Low Blood Sugar May Raise Dementia Risk

Older individuals with type 2 diabetes who have been hospitalized with severe low blood sugar levels seem to have a greater risk of developing dementia, new research suggests.

It's not yet clear whether less severe episodes of low blood sugar, which are more common, are also linked with an increased dementia risk, according to a study in The Journal of the American Medical Association (JAMA).

The issue is an important one, with an ever-growing population of people suffering from type 2 diabetes. In the United States alone, some 24 million people have the condition, with lots more to come as the population ages.

Hypoglycemic episodes are marked by dizziness, fainting and even seizures.

The Study

Researchers followed 16,667 patients with type 2 diabetes, average age 65, from 1980 to 2007. Twenty-two years of the follow-up were devoted to chronicling hypoglycemic episodes, and more than four years were spent following dementia diagnoses.

The Results

"Hypoglycemic episodes that were severe enough to require hospitalization or an emergency-room visit were associated with a greater risk of dementia, particularly for patients who had multiple episodes. And these findings, a little bit to our surprise, were independent of glycemic control," said study author Rachel A. Whitmer, PhD, a research scientist at Kaiser Permanente in Oakland, California. "Episodes of hypoglycemia may be associated with neurological consequences in patients already at risk for dementia. This study seems to suggest that hypoglycemia is one of the reasons people with type 2 diabetes are at a higher risk for dementia It also adds to the evidence base that balance of glycemic control is a critical issue, and particularly for the elderly."

People with type 2 diabetes are at a 32% greater risk for dementia, although the reasons for that are not clear. People with prediabetes are also at greater risk, Dr. Whitmer noted.

Possible Explanations

The association that was found could be attributable to any of a number of possible mechanisms, including accelerated death of nerve cells in the brain or reduced blood supply to the brain, the authors stated. Such a link could also be a result of too much insulin over time, again possibly contributing to neuronal damage or other brain changes.

However, the study looks at association only, and doesn't actually prove any cause-and-effect link between the two conditions, cautioned Nir Barzilai, MD, director of the Institute for Aging Research at Albert Einstein College of Medicine and the Montefiore Hospital Diabetes Clinic in New York City.

"It could be fluctuation of glucose. We know that hyperglycemia (high blood sugar) is also very toxic to the cells. All those things cannot be dissected on a study like this," he said.

Dr. Whitmer also noted that hypoglycemia is likely only one reason for the heightened risk of dementia in individuals with type 2 diabetes.

But the whole picture is likely to be much more complicated, Dr. Barzilai said. "The glucose concentrations in the brain are much, much lower than in the [rest of the body], and it takes it a long time to actually adjust if you change the peripheral glucose for the brain to have lower glucose," he explained. "Not only that, but the neurons in the brain are really not fed by glucose but by other metabolites. The rest of the body, when glucose goes down, will feel it. The brain is a totally different story."

Balancing Blood Sugar

Although balanced blood-sugar control is a good strategy in theory, it's difficult to attain and difficult to monitor.

"The trouble is, when you try to keep blood sugar within the normal range, there's a higher risk of hypoglycemia," said Michael Horseman, PharmD, an associate professor of pharmacy practice at the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy. "There hasn't been a study that I'm aware of where they made a serious attempt to keep blood sugar in the normal range that didn't have episodes of hypoglycemia."

Dr. Barzilai agreed. "You give them a little bit of insulin, and they get hypoglycemia. You give them a little less and the glucose goes very high. It's individual. It's not that you know what to do with every patient."

"It does underline the fact that if we had drugs that didn't produce hypoglycemia, we certainly would be better off," he added.