Pancreatic cancer and diabetes mellitus

Pancreatic ductal adenocarcinoma (PDAC) has a poor overall prognosis since the vast majority of cases present at an advanced stage. There are no symptoms in the early stage and cancer-specific symptoms occur late in the course of the disease. Developing strategies for early detection of PDAC when it is still resectable and potentially curable may lead to reduced cancer death. However, screening for sporadic PDAC in the general population is not feasible due to its low incidence. A strategy for early detection of PDAC is to define a high-risk group primed for surveillance with imaging techniques. A high-risk group has been identified in patients at least 50 years of age with new-onset diabetes (NOD) in whom there is an eightfold higher risk of being diagnosed with PDAC within 3 years of diagnosis of NOD compared to the general population (Chari et al., Gastroenterology 129:504-511, 2005). Patients with PDAC develop a distinct type of diabetes called pancreatic cancer-associated diabetes (PC-DM) which improves following pancreatic cancer resection suggesting that diabetes is caused by the cancer (Pannala et al., Gastroenterology 134:981987, 2008). There is emerging data for the role of adrenomedullin in mediating pancreatic cancer induced inhibition of insulin secretion in beta cells and insulin resistance. However, it is difficult to clinically distinguish PDAC-associated NOD (PDAC-NOD) from the more common type 2 diabetes mellitus (type 2 DM) which is present in 4% to 65% of patients with PDAC. Currently, there are no reliable biomarkers that differentiate PDAC-NOD and type 2 DM-associated NOD. There are encouraging preliminary results using clinical risk prediction models to differentiate PDAC-NOD and type 2 DM-NOD; however, further validation is needed in larger populations before being applied in clinical practice.