Frontline Cancer: Inflammation and the development of cancer

FRONTLINE CANCER:

When you have diabetes, your body cannot produce enough or effectively use the hormone insulin to regulate blood sugar (glucose) levels. The resulting complications are widespread and notorious, from stroke, blindness and kidney failure to nerve damage, skin problems, dental issues and loss of limb.

Diabetes kills or contributes to the deaths of more than 230,000 Americans each year. It is a great and growing public health threat. Nearly 30 million Americans are estimated to have the disease; three times that number are pre-diabetic. They have some of the symptoms. They are on the cusp.

The simplest way to treat the condition — or better yet, prevent it — is to eat a healthy, balanced diet and exercise regularly. This is advice we've all heard. What is less well understood and perhaps under-appreciated is the deeper pathology driving not just diabetes, but many modern maladies, from an obesity epidemic with no end in sight to this nation's two greatest killers — heart disease and cancer.

Diabetes is a disease of the metabolism, a term describing the sum of all the chemical reactions that take place within every cell to provide the energy necessary to maintain function and life. If your metabolism — or more precisely, the metabolic state within your cells — is abnormal, nothing good can result, but a lot of bad things may happen.

In recent years, scientific evidence connecting metabolic dysfunction to numerous, diverse diseases has accumulated with speeding frequency. The importance of this research, with its massive social implications, is one of the reasons UC San Diego School of Medicine launched this year the Institute for Diabetes and Metabolic Health, whose four centers reflect the spectrum of concern and interest: Type 1 diabetes, basic research, human nutrition and clinical care. The institute is headed by Alan Saltiel, one of the nation's leading metabolics researchers.

Most patients with type 2 diabetes are obese, and the global epidemic of obesity largely explains the dramatic rise of type 2 diabetes over the last 20 years. More than one-third of American adults are obese and more than 10 percent of people over age 20 have diabetes, both numbers projected to increase over time.

Excess weight is an established risk factor for type 2 diabetes. Obesity itself causes an inflammatory state in metabolic tissues, a sort of low-grade, chronic state of war within the body. It's even worse than it sounds. Inflammation, as my colleague Michael Karin and others have shown, promotes the development of cancer.

Of course, not everybody who is obese develops diabetes. Not everybody who drinks develops cirrhosis. But people with diabetes are more often diagnosed with some types of cancer and more likely to die from cancer than people without diabetes. Some of that increase may be due to the likelihood that these patients being more closely followed by their doctors, but an overabundance of insulin due to metabolic dysfunction may be promoting the growth of cancer cells, particularly in organs like the pancreas, liver, kidney and thyroid.

There is a bright side. The intersection between diabetes and cancer offers ways to attack the latter. For example, metformin is a common frontline drug for treating some kinds of type 2 diabetes. It works by boosting the liver's sensitivity to insulin, reducing overproduction of glucose. New studies suggest it may be effective in treating or preventing a variety of cancers, including colorectal, prostate, endometrial and breast. Saltiel with colleagues at Moores Cancer Center are investigating whether established diabetes drugs might also treat cancer. They are also conducting clinical trials to explore how much cancer risk is reduced by increased physical activity and whether weight loss programs and routine exercise might protect overweight or obese cancer survivors from tumor relapse.

Diabetes and cancer are just two heads of a many-headed monster. To kill the beast, we must fight both — and other related conditions — smartly and simultaneously.

 

Scott M. Lippman, M.D., is director of UC San Diego Moores Cancer Center. His column on medical advances from the front lines of cancer research and care appears in La Jolla Light the fourth Thursday of each month. You can reach Dr. Lippman at mcc-dir-lippman@ucsd.edu

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