Serum Proteomics Pre diabetic
Type-1 diabetes (T1D) is an autoimmune disease that is characterized by the destruction of the insulin producing β cells in the Islets of Langerhans of the pancreas. Currently the measurement of autoantibodies (Aabs) like islet-cell autoantibodies, protein tyrosine phosphatase, glutamic acid decarboxylase, insulin and zinc transporter Slc30A8 protein indicates the manifestation of β cells autoimmunity and increased disease risk. However, the destruction of β cells usually starts early in life and symptoms appears when 90% of the cells are destroyed. The time period of appearance of first Aabs to the onset of the clinical disease can vary from 1 month to over 10 years, moreover, not all Aab positive subjects develop T1D. Thus additional indicators of early disease process and progression are needed. To identify disease associated changes, a careful selection of study group is essential such as The Finnish Type-1 Diabetes Prediction and Prevention project DIPP has initiated in 1994. The DIPP cohort has collected blood serum samples at 3 to 6 months intervals from children with a genetically conferred T1D risk and tested for T1D associated autoantibodies. These longitudinal series of samples cover all the stages of disease progression from birth to clinical T1D and matching samples from carefully matched healthy children.
We utilized such unique samples from the DIPP cohort to identify early serum protein biomarkers associated with T1D using quantitative mass spectrometry based approach. The study involved LC-MS/MS analysis with both iTRAQ and label-free quantification strategy on the immunodepleted serum.
Previous serum proteomics biomarker studies of T1D have typically compared disease end points with control groups, i.e. the differences between patients with T1D and healthy controls. In contrast to the published reports, to our knowledge we have shown for the first time serum proteomics profile of pre-diabetic children, mapping the changes from early infancy, seroconversion and diagnosis. The main finding included lower and higher levels of APOC4 and AFAM in cases compared to controls respectively and, the combination of this two proteins classified T1D developing children from controls with 91% success rate with an area under the curve value of 0.85. Notably the levels of APOC4 were found to be lower even before seroconversion.
