Aggressive Treatment in Type 2 Diabetes May Be Early Sign of Pancreatic Cancer

Rapid deterioration in patients with type 2 diabetes may be an early warning sign of pancreatic cancer, according to findings presented at the European Cancer Congress 2017.

The analysis showed that 50% of all pancreatic cancer cases in Lombardy, Italy, and Belgium were diagnosed within 1 year of patients being diagnosed with type 2 diabetes.

“In Belgium, 25% of cases were diagnosed with 90 days, and in Lombardy it was 18%,” said author Alice Koechlin. “After the first year, the proportion of diagnosed pancreatic cancers dropped dramatically.”

For the study, investigators used prescription data to identify 368,377 patients with type 2 diabetes in Belgium between 2008 and 2013, and 456,311 patients in Lombardy between 2008 and 2012.

The data were linked to pancreatic cancer cases in the Belgian Cancer Registry, as well as the hospital discharge databases in Lombardy. During the time period, 885 cases of pancreatic cancer were diagnosed in Belgium and 1872 cases in Lombardy.

Compared with patients who could continue taking oral diabetes drugs, the results of the study showed patients in Belgium and Lombardy had a 3.5-fold greater risk of being diagnosed with pancreatic cancer in the first 3 months after receiving their first prescription for incretins.

The figures dropped to a 2.3-fold risk over the next 3 to 6 months; to a 2-fold risk for the next 6 to 12 months; and 1.7-fold risk after 1 year.

The switch to incretins or insulin occurred faster among patients with type 2 diabetes, who were subsequently diagnosed with pancreatic cancer compared with those who already had diabetes and were managing the disease with oral anti-diabetic drugs.

The investigators also found that a deterioration in health that caused patients to switch to a more aggressive diabetes treatment, with injections of insulin, was associated with a 7-fold increased risk in pancreatic cancer.

“Although it has been known for some time that there is an association between type 2 diabetes and pancreatic cancer, the relationship between the 2 conditions is complex,” the authors said. “Incretin therapies reduce diabetic hyperglycemia through stimulating the release of insulin by the pancreas. These drugs are typically prescribed when the oral anti-diabetic drugs can no longer control blood glucose levels.”

Due to the drugs stimulating effects on the pancreas, it was long believed that incretin therapies could promote pancreatic cancer occurrence, according to the investigators. However, it is known that pancreatic cancer can cause diabetes.

“Our study shows that incretin therapies are often prescribed to patients whose diabetes is caused by a still undiagnosed pancreatic cancer,” said Koechlin and author Philippe Autier. “Because the pancreatic cancer finally becomes symptomatic and is thus diagnosed, it looks like it is the intake of incretin drugs that could be the trigger of the pancreatic cancer, while in reality, it is the pancreatic cancer that causes a deterioration of diabetes, which is followed by the prescription of incretins. This phenomenon is called 'reverse causation'. Our study also shows that the reverse causation observed for incretin drugs is also observed for other anti-diabetic therapies, in particular for insulin therapy.

“Doctors and their diabetic patients should be aware that the onset of diabetes or rapidly deteriorating diabetes could be the first sign of hidden pancreatic cancer, and steps should be taken to investigate it.”

Determining whether a patient has undiagnosed pancreatic cancer can be challenging, and investigators recommend that prescription databases could be used to help develop new techniques for identifying patients with early, asymptomatic pancreatic cancer.

“There is currently no good, noninvasive method for detecting pancreatic cancer that is not yet showing any visible signs or symptoms,” the authors concluded. “We hope that our results will encourage the search for blood markers indicating the presence of pancreatic cancer, which could guide decisions to perform a confirmation examination like endoscopy.”

An estimated 338,000 cases of pancreatic cancer were diagnosed worldwide in 2013, of which 330,000 individuals died from the disease.

“Due to the severity of pancreatic cancer and because only a minority of cases are detected at a curable stage, we must find better ways for early detection,” said Peter Naredi, chair of the congress and president of the European Cancer Organization. “Some advances have been made in the search for blood markers. The study by Autier and colleagues opens up the possibility to combine the diagnosis of an associated disease, type 2 diabetes, with blood biomarkers. It is a step in the right direction if we can increase the proportion of early diagnosed pancreatic cancers.”