Significance of glucose excursions in hospitalized patients

Issue: July 2008

ByKathleen M. Dungan, MD

Data from large studies have demonstrated benefits of intensive insulin therapy for patients in intensive care units, prompting the publication of guidelines that advocate strict glycemic control. However, more recent reports in the medical intensive care unit have tempered the initial enthusiasm for strict glycemic control, mainly due to what has been considered an unacceptable risk for hypoglycemia.

These findings have triggered appeals for individualization of glycemic targets and efforts to identify patients who are more likely to receive benefit from interventions. One factor that is receiving increasing attention both in the inpatient and outpatient setting is glycemic variability.

Kathleen M. Dungan, MD
Kathleen M. Dungan

Management of glycemic control

After one large review of more than 7,000 medical and surgical patients in the ICU, the investigators found that the standard deviation of glucose was a better predictor of mortality than mean glucose.

The results from another study in the pediatric ICU showed that glucose variability was associated with increased length of stay and mortality on multivariate analysis. Among 1,246 patients with sepsis and below average mean glucose, those with higher glucose lability had increased odds of hospital mortality (OR=4.73; 95% CI, 2.6-8.7) compared with those with lower lability, even after adjustment for hypoglycemia and other covariates. However, it is unclear whether interventions that improve glycemic variability will improve these outcomes.

Outside of the inpatient setting, intermittent glycemic excursions are associated with more profound endothelial toxicity than tonic glucose elevations in vitro, and in patients with diabetes, glycemic variability is independently associated with higher levels of oxidative stress.

In a prospective study of patients with type 2 diabetes and coronary artery disease, the investigators found that ischemic electrocardiogram changes were more common during rapid glucose changes (>100 mg/dL per hour) than during normoglycemia or sustained hyperglycemia. Investigators of another prospective study using a euinsulinemic, hyperglycemic clamp in patients with or without diabetes reported that oscillating glucose levels between 90 mg/dL and 270 mg/dL resulted in increased endothelial dysfunction and oxidative stress that exceeded the effects of sustained hyperglycemia at 270 mg/dL in both groups.

In the DCCT, patients treated with a physiologic regimen of multiple injections of insulin per day had a 50% lower incidence of retinopathy than those with a similar HbA1c treated with only two injections of normal pressure hydrocephalus per day, suggesting that improvements in glycemic variability may play a role.

Data from several studies indicated that physiologic insulin regimens reduce both mean glucose and glycemic variability. Such regimens, particularly in lieu of traditional sliding scale insulin, could also reduce glycemic fluctuations in the hospital. To date, dozens of studies have investigated the efficacy of various IV insulin protocols. Computerized IV insulin protocols demonstrate reductions in hypoglycemia and hyperglycemia, indicating that they may also reduce glycemic variability. However, efficacy is usually not defined in terms of established measures of glycemic variability, and no controlled trials are available.

Measures to stabilize glucose may have the potential to preserve or enhance the benefits of glycemic control while reducing the risks for hypoglycemia. More studies are needed to recommend for or against specific measures to reduce glycemic variability outside of the traditional framework for “tight glycemic control.”

Kathleen M. Dungan, MD, is an Assistant Professor of Medicine in the Division of Endocrinology, Diabetes & Metabolism at Ohio State University.

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