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Gene Variant Ups Type 2 Diabetes Risk

But lifestyle changes, such as exercise, counteract effects of this gene, study suggests

WEDNESDAY, July 19, 2006 (HealthDay News) -- Having certain variations in a particular gene increases your risk of type 2 diabetes by 80 percent, a new study finds.

However, that same study found that people with those variations who lost a little weight and exercised moderately for 30 minutes a day at least five times a week could virtually eliminate the risk conferred by their genetic makeup.

"If you engage in a healthy lifestyle, you can trump the bad deck of cards given to you by your genes," said study author Dr. Jose C. Florez, a clinical assistant in endocrinology at Massachusetts General Hospital, and an instructor at Harvard Medical School in Boston. "Environment can overcome the genetics you have received."

The findings are published in the July 20 issue of the New England Journal of Medicine.

Type 2 diabetes occurs when the body stops producing enough insulin or doesn't use insulin properly to process blood glucose. More than 20 million Americans have diabetes, according to the American Diabetes Association.

Researchers had previously identified variations in a gene known as TCF7L2 as being associated with type 2 diabetes, and last year Harvard researchers discovered another gene, ARNT, that is also associated with type 2 diabetes.

"Instead of just talking about genetic determinants for type 2 diabetes, we are now really beginning to identify them in earnest," said Dr. Stephen O'Rahilly, a professor of clinical biochemistry and medicine at the University of Cambridge in England. O'Rahilly wrote an accompanying editorial in the same issue of the journal.

"Ultimately, when a combination of such genetic risk factors are identified they may be sufficiently predictive that you might want to aggressively target preventive measures at those at very high risk," he said, noting that researchers aren't at that stage yet.

The new study hoped to build off the previous research on TCF7L2 to see if variants in that gene could, in fact, predict who would have type 2 diabetes.

To test that theory, the researchers gathered information from a multi-ethnic group of almost 3,500 people. The researchers did a genetic analysis, and checked insulin secretion and sensitivity at the start of the study and one year later.

They found that variations in the TCF7L2 gene indicate an increased risk. In someone with two copies of the variation, the risk of type 2 diabetes is increased by 80 percent. According to Florez, about one in 10 Americans has two copies of this variation.

The study participants had been randomly assigned to one of three treatment groups at the start of the trial -- a placebo; treatment with metformin, an insulin-sensitizing medication; or lifestyle intervention consisting of moderate weight loss and 150 minutes of exercise weekly.

The good news from the study is that you can overcome your genetics, at least when it comes to this particular gene. People with two copies of the variation who lost weight and exercised reduced their increased risk of type 2 diabetes to 15 percent, compared to 80 percent for those on a placebo. Those taking metformin had a 62 percent increased risk of diabetes.

Florez said it's too soon to start testing people to see if they have these genetic variations. "Before we recommend clinical testing, a regular clinical trial must be conducted to make sure it's clear that having this information is better for patients and that it's cost-effective," he said.

In the meantime, if you're overweight or know that you have abnormal sugar metabolism, losing just 7 percent to 10 percent of your body weight and participating in 30 minutes of moderate exercise daily can reduce your risk of diabetes, even if you have an increased risk because of the TCF7L2 gene variation, Florez said.

More information

To learn if you're at risk for type 2 diabetes, visit the National Institute for Diabetes and Digestive and Kidney Diseases.

SOURCES: Jose C. Florez, M.D., Ph.D., clinical assistant, endocrinology, Diabetes Unit, Research Fellow, Molecular Biology, Massachusetts General Hospital, and instructor, Harvard Medical School, Boston; Stephen O'Rahilly, M.D., professor, clinical biochemistry and medicine, University of Cambridge, U.K.; July 20, 2006, New England Journal of Medicine
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