Insulin levels and resistance linked to risk of pancreatic cancer

December 13, 2005

Higher insulin concentrations and insulin resistance are associated with an increased risk of pancreatic cancer in men, according to a study in the December 14 issue of JAMA.

Based on the findings from several retrospective and prospective observational studies, type 2 diabetes mellitus and glucose intolerance are fairly consistent, albeit somewhat controversial, risk factors for pancreatic cancer, according to background information in the article. This is because it has been unresolved whether diabetes mellitus is involved in pancreatic carcinogenesis or the result of subclinical malignancy. One biologically plausible mechanism whereby type 2 diabetes mellitus may be related to pancreatic carcinogenesis is through the growth-regulatory effects of insulin. Experimental studies show that insulin has growth promoting effects on pancreatic cancer cells and patients with type 2 diabetes mellitus are known to exhibit hyperinsulinemia, during the early stages of their disease.

The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (1985-1988) of male smokers previously reported a significant 2-fold increased risk between self-reported diabetes mellitus and pancreatic cancer. Rachael Z. Stolzenberg-Solomon, Ph.D., of the National Cancer Institute, Department of Health and Human Services, Rockville, Md., and colleagues examined a cohort from the ATBC study to determine whether fasting serum insulin and glucose concentrations were associated with risk for incident pancreatic cancer. The study consisted of 29,133 male Finnish smokers ages 50 to 69 years. The study included 400 randomly sampled subcohort control participants and 169 incident pancreatic cancer cases that occurred after the 5th year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up).

The researchers found that after adjustment for age, years smoked, and body mass index, higher concentrations of glucose, insulin, and insulin resistance tended to show positive dose-response associations with pancreatic cancer. Biochemically defined diabetes mellitus and insulin concentration in the highest quartile demonstrated significant 2-fold increased risks. There were significant interactions between quartile-categorized glucose, insulin, and insulin resistance and pancreatic cancer by follow-up time, such that risks were greater among the cases that occurred with longer follow-up time.

"In conclusion, our results support the hypothesis that higher insulin concentrations and insulin resistance may be a mechanism that explains the associations between diabetes mellitus, higher glucose concentration, and pancreatic cancer observed in previous studies. Although based solely on male smokers, our findings for glucose and biochemical-defined diabetes mellitus are consistent with previous studies conducted in diverse populations that have included women and nonsmokers," the authors write.

"The associations for insulin and insulin resistance reported herein require confirmation and along with observations of other studies could potentially have important implications for nutrition and treatment-related cancer preventive strategies that modify or interfere with the insulin resistance pathway to help decrease the burden from this devastating disease. Lifestyle changes to decrease glucose and insulin concentrations through weight reduction, increasing physical activity, and diet such as decreasing saturated fat intake, and identification of other modifiable factors that may contribute to higher glucose and insulin concentrations could possibly impact pancreatic cancer development, as well as other cancer and chronic disease," the researchers write.
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(JAMA.2005; 294:2872-2878. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This study was supported by the Intramural Research Program of the National Institutes of Public Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services.

The JAMA Network Journals

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