Evidence mapPaperPMID 41369591Full record

ArticleDiabetes2026

Type 2 Diabetes Genetic Risk and Type 1 Diabetes Heterogeneity and Progression.

Taylor M Triolo, Jay M Sosenko, David Cuthbertson, Richard A Oram, Hemang M Parikh, Andrea K Steck, Emily K Sims, Laura M Jacobsen, Brandon Nathan, Erin L Templeman and 6 more

Abstract read
In one paragraph

Article in Diabetes, 2026. 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. Review
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

16 authors.

Taylor M TrioloBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.ORCID 0000-0003-4796-6542
Jay M SosenkoDiabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL.
David CuthbertsonHealth Informatics Institute, University of South Florida, Tampa, FL.
Richard A OramUniversity of Exeter, Exeter, U.K.
Hemang M ParikhHealth Informatics Institute, University of South Florida, Tampa, FL.
Andrea K SteckBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO.
Emily K SimsDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
Laura M JacobsenDivision of Pediatric Endocrinology, University of Florida, Gainesville, FL.
Brandon NathanDivision of Pediatric Endocrinology, University of Minnesota, Minneapolis, MN.
Erin L TemplemanUniversity of Exeter, Exeter, U.K.
Suna Onengut-GumuscuDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA.
Carmella Evans-MolinaDepartment of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
Stephen S RichDepartment of Genome Sciences, University of Virginia School of Medicine, Charlottesville, VA.
Mark A AtkinsonDepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL.
Maria J RedondoDepartment of Pediatrics, Baylor College of Medicine, Houston, TX.ORCID 0000-0001-5871-4645
Type 1 Diabetes TrialNet Study Group*

Funding

Data Coordinating Center for Type 1 Diabetes TrialNetU01DK106993 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · 2022 to 2025
$43.4M
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
Prediction and Prevention of Type I DiabetesU01DK061058 · CHILDREN'S HOSP PITTSBURGH/UPMC HLTH SYS · 2001 to 2005
$1.2M
Type 1 diabetes genetic risk scores for the diagnosis of diabetes type in children of diverse racial and ethnic backgroundR01DK124395 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI Maria Jose Redondo · 2023 to 2024
$1.2M
UCSF TrialNet: A Phase II Trial of hokT3gamma1 (Ala-Ala)U01DK061010 · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · 2001 to 2005
$1.2M
Interrogating beta cell function and heterogeneity of C-peptide preservation in patients with type 1 diabetes or chronic pancreatitisK23DK136931 · UNIVERSITY OF COLORADO DENVER · 2025 to 2025
$190k
Eunice Kennedy Shriver National Institute of Child Health and Human Development UC4 DK117009-01NIDDK NIH HHS K23 DK136931NIDDK NIH HHS R01 DK121843NIDDK NIH HHS R01 DK124395NIDDK 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 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 UC4 DK106993NIDDK NIH HHS UC4 DK117009
6 · The paper itself

Abstract

Insulin secretion varies widely in preclinical type 1 diabetes. To understand the pathogenesis of this metabolic heterogeneity, we asked whether genetic predisposition to type 2 diabetes, quantified by a type 2 diabetes genetic risk score (T2D-GRS), modulates β-cell function and disease progression in individuals at risk of type 1 diabetes. We analyzed 4,324 islet autoantibody–positive TrialNet Pathway to Prevention participants with genome-wide genotyping and oral glucose tolerance testing. Both T2D-GRS and the type 1 diabetes genetic risk score 2 (T1D-GRS2) differed significantly across five previously described groups defined by C-peptide area under the curve (AUC; a measure of insulin secretion). The highest C-peptide AUC group, compared with the lowest, had significantly higher T2D-GRS, lower T1D-GRS2, higher BMI z-score, greater insulin resistance, older age, and lower prevalence of male participants; multiple islet autoantibody positivity; and IA-2 or insulin autoantibody positivity. Progression to clinical (stage 3) type 1 diabetes was significantly associated with T1D-GRS2 across all groups and with T2D-GRS in all but the lowest C-peptide AUC group. In conclusion, type 2 diabetes genetic burden shapes metabolic heterogeneity and accelerates progression in preclinical type 1 diabetes. These results support the evaluation of type 2 diabetes–related mechanisms as targets to improve the prediction and prevention of type 1 diabetes. ARTICLE HIGHLIGHTS: Heterogeneity in β-cell function is a barrier to precision medicine in type 1 diabetes. We asked whether type 2 diabetes-associated genes influence insulin secretion and progression to clinical type 1 diabetes in autoantibody-positive individuals. A type 2 diabetes genetic risk score was associated with higher C-peptide area under the curve (AUC) and increased clinical type 1 diabetes risk in all but the lowest C-peptide AUC subgroup. Addressing type 2 diabetes mechanisms could improve type 1 diabetes prediction and prevention.

Indexed as

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2Genetic Predisposition to DiseaseAdultAutoantibodiesC-PeptideDisease ProgressionFemaleHumansInsulinInsulin-Secreting CellsInsulin SecretionMaleMiddle AgedPolymorphism, Single NucleotideRisk FactorsAutoantibodiesC-PeptideInsulin

Identifiers

PMID41369591
PMCPMC12823339

What Socratic holds

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Registered trials

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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.