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Protein predicts diabetes risk many years in advance

Wednesday, November 14, 2012

When a patient is diagnosed with type 2 diabetes, the disease has usually already progressed over several years and damage to areas such as blood vessels and eyes has already taken place. To find a test that indicates who is at risk at an early stage would be valuable, as it would enable preventive treatment to be put in place.

Researchers at Lund University have identified such a candidate, a protein called SFRP4 in the blood, which serves as a risk marker for individuals who will likely develop type 2 diabetes. The findings were published in the journal Cell Metabolism.

“We have shown that individuals who have above-average levels of a protein called SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels,” said Anders Rosengren, a researcher at the Lund University Diabetes Centre (LUDC), who has led the work on the risk marker.

This is the first time a link has been established between the protein SFRP4, which plays a role in inflammatory processes in the body, and the risk of type 2 diabetes. Studies at LUDC, in which donated insulin-producing beta cells from diabetic individuals and non-diabetic individuals have been compared, show that cells from diabetics have significantly higher levels of the protein. This is also the first time the link between inflammation in beta cells and diabetes has been proven.

“The theory has been that low-grade chronic inflammation weakens the beta cells so that they are no longer able to secrete sufficient insulin. There are no doubt multiple reasons for the weakness, but the SFRP4 protein is one of them,” said Taman Mahdi, main author of the study and one of the researchers in Anders Rosengren’s group.

The level of the protein SFRP4 in the blood of non-diabetics was measured three times at intervals of three years. Thirty-seven percent of those who had higher than average levels developed diabetes during the period of the study. Among those with a lower than average level, only nine percent developed the condition.

“This makes it a strong risk marker that is present several years before diagnosis. We have also identified the mechanism for how SFRP4 impairs the secretion of insulin. The marker therefore reflects not only an increased risk, but also an ongoing disease process,” said Rosengren.

However, the marker works independently of other known risk factors for type 2 diabetes, for example obesity and age.

“If we can point to an increased risk of diabetes in a middle-aged individual of normal weight using a simple blood test, up to 10 years before the disease develops, this could provide strong motivation to them to improve their lifestyle to reduce the risk,” said Rosengren. “In the long term, our findings could also lead to new methods of treating type 2 diabetes by developing ways of blocking the protein SFRP4 in the insulin-producing beta cells and reducing inflammation, thereby protecting the cells.”

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