What does this research mean for the field?

Rapid disease progression in children under 8 years old with preclinical Type 1 Diabetes is characterized by a paradoxical increase in insulin clearance and higher insulin sensitivity, alongside declining β-cell function. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to explore how insulin clearance and metabolic factors differ between rapid and slow progressors of preclinical type 1 diabetes in children.

June 7, 2026

1022-OR: Increase in Insulin Clearance Features Rapid Disease Progression in Children with Preclinical Type 1 Diabetes (T1D)

Key Points

This research aims to explore how insulin clearance and metabolic factors differ between rapid and slow progressors of preclinical type 1 diabetes in children.
Included data from 620 participants in four TrialNet trials with 3.2 years follow-up.
Used an oral glucose tolerance test (OGTT) to measure insulin and C-peptide levels every six months.
Applied linear mixed models to compare insulin secretion and clearance trajectories in different age groups.
No baseline differences in insulin secretion and sensitivity between rapid and slow progressors were noted.
Rapid-progressors under 8 years exhibited higher insulin sensitivity (p=0.048) and increased insulin clearance (p=0.016) compared to their slow-progressing counterparts.
Overall decline in insulin secretion was steeper in rapid-progressors across all age groups.

Abstract

Introduction and Objective: Age is a major determinant of time to disease progression in preclinical T1D with faster disease progression in younger kids. Yet, the metabolic phenotypes outlining such a difference remain largely unexplored. We describe insulin secretion, sensitivity and clearance(IC) of rapid(2y) vs slow(≥2y) progressors across different age groups. Methods: We included data from 620 participants(262/358 F/M) to 4 TrialNet trials (TN10,18,20,22) with follow-up 3.2y 1.8, 5. Participants underwent an OGTT at baseline and every 6 months. The oral minimal model was used to compute β-cell responsivity(Phitot) and insulin sensitivity(SI). IC was estimated as AUC C-peptide/insulin, with higher IC representing greater clearance. Trajectories of Phitot, SI, IC during the first 12 months were compared between rapid- vs slow-progressors using linear mixed model for 3 age ranges(8,8-16,16y). Results: Phito, SI and IC did not differ at baseline between rapid- and slow-progressors. Phitot displayed a steeper decline in rapid-progressors in all 3 groups. Rapid-progressors aged8y showed higher IS(p=0.048) and an increase in IC(p=0.016) compared to slow-progressors. IS and IC trajectories did not differ between rapid and slow progressors in those ≥8y. Conclusion: A paradoxical higher insulin clearance characterizes rapid-progressors 8y, paralleling a declining β-cell function, and contributing to lower circulating insulin concentrations. Disclosure A. Galderisi: Advisory Panel; Current; Sanofi. Advisory Panel; Ended; Novo Nordisk. Advisory Panel; Current; vTv Therapeutics. H. Marchiori: None. J. Bonet: None. C. Dalla Man: Other - Webinar provider; Ended; Sanofi. Other - Joint research project; Current; Sanofi-Aventis Deutschland GmbH. C.M. Dayan: Consultant; Current; Sanofi, SAB Biotherapeutics, Inc., Immunocore, Ltd. Consultant; Ended; Vertex Pharmaceuticals Incorporated. Consultant; Current; Quell. Advisory Panel; Current; Amarna, ArgenX, Amgen Inc. A.L. Carr: None. T. Moran: Other - Data Safety Monitoring Board Member; Ended; Novo Nordisk. Advisory Panel; Ended; Abbott Diabetes. Research Support; Current; Abbott Diabetes. K. Herold: Consultant; Current; Sanofi. Consultant; Ended; Dompé. D. Cuthbertson: None. A. Petrelli: None. H. Ismail: None. Funding A.G. : Breakthrough T1D (3-SRA-2022-1186-S-B, 3-SRA-2023-1422-S-B); A.L.J.C. : Charles A. Allard Chair in Dia- betes Research, the Blanch family, the Alberta Diabetes Institute, and the Chan family. K.H. received support from NIH (DK057846, AI66387, and DK106993) (Type 1 Diabetes TrialNet). A.M. received support for this project from NIH (DK106993) (Type 1 Diabetes TrialNet); has received grant funding from the NIH, JDRF, and the Cystic Fibrosis Foundation (to institution); has served on data and safety monitoring boards funded by the Leona M. and Harry B. Helmsley Charitable Trust. C.D. : BreakthroughT1D (3-SRA-2023-1422-S-B,.The Type 1 Diabetes TrialNet Study Group is a clini- cal trials network currently funded by the NIH through the NIDDK; the National Insti- tute of Allergy and Infectious Diseases (NIAID); and the Eunice Kennedy Shriver National Institute of Child Health and Human Development via cooperative agreements (U01 DK060782, U01 DK060916, U01 DK060987, U01 DK061010, U01 DK061016, U01 DK061029, U01 DK061030, U01 DK061034, U01 DK061035, U01 DK061036, U01 DK061037, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085465, UC4 DK085466, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK097835, U01 DK103153, U01 DK103180, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106993, U01 DK106994, U01 DK107013, U01 DK107014) and contract (HHSN267200800019C); the National Center for Research Resources through Clinical Translational Science Awards (UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986, and UL1 TR001872); and General Clinical Research Center Award (M01 RR00400).

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1022-OR: Increase in Insulin Clearance Features Rapid Disease Progression in Children with Preclinical Type 1 Diabetes (T1D)

Key Points

Abstract

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