Category:

Novel Therapeutic,Diagnostic,Research Tool

Description:

Despite considerable advances in the treatment of type I diabetes, cardiovascular complications remain the primary cause of death and accounts for the greatest component of health care expenditures in people with diabetes. However, the risk factors for developing cardiovascular disease in diabetics remain undefined, until now. Researchers at the Medical University of South Carolina recently discovered a blood plasma biomarker in type I diabetes patients, that, when elevated, indicates an elevated risk of diabetic vascular disease.

A recent study was conducted based on cross-sectional data generated from the Diabetes Control and Complications Trial (DCCT) / Epidemiology of Diabetes Interventions and Complications (EDIC)-cohort of type 1 diabetic patients. An independent association was found between the biomarker levels in blood plasma of diabetics and microalbuminuria (an early indicator of renal dysfunction), hypertension, and elevated lipids. Furthermore, multivariable regression analysis provided the first evidence of an independent and positive association between the biomarker levels and surrogate markers of atherosclerosis in diabetics.

In addition, a novel single nucleotide polymorphism (SNP) in the coding region of the biomarker gene was identified. Survival analyses demonstrated that the onset of microalbuminuria occurs at a more rapid rate in diabetic subjects with the SNP than without the SNP.

Finally, the researchers discovered a novel mechanism by which the biomarker is thought to contribute to vascular inflammation/ endothelial dysfunction: The biomarker stimulates MAPK phosphorylation, independent of bradykinin signaling, and induces apoptosis of vascular smooth muscle cells. As a result, atherosclerotic plaques become instable, enhancing the risk of plaque rupture with subsequent myocardial infarction, organ failure, or stroke.

Potential Applications:

• First test of its kind.
• Test for diabetic patients under consideration for intensive v.s. standard glycemic control, blood pressure regulation, and treatment with ACE inhibitors.
• Those positive for the polymorphism could be considered for intensive treatment.

Inventor(s):

Dr. A.A. Jaffa, Dr. L.M. Luttrell

Relevent Publications:

Jaffa AA, et al; Diabetes 52(5):1215-21, 2003

Patent Status:

Application to be filed (MUSC-FRD #P0918)

Availability:

Available for:
exclusive
non-exclusive
licensing.

Technology Status:

in vitro data; in vivo data (843 human subjects genotyped)

Licensing Contact:

Ryan N. Fiorini, Ph.D., MBA, MHA
MUSC Foundation for Research Development
PO Box 250828
Charleston, SC 29425
843.876.1906
fiorinir@musc.edu