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.
It seems that blood glucose elevation may be 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.
The bottom line is we do not understand why diabetes is related to cancer, but there are several biologic hypotheses, and some evidence that supports each of these possibilities. There is no compelling evidence whatsoever that elevated glucose levels cause cancer; that insulin resistance causes cancer; or that insulin therapies cause cancer. 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.
Baseline insulin levels.
Insulin may be one of the contributing factors to this link, and there is growing evidence that it is important especially in outcomes of breast cancer. My group and three others have shown that in women diagnosed with early stage breast cancer, baseline insulin levels within the normal range can predict outcomes.
|
|
It is well known that overweight women have poor outcomes in cancer. When looking at potential mechanisms, insulin is strongly correlated with being overweight. Insulin is a member of the insulin-like growth factor family. It is an essential component of the cell culture media that make tumors grow on. Insulin typically has metabolic effects but it is also recognized to have growth effects in the human fetus, infants and also cancer cells, particularly breast cancer cells. These breast cancer cells overexpress the insulin receptor on their cell surface; it is an abnormal type of insulin receptor, the fetal insulin receptor. The fetal receptor stimulates the mitogenic pathways more than the regular adult insulin receptor, and also hybridizes the IGF-I receptor; together, the two sit on the surface of breast cancer cells to bind insulin and stimulate growth.
Once our group showed that insulin was independently associated with breast cancer outcome, we looked at approaches to lowering insulin such as weight loss through physical activity and caloric modification. Another way is utilization of drug metformin, a drug that is causing a lot of excitement in oncology circles. It is being studied in breast, colon, endometrial and prostate cancer. Metformin lowers insulin levels by about 20%, even in nondiabetic patients. Moreover, metformin may impact cancer growth by stimulating AMP kinase and inhibiting the M tour signaling pathway. We estimate that it might lower the risk for cancer recurrence by as much as 20% to 25%.
I suspect that there will be much additional data over the next few years but there is certainly a strong biologic plausibility for a link between insulin, metformin and cancer.
Pamela J. Goodwin, MD, is the Marvelle Koffler Chair in Breast Research and Professor of Medicine at University of Toronto and Mount Sinai Hospital, Toronto, Canada.