The Relationship Between Insulin Resistance and Cancer in
                    Humans

María M Adeva-Andany; Lucia Adeva-Contreras; Eva Ameneiros-Rodriguez; Natalia Carneiro-Freire; Matilde Vila-Altesor; Raquel Funcasta-Calderon

doi:10.1055/a-2715-0775

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2025; 57(10): 539-556
DOI: 10.1055/a-2715-0775

Review

The Relationship Between Insulin Resistance and Cancer in Humans

Authors

María M Adeva-Andany

¹Internal Medicine, Hospital Juan Cardona, Ferrol, Spain (Ringgold ID: RIN221806)
Lucia Adeva-Contreras

²Internal Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain (Ringgold ID: RIN16780)
Eva Ameneiros-Rodriguez

¹Internal Medicine, Hospital Juan Cardona, Ferrol, Spain (Ringgold ID: RIN221806)
Natalia Carneiro-Freire

¹Internal Medicine, Hospital Juan Cardona, Ferrol, Spain (Ringgold ID: RIN221806)
Matilde Vila-Altesor

¹Internal Medicine, Hospital Juan Cardona, Ferrol, Spain (Ringgold ID: RIN221806)
Raquel Funcasta-Calderon

¹Internal Medicine, Hospital Juan Cardona, Ferrol, Spain (Ringgold ID: RIN221806)

Abstract

An independent association between insulin resistance and cancer has been consistently reported in humans. Patients with cancer display insulin resistance or its clinical manifestations, and this metabolic adaptation precedes the clinical diagnosis of cancer. Insulin resistance in cancer patients is associated with a metabolic switch from oxidative metabolism toward glycolysis that spares oxygen to be used in anabolic processes and facilitates the fast production of energy and intermediate metabolites required for the rapid proliferation of cancer cells. In malignant cells, glucose consumption via glycolysis occurs under normoxic conditions (aerobic glycolysis). Pathogenic mechanisms underlying insulin resistance in cancer patients include hypoxia-inducible factor-1 upregulation and overproduction of cytokines, such as interferon, interleukin-6, interleukin-18, and interleukin-1β. Deficit of 2-oxoglutarate (α-ketoglutarate) has been detected in cancer cells and may facilitate hypoxia-inducible factor-1 assembly and activity. Overproduction of cytokines in cancer patients follows activation of the immune system by abnormal nucleic acid variants. Anomalous DNA or RNA structures are recognized by immune sensors and stimulate signaling pathways that ultimately increase cytokine production. Likewise, interferon overproduction occurs in congenital disorders that feature ineffectively repaired DNA lesions, such as Werner syndrome, Bloom syndrome, mutations in DNA polymerase-δ1, and ataxia telangiectasia. These diseases cause simultaneous insulin resistance and a high tendency to develop cancer, highlighting the relationship between the two processes. Defectively repaired DNA injury endangers genomic integrity, predisposing to cancer, and activates the immune system to increase interferon production and subsequent insulin resistance. Hypoxia-inducible factor-1 and cytokines induce insulin resistance by suppressing peroxisome proliferator-activated-γ in the subcutaneous adipose tissue.

Keywords

insulin resistance - cancer - hypoxia inducible factor - peroxisome proliferator-activated-γ - interferon - DNA repair

Full Text

References

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