Diabetes Dateline
Fall 2006

Gene Variant Increases Type 2 Diabetes Risk

Lifestyle Changes Can Trump Genetics

Having a copy of a particular gene variant ups the risk of developing type 2 diabetes, a new study confirmed. But even study participants at highest genetic risk benefited from healthy lifestyle changes, such as increased physical activity and a nutritious diet, as much as—if not more than—those without that risk.

Researchers from the Diabetes Prevention Program (DPP) Genetics subgroup—a collaborative effort involving the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Massachusetts General Hospital, George Washington University, and the University of Maryland—found one copy of the gene variant called TCF7L2 in 40 percent of the DPP participants and two copies in 10 percent of participants.

For carriers of two copies of the gene variant, the risk of developing type 2 diabetes is about 80 percent higher than for noncarriers.

Lifestyle Matters

Researchers found that lifestyle changes can have a big impact on type 2 diabetes. “The lifestyle intervention reduced risk even in those who carried both copies of the risk variant,” said lead study author Jose Florez, M.D., Ph.D., a staff endocrinologist at Massachusetts General Hospital in Boston. “This finding emphasizes that people at risk of diabetes, whether they’re overweight, have elevated blood glucose levels, or have this particular gene variant, can benefit greatly by implementing a healthy lifestyle.”

Building on the work of the biopharmaceutical company deCode Genetics that linked a gene variant and type 2 diabetes, the DPP Genetics subgroup

• confirmed the finding in an independent population that included the racial and ethnic diversity typical of the U.S. population with diabetes

• showed that the gene variant increased risk in those with pre-diabetes, and in those in a prospective study where patients are followed over time

• examined for the first time the relationship between the genetic risk factor and interventions that delay diabetes onset

• demonstrated that the gene variant affects insulin production, not cell response to insulin

Even though the gene link predicts a greater risk of developing type 2 diabetes, researchers do not recommend routine genetic testing.

The DPP, spearheaded by the NIDDK in 1995, was a major clinical trial aimed at discovering whether diet or exercise or both—or the oral diabetes drug metformin—could delay type 2 diabetes onset in people with impaired glucose tolerance. The program ended in 2001.

Visit www.diabetes.niddk.nih.gov/dm/pubs/preventionprogram for more information about the DPP.

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NIH Publication No. 07–4562
December 2006