1117-P: Characterizing Glucose/C-Peptide Response Curve (GCRC) Phenotypes to Enhance Selection Specificity for Type 1 Diabetes (T1D) Prevention Trials

Abstract

The specificity of subject selection is crucial for T1D prevention trials. GCRCs are glucose and C-peptide values at 30 to 120-minute OGTT timepoints plotted on a glucose (y-axis) and C-peptide (x-axis) grid. Since GCRCs change characteristically on the grid during T1D progression, the identification of GCRC phenotypes among screening OGTTs would refine selection for T1D prevention trials. We aimed to determine if AUC glucose (AUCglu) and AUC C-peptide (AUCpep) identify GCRCs at screening that match GCRCs specific to times pre-diagnosis. We analyzed OGTT data from DPT-1 and TrialNet (TN) participants, both antibody positive (Ab+) populations. AUCglu and AUCpep of 52 TN participants at screening were matched to AUCglu and AUCpep 1.5 yrs pre-diagnosis in 162 DPT-1 participants (AUCglu means: 152.7 vs. 152.3 mg/dl; AUCpep means: 3.7 vs. 3.7 ng/dl, respectively). By matching the AUC values at TN screening to the DPT-1 AUC values 1.5 yrs pre-diagnosis, we were able to match GCRCs at TN screening to the DPT-1 GCRCs 1.5 yrs pre-diagnosis. Figure 1 shows the matched GCRCs obtained by matching AUC values. In conclusion, AUCglu and AUCpep can identify GCRCs at screening that match GCRCs specific to a time before diagnosis, even across Ab+ populations. This novel finding should considerably enhance the metabolic specificity of subject selection for T1D prevention trials. Disclosure H. M. Ismail: None. B. M. Nathan: None. M. A. Atkinson: None. L. Dimeglio: Advisory Panel; Self; MannKind Corporation. J. Sosenko: None. D. D. Cuthbertson: None. M. J. Redondo: Advisory Panel; Self; Provention Bio, Inc. C. Evans-molina: Advisory Panel; Self; Provention Bio, Inc., Consultant; Self; Dompe, Other Relationship; Self; Bristol-Myers Squibb Company, Nimbus Pharmaceuticals, Pfizer Inc. A. Steck: None. H. Rodriguez: Advisory Panel; Self; Provention Bio, Inc., Other Relationship; Self; Merck & Co., Inc., Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Medtronic, Precigen, Inc., Provention Bio, Inc., Takeda Pharmaceutical Co., Tolerion, Inc. S. E. Gitelman: Advisory Panel; Self; Provention Bio, Inc., Tolerion, Inc., Consultant; Self; Avotres Inc., Biolojic, Research Support; Self; Intrexon, Janssen Research & Development, LLC, Provention Bio, Inc., Tolerion, Inc. K. C. Herold: Consultant; Self; Provention Bio, Inc., Viela Bio, Consultant; Spouse/Partner; Provention Bio, Inc. J. S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Oramed Pharmaceuticals, Inc., Orgenesis Inc., Tolerion, Inc., Viacyte, Inc., Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics, Inc., Consultant; Self; AstraZeneca, Avotres Inc., Bayer AG, IM Therapeutics, Novo Nordisk, Precigen, Inc., Provention Bio, Inc., Sanofi, Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc.