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