Evidence mapPaperPMID 42353211Full record

ReviewInternational journal of molecular sciences2026

Insulin Resistance as a Systemic Metabolic Risk State for Cancer: Mechanisms, Biomarkers, and Prevention.

Marijana Matek Sarić, Nataša Lisica Šikić, Tamara Sorić, Ana Sarić, Andrija Ivanišin, Ivona Brodić, Mirta Milić

Abstract readReview
In one paragraph

Review in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Marijana Matek SarićDepartment of Health Studies, University of Zadar, Splitska 1, 23000 Zadar, Croatia.ORCID 0000-0003-2734-7955
Nataša Lisica ŠikićDepartment of Health Studies, University of Zadar, Splitska 1, 23000 Zadar, Croatia.ORCID 0000-0003-3371-1151
Tamara SorićPsychiatric Hospital Ugljan, Otočkih dragovoljaca 42, 23275 Ugljan, Croatia.ORCID 0000-0002-4435-8472
Ana SarićSchool of Medicine, Catholic University of Croatia, Ilica 242, 10000 Zagreb, Croatia.
Andrija IvanišinIndependent Researcher, 10000 Zagreb, Croatia.
Ivona BrodićIndependent Researcher, 10000 Zagreb, Croatia.
Mirta MilićDivision of Toxicology, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000 Zagreb, Croatia.ORCID 0000-0002-9837-7185

Funding

European Union - Next Generation EU 533-03-23-0006
6 · The paper itself

Abstract

Insulin resistance (IR) is traditionally viewed within the context of type 2 diabetes. However, it increasingly appears to represent a broader systemic metabolic risk state with potential relevance for carcinogenesis. Chronic hyperinsulinemia can activate insulin-like growth factor-1-dependent pathways, including phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin and mitogen-activated protein kinase signaling, promoting cellular proliferation while limiting apoptosis. At the same time, IR is closely linked to oxidative stress, chronic low-grade inflammation, and epigenetic alterations, together shaping a tumor-promoting microenvironment. Epidemiological studies report consistent associations between IR and increased cancer risk, particularly for endometrial, liver, and colorectal cancers. Yet causality remains uncertain and likely varies by tumor type. Notably, metabolic dysfunction may also occur in individuals with normal body mass index (BMI), underscoring the limitations of BMI-based risk assessment. Unlike previous reviews that primarily focused on individual mechanisms or epidemiological associations, this review examines IR as a systemic metabolic risk state by integrating molecular, epidemiological, biomarker-based, and prevention-oriented perspectives. Particular emphasis is placed on strategies for earlier risk identification using integrated biomarker approaches, including fasting glucose, homeostatic model assessment of insulin resistance, triglyceride-to-high-density lipoprotein ratio, high-sensitivity C-reactive protein, and insulin-like growth factor-1. Emerging tools such as continuous glucose monitoring and hepatokine profiling may further refine risk detection. Sustained lifestyle modification-diet, physical activity, sleep, and stress regulation-remains central to prevention. Pharmacological therapies, including glucagon-like peptide-1 receptor agonists and dual incretin agents, offer additional metabolic benefits, although their long-term impact on cancer risk is still unclear. Therefore, IR is best understood not as an isolated risk factor, but as a systemic metabolic risk state that may influence cancer development, with implications for prevention and early risk stratification.

Indexed as

Insulin ResistanceNeoplasmsAnimalsBiomarkersHumansRisk FactorsBiomarkerscancer preventioncancer riskcontinuous glucose monitoringGLP-1 receptor agonistshyperinsulinemiainsulin resistancemetabolic biomarkersmetabolic risk staterisk stratificationtirzepatide

Identifiers

PMID42353211
PMCPMC13299947

What Socratic holds

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LicenceCC BY
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 Socratic graph.