Development of Predictive Biomarkers
Condition: Type1diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Observational

Summary: 
      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.
    


Intervention name(s): Mixed Meal Tolerance Test
Intervention type(s): Other
Intervention description(s): After a 10-hour overnight fast (not eating or drinking anything except water), participants will complete a mixed meal tolerance test (MMTT):
This involves participants drinking a "Boost" drink, like a milkshake, which will raise participants' blood sugar.
The amount of "Boost" will be based on participants body weight, up to a maximum of 360 mL or about 1 ½ cups, and should be consumed within 5 minutes.
An IV will be placed in participants arm and blood will be drawn from it. Blood will be drawn from the IV before and then 6 times over the next 2 hours after participants drink the "Boost".
Other intervention name(s): MMTT
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Males and females between the ages of 6 and 17 years who were diagnosed with type 1
        diabetes within the 3 months prior to their first study visit, who are being treated at
        Children's Hospital of Wisconsin.
      
Biospecimen description: 
      We will be collecting stool samples as well as blood samples. Blood samples will be analyzed
      for HLA haplotype (a genetic sequence related to type 1 diabetes susceptibility), RNA,
      plasma-induced signature, simulated c-peptide by 2 hour MMTT, diabetes autoantibodies, CBC
      with differential, HbA1c and serum and plasma for storage. Specimens will be used and stored
      until none is left or until 10 years after the close of the study. Research records and data
      will be stored until 10 years after the close of the study.