Diabetes mellitus in pancreatic cancer: is it a causal relationship?

The relationship between type 2 diabetes mellitus and pancreatic cancer (PC) is not clear. It has been reported that the increased release of islet amyloid polypeptides (IAPPs) is responsible for the impaired glucose tolerance in PC patients. However, no information exists on the patterns of IAPP expression in PC tissue in comparison with tissue from the normal pancreas and that of a patient with type 2 diabetes. Therefore, we performed a morphometric study and compared the patterns of IAPP expression in 5 normal pancreases (as a control), 6 pancreases from patients with type 2 diabetes, and 11 surgical PC specimens, which were processed for immunohistochemistry using anti-insulin and an anti-IAPP antibody. From the cancer tissue, sections were taken from the tumor (T) and from adjacent tumor-free areas (TF). The size of islets and the number of immunostained cells in these islets were recorded. In diabetes and PC, the size of islets and the number of beta-cells was significantly lower than in the controls. Also, the number of IAPP-expressing cells was significantly lower in diabetes and in the T area but not in the TF region. In addition, no characteristic changes found in diabetic pancreases were observed in the TF area, indicating that PC patients had no prior diabetic diseases. The reduction in the number of IAPP in the T area seems to argue against the role of IAPP in glucose abnormality in PC patients. The primary endocrine alteration in the tumor area suggests that cancer cells produce diabetogenic substances, the nature of which awaits further research.