Gestational diabetes mellitus and long-term cancer risk: a narrative review of epidemiological and mechanistic evidence

Abstract

Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy and is increasingly recognized as a marker of long-term metabolic vulnerability. Beyond its established association with cardiometabolic diseases, emerging epidemiological evidence suggests a potential link between GDM and increased cancer risk, particularly hormone-sensitive malignancies such as endometrial and breast cancer. This narrative review integrates epidemiological and mechanistic evidence exploring the relationship between GDM and long-term oncological susceptibility. Hyperglycemia, hyperinsulinemia, and chronic low-grade inflammation associated with GDM may contribute to proliferative signaling and metabolic dysregulation. Among the proposed mechanisms, insulin/IGF-1 signaling represents one of the most biologically plausible links, whereas pathways involving PI3K/Akt/mTOR activation, metabolic reprogramming, and tumor microenvironment alterations remain largely inferred from broader oncological literature. In addition, persistent metabolic stress during pregnancy may induce long-term epigenetic and immunometabolic changes potentially associated with carcinogenic susceptibility. Although current evidence does not establish a direct causal relationship between GDM and cancer, the integration of epidemiological and mechanistic findings supports the hypothesis that GDM may function as an early marker of systemic metabolic vulnerability associated with increased long-term oncological risk. Further longitudinal and mechanistic studies are needed to clarify this relationship and its clinical implications.