Insulin resistance and cancer risk: An overview of the pathogenetic mechanisms
Open accessAbstract
Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D), in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance) and the increase in bioavailable insulin-like growth factor I (IGF-I) appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG), whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS) that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.
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T2D is associated with increased risk of developing common female malignancies, including breast, endometrial, and ovarian cancers.
“A large body of epidemiological evidence indicates an association between T2D and increased risk of developing some common female malignancies, including breast, endometrial and ovarian cancers [7,153].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [7]
Adjustment for BMI attenuated the magnitude of the correlation between Western diet and risk of breast cancer, suggesting that this eating pattern increases oncological risk indirectly through promotion of obesity and consequent adipose tissue dysfunction.
“However, adjustment for BMI attenuated the magnitude of the correlation between Western diet and risk of breast cancer, suggesting that this eating pattern increases the oncological risk indirectly, through promotion of obesity and consequent adipose tissue dysfunction [7,167].”
From Mediterranean diet nutrients to turn the tide against insulin resistance and related diseases (2020) · cites this paper as [7]
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Self-citation
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Cited by
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- Authors
- Arcidiacono, B., Iiritano, S., Nocera, A., Possidente, K., Nevolo, M. T., Ventura, V., Foti, D., Chiefari, E., & Brunetti, A.
- Affiliations
- Magna Graecia University (IT)
- Corresponding author
- Brunetti, Antonio
- Venue
- Experimental Diabetes Research
- Publisher
- Wiley
- Published
- 2012
- Volume
- 2012
- Pages
- 1-12
- ISSN
- 1687-5214 (ISSN-L)
- 1687-5303
- PMC
- PMC3372318
- OpenAlex
- W2065417819
- Cited by
- 606
- References
- 130
- Citations by year
- 2026: 36 · 2025: 46 · 2024: 69 · 2023: 44 · 2022: 54 · 2021: 52 · 2020: 51 · 2019: 36 · 2018: 37 · 2017: 38 · 2016: 35 · 2015: 33 · 2014: 37 · 2013: 31 · 2012: 5
- FWCI
- 3.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Experimental Diabetes Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Ministry of Education, University and Research (2004062059-002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- insulin resistance, cancer risk, hyperinsulinemia, insulin-like growth factor I, sex hormone-binding globulin, sex steroids, breast cancer, endometrial cancer, reactive oxygen species, DNA damage, carcinogenesis, adipose tissue inflammation, obesity, type 2 diabetes, tumor progression
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, DNA Damage, Female, Humans, Insulin Resistance, Insulin-Like Growth Factor I, Models, Biological, Neoplasms, Obesity, Ovary, Risk, Sex Hormone-Binding Globulin, Steroids, Gene Expression Regulation, Neoplastic, Apoptosis, Reactive Oxygen Species, Cell Proliferation
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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