Diabetes and Pancreatic Cancer: Testing the Insulin Hypothesis
As the incidence of diabetes rises around the world, researchers are starting to recognize the possibility that in the coming decades cancers associated with diabetes may become more common as well, particularly in the United States as the population ages.
Cancers of the colon, breast, liver, and pancreas are among those that tend to occur with type 2 diabetes among adults. But the epidemiological studies on the subject are inconsistent, and researchers are only beginning to understand how the diseases might be related and how best to treat patients with both.
"We know what happens to patients with cancer, and we know what happens to patients with diabetes, but we know little about how the two diseases interact in patients who have both," says Dr. Lisa Richardson, a medical oncologist in the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention.
Surprisingly few studies have been done specifically to understand how the diseases are related, notes Dr. Richardson. Instead, researchers have focused largely on identifying cancers that occur with diabetes (or prediabetic states) and explaining why this happens.
A theory about pancreatic cancer and diabetes, to take one example, says that during the early stages of diabetes the pancreas produces extra insulin, and this insulin may spur the growth of cells, leading to tumors.
The insulin hypothesis is supported by experiments in human cells and in animals. Now more support comes from a study involving 29,000 male smokers in Finland that appears in tomorrow's Journal of the American Medical Association (JAMA).
In the study, men with the highest insulin levels were twice as likely to develop pancreatic cancer as men with the lowest levels, says lead researcher Dr. Rachael Stolzenberg-Solomon of NCI's Division of Cancer Epidemiology and Genetics.
Similarly, men with glucose levels in the range of clinical diabetes were twice as likely to develop the cancer as men with normal levels.
When the men joined the study in the mid-1980s, they had their blood drawn after fasting overnight. This allowed the researchers to know insulin and glucose levels many years before the cancers appeared; over the course of 17 years, 169 men developed the cancer.
"This is a very well done study, and it supports the long-standing hypothesis that insulin is a growth promoter for pancreatic cancer," says Dr. Charles Fuchs of Harvard Medical School, an expert on pancreatic cancer who was not involved in the study.
In their analysis, the researchers excluded men who developed the cancer within 5 years of having their blood drawn. This reduced the likelihood of including men whose elevated insulin levels were caused by undetected pancreatic tumors, as can happen.
Smoking, aging, and perhaps obesity are the only known risk factors for pancreatic cancer, one of the most deadly cancers. There are few treatments, and the cancer is frequently discovered only after a tumor has spread.
"This study of insulin levels gives us another important clue about the various influences that are probably important in the risk of developing pancreatic cancer, particularly in smokers," says Dr. Demetrius Albanes, the senior researcher of the NCI team.
The findings need to be replicated in other groups, including women and nonsmokers, but the results are consistent with other recent studies.
Last January, for instance, a study in JAMA found that diabetes and elevated fasting glucose levels were independent risk factors for several major cancers, including pancreatic cancer, among 1.3 million Koreans.
The participants were "far leaner" than those found in studies involving Westerners. Noting that obesity was not a factor in the results, the researchers suggested that elevated insulin levels may account for the increased cancer risk.
In May, an analysis of 36 studies involving diabetes and pancreatic cancer found a "modest causal association" between type 2 diabetes and the cancer. After obesity and smoking, diabetes may be the third modifiable risk factor for pancreatic cancer, the researchers concluded in the British Journal of Cancer.
"Unless the increasing worldwide prevalence of all three risk factors is halted, the incidence of pancreatic cancer will rise substantially within the next couple of decades," warned Dr. Rachel Huxley of the University of Sydney and her colleagues.
By Edward R. Winstead