Diabetes and Stress Hyperglycemia Linked with Worse Outcomes After Stroke

With William (Lik-Hui) Lau, MBBS, and Walter N. Kernan, MD

People with diabetes face greater complications after having a stroke. And, if you have diabetes, the chance that you might experience a cardiovascular event is 1.5 times greater than someone who doesn’t have diabetes.

In fact, patients with diabetes have poorer health outcomes and longer hospital stays when experiencing an ischemic stroke, the most common type of cerebrovascular event,1 according to a review published in Journal of Diabetes Investigation.

In a review of 39 studies that encompassed nearly 360,000 patients,1 the investigators also found that an estimated 28% of people who had been hospitalized for a stroke had diabetes, indicating that diabetes was more common in stroke patients than in the general population.

Some with diabetes who has a stroke is at increased risk for more cardiac events.

Stress Hyperglycemia: A Warning to Patients with Diabetes

Stress hyperglycemia—a form of high blood sugar—is a condition brought on by an acute illness, or a cardiovascular event, and is usually discovered during a hospital stay. Stress hyperglycemia (incident high blood sugar) generally resolves after the patient recovers from the illness, but the effects can be long-lasting.2,3

"The most appropriate cutoff point for stress hyperglycemia in patients with pre-existing diabetes needs to be established, but certainly a patient with a well controlled (< 7%) hemoglobin A1Cc  (HbA1c) whose glucose concentration is consistently higher than the threshold defined for hospital-related hyperglycemia would qualify," according to Dr. Dungan. 

So you could  say, "stress hyperglycemia can be defined as a fasting blood sugar higher than 124 mg/dL (milligrams per deciliter of blood), 3,4 or a random blood sugar higher than 200 mg/dL for both patients with established, well-controlled diabetes and those without diabetes."4  

In patients, with or without diagnosed diabetes, stress hyperglycemia is associated with worse cardiac functioning after an ischemic stroke. But for patients without diabetes, stress hyperglycemia appears linked with more severe strokes—and a greater risk of dying.

“Stress hyperglycemia appears to be more consistently associated with poorer outcomes after stroke compared with established diabetes,” says the study first author, William (Lik-Hui) Lau, MBBS (equivalent to an MD from a US medical school) and confirmed by the senior author, Elif I. Ekinci, MBBS, PhD, associate professor at the University of Melbourne in Australia. This “supports the hypothesis that stress hyperglycemia reflects stroke severity.”

“However, even after adjusting for this, stress hyperglycemia and established diabetes are both still independently associated with poorer outcomes after stroke,” Dr. Lau tells EndocrineWeb. In addition, anyone who has a stroke should also be aware of their increased risk of experiencing another stroke event.1

Stress hyperglycemia is linked with other health issues as well. And in hospitalized patients, it’s associated with a greater likelihood of complications like sepsis, urinary tract infections, and pneumonia.5 Finally, in patients without no known diabetes, experiencing stress hyperglycemia raises the risk of diabetes.6

How Common Is Stress Hyperglycemia?

It’s difficult to estimate how many people experience stress hyperglycemia, since a patient with abnormally high blood sugar may actually have undiagnosed diabetes. Of the estimated 30 million people in the US with diabetes, 7.2 million, or nearly one in four people, have diabetes,7 according to the Centers for Disease Control and Prevention. "Not all patients are necessarily evaluated for diabetes during an inpatient stay,” says Dr. Lau.

The prevalence of nondiabetes-related stress hyperglycemia “has been quoted to be between 8-35 percent of patients who presented with an ischemic stroke,”8 says Dr. Lau. “This variability is in part due to the heterogeneity [or differences] in the definition of stress hyperglycemia between the studies”9 he says. For instance, the American Association of Clinical Endocrinologists and the American Diabetes Association have defined hyperglycemia as any blood sugar above 140 mg/dL.10

While Study Design is Lacking, Findings Raise Valid Concerns

The findings of the meta-analysis and literature review are intriguing, but the methods used to leave room for some questions, says Walter N. Kernan, MD, professor of medicine at Yale School of Medicine in New Haven, Connecticut.

“I’m not sure that they looked at evidence from clinical trials. I was able to identify at least one paper in this field that they did not include in their analysis,” he tells EndocrineWeb. Nonetheless “I don’t have criticisms of the findings—that diabetes is common among patients with stroke, and is associated with adverse outcomes.”

“I think this field is rapidly moving towards greater insights about the role of diabetes in affecting outcome after stroke,” says Dr. Kernan who was not involved in this study. “This paper is addressing a really important area in vascular neurology that’s full of promise.” The recommended treatment for stress hyperglycemia is to begin patients on insulin and with very close monitoring of blood sugar levels.11,12

To prevent a second episode, or recurrence of vascular events such as heart attack or stroke, often heralded by a surge in blood sugar, “two new agents, SGLT2i (sodium-glucose cotransporter 2 inhibitors) and the GLP-1 (glucagon-like peptide-1) receptor agonists are effective at lowering the risk for major adverse cardiac events in patients with type 2 diabetes, as these patients are at higher risk for, or who have, vascular disease,”13,14 says Dr. Kernan.

Furthermore, the recent Insulin Resistance Intervention After Stroke (IRIS) trial found that in patients with prediabetes who experienced an ischemic stroke, the diabetes medication pioglitazone can “substantially reduce the risk for stroke and myocardial infarction [heart attack],” 15 says Dr. Kernan. He points out that prediabetes is “at least as common as diabetes” in patients with ischemic stroke. 

Need for Further Research on the Relationship of Hyperglycemia and Stroke

“Larger, more robust studies using defined diabetes diagnostic and stroke outcome measures are needed,” Dr. Lau tells EndocrineWeb. “Specifically, the use of combined glucose testing to include fasting blood glucose, glucose tolerance testing, and hemoglobin A1c to determine if—and how—these measures estimate the true prevalence of existing and newly diagnosed diabetes, and can predict outcomes in both ischemic and hemorrhagic stroke.

The HbA1c test, which estimates average blood sugar control over the past three months, may be a particularly valuable measure since HbA1c results not only remain unaffected by stress hyperglycemia, but higher HbA1c levels are also linked with worse outcomes—including stroke recurrence and greater risk of death—after stroke.

Finally, Dr. Lau concludes, “Whether the treatment of stress hyperglycemia improves stroke outcomes is an important question to answer.”

No financial conflicts regarding this study were reported.

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