ATLANTA--Diabetes mellitus appears to reduce the risk of acute respiratory distress syndrome (ARDS) in patients with septic shock. In a recent study of 113 consecutive septic shock patients, the incidence of ARDS was only 25% among those with diabetes but 47% among nondiabetic patients.[1]

How diabetes protects against ARDS remains a mystery, though. "This was an epidemiological study that did not examine the pathogenesis of our findings," lead author Marc Moss, MD, told PULMONARY REVIEWS.

One explanation for diabetes' protective effect may be neutrophil impairment. In diabetic patients, the ability of neutrophils to migrate to the lung--and to cause oxidant damage once there--may be reduced. "Therefore, the same alterations in the inflammatory cascade that predispose diabetic patients to infection may protect them against ARDS," suggested Dr. Moss, who is an Assistant Professor of Medicine at Emory University in Atlanta. "But that is pure speculation."

A UNIQUE ARDS STUDY

Many current studies examine cytokines and other biochemical markers that are thought to predict which critically ill patients may develop ARDS. "But we took a different approach and looked at preexisting comorbid conditions," Dr. Moss explained. The authors chose diabetes because of its known effects on neutrophil function.

The study was limited to septic shock patients because they are known to have a significantly increased risk of ARDS. This approach also eliminated a potential source of bias: The incidence of ARDS varies widely among the different groups of patients at risk for this disease, which can make it difficult to ensure that the two populations studied (patients with and patients without diabetes) are truly well matched.

To enroll a suitably large number of subjects in their study, Moss et al prospectively identified patients with septic shock who were treated in the intensive care units (ICUs) at four hospitals. The patients could be enrolled only during the first 10 days of hospital admission and only within the first 72 hours of ICU admission. In addition, all patients had to meet the American College of Chest Physicians/Society of Critical Care Medicine criteria for the diagnosis of sepsis, have a clear source of infection, and have one of the following signs of shock:

• Systolic blood pressure below 90 mm Hg for more than an hour.
• Need for vasopressor therapy (excluding dopamine at 4 µg/kg/min or less).
• Systemic vascular resistance below 800 dyne·sec/cm5.
• Unexplained metabolic acidosis with an anion gap greater than 15 mEq/L.

PATIENT OUTCOMES

ARDS was defined using the American-European Consensus Conference definition. Of the 113 patients enrolled, 32 (28%) had diabetes. ARDS developed in only eight (25%) of the diabetic patients but in 38 (47%) of those without diabetes (Table 1). The difference in incidence between diabetic and nondiabetic patients remained significant even after the authors controlled their analysis for a number of confounding variables, such as patients' age, source of infection, and history of cirrhosis.

Also of note is the finding that septic shock was less apt to be from a pulmonary source in diabetic than in nondiabetic patients (25% vs 48%). This difference was also significant.

Not surprisingly, the likelihood of death was far greater for patients with ARDS than for those without it (61% vs 22%). Among the patients with ARDS, there was no significant difference in mortality between diabetic and nondiabetic patients (50% vs 63%). Mortality was also similar among the diabetic and nondiabetic patients without ARDS (17% vs 26%).

DIABETES OR HYPERGLYCEMIA?

What role acute hyperglycemia may play in protecting patients against ARDS remains unclear. The median blood glucose level at admission was significantly higher among the patients who did not develop ARDS than among those who did (152 vs 110 mg/dL).

Moreover, the incidence of ARDS was 33% among those with an elevated blood glucose level at admission (defined as a value above 120 mg/dL) but 51% for those with a normal admission blood glucose level. However, the difference in ARDS incidence was not significant when the analysis was adjusted for confounding variables.

The authors suggest that additional studies with larger numbers of patients are needed to differentiate the effects of chronic diabetes from those of acute hyperglycemia on the development of ARDS. Analysis of admission hemoglobin A1 levels could also help clarify this issue.

CLINICAL IMPLICATIONS

"I would not alter clinical practice based on this study, particularly in terms of treatment, since we have no idea why ARDS risk is reduced in septic shock patients with diabetes," commented Polly E. Parsons, MD, a study author and a Professor of Medicine at the University of Vermont in Burlington. "For example, we would not make septic shock patients hyperglycemic to reduce their chances of developing ARDS."

However, the results of this study should improve physicians' ability to prospectively identify critically ill patients who are likely to develop ARDS, Dr. Parsons said. That, in turn, could allow for the development of more targeted therapeutic interventions. Such an approach could increase the likelihood that trials of these therapies are successful; it could also enable these trials to detect a benefit from a potential ARDS treatment with fewer patients, more quickly, and at a lower cost.

--Timothy Begany

Reference
1. Moss M, Guidot DM, Steinberg KP, et al. Diabetic patients have a decreased incidence of acute respiratory distress syndrome. Crit Care Med. 2000;28:2187-2192.

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