Diabetes mellitus and cancer are characterized in the literature as two major global public health burdens. Recent systematic reviews and analyses synthesize epidemiological data indicating a complex relationship between diabetes and cancer risk. The association is not uniform: it shows significant organ specificity, variation across geographic regions and populations, and differences by diabetes subtype. The review emphasizes that epidemiological findings must be interpreted in light of these heterogeneities.
Epidemiological data reported in the review identify several cancers with notably increased risk in individuals with diabetes. Diabetes mellitus is associated with a higher risk of hepatocellular carcinoma, pancreatic cancer, breast cancer, and colorectal cancer. In contrast, an inverse association between diabetes and prostate cancer risk is observed in the aggregated data. The authors highlight that these organ-specific relationships reflect both biological mechanisms and population- or region-specific factors discussed elsewhere in the review.
A principal mechanistic axis linking diabetes to tumorigenesis is hyperinsulinemia, which operates through the insulin/IGF-1 axis. Elevated insulin and IGF-1 signaling can directly stimulate tumor cell proliferation by engaging canonical growth and survival pathways. Specifically, activation of the PI3K/AKT/mTOR cascade and the Ras/MAPK/ERK pathway are described as routes by which insulin/IGF-1 signaling promotes oncogenic processes. These signaling events provide a molecular basis for how systemic metabolic disturbance in diabetes may translate into enhanced tumor growth potential.
Beyond insulin-mediated signaling, hyperglycemia itself creates a microenvironment conducive to tumorigenesis. The review summarizes mechanisms through which elevated glucose promotes malignant transformation and progression:
These hyperglycemia-driven processes complement hyperinsulinemia-mediated growth signaling to create a metabolic and inflammatory milieu that can accelerate cancer development.
The review notes that research has expanded beyond the classical concepts of hyperinsulinemia and hyperglycemia to explore additional mechanisms linking systemic metabolic disorders to cancer biology. Key emerging areas include:
These newer frameworks aim to explain aspects of the diabetes–cancer relationship that are not fully accounted for by insulin or glucose alone.
One highlighted mechanism involves exosomes acting as long-range messengers of systemic metabolic disorders. The review describes exosomes as carriers that can transmit metabolic signals from diabetic tissues to distant cells, potentially influencing tumor behavior across organ systems.
Recent studies reviewed identify novel molecular players implicated in the diabetes–cancer axis. Examples cited include inhibin subunit βB (INHBB) and fibrinogen C domain containing 1 (FIBCD1) as newly recognized signaling molecules linked to tumorigenesis in the context of metabolic disturbance. The authors also describe remodeling of Schwann cells within the tumor microenvironment as a mechanism of interest, suggesting neural-stromal interactions may be modulated by diabetic states.
The review highlights several potential targets for clinical intervention that arise from mechanistic discoveries. Candidate targets mentioned include INHBB, Gli-1, FIBCD1, and estrogen-related receptor alpha (ERRα). The authors propose that these molecules and pathways could inform novel approaches to tumor screening, prevention, and therapy in patients with diabetes. The review underscores that translating mechanistic insights into clinical strategies will require further validation.
This article is a systematic review synthesizing recent epidemiological and molecular studies on the association between diabetes mellitus and cancer risk. The review emphasizes organ specificity, population variability, and multiple mechanistic layers—from classical insulin/glucose effects to tumor microenvironment, epigenetics, and immunometabolism. The authors declare no competing financial interests or personal relationships that could have influenced the reported work. For full methodological details and primary data sources, readers are directed to the original article (PMID 42364319; DOI 10.1016/j.bbrc.2026.154205).