When a person becomes critically ill, their body responds by increasing blood glucose levels — part of its way of adapting to a serious illness.
For many years, researchers have embarked on studies using intensive insulin therapy to bring blood glucose levels within normal range with the hope of decreasing a patient’s risk of dying. Survival rates, they believed, would be higher among critically ill patients with normal glucose levels.
But newly released international study involving McMaster University researchers found that just the opposite is true — tight glucose control is associated with an increased risk of dying.
The findings appear in this week’s New England Journal of Medicine and have been called "provocative" and "surprising."
"It has traditionally been thought that normal blood sugar in critically ill patients is what we should try to achieve. But, this study suggests that during critical illness that it’s not ideal to try to achieve a precisely normal blood sugar level and that it may, in fact, be harmful," said Dr. Deborah Cook, chair of the Canadian Critical Care Trials Group which developed the Canadian part of the trial and academic chair of critical care medicine at McMaster University and St. Joseph’s Healthcare.
Cook said the study’s conclusions run counter to many practices as well as practice guidelines put forward by professional societies.
"It’s been a long-standing, well-accepted goal to try to achieve normal blood sugar levels in critically sick patients and a lot of effort is spent trying to normalize blood glucose. It turns out, surprisingly, that this is not only unnecessary but may be harmful and that more moderate levels are probably best," said Cook, the Canada Research Chair of Research Transfer in Intensive Care.
The NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) study of more than 6,000 patients was undertaken in Canada, Australia, New Zealand and the United States by researchers from the Australian and New Zealand Intensive Care Society Clinical Trials Group, the George Institute for International Health, the Canadian Critical Care Trials Group and Vancouver Coastal Health Research Institute.
Thirty-five Hamilton patients hospitalized at St. Joseph’s Healthcare were among nearly 800 Canadian patients who participated in the study. Seriously ill, they were admitted to the intensive care unit (ICU) and most were on life-support. (Every year in North America, more than six million patients are admitted to ICUs for treatment).
For the study, researchers randomly assigned critically ill adults who were expected to require treatment in the ICU for three or more days into one of two different target ranges. One was an intensive blood glucose control which was aiming to achieve a normal glucose level with intensive insulin therapy. The other arm was a conventional control target. The primary end point was death from any cause within 90 days.
They found intensive lowering of blood glucose levels increased a patient’s risk of dying by 10 per cent.
"On the basis of our results, we do not recommend use of the lower target in critically ill adults," the researchers wrote.
Their findings are similar to those in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial whose Canadian arm was led by Dr. Hertzel Gerstein, a professor of medicine and the Population Health Institute Chair in Diabetes Research at McMaster University. Last June, the ACCORD trial was terminated early because of an increased death rate in patients with Type-2 diabetes who were undergoing intensive glucose lowering.
An accompanying editorial in the NEJM suggests past attempts to attain normal blood glucose control during critical care may have been "overly enthusiastic."
"Similar and well-intentioned exuberance for rigid glucose targets in outpatient care was challenged this past summer by the jarring results from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial," wrote Dr. Silvio E. Inzucchi, professor of medicine at Yale University, and Dr. Mark D. Siegel, head of the Medical Intensive Care Unit at Yale-New Haven Hospital.
Inzucchi and Siegel cautioned against any "overreaction" to the NICE-SUGAR findings suggesting the study simply states there is no additional benefit to significantly lowering blood glucose levels and it would be a disservice to critically ill patients to infer from the trial that their current treatment is neglectful.
The study was supported by grants from the Australian National Health and Medical Research Council, the Health Research Council of New Zealand and the Canadian Institutes for Health Research.