Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers

Context: Obesity, diabetes mellitus, and glucose intolerance have been associated with increased pancreatic cancer risk; however, prediagnostic serum insulin concentration has not been evaluated as a predictor of this malignancy. Objective: To investigate whether prediagnostic fasting glucose and insulin concentrations and insulin resistance are associated with subsequent incidence of exocrine pancreatic cancer in a cohort of male smokers. Design, Setting, and Participants: A case-cohort prospective study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-1988) cohort 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 fifth year of follow-up. All participants were followed up through December 2001 (up to 16.7 years of follow-up). Main Outcome Measures: Incident exocrine pancreatic cancer identified from the Finnish Cancer Registry. Results: After adjusting for age, smoking, and body mass index, higher baseline fasting serum concentrations of glucose, insulin, and insulin resistance were positively associated with pancreatic cancer. The presence of biochemically defined diabetes mellitus (glucose, ≥126 mg/dL [≥6.99 mmol/L]) and insulin concentration in the highest vs lowest quartile both showed a significant 2-fold increased risk (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.04-4.35; and HR, 2.01; 95% CI, 1.03-3.93; respectively). There were significant interactions for all the biomarker exposures by follow-up time, such that the positive associations were stronger among the cases that occurred more than 10 years after baseline (highest vs lowest quartile: glucose, HR, 2.16; 95% CI, 1.05-4.42; P for trend=.02; insulin, HR, 2.90; 95% CI, 1.22-6.92; P for trend=.005; and insulin resistance, HR, 2.71; 95% CI, 1.19-6.18; P for trend=.006). Conclusions: These results support the hypothesis that exposure to higher insulin concentrations and insulin resistance predicts the risk of exocrine pancreatic cancer.