85-OR: Modifiers of C-Peptide Change during the Progression to Type 1 Diabetes (T1D) in the TrialNet Pathway to Prevention Study
Authors: ISMAIL HEBA M. , CLEVES MARIO A. , GITELMAN STEPHEN E. , SKYLER JAY S. , STECK ANDREA , RODRIGUEZ HENRY , ATKINSON MARK A. , NATHAN BRANDON M. , REDONDO MARIA JOSE , HEROLD KEVAN C. , PALMER JERRY P. , EVANS-MOLINA CARMELLA , DIMEGLIO LINDA , SOSENKO JAY M. 
Published: June 2019

It is not known to what extent characteristics of individuals modify C-peptide changes prior to T1D diagnosis. Thus, we assessed whether 4 characteristics [age, BMIZ, autoantibodies (abs), and HLA genotype] modified changes in 2-hr OGTT indices [AUC C-peptide and 30-0 minutes (early) C-peptide in ng/ml] during the progression to T1D. We studied 519 progressors to T1D (mean±SD age at first OGTT: 14.2±11.0 yo; BMIZ: 0.8±1.2; 50.0% male). Slopes were derived for changes in C-peptide indices from 36 to 6 months before diagnosis using mixed effects regression models. Slopes differed significantly by DR3/DR4 both (more inverse) vs. not both (30-0 minutes: p=0.005; AUC: p=0.034) and by ≥12.0 (more inverse) vs. &lt;12.0 yo (30-0 minutes: p=0.002; AUC: p=0.001) with narrowed differences in C-peptide at 6 months. In contrast, the slopes were similar in 1 vs. ≥2 abs and BMIZ ≤1.0 vs. &gt;1.0 comparisons. The Figures show curves for the changes in the C-peptide indices according to age and BMIZ categories from 36 to 6 months (* indicates significant differences at the 36 and 6 months time points). These novel findings indicate that slopes of C-peptide change vary according to DR3/DR4 and age during the progression to T1D, resulting in smaller differences at 6 months. BMIZ and ab slopes have little variation. Attributes of individuals should be considered when studying β-cell function decline during the progression to T1D.

Disclosure
H.M. Ismail: None. M.A. Cleves: None. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research & Development. Other Relationship; Self; Novo Nordisk Inc. J.S. Skyler: Advisory Panel; Self; ADOCIA, Applied Therapeutics, Dance Biopharm Holdings Inc., Orgenesis Ltd., Tolerion, Inc., Viacyte, Inc. Board Member; Self; Dexcom, Inc., Intarcia Therapeutics, Inc., Moerae Matrix, Inc. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Dalcor, Dialogics, Elcelyx Therapeutics, Inc., Esperion, GeNeuro Innovation, Ideal Life, Immunomolecular Therapeutics, Intrexon, Kamada, Nestlé, Sanofi, Valeritas, Inc., Zafgen, Inc. Stock/Shareholder; Self; Dexcom, Inc., Ideal Life, Intarcia Therapeutics, Inc., Intrexon, Moerae Matrix, Inc. A. Steck: None. H. Rodriguez: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Daiichi Pharm Corp, MannKind Corporation, Medtronic MiniMed, Inc. Research Support; Spouse/Partner; Medtronic MiniMed, Inc. Research Support; Self; Takeda Pharmaceutical Company Limited. Other Relationship; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc. M.A. Atkinson: None. B.M. Nathan: None. M.J. Redondo: None. K.C. Herold: Consultant; Self; Provention Bio, Roche Pharma. J.P. Palmer: None. C. Evans-Molina: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research & Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None.

Funding
National Institutes of Health