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Glucose Control Cuts Death Rate for Very Ill

Intensive insulin therapy produces dramatic results

WEDNESDAY, Nov. 7, 2001 (HealthDayNews) -- Therapy to keep runaway blood sugar in check for patients in intensive care can greatly improve their survival odds, a new study says.

Severely elevated blood glucose, the product of muscle breakdown, is common after trauma that puts patients in prolonged intensive care. Why that's true isn't clear, though it could be the body's evolutionarily ingrained way of feeding itself when injury prevented hunting for food.

However, while glucose is necessary for survival, too much is toxic, especially for nerve cells, which suffer a death called neuropathy. And thanks to intensive-care technology, patients who in caveman days would have died from their injuries now survive, though they often are exposed to harmful levels of blood sugar.

Previous efforts to solve the problem for intensive-care patients have included drugs to control inflammation, but in some cases, they have worsened the prognosis.

"There was no treatment at all for this type of neuropathy until now," says lead study author Dr. Greet Van den Berghe, an intensive-care expert at the Catholic University of Leuven, in Belgium. The study was stopped early because of the dramatic improvements in survival rates. The therapy also is cheaper than conventional treatments, since it cuts intensive-care costs and reduces the need for long-term antibiotics to control blood infections.

The study is reported in the Nov. 8 issue of The New England Journal of Medicine.

Van den Berghe recognized that intensive-care patients were more likely to die in the short term if they had increased insulin activity in their liver, reflecting problems with the hormone's ability to control blood sugar. Knowing that extreme spikes in glucose can kill cells, Van den Berghe and her colleagues sought to learn if intensive doses of insulin could overwhelm surging blood sugar and improve survival rates.

The researchers followed 1,548 people, most of whom were recovering from cardiac surgery and other major operations. Roughly half received intensive insulin infusions to keep glucose at normal levels, between 80 and 110 milligrams per deciliter of blood. Other subjects were given the hormone only when blood glucose rose above 215 milligrams per deciliter. Thirteen percent of the patients in each group, who were typically men in their early 60s, had a history of diabetes.

Those who got the aggressive regimen were far less likely to die under intensive care than patients in the other group; 35 people in the intensive insulin group died, compared with 63 deaths in the second, or a difference of about 43 percent. But the effect was limited to people who stayed longer than five days in intensive care units. After adjusting for various factors, such as a patient's age or the nature of the surgery, the researchers say the true decrease in mortality was 32 percent.

The treatment led to significantly fewer deaths from multiple organ failure, as well as fewer cases of bloodstream infection and kidney failure, both of which can be fatal. The need for blood transfusions in the intensive insulin patients was 50 percent lower than in the conventional therapy group.

Van den Berghe says one mystery is why diabetics don't suffer similarly catastrophic reactions to rampant glucose. "There's something else predisposing" trauma patients to a toxic reaction to sugar, she says. "They're in an inflammatory state, and the mediators that come along with it may exacerbate toxicity."

Van den Berghe and her colleagues plan to study whether intensive insulin therapy works in patients with more general sources of trauma, such as burns and accidents. She sees no reason it shouldn't.

And the group would like to explore the potential mechanisms that make the treatment effective; for example, whether the beneficial effects of insulin therapy are the result of the hormone itself, the suppression of blood sugar, or both.

Aggressive control of blood sugar "appears to reduce mortality and morbidity substantially in surgical patients who require prolonged intensive care," Dr. Timothy Evans of the Royal Brompton Hospital in London, writes in an editorial accompanying the journal article. However, Evans says until the approach has been proven in other groups of patients, "widespread adoption of this treatment would be premature."

The study was funded in part by Novo Nordisk, a Danish drug company specializing in diabetes treatments.

What To Do

To find out more about insulin and its role in diabetes, try this Stanford University Web site.

For more on diabetes, check the American Diabetes Association or the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCES: Interviews with Greet Van den Berghe, M.D., Ph.D., professor of intensive care medicine, Catholic University, Leuven, Belgium; Nov. 8, 2001 New England Journal of Medicine
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