The newsletter of the Memory Disorders Project at Rutgers University

Inadequately controlled diabetes is a major cause of blindness, kidney damage, heart disease, and loss of sensation leading to limb amputation. Few parts of the body seem to be immune from the ravages of chronically high blood sugar (glucose) that characterizes diabetes—including, it appears, the brain. Some studies suggest that older people with diabetes tend to suffer more from impairments in memory and thinking. Scientists have also uncovered some intriguing possible connections between diabetes and Alzheimer’s disease.

Diabetes 101

Fundamentally, diabetes is an inability to make or use insulin normally. Insulin is the hormone that regulates the level of glucose in the blood and helps our bodies use the food we eat. Food must be converted into glucose before our cells can use it as fuel, but glucose can’t enter the cells without insulin. In lock-and-key fashion, insulin enters structures on the cell surface called receptors. Only when insulin “docks” with the receptors does the cell allow glucose to enter.

Cells use glucose to produce energy

In type 1 diabetes, which typically develops by young adulthood, the pancreas stops making insulin altogether and the person must inject the hormone daily to survive. In type-2 diabetes, which typically strikes in middle age and is by far the most common form of the disease, cells gradually become “resistant” to insulin. Glucose cannot enter the cells as readily, so the amount of it in the blood rises. Left unchecked, chronically high blood sugar damages the blood vessels, kidneys, eyes, and nerves.

You’ve probably heard about the current “epidemic” of diabetes (type 2), driven by rising rates of obesity and sedentary lifestyles. Media reports dramatize the trend with anecdotes about 14-year-old children who are developing the disease. But strictly in terms of the numbers, it’s older people who are most affected, says Edward Gregg, Ph.D., an epidemiologist with the Division of Diabetes Translation at the Centers for Disease Control and Prevention (CDC). “There’s a lot of concern these days with diabetes and youth, but in terms of the total numbers it’s really the older segment of the population where the diabetes actually occurs and it’s going to be more so. In people 65 and older, about 20 percent have diabetes, and a third don’t know it.”

Diabetes and the brain

As if loss of limb, vision, and kidney function weren’t bad enough, a number of studies suggest that diabetes may be associated with memory loss and other cognitive impairments. Indeed, in a study reported in the February 18, 2003, Proceeding of the National Academy of Sciences, scientists linked “pre-diabetic” problems with controlling blood sugar to changes in a part of the brain important to memory.

The study, involved 30 healthy middle-aged and elderly people ranging in age from 53 to 89. All had a condition called impaired glucose tolerance (IGT). This means their blood sugar remains elevated after eating, although not elevated enough for a diagnosis of diabetes. People with IGT often go onto develop type 2, or adult onset, diabetes eventually.

Brain scans showed that an area of the brain called the hippocampus, which is important to creating new memories, tended to be smaller than average in these “pre-diabetic” people. They also scored lower than average on standard memory tests.
Previous research has found that people with diabetes sometimes show impairments in certain kinds of memory tasks, such as the ability to repeat a short story from memory (i.e., verbal memory). This may be because in diabetes, cells in the body—including brain cells—aren’t able to obtain sufficient glucose to fuel memory tasks. As a result, levels in the blood remain high even as cells “starve” for energy. Or, high blood sugar may have some direct damaging effect on brain cells. Nobody knows.

Another thing that remains unclear is whether these impairments even matter in the real world. From a scientific point of view, it’s interesting that the brains of diabetics may be different, or that people with diabetes score slightly lower on “pencil and paper” tests of memory and other thinking skills. However, “whether because of that, somebody can’t go out and get their groceries, or deal with their bills and mail, there’s no direct evidence,” Gregg says.

Diabetes and dementia

Researchers have also discovered possible links between diabetes and dementia. Particularly as it relates to Alzheimer’s disease—the most common form of dementia in older people—this could be very important. It could, for example, reveal something about Alzheimer’s disease that would point to a new treatment. Or at the very least, it might motivate people with diabetes to achieve “tight control” of blood sugar, keeping it neither too high nor too low with a combination of diet, exercise, and (if needed) medication. Tight blood sugar control is proven to prevent the major complications of the disease.

The findings on diabetes and dementia are contradictory, however. In 1999, scientists reported the findings of a large study involving about 8,000 people, average age 69, living near the Dutch city of Rotterdam. At the beginning, they were tested for dementia (Alzheimer’s and other types) and other health factors, including diabetes. After an average of about two years, 126 of the participants in the study had developed dementia. Most of the cases were Alzheimer’s disease (88 people). The rest was diagnosed as vascular dementia, related to damage to the brain caused by repeated small strokes (“ministrokes”). The people with diabetes were found to be at nearly twice the risk of developing dementia, compared to people without diabetes.

Protection from Alzheimer’s?

On the other hand, another study reported in 1999—this one of nursing residents—suggested that people with Alzheimer’s had diabetes at a much lower rate than people without Alzheimer’s: 6 percent (people with Alzheimer’s) compared to 20 percent (non-Alzheimer’s). On the other hand, nearly half of the people in the home with vascular dementia had diabetes.

The association of diabetes and vascular dementia makes sense. Diabetes is known to harm the cardiovascular system, which is why it is a major risk factor for heart attacks and heart disease in general. But it’s more difficult to account for why people with Alzheimer’s disease had such a low rate of diabetes (6 percent).

One possible explanation centers on a protein called insulin degrading enzyme, or IDE. The body makes this protein to break down “used” insulin in the bloodstream. As diabetes develops and the body grows ever more resistant to insulin, the pancreas must crank out more and more insulin in order to get blood sugar into the cells. High levels of insulin, then, mean higher levels of IDE.

IDE also happens to break down beta-amyloid, the abnormal protein that collects in the brains of people with Alzheimer’s disease. Thus, as the person develops diabetes, high levels of IDE in the brain could, in theory, help to slow down the accumulation of beta-amyloid deposits. The result would be to delay symptoms of Alzheimer’s.

Reality check

However, this is all speculation based on a handful of studies. It is still not clear whether diabetes is a risk factor for memory loss, dementia, or other cognitive impairments. The reason researchers study these connections is because they may lead to a more fundamental understanding of the causes of disease and possibly suggest innovative treatments.

For the average person, the message of all this is clear: Diabetes, if left undiagnosed or inadequately treated, can have a number of serious complications down the road—possibly including damage to the brain. To avoid such complications, have your blood sugar checked by middle age and, if it’s high, take serious steps to lower it.

PREVENTING DIABETES

In 2002, health researchers reported important findings from the Diabetes Prevention Program or DPP, a major study sponsored by the National Institutes of Health. The key finding was that moderate weight loss and regular exercise offer powerful protection against diabetes in people with a "pre-diabetic" condition called impaired glucose tolerance (IGT). This means that blood sugar (glucose) is elevated but not so much that the person is officially diabetic. The participants were overweight-a key risk factor for diabetes. In the DPP, the following steps were found to slash the risk of developing full-blown diabetes by 71 percent in people aged 60 and older:

- 2.5 hours (150 minutes) per week of moderate exercise, such as walking.
- Staying on a diet limited to 1,200 to 1,800 calories per day, with no more than 25 percent of the total calories coming from fats.
- Reducing current body weight by 7 percent. For example, a 240-pound man would try to slim down to 216 pounds.

EDUCATE YOURSELF ABOUT DIABETES

Your doctor can tell you more about how to manage diabetes or IGT. Certified diabetes educators (CDEs) can also help you to find a way to combat diabetes and win. Here's how to find one:

- Contact the American Diabetes Association (ADA) to find a diabetes education program in your area recognized by the organization. Call 800-DIABETES or visit the ADA web site.

- Call the American Association of Diabetes Educators (AADE) at 800-TEAMUP4 or go to the AADE web page and click on "Find an Educator."

RESOURCES

  • “Complications of diabetes in elderly people,” by Edward W. Gregg, Michael M. Engelgau, and Venkat Narayan. (British Medical Journal, October 26, 2002, Volume 325, Number 7370, pp. 916-917).
  • “Diabetes mellitus and the risk of dementia: The Rotterdam Study,” by A. Ott and others. (Neurology, Volume 53, Number 9, pp. 1937-42).


American Diabetes Association

This large membership organization for people with diabetes provides news coverage and health information about diabetes. Members receive a subscription the organizations helpful monthly magazine, “Diabetes Forecast.”

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIDDK conducts research and provides a wealth of health information to the general public about diabetes and its treatment. Browse the NIDDK web site for information and publications you can receive free of charge.