Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory

With growing concerns for the increasing worldwide incidence of type 1 diabetes, there is a need for markers that can be used to monitor the progression, treatment and remission of the disease. In the present study, selected reaction monitoring (SRM) mass spectrometry was used to measure the levels of 85 type 1 diabetes-associated proteins from longitudinal serum samples of youth newly diagnosed (ND) with type 1 diabetes. To understand associations with beta cell function, the measurements were compared with changes in fasting C-peptide/glucose levels. Additional comparisons were made between the data from ND individuals and cross-sectional measurements obtained from autoantibody-negative unaffected family members (UFMs).

In the samples from under 18-year-old ND youth (n=86) recruited among the first 100 ND individuals, statistically significant associations with changes in fasting C-peptide glucose were found in eleven protein, and the levels of 13 proteins differed between ND and UFMs (n=194). Among these were apolipoproteins, insulin-like growth factor (IGF)-family members, coagulants and proteins involved in oxidative stress and beta cell function and integrity.

These 21 significant proteins were further validated in ND youth (n=146) subsequently enrolled in the next 150 study and UFMs (n=272). Here, we were able to replicate the majority of the differences between ND and UFMs and confirm association with C-peptide/glucose for three out of the eleven targets. Our study highlights a panel of protein markers reflecting changes accompanying type 1 diabetes progression and their clinical potential to monitor beta cell function.