From Risk Factors to Biological Mechanisms
Cancer prevention has long focused on reducing exposure to well-established risk factors such as smoking, alcohol consumption, physical inactivity, and obesity. However, Birkenfeld and Heikenwälder argue that many of these factors ultimately converge on common biological pathways. These include elevated blood glucose levels, insulin resistance, chronic inflammation, and altered metabolic processes—conditions that may also contribute to tumor initiation and progression.
The authors therefore advocate for a shift in perspective. In addition to addressing individual risk factors, future prevention strategies could place greater emphasis on improving overall metabolic health.
Prediabetes Remission as a Measurable Prevention Target
At the center of the commentary is the concept of prediabetes remission, defined as the sustained return from prediabetes to normal glucose regulation. While this state has already been associated with a lower risk of type 2 diabetes and cardiovascular disease, its potential role in cancer prevention has received little attention to date.
Large population-based studies from South Korea involving several million participants provide intriguing epidemiological evidence. These analyses found that individuals with persistent prediabetes had an increased risk of developing pancreatic and gallbladder cancer. By contrast, people whose glucose levels returned to the normal range showed no statistically significant increase in cancer risk compared with individuals who remained normoglycemic.
New Perspectives for Prevention Research
The authors emphasize that these findings do not establish a causal relationship between prediabetes remission and reduced cancer risk. Nevertheless, they offer a biologically plausible hypothesis: long-term disturbances in glucose metabolism may create conditions that favor cancer development, whereas remission of prediabetes could potentially mitigate these processes.
Importantly, returning to normoglycemia appears to be an achievable goal. In the cohorts analyzed, more individuals transitioned from prediabetes back to normal glucose regulation than remained in a persistent prediabetic state. According to the authors, this makes prediabetes remission a realistic and measurable target for future prevention strategies.
Original publication
Birkenfeld AL, Heikenwälder M. Cancer Prevention Through Metabolic Remission. Nature Reviews Endocrinology (2026). DOI: 10.1038/s41574-026-01268-3.