A Link Between Cancer and Diabetes?

Cancer and diabetes aren’t mentioned too often in the same sentence. The major clinical trials linking tight control to a reduction in “risk” talk about nephropathy, neuropathy and retinopathy. Rarely in the dense verbiage of statistical analysis was made mention of a reduction in cancer risk. Maybe this was because in previous years the other complications took their toll before cancer ever had a chance to take hold. Yet, cancer and diabetes certainly are linked.

The risk of breast, bladder, endometrial and other cancers go up several fold if you have type 2 diabetes. People who have type 1 diabetes don’t seem to have the same risk profile, although as those with type 1 begin to look more like the type 2 population their cancer risk may escalate also. Obesity explains some of the increased risk people with diabetes have of developing cancer. For each additional 5 kilograms (11 pounds) per meter squared increase in body mass, the hazard rises.

But obesity explains only so much. People with type 2 diabetes get more cancers than those without even when their extra body weight is accounted for. Scientists have posited three possible explanations for this.

The first has to do with blood glucose levels. It goes something like this. Cancer cells love glucose, so the more glucose in the body, the more food for the cancer to feed upon. Great theory, but it didn’t pan out. Cancer cells, as it turns out, get more than enough glucose when the blood glucose levels are around 90mg/dl. That level is within the normal range for glucose. Glucose levels above that, the kind you find in diabetes, don’t have any additional effect because the cancer cells are already saturated with glucose.

Theories number two and three have more legs. One of the causes of type 2 diabetes is insulin resistance. In an attempt to overcome the resistance, the pancreas produces even more insulin. Insulin is a growth hormone. It stimulates the proliferation of cells. The more insulin there is and the longer it stays around the greater the possibility for cell growth. And insulin has no internal bias, meaning it doesn’t have a preference for healthy over cancerous cells. When insulin levels are increased, as they often are in many stages of type 2 diabetes (when the beta cells burn out completely, those with type 2 begin to resemble someone with type 1 diabetes) the hormone insulin-like growth factor (IGF) is also increased.

IGF is responsible for maintaining normal growth patterns in children and anabolism in adults. It has an important role in cell proliferation and the inhibition of cell death using two signaling pathways to communicate with its surrounding environment. One pathway called MAPK-signaling increases cell survival and another called Path PI3K increases cell proliferation (of cancer cells as well as normal cells). So no matter which pathway is used, there is a chance for the genesis of cancer cells.

The third theory deals with the fact that high blood glucose levels in diabetes cause inflammation. While the inflammation that accompanies an acute injury, say a broken bone or an infection, is the body’s way of fighting foreign invaders such as bacteria and helping the injured tissue heal, chronic inflammation can be damaging. Chronic levels of inflammation, such as is found in type 2 diabetes, can destroy cells. Infection fighting agents such as some white blood cells have the propensity to be mutagenic- i.e. to turn healthy cells into cancer cells.

So what can you do?

Jason Gaglia, M.D., M.MSc., Assistant Investigator at Joslin Diabetes Center says that people with type 2 diabetes should take steps to decrease insulin resistance including losing weight if necessary, engaging in regular exercise and adding metformin to their medication regimen if not counter-indicated. (Metformin reduces insulin resistance and has been recommended even for people with pre-diabetes).

“One of the most important ways to avoid receiving a diagnosis of advanced cancer is to make sure you are up-to-date on your cancer screening tests, including colonoscopy and mammogram,” said Dr. Gaglia.

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