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1801-P — 2015 [Board 1801]
Heterogeneity in Type 1 Diabetics Is Defined by Contrasting C-Peptide Declines, Autoreactive T Cell Burdens, and Metabolomic Differences
The Full Poster will be available Saturday, June 6, 2015 at 10:00:00 AM Eastern.
Immunology
Presented on Saturday, June 6, 2015 11:30 AM
Author(s): WILLEM M. KÜHTREIBER, DOUGLAS BURGER, PETER E. REINHOLD III, SOPHIE L.L. WASHER, MENGHAN ZHAO, ELISE HSU, DENISE L. FAUSTMAN, Boston, MA
Immunointervention trials have proven difficult in type 1 diabetes (T1D). The answer could lie in heterogeneity in T1D etiology. Four recent human studies show loss of insulin secretion, measured through C-peptide, is highly correlated with the age of onset of T1D. Subjects with early onset of disease (< 20 years of age) lose remaining insulin secretion at a faster rate compared to patients who become diabetic during adulthood (> 20 years of age). Here we expand these studies of possible subject heterogeneity by examining autoreactive T cells and metabolite patterns in subjects with either rapid or slow decline in insulin secretory capacity.
We first confirmed significantly different rates of C-peptide loss in early and late onset diabetics (p < 0.0001). C-peptide in early onset diabetics (n=290) became undetectable within a few years of onset. In contrast, low levels of C-peptide were detected in late onset diabetics (n=200), even decades after onset.
Flow cytometry studies then demonstrated a surprising difference in abundance of autoreactive T cells (p=0.0002). While such cells were undetectable in most early onset patients even when C-peptide was still present (n=43), many of the late onset patients (n=200) maintained detectable autoreactive T cells even with long-standing disease and with no detectable C-peptide.
We analyzed blood serum of 25 early and 25 late onset diabetics on a metabolomics GC/HPLC/MS platform for distinct metabolic fingerprints of contrasting disease etiology based on age of onset and rate of C-peptide decline. We uncovered significant differences (p < 0.05, q < 0.05) in 32 of 690 detected metabolites between the two T1D groups.
Taken together, our data suggests early and late onset T1D may have different disease etiologies related to the rate of C-peptide decline and also related to the abundance of autoreactive T cells and unique metabolic profiles
Disclosure: W.M. Kühtreiber: None. D. Burger: None. P.E. Reinhold III: None. S.L. Washer: None. M. Zhao: None. E. Hsu: None. D.L. Faustman: None.
© 2015 Digital Acumen, Inc. — Content © 2015 The American Diabetes Association, All rights reserved.
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