Insulin Levels And Resistance Linked To Risk Of Pancreatic Cancer

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Insulin Levels And Resistance Linked To Risk Of Pancreatic Cancer

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. Z. Stolzenberg-, 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.