PNNL

Abstract

Type 1 diabetes (T1D) is characterized by the destruction of pancreatic ß-cells and results in the loss of endogenous insulin production. Due to the reliance on exogenous insulin, individuals with T1D often have higher than normal blood glucose levels, which are linked to the development of chronic diabetic complications. To assess whether changes in the urinary proteome of juveniles with T1D, having normal or elevated HbA1C levels, can be indicative of early, pre-symptomatic stages of diabetic complications, we profiled the urinary proteome of 40 T1D patients in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1,036 proteins per experiment were identified on average, and 50 proteins showed significant differences using the Wilcoxon signed-rank test (FDR q-value = 0.05) between these cohorts. Thirteen lysosomal enzymes were increased in abundance in the T1D cohort. Fifteen proteins with functional roles in vascular permeability and cellular adhesion were quantitatively changed, including CD166 and angiotensin-converting enzyme 2. The direction of the abundance change was confirmed for four proteins, plasma a-fucosidase, collectin-12, CD166, and apolipoprotein M, by Western blots. Considering the roles of aberrant protein glycosylation and vascular inflammation in T1D progression, we hypothesize that surveying the urinary proteome is useful to predict the risk of diabetic complications.