C05104: Early Detection of Diabetes ("Pre-Diabetes") Based Upon O-GlcNAc

UNMET NEED
Type II diabetes is a metabolic disorder characterized by chronic hyperglycemia and disturbances of carbohydrate, fat, and protein metabolism. Much evidence has accumulated to suggest that screening early in the natural history of diabetes, followed by lifestyle changes, can reverse or delay progression of hyperglycemia and the development of complications. The state of the art for diagnosing diabetes are the oral glucose tolerance test (OGTT) and the hemoglobin A1c test (HbA1c). While the OGTT is reliable, it is expensive and incapable of detecting diabetes at its earliest stages. Furthermore, the HbA1c test relies on detection of long periods of hyperglycemia, and is therefore fairly insensitive at early stages.
 
PROBLEM SOLVED
Dr. Gerald Hart and colleagues have identified markers in human blood that might readily identify individuals at the early stages of type II diabetes. These markers are based on the discovery that dynamic O-GlcNAc modification of proteins causes insulin-resistance and is responsible for glucose toxicity. Furthermore, analysis of blood samples revealed that O-GlcNAcase expression and O-GlcNAcase-modified proteins are strikingly up-regulated in erythrocytes of patients with diabetes, but not in normal individuals. The up-regulation of this enzyme can be used as a predictive marker of the "pre-diabetic" state. The inventors suggest that this marker can serve as the foundation for a test that is capable of readily screening large populations at risk for type II diabetes.
 
STAGE OF DEVELOPMENT
The inventors compared site specific O-GlcNAc occupancy levels between normal and diabetic erythrocyte proteins isolated from human blood. This data suggests that both site-specific O-GlcNAc levels and O-GlcNAc site occupancy reflect the glycemic status of an individual.
 
PUBLICATIONS
Diabetes 2009
 

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