Team Discovers Prediabetic Diagnostic Enzyme

Having discovered a dramatic increase of an easy-to-detect enzyme in the red blood cells of people with diabetes and pre-diabetes, Johns Hopkins scientists say the discovery could lead to a simple, routine test for detecting the subtle onset of the disease, before symptoms or complications occur and in time to reverse its course.

Pilot studies show the enzyme O-GlcNAcase is up to two to three times higher in people with diabetes and pre-diabetes than in those with no disease.

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

Building on their previous research, which showed how an abundant but difficult-to-detect sugar switch known as O-GlcNAc responded to nutrients and stress, the Hopkins team 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 stated.

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.

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

Hart speculates that in diabetes and prediabetes, it’s not a good thing for the increased amount of sugar to be attached to proteins, so the cell is responding by elevating the enzyme that gets rid of it.

Hart explained that his team’s pilot studies encourage further investigation of a method that potentially could fill the void that currently exists for an easy, accurate routine test for prediabetes.

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