Very Low Blood Sugar Linked to Dementia

Study Raises Concerns About Aggressive Diabetes Treatment in Older Patients

From the WebMD Archives

April 17, 2009 -- New research that suggests a link between dangerously low blood sugar and dementia in older patients with type 2 diabetes raises more questions about the strategy of aggressively treating diabetes patients to achieve tight glycemic control.

Older patients in the study whose blood sugar fell so low that they ended up in the hospital were found to have a higher risk for dementia than patients with no history of treatment for low blood sugar, known medically as hypoglycemia.

Having uncontrolled diabetes is associated with an increased risk for Alzheimer's disease and other age-related dementias in elderly patients.

The thinking has been that aggressive treatment to achieve tight glycemic control would lower this risk.

But the new study suggests such treatment may do more harm than good in older patients if blood sugar levels drop to very low levels.

Several other recent high-profile studies have raised similar concerns.

Researcher Rachel Whitmer, PhD, of Kaiser Permanente Division of Research in Oakland, Calif., says understanding the impact of blood sugar on cognitive function is older patients is critical.

"We are in the midst of an epidemic of type 2 diabetes and we are going to see more dementia than we have ever seen before as these patients age," she tells WebMD. "We really have to get a handle on the role of glycemic control in this."


Blood Sugar and Dementia

The study included 16,667 patients with type 2 diabetes enrolled in a northern California diabetes registry. The average age of the patients at study entry was 65.

Whitmer and colleagues examined more than two decades of medical records to determine whether the participants had ever been hospitalized or treated in a hospital emergency department for hypoglycemia.

Symptoms of hypoglycemia can include dizziness, disorientation, fainting, and even seizures. Mild to moderate episodes often don't require treatment, but severe episodes can lead to hospitalization.

None of the study participants had a diagnosis of dementia when they were enrolled in the study in 2003. Four years later, however, 1,822 of the more than 16,600 patients (11%) had been diagnosed with dementia.

Compared to patients with no history of low blood sugar requiring treatment, patients with a single episode of hospital-treated hypoglycemia were found to have a 26% increase in dementia risk.

Patients treated three or more times for hypoglycemia had nearly double the dementia risk of patients who had never been treated.

The study appears in this week's issue of Journal of the American Medical Association.

Aggressive Treatment: Risks vs. Benefits

Alan M. Jacobson, MD, is the director of psychiatric and behavioral research at Harvard Medical School's Joslin Diabetes Center.

He calls the study "compelling" but adds that more research is needed to prove that severe hypoglycemia is a cause of dementia.

"If you believe these findings, that means that just one episode of hypoglycemia can increase risk," he tells WebMD.

The dementia study is just the latest to raise safety concerns about the use of aggressive treatment to achieve tight glucose control in older patients.

Aggressive treatment to achieve blood sugar levels similar to those seen in people without diabetes was linked to an increased risk of death in older patients with type 2 diabetes participating in a large, ongoing clinical trial sponsored by the National Heart Lung and Blood Institute.

Over an average of 3.5 years of treatment, patients in the aggressive treatment arm of the study were 22% more likely to die than patients who were not treated as aggressively.


Jacobson says it is clear that a better understanding of the impact of aggressive treatment on older patients with type 2 diabetes is needed.

But he warns that it is too soon to change treatment, based on the research reported so far.

"It would be a mistake to throw the baby out with the bath," he says. "We have a substantial body of research showing the benefits of improving glycemic control. But we also have to recognize that, like with any intervention, there may be a downside."

WebMD Health News Reviewed by Louise Chang, MD on April 17, 2009



Whitmer, R.A. The Journal of the American Medical Association, April 15, 2009; vol 301.

Rachel A. Whitmer, PhD, senior research scientist, Kaiser Permanente Division of Research, Oakland, Calif.

Alan M. Jacobson, MD, professor of psychiatry, Harvard Medical School; director, psychiatric and behavioral research, Joslin Diabetes Center, Boston.

Q&A, ACCORD Trial, National Heart Lung and Blood Institute.

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