Evidence mapPaperPMID 40877213Full record

Trial reportDiabetes2025

Novel Approach for Assessing Outcomes of Type 1 Diabetes Prevention Trials Over a Fixed Time Interval.

Emily K Sims, William E Russell, David Cuthbertson, Jay S Skyler, Laura M Jacobsen, Heba M Ismail, Maria J Redondo, Brandon M Nathan, Alice L J Carr, Peter N Taylor and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Emily K SimsCenter for Diabetes and Metabolic Diseases, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0002-4393-954X
William E RussellDepartments of Pediatrics and Cell and Developmental Biology, Vanderbilt University, Nashville, TN.
David CuthbertsonHealth Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL.
Jay S SkylerUniversity of Miami, Coral Gables, FL.
Laura M JacobsenDepartments of Pediatrics and Pathology, University of Florida College of Medicine, Gainesville, FL.
Heba M IsmailCenter for Diabetes and Metabolic Diseases, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.ORCID 0000-0003-0102-0030
Maria J RedondoTexas Children's Hospital, Baylor College of Medicine, Houston, TX.
Brandon M NathanDepartment of Pediatrics, University of Minnesota, Minneapolis, MN.
Alice L J CarrAlberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
Peter N TaylorCardiff University School of Medicine, Cardiff, U.K.
Colin M DayanCardiff University School of Medicine, Cardiff, U.K.
Alfonso GalderisiDepartment of Pediatrics, Yale University, New Haven, CT.
Kevan C HeroldDepartment of Pediatrics, Yale University, New Haven, CT.
Jay M SosenkoUniversity of Miami, Coral Gables, FL.

Funding

Immune Tolerance NetworkUM1AI109565 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 to 2025
$94.0M
Type 1 Diabetes Trialnet: Operations Coord. CenterU01DK061055 · GEORGE WASHINGTON UNIVERSITY · 2001 to 2005
$74.3M
Data Coordinating Center for Type 1 Diabetes TrialNetU01DK106993 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · 2022 to 2025
$43.4M
WOMEN'S HEALTH IN CYSTIC FIBROSISM01RR000400 · UNIVERSITY OF MINNESOTA TWIN CITIES · 1985 to 2005
$19.6M
Yale Diabetes Research CenterP30DK045735 · YALE UNIVERSITY · 1993 to 2025
$10.2M
Clinical and Translational Science InstituteUL1TR001872 · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2025 to 2025
$8.5M
Type 1 Diabetes TrialNetU01DK061041 · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2001 to 2004
$5.3M
TrialNet: DiabetesType 1 Prevention TrialU01DK060782 · UNIVERSITY OF COLORADO DENVER · 2001 to 2005
$2.2M
Type I Diabetes Trialnet at StsnfordU01DK061042 · STANFORD UNIVERSITY · 2001 to 2005
$2.1M
Type 1 Diabetes TrialNet Clinical Network HubU01DK103282 · NIDDK · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 to 2025
$2.1M
Northwest Clinical Center for Type 1 Diabetes - TrialNetU01DK061034 · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2001 to 2005
$2.1M
Type 1 Diabetes TrialNet: Clinical CentersU01DK061040 · JOSLIN DIABETES CENTER · 2001 to 2005
$1.7M
Alberta Diabetes InstituteCharles AAllardDoris Duke Charitable Foundation 2021258Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U01 DK061016Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U01 DK084565Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) U01 DK097835Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) UC4 DK085466General Clinical Research M01 RR00400JDRF 1-SRA-2020-900-M-XJDRF 2-SRA-2018-609-Q-RJDRF 2-SRA-2020-900-S-BJDRF 3-SRA-2015-27-Q-RJDRF 82-2013-652John Templeton Foundation 62288Juvenile Diabetes Research Foundation 3-SRA-2022-1186-S-BNational Institute of Allergy and Infectious Diseases (NIAID)National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)National Institutes of Health (NIH)NCATS NIH HHS UL1 TR001872NCRR NIH HHS M01 RR000400NCRR NIH HHS UL1 RR024131NCRR NIH HHS UL1 RR024139NCRR NIH HHS UL1 RR024153NCRR NIH HHS UL1 RR024975NCRR NIH HHS UL1 RR024982NCRR NIH HHS UL1 RR025744NCRR NIH HHS UL1 RR025761NCRR NIH HHS UL1 RR025780NCRR NIH HHS UL1 RR029890NCRR NIH HHS UL1 RR031986NCRR NIH HHS UL1 TR001872NIAID NIH HHS UM1 AI109565NIAID NIH HHS UM1AI109565NIDDK NIH HHS K23 DK129799NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK121843NIDDK NIH HHS R01 DK121929NIDDK NIH HHS R01 DK133881NIDDK NIH HHS U01 DK060782NIDDK NIH HHS U01 DK060916NIDDK NIH HHS U01 DK060987NIDDK NIH HHS U01 DK061010NIDDK NIH HHS U01 DK061029NIDDK NIH HHS U01 DK061030NIDDK NIH HHS U01 DK061034NIDDK NIH HHS U01 DK061035NIDDK NIH HHS U01 DK061036NIDDK NIH HHS U01 DK061037NIDDK NIH HHS U01 DK061040NIDDK NIH HHS U01 DK061041NIDDK NIH HHS U01 DK061042NIDDK NIH HHS U01 DK061055NIDDK NIH HHS U01 DK061058NIDDK NIH HHS U01 DK085453NIDDK NIH HHS U01 DK085461NIDDK NIH HHS U01 DK085463NIDDK NIH HHS U01 DK085465NIDDK NIH HHS U01 DK085466NIDDK NIH HHS U01 DK085476NIDDK NIH HHS U01 DK085499NIDDK NIH HHS U01 DK085504NIDDK NIH HHS U01 DK085505NIDDK NIH HHS U01 DK085509NIDDK NIH HHS U01 DK103153NIDDK NIH HHS U01 DK103180NIDDK NIH HHS U01 DK103266NIDDK NIH HHS U01 DK103282NIDDK NIH HHS U01 DK106984NIDDK NIH HHS U01 DK106993NIDDK NIH HHS U01 DK106994NIDDK NIH HHS U01 DK107013NIDDK NIH HHS U01 DK107014NIDDK NIH HHS U01 DK127382NIDDK NIH HHS UC4 DK097835NIH HHSNIH HHS R01 DK121843-01NIH HHS R01DK121929NIH HHS R01DK133881NIH HHS U01DK127382-012NLM NIH HHS HHSN267200800019CSRA 2023-1422-S-Bthe Helmsley Charitable Trust, the Showalter Scholar Program
6 · The paper itself

Abstract

We evaluated whether a binary metabolic end point for change (Δ) from baseline to 1-year postrandomization could be useful in type 1 diabetes (T1D) prevention trials. Using 2-h oral glucose tolerance testing data from the stage 1 participants in the recent abatacept prevention trial and similar participants in the observational TrialNet Pathway to Prevention (PTP) study, we assessed Δmetabolic measures, plotted glucose and C-peptide response curves, and categorized vectors for Δ from baseline to 1 year as metabolic treatment failure versus success. Analyses were validated using the teplizumab prevention study. PTP participants with Δglucose >0 and ΔC-peptide <0 from baseline to 1 year were at substantially higher risk for stage 3 T1D than those with Δglucose <0 and ΔC-peptide >0 (P < 0.0001). Based on this, we compared placebo versus treatment groups in both trials for failure (Δglucose >0 with ΔC-peptide <0) versus success (Δglucose <0 with ΔC-peptide >0) after 1 year. Using this end point, a favorable metabolic impact of abatacept was found after 12 months of treatment. An analytic approach using a binary metabolic end point of failure versus success at a fixed time interval appears to detect treatment effects at least as well as standard primary end points with shorter follow-up. ARTICLE HIGHLIGHTS: Challenges in time to event type 1 diabetes (T1D) prevention trial design can yield negative results even for treatments that may actually improve disease pathology. We evaluated whether a binary metabolic end point for 12-month change from baseline to 1 year postrandomization could be useful in T1D prevention trials. This approach detected treatment effects at least as well as standard primary end points with shorter follow-up. Fixed interval metabolic end points should be used in combination with traditional T1D end points to better understand treatment effects of preventive agents.

Indexed as

AbataceptDiabetes Mellitus, Type 1AdolescentAdultAntibodies, Monoclonal, HumanizedBlood GlucoseChildC-PeptideFemaleGlucose Tolerance TestHumansMaleTreatment OutcomeAbataceptAntibodies, Monoclonal, HumanizedBlood GlucoseC-Peptideteplizumab

Identifiers

PMID40877213
PMCPMC12585163

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.