Development of Predictive Biomarkers

Investigators aim to further the understanding of the various factors that govern the
progression of beta-cell death in individuals recently diagnosed with Type 1 diabetes (T1D).
Specifically, the investigators wish to examine the utility of plasma-induced signatures and
other measures as predictive biomarkers for the rate of C-peptide decline in individuals with
recent onset T1D. Persistent C-peptide in individuals with T1D reflects some degree of β-cell
function and is clinically associated with a reduction in both severe hypoglycemic events and
microvascular complications such as diabetic nephropathy and retinopathy. There is
significant heterogeneity in the rate of C-peptide decline in individuals with T1D,
reflective of the complex disease process. For example, ~10% of individuals have no
discernable fall in stimulated C-peptide after two years from clinical diagnosis as compared
to other individuals with very rapid C-peptide decline. It is currently impossible to predict
how long, and to what extent, someone will have residual C-peptide production. This
complicates clinical management but also the design and interpretation of T1D β-cell
preservation trials. The "gold standard" outcome measure of any T1D β-cell preservation trial
is the stimulated C-peptide to a mixed meal tolerance test (MMTT). Given the variability in
this measure, intervention studies must include more subjects over a longer period of time.
This slows the rate of scientific discovery and increases cost. This study aims to define the
governing mechanisms of post-onset T1D disease trajectory. Understanding the trajectory of
the disease may lead to the development of biomarkers to predict disease progression and
therapies that could reverse or prevent the development of Type 1 diabetes.