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Low Blood Sugar Increases Older Diabetics' Dementia Risk

Posted: Wednesday, April 29, 2009

Older adults with Type 2 diabetes who experience an episode of hypoglycemia serious enough to require a trip to the emergency department or admission to the hospital are at increased risk of developing dementia, new research suggests.

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 new study.

Study author Rachel A. Whitmer, of Kaiser Permanente in Oakland, Calif., said,  "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…. 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 percent greater risk for dementia, although the reasons for that are not clear. People with pre-diabetes are also at greater risk, Whitmer noted.

However, the study looks at association only, and doesn't actually prove any cause-and-effect link between the two conditions, cautioned Dr. Nir Barzilai, 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.

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

While previous studies have linked cognitive impairment in children and adults with Type 1 diabetes, it's not clear whether the same link applies to older individuals with Type 2 diabetes or what mechanism might be underlying such a connection.

The authors 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.

According to the authors, there are several mechanisms that might explain the link between hypoglycemia and dementia. Severe hypoglycemia can cause neuronal cell death and may damage regions of the brain that oversee memory, particularly in brains already vulnerable due to age. Undiagnosed cerebrovascular damage may be another possible contributing factor.

Hypoglycemia is also a marker for diabetes severity, and although the researchers adjusted for various indicators of severity, including comorbidities and duration of insulin use, it is still possible that the severity of diabetes increases the risk for dementia, the authors note.

Insulin itself may also increase the risk for dementia through direct actions on neurons or changes in energy metabolism in the brain. The authors pointed out that patients with Alzheimer's disease have elevated levels of insulin in some areas of the brain.
While earlier research showed no link between hypoglycemia and cognitive impairment, these studies were in younger people with Type 1 diabetes. Older patients with Type 2 diabetes may be less able to recover from neurological insults. It is also possible that neurological changes linked to hypoglycemia do not affect young people but can make older patients more susceptible to dementia.

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 less 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.

"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 totally different story."

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

Source: Diabetes In Control: Journal of the American Medical Association, April 15, 2009 special issue on diabetes.

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