Abstract
AbstractBetter understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.
Funder
Academy of Finland
JDRF
Novo Nordisk
Business Finland Novo Nordisk Foundation Finnish Diabetes Foundation Finnish Cancer Foundation
Finnish Cultural Foundation | Varsinais-Suomen Rahasto
Turku Doctoral Programme of Molecular Medicine Turku University Foundation Kyllikki and Uolevi Lehikoinen Foundation Finnish Diabetes Research Foundation
European Foundation for the Study of Diabetes
Lastentautien Tutkimussääiö
Turun Yliopistollinen Keskussairaala
Finnish Diabetes Foundation
Publisher
Springer Science and Business Media LLC