T1D screening and monitoring studies suggest opportunities for scaling up to public health population-based programs. Genetic Risk Scores (GRS) for T1D are also demonstrating the ability to identify those at higher risk of progressing to T1D as well as an increased opportunity for implementation into public health settings potential as a result of practical considerations, including falling gene sequencing costs.Previous studies have shown that screening and monitoring children for T1D progression significantly decreases DKA events at diagnosis, which has been shown to have both short- and long-term benefits. Furthermore, identification of those at higher risk of T1D provides an opportunity to intervene and delay T1D onset. A non-stochastic, state transition cohort simulation projected 20US births through adolescence. Data from previously collected natural history studies, including TEDDY, DIPP & DAISY were used to model the patient journey. Children seroconverting to islet autoantibodies (IAB) each year and children with lower T1D risk were simulated as separate cohorts with distinct progressions. Interception strategies were layered over this natural history projection. Success of GRS screening followed by annual IAB and glucose monitoring to intercept T1D progression and reduce DKA events was explored. Therapeutic intervention to delay T1D onset was also simulated.Real-world benchmarks for newborn screening (85%) and patient follow-up (80%) as well as rapid T1D progression (<12 months) for some children limited maximum interception at dysglycemia to 52% of children progressing to T1D by age 15 using a GRS screening strategy. Short-term net incremental costs range reach $1.1B at current test costs or $225K per T1D case interception. Breakeven costs could be achieved with $40 IAB test cost and $5 GRS costs with a therapeutic to delay T1D onset by 3 years or possibly by including assessment potential long-term benefits of early intervention and improved glycemic control.


M.Trusheim: Other Relationship; CO BIO CONSULTING LLC. S.Kostense: Employee; Janssen Research & Development, LLC. L.A.Ferrat: None. R.Mcqueen: Consultant; Merck & Co., Inc., Monument Analytics, Research Support; Eli Lilly and Company. R.D.Neusner: Employee; Janssen Pharmaceuticals, Inc. R.A.Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. M.Rewers: Consultant; Janssen Research & Development, LLC, Medscape, Provention Bio, Inc., Research Support; Dexcom, Inc., JDRF, Roche Diagnostics USA. J.L.Dunne: Employee; Janssen Research & Development, LLC, JDRF.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.