Increasing blood glucose variability heralds hypoglycemia in the critically ill

Abstract

Background: Control of hyperglycemia improves outcomes, but increases the risk of hypoglycemia. Recent evidence suggests that blood glucose variability (BGV) is more closely associated with mortality than either isolated or mean BG. We hypothesized that differences in BGV over time are associated with hypoglycemia and can be utilized to estimate risk of hypoglycemia (<50 mg/dL).

Materials and methods: Patients treated with intravenous insulin in the Surgical Intensive Care Unit of a tertiary care center formed the retrospective cohort. Exclusion criteria included death within 24 h of admission. We describe BGV in patients over time and its temporal relationship to hypoglycemic events. The risk of hypoglycemia for each BG measurement was estimated in a multivariable regression model. Predictors were measures of BGV, infusions of dextrose and vasopressors, patient demographics, illness severity, and BG measurements.

Results: A total of 66,592 BG measurements were collected on 1392 patients. Hypoglycemia occurred in 154 patients (11.1%). Patient BGV fluctuated over time, and increased in the 24 h preceding a hypoglycemic event. In crude and adjusted analyses, higher BGV was positively associated with a hypoglycemia (OR 1.41, P < 0.001). Previous hypoglycemic events and time since previous BG measurement were also positively associated with hypoglycemic events. Severity of illness, vasopressor use, and diabetes were not independently associated with hypoglycemia.

Conclusions: BGV increases in the 24 h preceding hypoglycemia, and patients are at increased risk during periods of elevated BG variability. Prospective measurement of variability may identify periods of increased risk for hypoglycemia, and provide an opportunity to mitigate this risk.

Figure I. Computing recent blood glucose variability

Recent blood glucose variability is the absolute difference between the four preceding BG values.

Figure II. Blood glucose over time for Hypoglycemic and Non-Hypoglycemic patients

Blood glucose values for 50 randomly-selected hypoglycemic patients (defined as one or more hypoglycemic events) and 50 randomly-selected non-hypoglycemic patients (defined as zero hypoglycemic events) plotted over time. Each plot represents 10 patients.

Figure III. Blood glucose variability in 24 hours preceding BG measurement of interest (index BG)

Blood glucose variability is higher prior to hypo- and hyper- glycemic glucose values, while euglycemic values are preceded by very low blood glucose variability. For all patient glucose values within a particular range (line style) at the index BG, variability is plotted for the preceding 24 hours in 6-hour intervals. Immediately prior to hypoglycemic events (BG <= 50 mg/dL), BG variability increases rapidly. BG variability also increased in the 24 hours preceding a BG value of >200 mg/dL.

Figure IV. The Relationship Between Hypoglycemia, Blood Glucose Variability, and Time in ICU Stay

This figure shows the relationship between hypoglycemia and BG variability. Proportion of patients are on the y axis, and time is on the x axis. Each horizontal row is a patient, showing BG variability over time, with similar patients grouped together. Medium gray is low variability and dark grey is high variability. Hypoglycemic events during periods of low variability are noted by light dots, and hypoglycemic events during periods of high variability are noted by dark dots. The size of the dot corresponds to number of events, with larger dots indicating more events. Most patients have low BG variability. But, variability changes over time, with patients moving from periods of low variability to periods of high variability. When BG variability is high, the risk of hypoglycemia is higher. Overall, there are 3.3 hypoglycemic events (BG <= 50 mg/dL) for every 1,000 hours of high blood glucose variability and 1 hypoglycemic event for every 1,000 hours of low BG variability.