Evidence map›Paper›PMID 39706874›Full record

Trial reportDiabetologia2025

Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial.

Kristen J Nadeau, Silva A Arslanian, Fida Bacha, Sonia Caprio, Lily C Chao, Ryan Farrell, Kara S Hughan, Maria Rayas, Melinda Tung, Kaitlyn Cross and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
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. It reports registered trial NCT00081328. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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.

NCT00081328 phase3completed

Studies to Treat Or Prevent Pediatric Type 2 Diabetes (STOPP-T2D) Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Clinical Trial

Ran2004Enrolled699Registered outcomes11Posted comparisons0ConditionsDiabetes Mellitus, Type IIArmsLifestyle Program, Metformin, Rosiglitazone
Open the trial in the graph
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
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

12 authors.

Kristen J NadeauUniversity of Colorado Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-0477-3356
Silva A ArslanianUPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-1528-9324
Fida BachaChildren's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Sonia CaprioPediatric Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
Lily C ChaoChildren's Hospital Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6294-0589
Ryan FarrellUniversity Hospitals Cleveland Medical Center, Rainbow Babies and Children's Hospital, Cleveland, OH, USA.ORCID http://orcid.org/0009-0005-2497-5253
Kara S HughanUPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-3595-0666
Maria RayasUniversity of Texas Health Science Center San Antonio, San Antonio, TX, USA.ORCID http://orcid.org/0000-0001-8658-7831
Melinda TungThe Biostatistics Center, George Washington University, Rockville, MD, USA.
Kaitlyn CrossThe Biostatistics Center, George Washington University, Rockville, MD, USA.
Laure El GhormliThe Biostatistics Center, George Washington University, Rockville, MD, USA. elghorml@bsc.gwu.edu.ORCID http://orcid.org/0000-0003-4223-8407
TODAY Study Group

Funding

Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) StudyU01DK061230 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI BRAFFETT, BARBARA HALINA, ZEITLER, PHILIP S. · 2001 to 2019
$231.8M
HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
ZOPOLRESTAT IN NORMOTENSIVE, TYPE 1 DIA WITH INCIPIENT NEPHROPATHYM01RR000043 · NCRR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PULIAFITO, CARMEN A · 1985 to 2010
$76.4M
UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
INSTITUTIONAL CLINICAL AND TRANSLATIONAL SCIENCE AWARDUL1RR024134 · NCRR · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2006 to 2011
$70.4M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR025780 · NCRR · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2008 to 2011
$61.3M
YALE UNIVERSITY CLINICAL AND TRANSLATIONAL SCIENCE AWARD PROGRAMUL1RR024139 · NCRR · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2006 to 2011
$56.8M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024989 · NCRR · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B · 2007 to 2011
$53.7M
Washington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4M
ZD6416 Analgesic--Painful Distal Symmetrical PolyneuropaM01RR001066 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI GRINSPOON, STEVEN K. · 1985 to 2008
$37.4M
PILOT STUDY--SUBSTRATE METABOLISM IN EXTREMELY LOW BIRTH WEIGHT INFANTSP30DK048520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI BRYAN C BERGMAN · 1995 to 2026
$32.6M
YOGA FOR THE MANAGEMENT OF HIV-METABOLIC SYNDROMESM01RR000036 · NCRR · WASHINGTON UNIVERSITY · PI SHELINE, YVETTE I · 1985 to 2007
$25.4M
NCRR NIH HHS M01 RR000036NCRR NIH HHS M01 RR000043NCRR NIH HHS M01 RR000069NCRR NIH HHS M01 RR000084NCRR NIH HHS M01 RR000125NCRR NIH HHS M01 RR001066NCRR NIH HHS M01 RR014467NCRR NIH HHS UL1 RR024134NCRR NIH HHS UL1 RR024139NCRR NIH HHS UL1 RR024153NCRR NIH HHS UL1 RR024989NCRR NIH HHS UL1 RR024992NCRR NIH HHS UL1 RR025758NCRR NIH HHS UL1 RR025780NIDDK NIH HHS P30 DK048520NIDDK NIH HHS U01 DK061212NIDDK NIH HHS U01 DK061230NIDDK NIH HHS U01 DK061239NIDDK NIH HHS U01 DK061242NIDDK NIH HHS U01 DK061254NIDDK NIH HHS U01-DK61212NIDDK NIH HHS U01-DK61230NIDDK NIH HHS U01-DK61239NIDDK NIH HHS U01-DK61242
6 · The paper itself

Abstract

aims/hypothesisInsulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin plus rosiglitazone.

methodsA total of 640 youth aged 10-18 years with type 2 diabetes underwent fasting blood tests, anthropometric measurements, dual-energy x-ray absorptiometry to estimate subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) mass, and OGTTs longitudinally over 5 years. IC was calculated from the fasting C-peptide:insulin ratio (fasting IC) and 2 h OGTT C-peptide incremental AUC (iAUC):insulin iAUC ratio (2 h IC). Linear mixed models were used to assess covariate effects on the mean of IC over repeated time points.

resultsBaseline fasting IC (×10 CONCLUSIONS/

interpretationIn youth with type 2 diabetes, low IC is correlated with female sex, non-Hispanic Black race and ethnicity, and markers of adiposity and insulin resistance, but not with beta cell function. Along with insulin sensitivity and adiponectin, IC increased in response to rosiglitazone treatment. These findings suggest that, in youth-onset type 2 diabetes, low IC is a compensatory response to changes in insulin sensitivity and/or adiponectin concentrations and is not a mediator of beta cell function.

trial registrationClinicalTrials.gov NCT00081328 DATA AVAILABILITY: Data from the TODAY study (V4; https://doi.org/10.58020/2w6w-pv88 ) reported here are available on request from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository (NIDDK-CR) Resources for Research ( https://repository.niddk.nih.gov/ ).

Indexed as

Diabetes Mellitus, Type 2Hypoglycemic AgentsInsulinAdolescentBlood GlucoseChildFemaleHumansInsulin ResistanceMaleMetforminRosiglitazoneBlood GlucoseHypoglycemic AgentsInsulinMetforminRosiglitazoneInsulin clearanceObesityRace and ethnicityType 2 diabetesYouth

Identifiers

PMID39706874
PMCPMC12720407

What OpenQuestion holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

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.