1678-P: Comparisons of Combined C-Peptide and Glucose Intermediate Endpoints for Identifying Individuals at Very High Risk for Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) prevention trials can be shortened if intermediate endpoints indicative of a very high risk of progression are reached before diagnosis. Since Index60, a composite C-peptide and glucose measure, has been shown to have potential use as such an endpoint, we evaluated additional combinations of C-peptide and glucose as endpoints. Diabetes Prevention Trial-type 1 participants (n=702) with baseline values below threshold (set arbitrarily at 95th percentile for each endpoint) were followed at 0.5-1.0 year intervals with 2-hour OGTTs for the first (incident) OGTT that thresholds were exceeded. Participants were then followed for T1D. All endpoints were reached, on average, over 1 year prior to the diagnosis of T1D. Risks for subsequent T1D after the incident OGTT were substantial, but variable (3-year risk=0.66-0.81). There was also appreciable variation in numbers reaching endpoints (n=55-117) and positive predictive values for T1D (PPV=62-77%). Ages were lowest for Glucose/C-peptide measures at incident OGTTs. Index60 performed best regarding key endpoint criteria: number reaching endpoint, 3-year risk, and PPV. In conclusion, individuals highly likely to ultimately develop T1D can be identified over 1 year before diagnosis by combined C-peptide and glucose endpoints. It appears that such endpoints should be considered for T1D prevention trials. Disclosure L.M. Jacobsen: None. M.A. Clements: Advisory Panel; Self; Glooko, Inc. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Medtronic. M.J. Redondo: None. B.M. Nathan: None. D. Schatz: None. J.M. Sosenko: None. Funding National Institutes of Health; JDRF