Genetic Testing No Help in Predicting Type 2 Diabetes

Testing for 18 different gene variations associated with type 2 diabetes was no better at predicting a person's risk for the blood sugar disease than a doctor's assessment, researchers report.

The news is both encouraging and discouraging.

"The genomics revolution is here. You can be tested for disease risk," said Dr. James Meigs, lead author of one of two studies published in the Nov. 20 issue of the New England Journal of Medicine. "In the framework of diabetes, the more risk genes you have, the higher risk you are. We didn't really know before that you could add up risks across genes."

"But, we don't know enough about diabetes genetics to make a recommendation for widespread testing," added Meigs, an assistant professor of medicine at Harvard Medical School and Massachusetts General Hospital, in Boston. "For adults, the information you can get at a check-up with your doctor tells you everything you need to know for your risk of diabetes. In youth, genetic testing could be useful. The value of any of this is going to lie in the question of how much knowing genetic information would cause you to change lifestyle factors."

Incorporating other gene variants, however, might fine-tune such genetic screening.

"More work needs to be done. The kind of genotypes they have studied are only 18. That's very insufficient," said Rajat Sethi, an assistant professor of pharmaceutical sciences with the Texas A&M Health Science Center Irma Lerma Rangel College of Pharmacy in Kingsville. "I think more genetic variations need to be studied. This is a good approach."

Many risk factors for type 2 diabetes are well known, including, notably, a family history of the disease, as well as poor nutrition, lack of exercise and carrying too much weight. Experts believe that both genetic and environmental factors -- such as diet and exercise -- and an interplay between the two contribute to developing diabetes.

Meigs and his colleagues examined 18 gene mutations associated with type 2 diabetes in 2,377 people participating in the Framingham Offspring Study, a three-decade-long study. Each gene conferred a 5 percent to 37 percent increased risk of developing diabetes, the researchers said.

Screening for these genes did predict who would develop diabetes, but not significantly better than a regular doctor's examination.

The authors of the second study looked at 16 gene variants associated with type 2 diabetes in 16,061 Swedish and 2,770 Finnish individuals. Again, this genetic screening performed only slightly better than conventional methods in predicting who would get the disease. But the ability of the genetic risk factors to predict future diabetes got better the longer the study participants were followed, the researchers said.

The researchers, from Lund University in Malmo, Sweden, suggested that this type of screening could help narrow the number of people needed in trials looking at prevention of type 2 diabetes.

"Although genetic information appeared to be useful when only factors known in youth were considered, genetic information in the context of risk factors measured in adulthood did not help to refine the prediction of diabetes risk," the study authors write. "Our findings underscore the view that identification of adverse phenotypic characteristics remains the cornerstone of approaches to predicting the risk of type 2 diabetes."

"It's wonderful that science is progressing, but this is not all that clinically useful," he added. "It looks like family history, high triglycerides [blood fats], and obesity together put you at very high risk and it's been clear to many people out there that this has been the case for quite a long time. Highlighting this is a good thing because we can talk to patients about it. The sooner we intervene and the more aggressive we are early on with diabetes, the better off we'll be."

Practice Pearls:

• A genotype score based on 18 risk alleles can predict the risk for type 2 diabetes mellitus with a 12% increased relative risk per risk allele.
• If family history or clinical risk factors of diabetes are known, the genotype score does not significantly improve the prediction of the risk for type 2 diabetes.

NEJM Nov. 20, 2008