JOHNS HOPKINS (US)—People on the threshold of developing diabetes appear to have dramatically higher blood levels of an easy-to-detect enzyme, making it possible to perform a simple test to detect the disease before symptoms or complications occur and in time to reverse its course.

Pilot studies, published online in the journal Diabetes, show the enzyme O-GlcNAcase is up to two to three times higher in the red blood cells of people with diabetes and prediabetes than in those with no disease.

“That’s a big difference, especially in an enzyme that’s as tightly regulated as this one is,” says Gerald Hart, the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine.

Building on previous research, which showed how an abundant but difficult-to-detect sugar switch known as O-GlcNAc (pronounced oh-GLICK-nack) responded to nutrients and stress, researchers knew this small molecule was elevated in the red cells of patients with diabetes.

“The question was whether the elevation happened in the earliest stages of diabetes and, therefore, might have value as a diagnostic tool,” Hart says.

To find out, Kyoungsook Park, a graduate student of biological chemistry working in Hart’s lab, focused on levels of O-GlcNAcase, an enzyme that removes O-GlcNAc in red cells. O-GlcNAc modifies many of the cell’s proteins to control their functions in response to nutrients and stress.

Nutrients, such as glucose and lipids, increase the extent of O-GlcNAc modification of proteins affecting their activities. When the extent of O-GlcNAc attached to proteins becomes too high, as occurs in diabetes, it is harmful to the cell.

Park tested human red blood samples and characterized 36 as normal, 13 as prediabetic and 53 as type 2 diabetic, according to traditional tests. He then measured and compared the amount of the enzyme protein within the red cells.

Prediabetes is an intermediate state of altered glucose metabolism with a heightened risk of developing type 2 diabetes and other associated complications.

“When I checked the enzyme levels and saw how dramatically different they were between the prediabetic cells and the controls, I thought I did something wrong,” Park says. “I repeated the test five times until I could believe it myself.”

Hart says it will take a much larger clinical trial to definitively determine if prediabetes can be accurately diagnosed by measuring O-GlcNAcase, filling the void that currently exists for an easy, routine test.

Funding for the research was provided by the National Institute of Diabetes, Digestive and Kidney Diseases.

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