Type 1 diabetes (T1D) results from autoimmune destruction of insulin-producing pancreatic ?- cells - a long asymptomatic period spanning many months to years. Currently, autoantibodies to islet cell antigens serve to identify those at increased risk for T1D, yet additional biomarkers are desperately in need to indicate this ?-cell destruction process and to help understanding the disease pathogenesis. Using liquid chromatography-mass spectrometry (LC-MS) based proteomics, we have identified a panel of novel serum proteins that are involved in the innate immune response, and can distinguish T1D from healthy controls with high sensitivity and specificity. In addition, most of these markers are not merely a result of hyperglycemia induced by type 2 diabetes. The long-term goal of this project is to provide thoroughly validated diagnostic and prognostic markers for T1D, and to gain additional insights into the pathogenesis of this disease. In the present application, we will extend our previous biomarker discovery effort to human pancreatic tissues obtained from T1D organ donors, and serial serum samples collected during the progression of T1D for a comprehensive identification of novel proteins and protein isoforms correlated to the progression of this disease. Findings from this new effort, along with our previous data, will be validated for disease early diagnosis and prognosis using longitudinally collected serum samples from the Diabetes Prevention Type 1 (DPT-1) cohort. Early diagnosis and risk assessment criteria will be established on the basis of the longitudinally changed peptide markers.

Public Health Relevance

The annual incidence rate of type 1 diabetes is increasing at 3% over the past 20 years and currently, it affects approximately 1.4 million people in the U.S. The proposed research will comprehensively identify novel protein and peptide markers and evaluate their utility for early diagnosis and prognosis of type 1 diabetes and gain further insigh into the pathogenesis of this disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56DK099174-01
Application #
8716320
Study Section
Special Emphasis Panel (ZDK1-GRB-R (M4))
Program Officer
Sechi, Salvatore
Project Start
2013-09-05
Project End
2015-08-31
Budget Start
2013-09-05
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$499,965
Indirect Cost
$217,050
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352