Why do some people get type 2 diabetes, while others who live the same lifestyle don’t?

For decades, scientists have tried to solve this mystery — and have found more than 80 tiny DNA differences that seem to either raise the diabetes risk in some people or protect others from the disease’s damagingly high blood sugar levels.

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But no one type 2 diabetes signature has emerged from this search.

Now, a team of scientists reports a commonality among some diabetes-linked genetic defects, a discovery that might explain how multiple genetic flaws can lead to the same disease. Specifically, the flaws seem to change the way certain cells in the pancreas “read” genes.

It’s the first demonstration that many type 2 diabetes-linked DNA changes have to do with the same DNA-reading molecule. Called regulatory factor X, or RFX, it’s a master regulator for a number of genes.

The discovery could lead to more personalized treatments for diabetes.

The work from the University of Michigan, the National Institutes of Health, the Jackson Laboratory for Genomic Medicine, the University of North Carolina and the University of Southern California is published in the Proceedings of the National Academy of Sciences.

Many diabetes-linked DNA changes affect the ability of RFX to bind to specific locations in the genomes of pancreas cell clusters called islets, the team reports. This in turn changes the cells’ ability to carry out important functions.

Islets contain the cells that make hormones, including insulin and glucagon, which keep blood sugar balanced in healthy people. In people with diabetes, that regulation goes awry — leading to a range of health problems that can develop over many years.

“We have found that many of the subtle DNA spelling differences that increase risk of type 2 diabetes appear to disrupt a common regulatory grammar in islet cells,” says Stephen C.J. Parker, Ph.D., an assistant professor of computational medicine and bioinformatics, and of human genetics, at the U-M Medical School. “RFX is probably unable to read the misspelled words, and this disruption of regulatory grammar plays a significant role in the genetic risk of type 2 diabetes.”