent them from having a stroke.

Lindahl and his colleagues are from the University Hospital of Northern Sweden. They reported their findings in the December issue of Stroke: Journal of the American Heart Association.

In the study, the researchers compared proinsulin levels in almost 100 people who went on to have strokes to nearly 180 people who did not have strokes.

They found that high proinsulin levels more that tripled the overall risk of having a stroke. Nondiabetic men with the highest levels of proinsulin had twice the risk of stroke as men with the lowest levels, and women with the highest proinsulin levels had four times the risk of women with the lowest levels.

While describing the findings as "potentially significant," American Stroke Association spokesperson Mark Alberts, MD, adds that much more study is needed to determine whether the findings are of any real use. Alberts is an associate professor of neurology at Duke University, in Durham, N.C., and was not involved in the study.

"These researchers measured this risk factor at one point in time, and it is hard to know whether the impact they saw will be seen in future investigations," Alberts tells WebMD. "It is certainly interesting, but it would be premature to judge it as being either significant or insignificant at this point" without further research.

Even if further studies prove that proinsulin levels are a significant marker for stroke, the real-life implications may be somewhat limited. That's because there's currently no simple blood test for measuring proinsulin. The test now being used is highly technical, and remains largely confined to research projects.

Alberts says an easier way of measuring proinsulin in the blood could probably be developed if the protein was found to provide vital information for stroke risk. But he adds that knowing whether a patient has high levels of proinsulin may make little practical difference.

"This seems to be a risk factor that we can't do much about," he says. "It may help us in the sense that we can say somebody is in a high vs. low risk group for stroke or diabetes, but until we have a way to directly address this, our options are limited."

(From Excite.com)