New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer

Abstract

Pancreatic cancer has a dismal prognosis because cancer-specific symptoms occur only at an advanced stage. If the cancer is to be discovered early, screening will need to be done in asymptomatic individuals. Because the incidence of pancreatic cancer is low, screening for asymptomatic cancer in the general population is not feasible; therefore, screening will need to be restricted to people at high risk of this disease. The proportion of patients with pancreatic cancer who also have hyperglycaemia or diabetes has previously been under appreciated. New data show that up to 80% of patients are either hyperglycaemic or diabetic, both of which can be detected in the presymptomatic phase. Diabetes has been shown to improve after pancreatic-cancer resection, suggesting that diabetes is caused by the cancer. Conversely, older patients with new-onset diabetes have about an eight-times higher risk of having pancreatic cancer than the general population. Recognition of new-onset diabetes as an early manifestation of pancreatic cancer could lead to the diagnosis of asymptomatic, early-stage pancreatic cancer. However, primary type-2 diabetes is common in the general population and pancreatic cancer is relatively uncommon, and the two forms of diabetes are clinically indistinguishable. The success of a strategy using new-onset hyperglycaemia and diabetes as a screening tool to identify people with a high likelihood of having asymptomatic pancreatic cancer will depend largely on our ability to differentiate pancreatic-cancer-associated diabetes from the more common type-2 diabetes by use of a (serological) biomarker.

Figure 1

Gross pathological specimen of resected pancreatic ductal adenocarcinoma split in half to show its typical appearance. Cancer-specific symptoms occur at an advanced stage and less than 15% of patients have resectable disease at presentation. For early detection of pancreatic cancer, we will need to identify a high-risk group among asymptomatic individuals. Photograph courtesy of Dr Michael B. Farnell.

Figure 2

Representative case study of pancreatic cancer-associated diabetes. Patient is a 70-year old asymptomatic woman undergoing radiologic surveillance for recurrence of Hodgkin’s lymphoma treated with mantle radiation therapy in 1995. On yearly fasting glucose measurements, asymptomatic diabetes was noted in 2005, the same year her CT scan showed a pancreatic head mass (Table 1). She underwent an R0 surgical resection of a T3N0M0 ductal adenocarcimona and remains disease free to date.

Figure 3

Observed and expected prevalence of diabetes in 60 months prior to index date in pancreatic cancer and controls. Reproduced with permission from [29] Index date: Date of pancreatic cancer diagnosis

Figure 4

Proposed screening strategy for pancreatic cancer using hyperglycemia as an indicator of underlying pancreatic cancer. *A reliable biomarker for pancreatic cancer associated diabetes remains to be identified.

Figure 5

Proposed pathogenesis of type 2 diabetes (left panel) and pancreatic cancer-associated diabetes (right panel)