Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer

Abstract

The relationships between diabetes and pancreatic ductal adenocarcinoma (PDAC) are complex. Longstanding type 2 diabetes (T2DM) is a risk factor for pancreatic cancer, but increasing epidemiological data point to PDAC as also a cause of diabetes due to unknown mechanisms. New-onset diabetes is of particular interest to the oncology community as the differentiation of new-onset diabetes caused by PDAC as distinct from T2DM may allow for earlier diagnosis of PDAC. To address these relationships and raise awareness of the relationships between PDAC and diabetes, a symposium entitled Diabetes, Pancreatogenic Diabetes, and Pancreatic Cancer was held at the American Diabetes Association's 76th Scientific Sessions in June 2016. This article summarizes the data presented at that symposium, describing the current understanding of the interrelationships between diabetes, diabetes management, and pancreatic cancer, and identifies areas where additional research is needed.

Figure 1

Schematic representation of the islet–acinar–ductal axis. An endocrine islet consisting mostly of insulin-producing β-cells (green) but also other endocrine cell types such as glucagon (yellow) is shown receiving an arterial blood supply (red). Some of this arterial blood drains into an intrapancreatic (IP) portal circulation that bathes adjacent acinar and ductal cells. The insulin-rich blood supply exerts trophic effects on these cells that are most evident in the acinar cells making up one such acinus. The acinar cells are large and have many enzyme-rich zymogen granules (shown as small yellow circles within each acinar cell).

Figure 2

Prevalence of types of diabetes. Distribution of types of diabetes (A) and causes of T3cDM (pancreatogenic) diabetes (B) based on studies of 1,922 patients with diabetes reported by Hardt et al. (49). Reproduced from Cui and Andersen (47).

Figure 3

Prevalence of diabetes (DM) in PDAC. The prevalence of diabetes and impaired fasting glucose in 512 pancreatic cancer patients and 933 control subjects. Reproduced from Pannala et al. (3).

Figure 4

Prevalence of diabetes (DM) after pancreaticoduodenectomy for PDAC. The prevalence of diabetes after resection of PDAC in new-onset diabetes (<2 years duration), long-standing diabetes (>2 years duration), impaired fasting glucose (IFG) (100–125 mg/dL) preoperatively, and normal fasting glucose (NFG) (≤99 mg/dL) preoperatively. Reproduced from Pannala et al. (3).