Evidence mapPaperPMID 41398395Full record

ArticleDiabetologia2026

Diabetogenic processes for insulin resistance-linked hyperinsulinaemia are associated with colorectal cancer.

Xuan Zhou, Magdalena Sevilla-Gonzalez, Amanda I Phipps, Miriam Udler, Sergi Castellví-Bel, Andrew T Chan, Andrew J Pellatt, Robert E Schoen, Edward Giovannucci, Marc J Gunter and 4 more

Abstract read
In one paragraph

Article in Diabetologia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Xuan ZhouNovo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Magdalena Sevilla-GonzalezClinical and Translational Epidemiological Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6135-9998
Amanda I PhippsPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-1763-9623
Miriam UdlerDepartment of Medicine, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3824-9162
Sergi Castellví-BelGastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), University of Barcelona, Barcelona, Spain.ORCID http://orcid.org/0000-0003-1217-5097
Andrew T ChanClinical and Translational Epidemiological Unit, Massachusetts General Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7284-6767
Andrew J PellattIntermountain Health, Salt Lake City, UT, USA.ORCID http://orcid.org/0000-0002-0127-9790
Robert E SchoenDepartment of Medicine and Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0001-7153-2766
Edward GiovannucciDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Marc J GunterNutrition and Metabolism Branch, International Agency for Research on Cancer, World Health Organization, Lyon, France.ORCID http://orcid.org/0000-0001-5472-6761
Jose C FlorezDepartment of Medicine, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-1730-9325
Ulrike PetersPublic Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-5666-9318
Mingyang Song *Clinical and Translational Epidemiological Unit, Massachusetts General Hospital, Boston, MA, USA.
Jordi Merino *Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark. jordi.merino@sund.ku.dk.ORCID http://orcid.org/0000-0001-8312-1438

Funding

Ceramides as novel drivers of metabolic dysfunction and colorectal cancerU01CA272529 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$992k
An integrative omics approach to investigate gene-environment interaction in colorectal cancer riskR01CA273198 · FRED HUTCHINSON CANCER CENTER · 2025 to 2025
$882k
Harnessing DNA methylation in peripheral blood for improved colorectal cancer preventionR01CA285851 · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2025 to 2025
$659k
NCI NIH HHS R01 CA201407NCI NIH HHS R01 CA273198NCI NIH HHS R01 CA285851NCI NIH HHS U01 CA137088NCI NIH HHS U01 CA272529NIDDK NIH HHS L30 DK106874World Health Organization 001
6 · The paper itself

Abstract

aims/hypothesisType 2 diabetes has been associated with increased risk of colorectal cancer (CRC), but the specific diabetogenic pathways contributing to this risk remain unclear.

methodsWe analysed individual-level data from 129,420 participants of European ancestry in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR), comprising 58,531 patients with CRC and 70,889 control participants. We applied eight validated partitioned polygenic scores (PPSs) representing distinct diabetogenic processes: two related to relative insulin secretion insufficiency and six to insulin resistance with varying degrees of preserved insulin secretion. Adjusted ORs and 95% CIs for CRC and early-onset CRC were estimated using conditional logistic regression.

resultsPPSs reflecting insulin resistance-linked hyperinsulinaemia, particularly those related to lipodystrophy, body fat and obesity, were associated with higher odds of CRC (p<0.001 for each). Compared with individuals in the lowest decile, those in the highest decile had ORs of 1.09 (95% CI 1.05, 1.14), 1.13 (1.09, 1.18) and 1.15 (1.10, 1.20) for lipodystrophy, body fat and obesity, respectively. In contrast, PPSs for insulin secretion insufficiency or insulin resistance without hyperinsulinaemia were not associated with CRC. The obesity-related hyperinsulinaemic insulin resistance PPS was also associated with higher odds of early-onset CRC (OR for top vs bottom decile=1.26; 95% CI 1.13, 1.41), with the strongest association among those with obesity (OR 1.75; 95% CI 1.46, 2.11; p value for interaction with BMI <0.001). CONCLUSIONS/

interpretationDiabetogenic processes characterised by insulin resistance-linked hyperinsulinaemia were associated with increased odds of CRC, including early-onset disease. These findings offer new insights into diabetes-CRC pathogenesis, and may inform targeted prevention strategies.

Indexed as

Colorectal NeoplasmsDiabetes Mellitus, Type 2HyperinsulinismInsulin ResistanceAdultAgedFemaleHumansMaleMiddle AgedRisk FactorsColorectal cancerEpidemiologyGeneticsPolygenic scoresPrecision healthType 2 diabetes

Identifiers

PMID41398395
PMCPMC12957015

What Socratic holds

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LicenceCC BY-NC-ND
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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.