Research progress on the association between diabetes mellitus and risk of cancer: From epidemiology to molecular mechanisms.

Diabetes mellitus and cancer represent two major global health burdens. This paper systematically reviews and analyzes recent research advances on the relationship between diabetes and cancer risk, encompassing both epidemiological and molecular mechanism studies. Epidemiological data indicate that the association between diabetes and cancer exhibits significant organ specificity, geographic and population variability, as well as type-specific differences. Diabetes mellitus significantly increases the risk of hepatocellular carcinoma, pancreatic cancer, breast cancer, and colorectal cancer, yet exhibits a unique inverse association with prostate cancer risk. At the molecular level, hyperinsulinemia directly promotes tumor cell proliferation by activating the PI3K/AKT/mTOR and Ras/MAPK/ERK signaling pathways through the insulin/IGF-1 axis. Concurrently, hyperglycemia creates a favorable microenvironment for tumorigenesis by enhancing the Warburg effect, promoting advanced glycation end-product (AGE) accumulation, and inducing oxidative stress and chronic inflammation. Beyond the classical pathways of hyperinsulinemia and hyperglycemia in diabetes, recent research has explored novel directions, including tumor microenvironment remodeling, epigenetics, and immunometabolism. These discoveries encompass emerging mechanisms such as exosomes acting as long-range messengers of systemic metabolic disorders, novel key signaling molecules (e.g., inhibin subunit βB (INHBB) and fibrinogen C domain containing 1 (FIBCD1)), and the remodeling of Schwann cells within the tumor microenvironment. These mechanisms, coupled with potential intervention targets like INHBB, glioma-associated oncogene 1 (Gli-1), FIBCD1, and estrogen-related receptor alpha (ERRα), offer novel clinical approaches for tumor screening, treatment, and prevention.