Diabetes Forecast February 2004

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FOR TYPE 2

Research Profile

The Apple Shape
Causes And Effects
by Patty Walsh

Marguerite J. McNeely, MD, MPH, believes low birthweight may be linked to a tendency to store fat around the middle later in life.	Marguerite J. McNeely, MD, MPH Occupation Assistant Professor of Medicine at the University of Washington Research Focus Pre-diabetes Outside Interests Hiking, snowshoeing, gardening Research Funding ADA Career Development Award

If you have insulin resistance, your cells are unable to use insulin properly. Insulin resistance is one of the changes that occur in the body before type 2 diabetes develops. Scientists call it a precursor to diabetes, and they want to know more about it. What causes it? What other problems might be associated with it?

We know that excess fat is one potential cause of insulin resistance. Visceral fat, or fat stored in the abdomen near the organs, seems to have especially bad effects on the way cells work with insulin. Think of the "apple shape" (fat stored around the middle) versus the "pear shape" (fat stored on the hips and thighs). Visceral fat also causes more insulin resistance than subcutaneous fat, which is stored just under the skin.

With funding from an American Diabetes Association Career Development Award, Marguerite J. McNeely, MD, MPH, assistant professor of medicine at the University of Washington in Seattle, is looking into two aspects of visceral fat. First she'll investigate whether people who had low birthweights are more likely to develop visceral fat as adults. Then she'll look into whether the insulin resistance associated with visceral fat is related to subtle problems in thinking and memory in adults.

It may seem strange to investigate such widely differing topics, but both are two pieces of the same puzzle. "We're trying to fill in gaps in the knowledge base about what leads to visceral fat and what the consequences of it are—even before people get diabetes," McNeely says.

The Low-Birthweight Link

About 10 years ago, researchers discovered that low-birthweight babies were at higher risk than normal-weight babies for developing type 2 as adults.

"At first it flew in the face of everything we knew," says McNeely. "But later studies have consistently shown that lower birthweight is a risk factor of type 2 in adulthood. And it doesn't have to be ultra-low birthweight, as in the case of premature babies. It can just be the lower end of normal."

Scientists aren't sure why this is so. One theory is that when babies don't get enough nutrition in the womb, such as when their mothers smoke, they don't develop enough of the cells that make insulin and are more likely to develop diabetes later in life.

Another theory suggests that, because low-birthweight babies are at risk for becoming sick and not surviving infancy, those who can put on weight quickly are more likely to be healthy and survive. But once these babies become adults, their tendency to gain weight increases their risk for diabetes.

McNeely's research may provide evidence toward the second theory. "If that theory were true, then I would expect that people who were low birthweight would probably be more prone to have higher levels of visceral fat when they're adults, regardless of whether or not they have diabetes," she says.

McNeely will gather data from two groups of people who do not have diabetes and who have already had their visceral fat measured with CT scans. (A CT scan, also called a CAT scan, is a sophisticated type of x-ray that shows cross-sections of tissue.)

One group includes about 100 men and women aged 35 to 55 who participated in the Japanese American Community Diabetes Study, for which McNeely has been an investigator since 1998. The other is a group of 100 to 200 men, aged 45 to 65, who are participating in a visceral fat and testosterone study conducted by her colleague, Elaine Tsai, PhD. McNeely will record the visceral fat data from these studies and, with permission from each study participant, she'll collect birthweight records for comparison.

If those with greater amounts of visceral fat also had low birthweights, that might demonstrate a link between low birthweight and visceral fat.

New Ideas On Thinking And Memory

Recent studies have shown that people with type 2 have a tendency toward subtle thinking problems compared to people who don't have diabetes. Even those who haven't had many low blood glucose reactions or who aren't on medication show this effect. It's primarily seen in people who are middle-aged and older.

"I want to stress that this is a relatively subtle issue," says McNeely. "For example, if you read a fairly short story of three to four sentences to a group of people and then ask them right away how much they can remember about it, it's common that people with type 2 won't remember quite as much of what they hear compared to those without diabetes."

It's not clear why this happens. McNeely suspects that high levels of insulin might be the problem. Because visceral fat can affect the way the body uses insulin, she wonders if people who have visceral fat—but not diabetes—might also show problems with thinking and memory.

To test her theory, McNeely will ask the men in Tsai's study to take an oral glucose tolerance test to reveal if they show any signs of insulin resistance. Then the men will take a battery of several different cognitive tests.

"Each test captures a specific aspect of cognition, such as verbal memory, visual memory, motor speed, or attention," says McNeely. For example, in one test, each man will receive a piece of paper that contains randomly placed numbers. He will draw a line as fast as he can to connect the numbers in sequence.

If the participants whose oral glucose tolerance tests reveal insulin resistance don't perform as well on the cognitive tests as those without insulin resistance, that could indicate a relationship between insulin resistance and cognitive challenges.

McNeely's team began gathering data in April 2003. In 2006 they will conduct a follow-up study with the men, repeating all of the tests.

If low birthweight is found to be a predictor for visceral fat in adulthood, steps could be taken to help people prevent or reduce their visceral fat before they experience problems with insulin resistance and type 2 diabetes. And, if a link is found between visceral fat and problems with thinking and memory, more attention may be given to treating the insulin resistance associated with visceral fat.

Says McNeely, "It's worth getting a better handle on what is going on, particularly for people with diabetes. Relatively subtle changes in thinking might make a difference in how well people manage their diabetes."

Patty Walsh is a freelance writer in Columbus, Ohio.