The risks of tight glycemic control for patients in intensive care outweigh the benefits, a Belgian researcher said.  That's the clinical message from the aborted European Glucontrol Trial, which was halted prematurely last May when a monitoring committee found an excess of deaths associated with the low-glucose group in the study, according to Jean-Charles Preiser, M.D., Ph.D., of the University Hospital Center in Liège.

The safety signal was premature, however, and when more data were included, overall, patients kept under tight glycemic control were not at greater risk of death than those on a looser regimen, Dr. Preiser told a latebreaker session at the Critical Care Congress of the Society for Critical Care Medicine.

But equally, he said, there was no mortality benefit for the 536 patients randomized to a target of 80 to 110 milligrams per deciliter of glucose over the 546 patients whose blood glucose target was between 140 and 180 mg/dL.

On the other hand, he said, patients in the low glucose group had significantly more incidents of hypoglycemia (at P<0.001). Indeed, if the definition of hypoglycemia was set at 60 mg/dL, being in the low glucose group led to seven-fold greater risk of the condition, compared to those in the other group.  "There is no reason to recommend the use of 110 milligrams as a target for insulin therapy," Dr. Preiser said. In fact, aiming for the higher level of 140 or 150 would be "wise," he said.

The insulin regimens used were broadly successful in achieving the study goals:

• Patients in the low glucose group on average had a level of 118 milligrams per deciliter -- slightly above the target -- while those in the other group had an average level of 144.

• The difference between the groups in blood glucose was apparent early and remained significant at P<0.001 through the treatment period.

• The variability in glucose levels was identical in both groups.

Mortality in the ICU, during the hospital stay, and at 28 days was not significantly different between the groups. There was no difference in length of stay on the ICU.  Patients in the low glucose group had significantly fewer insulin-free days (at P<0.0001) than those in the other group.

The multi-center international study was intended to extend and verify two single-center Belgian studies published in 2001 and 2006 that showed about a 6% mortality benefit for surgical ICU patients kept under tight glycemic control.

Those studies were widely accepted despite their relatively small size and homogenous northern European patient population, commented Clifford Deutschman, M.D., of the University of Pennsylvania Medical School in Philadelphia, who moderated the late-breaker session.

Whether the results apply in a broader situation was unclear, but Dr. Preiser's data calls the issue into doubt, he said, and intensive care physicians need to "think hard and long" about aiming for tight glycemic control. "We need to be very conservative about starting insulin regimens the minute someone comes into the ICU."
Practice Pearls:

• Explain to interested patients that two small European studies suggested that keeping blood sugar at normal levels in patients on intensive care could reduce mortality.

• Note that results from the European Glucontrol Trial -- stopped prematurely last May -- show no mortality benefit and increased risks of hypoglycemia for patients in the tight glucose control group.

• This study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary as they have not yet been reviewed and published in a peer-reviewed publication.

The study was sponsored by the European Society for Intensive Care Medicine, the Communauté Française Wallonie-Bruxelles, and Roche Diagnostics. Dr. Preiser did not report any competing interests

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DID YOU KNOW:

Coffee cuts diabetes risk: Coffee continues to get good and bad press coverage, but a recent study published in the European Journal of Clinical Nutrition (Epub March 7, 2007) details an inverse association between higher coffee intake and incidence of type 2 diabetes. In the trial, 21,826 Finnish men and women 35 to 74 years of age and with no history of diabetes were followed from baseline—1982, 1987, 1992 or 1997—until one of three events occurred: onset of type 2 diabetes, death or the year 2002. Specifically, researchers monitored coffee consumption and serum gamma-glutamyltransferase (GGT), a liver enzyme that is used as a biomarker to indicate damage, especially oxidative. Results showed coffee consumption was significantly and inversely associated with incident diabetes among both men and women. The inverse association was most significant in those subjects who also had GGT levels higher than the 75th percentile, especially among women and both sexes combined. The researchers concluded, “Habitual coffee consumption is associated with lower incidence of type II diabetes, particularly in those with higher baseline serum GGT levels.”