After cigarette smoking and obesity, type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer. However, the relationship between diabetes and pancreatic cancer is complex and intertwined. On one hand, diabetes can be an early manifestation of pancreatic cancer. On the other, diabetes has been implicated as a predisposing factor for pancreatic cancer. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5-fold to 2.0-fold increase in the risk of pancreatic cancer.

One prospective study directly examined the relationship between pre-diagnostic serum insulin levels and pancreatic cancer risk, demonstrating a two fold increase in risk after excluding cases diagnosed in the first 5 yr of follow-up for the highest versus lowest quartile insulin level . Also, a meta-analysis of studies of cancers of the colon and rectum, pancreas, breast, and endometrium showed an excessively high risk of colorectal and pancreatic cancer associated with high levels of circulating C-peptide/insulin and markers of hyperglycemia. In three prospective cohort studies with follow-up durations of more than 20 yrs, researchers observed an increased risk of pancreatic cancer among subjects with high post-load plasma glucose levels. In the last of these studies, the risk of pancreatic cancer was 2.2-fold higher in individuals with a post load plasma glucose level greater than 200 mg/dL at baseline than in those with a level of no more than 119 mg/dL. These results indicate that glucose tolerance may precede the onset of pancreatic cancer rather than just be a consequence of this cancer.