December 16, 2008 — Cancer patients with preexisting diabetes at the time of their cancer diagnosis have an increased risk for death vs patients without diabetes. According to a meta-analysis reported in the December 17 issue of the Journal of the American Medical Association, diabetes was associated with an increased mortality hazard ratio (HR) of 1.41 across all cancer types.
Additional subanalysis of the data showed that preexisting diabetes was significantly associated with increased long-term, all-cause mortality for cancers of the endometrium (HR, 1.76), breast (HR, 1.61), and colorectum (HR, 1.32). The authors also found an association between diabetes and a nonsignificant increase in the risk for prostate, gastric, hepatocellular, lung, and pancreatic cancer.
At this time, it is difficult to speculate why diabetes has a higher association with all-cause death in certain cancers. "There are many possible reasons, and it's hard to say which one for each cancer," said senior author Frederick L. Brancati, MD, MHS, director of the Division of General Internal Medicine at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. "We're digging down into each cancer now to try to find out."
For clinicians, Dr. Brancati offers 2 suggestions. "Make certain that you're giving the most appropriately aggressive treatment you can, even in the presence of diabetes," he said. "And make sure the primary care physician stays engaged during and after cancer treatment to tend to diabetic control."
Possible Explanations for the Increased Risk
The researchers did offer several potential explanations for the association between increased all-cause mortality and preexisting diabetes in cancer patients. One was that a physiologic environment of hyperinsulinemia and hyperglycemia might cause greater tumor cell proliferation. A second possibility is that there may be differences in cancer treatment between patients with and without diabetes. Diabetic patients often have accompanying comorbidities, including ischemic heart disease, chronic kidney disease, and neuropathy, and these may influence clinical decisions regarding treatment.
A third reason, the researchers hypothesize, is that patients with preexisting diabetes may have a poorer response to cancer therapies, such as an increased risk for infection and intraoperative mortality. Fourth, individuals with preexisting diabetes might present with cancer at a more advanced stage because of suboptimal cancer screening practices. However, they note that in their analysis, stage at diagnosis did not appear to be a major explanatory factor.
A fifth reason could be that the diagnosis and treatment of cancer might distract both the patient and practitioner from the appropriate management of diabetes, such as controlling hyperglycemia, lipid levels, and blood pressure. Appropriate control of these factors has been proven to lower morbidity and mortality rates in adults with diabetes. Finally, the authors note that it is entirely possible that the excess mortality risk associated with diabetes is completely independent of cancer and accompanying cancer therapy.
"We embarked on the study because we were most concerned about diabetes care deteriorating during cancer treatment," Dr. Brancati told Medscape Oncology. "But after our systematic review, I think the other explanations are equally likely."
Additional Research Needed
It is estimated that 20 million Americans, or approximately 7% of the adult population, have diabetes. Previous studies have shown that some malignant tumors, including cancers of the breast, colorectum, endometrium, liver, and pancreas, occur more commonly in individuals with diabetes. In addition, there is a high prevalence of diabetes in newly diagnosed cancer patients, with estimates ranging from 8% to 18%.
However, the association of preexisting diabetes with long-term, all-cause death in cancer patients has not been systematically assessed. Dr. Brancati and colleagues identified 48 articles that met criteria for the study and included 23 studies in their meta-analysis, and studies reporting cumulative survival rates were summarized qualitatively.
The pooled data across 23 studies of various types of cancer showed that preexisting diabetes was associated with a higher risk for all-cause mortality vs patients without diabetes. Their estimate was robust across sensitivity analyses that took into account population source, diabetes and mortality ascertainment, and statistical adjustment.
Additional research is needed to determine the relative importance of the different pathways leading to the increased mortality risk associated with diabetes
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