May 7, 2007

New Risk Factors Identified for Type 2 Diabetes

Silhouette of people behind colorful combinations of A,T,C and G The letters A,T,C and G represent the 4 chemical units that form the genetic code of DNAJane Ades, NHGRI.

A collaborative effort by 3 international research teams has provided new clues to help us understand why some people develop type 2 diabetes and others do not.

Diabetes is a group of diseases marked by high levels of glucose in the blood. Persistent high blood sugar levels can lead to blindness, kidney failure, amputations, heart disease and stroke. Type 2 diabetes is by far the most common form. It usually appears in people over the age of 40 who are overweight and get little exercise. However, an increasing number of young adults, and even children, are now developing the disease.

Lifestyle and diet play clear roles in type 2 diabetes, but researchers have recently begun to understand the genetic factors involved. To identify new risk factors, 3 teams of scientists used a relatively new approach called a genome-wide association study. A group of U.S.-Finnish researchers supported by NIH published their findings, along with 2 other research teams, in separate reports on April 26, 2007, in the online edition of the journal Science.

The U.S.-Finland collaborative study involved more than 2,300 Finnish people, about half of whom had type 2 diabetes. The researchers scanned each participant’s entire DNA sequence, or genome, for genetic variations. When they found a particular variation more often in people with type 2 diabetes, they concluded that it was associated with the disease. The team validated their findings by comparing their data with results from the other 2 research groups, who were carrying out similar analyses. The 3 research teams then jointly analyzed the genetic variations they found in additional people from Finland, Poland, Sweden, the United Kingdom and the United States. All told, they tested the genomes of 32,554 people, making this one of the largest genome-wide association efforts conducted to date.

The groups identified 4 new genetic risk factors for type 2 diabetes and confirmed 6 other genetic variants previously associated with the disease. Two of the new variants were found in or near genes thought to play a role in the production or regulation of insulin, a hormone that signals cells to take up glucose from the blood. Variations in the third location have been heavily studied for their role in cancer, but their contribution to diabetes came as a complete surprise. The authors of the study were also intrigued by the fourth variant they identified, which is located in a region not known to contain any genes.

“It's been a formidable challenge to identify the complex genetic factors involved in common diseases, such as type 2 diabetes,” explained Dr. Francis Collins, director of NIH’s National Human Genome Research Institute (NHGRI), which provided major funding for the study along with NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and other institutions. “Now, thanks to the tools and technologies generated by the sequencing of the human genome and subsequent mapping of common human genetic variations, we finally are making significant progress.”

More research is still needed to understand exactly how these genetic changes contribute to the development of type 2 diabetes. The researchers are optimistic that this work will help lead to better approaches to detect, treat and prevent this widespread disease.

Related Links