A Medical Device Daily
A groundbreaking study of 216,000 critically ill patients conducted by the Veterans Affairs Inpatient Evaluation Center (Cincinnati) has demonstrated that hyperglycemia (high blood glucose levels) is associated with increased death in patients in intensive care units, according to a report presented at the American Diabetes Association's 66th annual scientific sessions in Washington.
“The increased deaths associated with hyperglycemia in intensive care units was highest in those without diagnosed diabetes and in those admitted with cardiovascular disorders, such as heart attacks, unstable angina, and strokes,” said Mercedes Falciglia, MD, assistant professor of medicine in the Division of Endocrinology at the University of Cincinnati College of Medicine. A staff endocrinologist at the Cincinnati Veterans Affairs Medical Center, she is the lead author of the study.
In the study, hyperglycemia was found to be an independent predictor of mortality starting at only one milligram per deciliter above normal glucose levels. The impact of high blood glucose levels was variable, but increased death to as high as 15 times that which would be expected in stroke patients with the highest blood glucose levels.
However, in some conditions, such as chronic obstructive pulmonary disease (COPD) and liver failure, high blood glucose levels did not appear to be linked to mortality.
“These findings suggest that different disease states are variably affected by hyperglycemia, with the strongest association in individuals with cardiovascular disorders,” Falciglia said.
Hyperglycemia independently predicted mortality in the medical, surgical and cardiac ICUs.
Hyperglycemia has previously been shown to be associated with increased mortality in hospitalized patients in smaller trials. However, the potential benefits of trying to reduce high blood glucose levels have been questioned because results from intervention trials with intensive insulin therapy have been variable, with some trials showing improved outcomes with treatment and others no effect.
Falciglia said, “Based on the outcome of this large study, we believe that the variable results of those studies may be due to the unique ways that high blood glucose may or may not affect mortality in different types of diseases – which can be uniquely revealed through large and diverse databases such as those generated by the network of Veterans Affairs hospital ICUs.”
To address that question, researchers evaluated the independent association between mean blood glucose and mortality in 216,000 severely ill individuals admitted to 177 Veterans Affairs ICUs. The risk of death for each patient was calculated based on the diagnosis that brought them to the hospital, presence of any other diseases, lab test results and age. In a second mathematical model, the independent link between an individual's average blood glucose during their ICU stay and their risk of mortality was calculated.
Normal blood glucose levels are 70 to 110 mg/dl. Hyperglycemia was an independent predictor of mortality starting at 111 mg/dl.
The effect was greatest in those admitted with acute myocardial infarction, unstable angina and stroke. In patients admitted due to heart attack, hyperglycemia increased the risk of death from 1.6 to 5 times what would be expected from others of similar age and comorbidities; with a stroke it raised risk from 3.4 to 15.1 times; and with unstable angina it raised risk from 1.7 to 6.2 times.
A significant but weaker effect was seen in patients with sepsis, pneumonia, and pulmonary embolism. Hyperglycemia was not found to be associated with mortality in diseases such as COPD and hepatic failure.
“These differential effects may explain the inconsistencies seen in the results of intervention trials to control inpatient hyperglycemia,” said Falciglia. “Since such randomized controlled trials are expensive and difficult to organize, it may be a wise use of resources in future trials to consider disease type and focus on those populations that appear to be at greatest risk.”
She added: “This effect seen was also greatest in patients without diagnosed diabetes, a finding that deserves further study because it is not clear why hyperglycemia occurs in hospitalized patients who do not have diagnosed diabetes nor why they may have worse outcomes in some cases than people with diagnosed diabetes.”
It is estimated that 6.2 million Americans have undiagnosed diabetes. Many never see a doctor and do not discover they have the disease until diabetes-related complications such as a heart attack or stroke hits. “All patients should have their blood glucose levels monitored when they are admitted to an intensive care unit because hyperglycemia occurs in one-third of ICU patients,” Falciglia said.
In another diabetes-related development, the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS; Wayne, Pennsylvania) and the Diabetes Technology Society (DTS; Foster City, California) reported they would be working cooperatively on the development of a consensus guideline for continuous glucose monitoring.
The project was approved in late April during a meeting of the CLSI Chairholders Council. Since then a subcommittee on continuous glucose monitoring has been formed and approved and plans are under way to begin the first in a series of meetings.
Continuous glucose monitors (CGM) measure glucose in the interstitial fluid using devices attached to the skin. They offer the potential of managing insulin levels without the cost and discomfort of more traditional methods that require costly supplies and repeated painful fingersticks.
However, there is no current consensus on how to compare CGM devices, how to define the appropriate level of agreement given the time lag between blood and interstitial fluid levels, or how to display and interpret data. The guideline being co-developed by CLSI and DTS will address these issues by reaching consensus on how CGM data should be presented and compared between different devices and different glucose methodologies.
“The joint project being spearheaded by CLSI and DTS will play an important role in the development of new technology for people with diabetes,” said Glen Fine, executive vice president of the Clinical and Laboratory Standards Institute. “It may even accelerate the development of an artificial pancreas by stimulating interest from industry in developing better continuous glucose monitoring products.”
Also at ADA, Abbott Diabetes Care (Alameda, California) cited the presentation of results from a new study designed to assess the accuracy of the company's FreeStyle Navigator Continuous Glucose Monitoring System for people with diabetes. The study met its primary endpoint of demonstrated accuracy and stability over five days of wear.
Study results were discussed by William Clarke, MD, professor of pediatrics at the University of Virginia Health System (Charlottesville).
The FreeStyle Navigator system is an investigational device under FDA review. It includes a five-day sensor, a transmitter and a wireless receiver with a built-in FreeStyle blood glucose monitoring system. The system is designed to provide glucose readings once per minute, high/low glucose alarms and projected glucose alarms.
The accuracy of the system was assessed in 58 subjects ranging in age from 18 to 64. Comparison of the FreeStyle Navigator system measurements with a laboratory reference method gave a mean absolute relative difference of 12.8% and a median absolute relative difference of 9.3%.
“Frequent and accurate glucose monitoring is an essential element of achieving tight glycemic control. The accuracy, particularly in the A zone, of continuous glucose monitoring sensors is critical to assessing the benefits that patients can derive from the technology,” said Clarke.