Evidence map›Paper›PMID 39560746›Full record

Trial reportDiabetologia2025

Trajectory of beta cell function and insulin clearance in stage 2 type 1 diabetes: natural history and response to teplizumab.

Alfonso Galderisi, Emily K Sims, Carmella Evans-Molina, Alessandra Petrelli, David Cuthbertson, Brandon M Nathan, Heba M Ismail, Kevan C Herold, Antoinette Moran

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetologia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Trial
  2. Article
  3. Type 1 Diabetes Mellitus Pathogenesis: Mechanisms, Early Diagnostic Strategies, and Emerging Therapeutic Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Review
  8. Review
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  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
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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

9 authors.

Alfonso Galderisi *Department of Pediatrics, Yale University, New Haven, CT, USA. alfonso.galderisi@yale.edu.
Emily K Sims *Department of Pediatrics, Center for Diabetes and Metabolic Diseases, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Carmella Evans-MolinaDepartment of Pediatrics, Center for Diabetes and Metabolic Diseases, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Alessandra PetrelliDepartment of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
David CuthbertsonHealth Informatics Institute, University of South Florida, Tampa, FL, USA.
Brandon M NathanDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
Heba M IsmailDepartment of Pediatrics, Center for Diabetes and Metabolic Diseases, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
Kevan C HeroldDepartment of Immunobiology, Yale University, New Haven, CT, USA.
Antoinette MoranDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, USA.

Funding

Revision to the Coordinating Center for Type 1 Diabetes TrialNetU01DK106993 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI JEFFREY P KRISCHER, SAMUEL S WU · 2019 to 2026
$181.3M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR001857 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2016 to 2025
$129.3M
Clinical and Translational Science InstituteUL1TR001872 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI COLLARD, HAROLD R, JACOBY, VANESSA · 2016 to 2025
$112.1M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
NIDDK Type 1 Diabetes TrialNet Data Coordinating CenterUC4DK097835 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2012 to 2012
$45.0M
RADx-UP: Improving the Response of Local Urban and Rural Communities to Disparities in Covid-19 TestingUL1TR002366 · NCATS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mario Castro, JAMES STEVEN LEEDER · 2017 to 2026
$44.3M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI WILLIAM V TAMBORLANE · 1993 to 2026
$44.0M
The Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR000445 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BERNARD, GORDON RAPHAEL · 2012 to 2016
$41.4M
NIDDK Type 1 Diabetes TrialNet Data Coordinating CenterUC4DK106993 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI KRISCHER, JEFFREY P · 2015 to 2015
$36.6M
University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR000114 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R · 2012 to 2015
$35.0M
Yale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8M
Division of Diabetes, Endocrinology, and Metabolic Diseases AI66387Division of Diabetes, Endocrinology, and Metabolic Diseases DK057846Division of Diabetes, Endocrinology, and Metabolic Diseases DK106993Division of Diabetes, Endocrinology, and Metabolic Diseases K23DK129799Division of Diabetes, Endocrinology, and Metabolic Diseases R01DK121929Division of Diabetes, Endocrinology, and Metabolic Diseases R01DK133881Division of Diabetes, Endocrinology, and Metabolic Diseases U01 DK06Division of Diabetes, Endocrinology, and Metabolic Diseases UL1TR000064Division of Diabetes, Endocrinology, and Metabolic Diseases UL1TR000142Division of Diabetes, Endocrinology, and Metabolic Diseases UL1TR000445Division of Diabetes, Endocrinology, and Metabolic Diseases UL1TR002366Division of Diabetes, Endocrinology, and Metabolic Diseases UM1 AI09565JDRF 3-SRA-2022-1186-S-BJDRF 3-SRA-2023-1422-S-BJohn Templeton Foundation 62288NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR000114NCATS NIH HHS UL1 TR000142NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001082NCATS NIH HHS UL1 TR001857NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR001872NCATS NIH HHS UL1 TR002366NCATS NIH HHS UL1 TR002529NCATS NIH HHS UL1 TR002537NIAID NIH HHS F31 AI009565NIDDK NIH HHS K23 DK129799NIDDK NIH HHS P30 DK045735NIDDK NIH HHS P30 DK097512NIDDK NIH HHS R01 DK057846NIDDK NIH HHS R01 DK121929NIDDK NIH HHS R01 DK133881NIDDK NIH HHS U01 DK061010NIDDK NIH HHS U01 DK061034NIDDK NIH HHS U01 DK061042NIDDK NIH HHS U01 DK061058NIDDK NIH HHS U01 DK085453NIDDK NIH HHS U01 DK085461NIDDK NIH HHS U01 DK085465NIDDK NIH HHS U01 DK085466NIDDK NIH HHS U01 DK085476NIDDK NIH HHS U01 DK085499NIDDK NIH HHS U01 DK085504NIDDK NIH HHS U01 DK085509NIDDK 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 DK097835NIDDK NIH HHS UC4 DK106993
6 · The paper itself

Abstract

aims/hypothesisWe aimed to analyse TrialNet Anti-CD3 Prevention (TN10) data using oral minimal model (OMM)-derived indices to characterise the natural history of stage 2 type 1 diabetes in placebo-treated individuals, to describe early metabolic responses to teplizumab and to explore the predictive capacity of OMM measures for disease-free survival rate.

methodsOMM-estimated insulin secretion, sensitivity and clearance and the disposition index were evaluated at baseline and at 3, 6 and 12 months post randomisation in placebo- and teplizumab-treated groups, and, within each group, in slow- and rapid-progressors (time to stage 3 disease >2 or

resultsBaseline metabolic characteristics were similar between 28 placebo- and 39 teplizumab-treated participants. Over 12 months, insulin secretion declined in placebo-treated and rose in teplizumab-treated participants. Within groups, placebo slow-progressors (n=14) maintained insulin secretion and sensitivity, while both declined in placebo rapid-progressors (n=14). Teplizumab slow-progressors (n=28) maintained elevated insulin secretion, while teplizumab rapid-progressors (n=11) experienced mild metabolic decline. Compared with rapid-progressor groups, insulin clearance significantly decreased between baseline and 3, 6 and 12 months in the slow-progressor groups in both treatment arms. In aggregate, both higher baseline insulin secretion (p=0.027) and reduced 12 month insulin clearance (p=0.045) predicted slower progression. A >25% loss of insulin secretion at 3 months had specificity of 0.95 (95% CI 0.86, 1.00) to identify rapid-progressors and correctly classified the 2 year risk for progression in 92% of participants, with a sensitivity of 0.19 (95% CI 0.08, 0.30). OMM-estimated insulin secretion outperformed AUC C-peptide to differentiate groups by treatment or to predict progression. Metabolic changes were paralleled by relative frequency of change in PD-1 CONCLUSIONS/

interpretationOMM measures characterise the metabolic heterogeneity in stage 2 diabetes, identifying differences between rapid- and slow-progressors, and heterogeneous impacts of immunotherapy, suggesting the need to account for these differences when designing and interpreting clinical trials.

Indexed as

Antibodies, Monoclonal, HumanizedDiabetes Mellitus, Type 1InsulinInsulin-Secreting CellsAdultCD8-Positive T-LymphocytesFemaleHumansInsulin SecretionMaleMiddle AgedAntibodies, Monoclonal, HumanizedInsulinteplizumabInsulin clearanceInsulin secretionInsulin sensitivityOral minimal modelStage 2 type 1 diabetesTeplizumab

Identifiers

PMID39560746
PMCPMC11832608

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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 OpenQuestion graph.