The bidirectional link between diabetes and pancreatic cancer: A diagnostic aid, risk factor, and potential target for future therapy

Historically, patients with pancreatic cancer presented with hyperglycemia and glycemic intolerance, leading to a hypothesis that diabetes may be associated with pancreatic ductal adenocarcinoma (PDAC). Nearly 50 years later, our understanding about the association and pathophysiological link between diabetes and PDAC continues to expand. What has been elucidated is that new-onset diabetes, especially in patients with weight loss or over the age of 50, may be an early clinical sign of PDAC. Additionally, long-standing diabetes remains an independent risk factor for development of PDAC. The pathophysiology of both new-onset and long-standing diabetes and PDAC is closely linked to non-alcoholic steatopancreatitis, the local inflammatory microenvironment, and metabolic alterations that bidirectionally arise from and worsen diabetes. This review summarizes current evidence evaluating the association between diabetes and pancreatic cancer. We also review the pathophysiology of this interaction, and discuss how understanding these mechanism may allow prevention, diagnosis, and treatment of pancreatic malignancy.