High Enzyme Level Could Predict Prediabetes


An unexpected finding by a graduate student at Johns Hopkins School of Medicine may lead to a simple test that could predict prediabetes. Kyoungsook Park discovered that high levels of a specific enzyme could signal who will develop prediabetes.

Approximately 57 million people in the United States have prediabetes, according to the American Diabetes Association. This condition is characterized by blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes. Based on the results of the Diabetes Prevention Program, about 11 percent of people who have prediabetes develop type 2 diabetes each year.

While the serious health implications of diabetes are well known (e.g., increased risk of heart disease, neuropathy, blindness, skin infections, kidney problems, and more), prediabetes is not without hazards as well. Studies show that people who have prediabetes experience some long-term damage to the body, especially to their heart and circulatory system. Currently there are two tests clinicians can use to identify prediabetes, the fasting plasma glucose test and the oral glucose tolerance test. However, so far there has not been a test to predict who may develop prediabetes.

Prior to the current study, researchers at Johns Hopkins already knew that a molecule called O-GlcNAc was elevated in the red blood cells of people who have diabetes. Scientists were then curious as to whether the high levels occurred in the earliest stages of diabetes and thus might serve as a diagnostic tool.


This challenge was undertaken by Park, who studied levels of an enzyme called O-GlcNAcase, which removes O-GlcNAc from red blood cells. O-GlcNAc attaches to a cell’s proteins and changes how they respond to nutrients and stress. Glucose and lipids increase the extent to which O-GlcNAc modify the proteins’ activities. When the extent of O-GlcNAc attached to the proteins becomes too great, which occurs in diabetes, the cells are damaged.

Park used purified human red blood cells classified as normal, prediabetes, and type 2 diabetes based on traditional tests, and depleted them of their hemoglobin, the oxygen-carrying, iron-containing protein found in these cells. She then measured and compared the levels of O-GlcNAcase in relation to O-GlcNAc.

When she checked the enzyme levels, Park noticed “how dramatically different they were between the prediabetic cells and the controls.” The finding was so surprising she repeated the test five times to verify her results.

Gerald Hart, PhD, the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine, speculated that the high enzyme level is the result of O-GlcNAcase attempting to get rid of the elevated amount of sugar that attaches to proteins in prediabetes and diabetes. He cautioned, however, that “only a much larger clinical trial will determine if, by measuring O-GlcNAcase, we can accurately diagnose prediabetes.”

American Diabetes Association
Johns Hopkins School of Medicine press release, July 8, 2010