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- Title
99-OR: An Inflection Point (IP) of C-Peptide (C-P) Decline during Progression to Type 1 Diabetes (T1D).
- Authors
ISMAIL, HEBA M.; SKYLER, JAY S.; SOSENKO, JAY; PALMER, JERRY P.; EVANS-MOLINA, CARMELLA; DIMEGLIO, LINDA; REDONDO, MARIA J.; STECK, ANDREA; ATKINSON, MARK A.; HEROLD, KEVAN C.; NATHAN, BRANDON M.
- Abstract
Evidence suggests the presence of an IP for accelerated β-cell loss during progression to T1D. Importantly, identification of an IP could guide subject selection for prevention trials. We used a 2-dimensional grid of area under the curve (AUC) glucose vs. AUC C-P to detect a C-P IP among Diabetes Prevention Trial-Type 1 (DPT-1; n=54) and TrialNet (TN; n=59) autoantibody positive (Ab+) participants. All analyzed were required to have OGTTs at baseline and every 6 months, then 2.0, 1.5, 1.0 and 0.5 yrs before diagnosis. In DPT-1, an IP was evident 1.5 yrs from diagnosis (Figure) (AUC C-P change from baseline to 1.5 yrs: 0.22±0.60 ng/ml, p=0.006; from 1.5 to 0.5 yrs: -0.42±1.23 ng/ml, p=0.026). In TN, a 1.5 yr IP was also evident (from baseline to 1.5 yrs: 0.18±0.95 ng/ml, p=0.184; from 1.5 to 0.5 yrs: -0.53±1.57 ng/ml, p=0.015), despite an older TN cohort (14.9±12.1 vs. 10.5±6.8 yrs, p=0.023) with higher AUC C-P (5.0±1.9 vs. 3.3±1.6 ng/ml, p<0.001). There was no IP in non-progressors. In summary, an IP occurred 1.5 yrs before diagnosis when C-P began to decline as glucose continued to increase in DPT-1 and TN, suggesting that a 1.5 yr IP of C-P decline is consistent among Ab+ populations. These findings emphasize the importance of identifying at risk individuals as potential participants in prevention trials prior to the IP, when the loss of insulin secretion becomes more severe. Disclosure: H.M. Ismail: None. J.S. Skyler: Advisory Panel; Self; Abvance Therapeutics, ADOCIA, Avotres, Boehringer Ingelheim Pharmaceuticals, Inc., Dance Biopharm Holdings, Inc., Immunomolecular Therapeutics, Intrexon, Oramed Pharmaceuticals, Orgenesis Inc., Sanofi, Tolerion, Inc., Viacyte, Inc. Board Member; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Tolerion, Inc. Stock/Shareholder; Self; Applied Therapeutics, Dexcom, Inc., Intarcia Therapeutics. J. Sosenko: None. J.P. Palmer: None. C. Evans-Molina: Consultant; Self; Bristol-Myers Squibb. L. DiMeglio: None. M.J. Redondo: None. A. Steck: None. M.A. Atkinson: None. K.C. Herold: Consultant; Self; Provention Bio, Inc. B.M. Nathan: None. Funding: National Institutes of Health
- Publication
Diabetes, 2020, Vol 69, pN.PAG
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db20-99-OR