This article is more than 5 years old. Information may no longer be current.
What are alternative hypotheses for the diabetes-cancer link?
Click Here to Manage Email Alerts
Elevated blood glucose.
The bottom line is we do not understand why diabetes is related to cancer, but there are several biologic hypotheses. It seems that glucose elevation is a potential risk factor for cancer. Looking at the general population, the higher the glucose levels, the higher the risk for death; the higher the glucose levels, the higher the risk for cancers; and the higher the glucose levels, the higher the risk for death from cancer. Although this hypothesis may not apply to all cancers, such as prostate cancer, there is a clear progressive relationship between dysglycemia and cancer or cancer mortality for many of the common cancers.
The question is: What explains this relationship? Cancer cells are dependent on a steady, uninterrupted supply of glucose for cancer cells to thrive, more so than non-cancer cells. It may be that as the glucose level is rising, it creates the perfect environment for cancer cells to grow.
|
|
It has been hypothesized that the underlying abnormalities that cause glucose levels to rise may also promote the initiation or growth of cancers. Others believe that elevated insulin levels along with elevated glucose levels may somehow promote small cell cancers. However, one problem with this hypothesis is that patients with type 1 diabetes who have lower insulin levels and glucose levels also are at risk for cancer.
There is no compelling evidence whatsoever that elevated glucose levels cause cancer; that insulin resistance causes cancer; or that insulin therapies cause cancer. But there are many biologic hypotheses and some evidence that supports each of these possibilities. It is important that cancer outcomes are measured in long-term trials to assess whether diabetes therapies have any effect and we not jump to conclusions based on biologic hypotheses.
Hertzel Gerstein, MD, MSc, is a Professor in the Department of Medicine and Department of Clinical Epidemiology and Biostatistics, and the Population Health Institute Chair in Diabetes Research at McMaster University, Ontario, Canada.
Insulin/IGF-1 receptor signaling.
Patients with type 2 diabetes have insulin resistance, thus elevated insulin levels. Numerous associative studies have suggested that type 2 diabetes is associated with cancer risk and poor outcomes from cancer. This association also correlates with obesity, and it has been hypothesized that type 2 diabetes and obesity elevate cancer risk through elevated insulin receptor signaling. There is good evidence in a variety of systems that cancer cells have insulin receptors and insulin-like growth factor 1 receptors. At the same time, many new therapies are being developed to block IGF-1 receptor signaling. Preliminary observations suggest that they do have activity in cancer. The idea that insulin/IGF-1 signaling has a role in cancer biology is supported by the ongoing trials.
|
|
The observation about obesity and cancer risk and outcomes has been around for quite some time. It is possible that cancer risk in obesity is due to something else such as a low grade inflammatory state and induction of inflammatory cytokines such as interleukin-6. There are a variety of interesting observations about chronic inflammatory states in cancer risk. Certainly, obesity has been linked to a chronic inflammatory state and may in fact be one of the reasons obese people are insulin resistant. There has been discussion about whether or not these observations are cause–and–effect. But I certainly think the observation suggests a role for insulin in this process.
It is hard to distinguish between insulin and IGF-I signaling in many tissues, and it is certainly plausible that insulin receptor activation in cancer target tissues impacts the malignant phenotype.
Douglas Yee, MD, is Director of the University of Minnesota Cancer Center and a member of the HemOnc Today Editorial Board.