Genetic Screening May ID Diabetes Risk

But Identifying Traditional Risks Such as Obesity, Family History May Be Just as Useful

From the WebMD Archives

Nov. 19, 2008 -- Genetic screening can help identify people at risk for type 2 diabetes, but it adds little to traditional methods for determining risk, two new studies show.

Researchers searched for 16 recently identified genetic variants associated with an increased risk for diabetes in one study and 18 diabetes-linked variants in another.

In both studies, the more genetic variants the participants had, the greater their diabetes risk.

But genetic screening was only marginally more predictive than recognized risk factors already used to determine type 2 diabetes, such as family history, obesity, and impaired glucose tolerance, says diabetes researcher James B. Meigs, MD, MPH, of Massachusetts General Hospital.

"The genomic revolution is here, and it is possible to predict risk for diseases like diabetes by assessing genetic risk factors," he tells WebMD. "But this field is in its infancy. The message here is, 'stay tuned.'"

Checking for Genetic Variants

In all, about 25 genetic variants associated with an increased risk for type 2 diabetes have been identified -- just a small fraction of the 500 or so that experts believe they will eventually find, Meigs says. "Once we have identified more of these genes, genetic screening may prove to be more useful for predicting risk."

Meigs led one of the two newly published studies, which appear in the Nov. 20 issue of TheNew England Journal of Medicine.

In their attempt to use genetic screening to predict type 2 diabetes risk, Meigs and colleagues looked for 18 diabetes-associated genetic variants in blood samples from just over 2,300 participants in the Framingham Heart Study.

These participants were followed for 28 years, during which time 255 developed type 2 diabetes.

Each participant was assigned a genotype score, based on the number of genetic variants he or she had.

The researchers then compared the predictive value of this score to family history or other risk factors, including obesity as measured by body mass index, age, blood pressure, cholesterol, fasting glucose, and tryglyceride level.

They found that the genotype score resulted in risk reclassification of no more than 4% of the study participants.

Continued

In the second study, researcher Valeriya Lyssenko, MD, of Sweden's Lund University and colleagues looked for 16 diabetes-linked genetic variants in blood samples taken from close to 19,000 residents of Sweden and Finland followed for an average of 23 years.

During the follow-up, 2,201 (almost 12%) developed type 2 diabetes.

Family history of diabetes, obesity, smoking, and impaired glucose tolerance were all found to be strong predictors of diabetes.

Eleven of the 16 genetic variants were associated with diabetes risk, and the association was independent of the clinical risk factors.

But the identification of these genetic variants had only a small impact on the ability to predict type 2 diabetes, Lyssenko and colleagues write.

Changing Behavior Based on Genetic Risk

Even if, as expected, many more genetic variants linked to diabetes are identified over the next few years, the value of genetic screening remains unclear, Meigs says.

That's because it is not known if people will actually change their behavior based on their genetic risk.

"If we could show that people at high risk for diabetes are more motivated to lose weight, eat healthier, and be more physically active you could make a case that screening would be very valuable," he says.

Harvard University diabetes expert David Altshuler, MD, who participated in the Lyssenko trial, tells WebMD that genetic screening may prove more useful as drugs are increasingly used for the prevention of diabetes.

"The current interventions for preventing type 2 diabetes involve lifestyle and diet, and whether you are high risk or not you should adopt a healthy lifestyle," he says. "If we had preventive drugs like we do for heart disease, knowing more about risk becomes more important. Drugs have side effects, and you don't want to treat everyone."

Future discoveries regarding the role of genes in type 2 diabetes could also lead to better treatments for the disease in the same way that studying cholesterol led to statins for the prevention of heart attack and stroke, he says.

American Diabetes Association Chief Scientific and Medical Officer Richard Kahn, PhD, tells WebMD that the latest research advances the search for genetic markers for type 2 diabetes that are clinically meaningful.

"We aren't there yet," he says. "But I think we are on the road toward actually having a genetic test that will be clinically useful."

WebMD Health News Reviewed by Louise Chang, MD on November 19, 2008

Sources

SOURCES:

Meigs, J.B. and Lyssenko, V. TheNew England Journal of Medicine, Nov. 20, 2008; vol 359: pp 2208-2231.

James Meigs, MD, MPH, general medicine division and the department of medicine, Massachusetts General Hospital, Boston.

Valeriya Lyssenko, MD, department of clinical sciences, Lund University and the Malmo University Hospital, Malmo, Sweden.

David Altshuler, MD, PhD, professor of genetics and medicine, Harvard Medical School; department of molecular biology and diabetes unit, Massachusetts General Hospital.

Richard Kahn, PhD, chief scientific and medical officer, American Diabetes Association.

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