The onset of diabetes, or a rapid deterioration in existing diabetes that requires more aggressive treatment, could be a sign of early, hidden pancreatic cancer, according to research presented by Autier et al at the 2017 European Cancer Congress (Abstract 540).1
Study Design and Key Findings
Alice Koechlin and Philippe Autier, MD, of the International Prevention Research Institute (iPRI) in Lyon, France, and colleagues in Belgium and Italy used prescription data to identify 368,377 patients with type 2 diabetes in Belgium between 2008 and 2013 and 456,311 patients in Lombardy, Italy, between 2008 and 2012. Ms. Koechlin is a statistician and epidemiologist, and Dr. Autier is Vice President, Population Research, at iPRI.
Philippe Autier, MD
The data were linked to pancreatic cancer cases in the Belgian Cancer Registry and the hospital discharge databases in Lombardy. There were 885 and 1,872 cases of pancreatic cancer diagnosed during this time in Belgium and Lombardy, respectively.
Ms. Koechlin described an analysis linking the nearly 1 million patients with type 2 diabetes with recorded cases of pancreatic cancer showed that 50% of all pancreatic cancer cases in the 2 regions were diagnosed within 1 year of patients being diagnosed with type 2 diabetes and being given their first prescription to control it.
“In Belgium, 25% of cases were diagnosed within 90 days, and in Lombardy, it was 18%. After the first year, the proportion of diagnosed pancreatic cancers dropped dramatically,” she said.
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.— Alice Koechlin
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The researchers found that compared with patients who were able to continue with oral antidiabetic drugs, patients in Belgium and in Lombardy had a 3.5-fold greater risk of being diagnosed with pancreatic cancer in the first 3 months after their first prescription for incretins (metabolic hormones that stimulate the pancreas to produce more insulin to lower blood glucose levels); this fell to a 2.3-fold risk in the next 3 to 6 months, to a 2-fold risk for the next 6 to 12 months and a 1.7-fold risk after the first year.
Among patients who already had type 2 diabetes and were managing it with oral antidiabetic drugs, the switch to incretins or insulin happened faster among diabetic patients who were subsequently diagnosed with pancreatic cancer. In addition, a deterioration in their condition that necessitated them being switched to more aggressive antidiabetic therapy with injections of insulin was associated with a sevenfold increased risk of being diagnosed with pancreatic cancer.
Study Implications
The researchers said, “Although it has been known for some time that there is an association between type 2 diabetes and pancreatic cancer, the relationship between the two conditions is complex. Incretin therapies reduce diabetic hyperglycemia through stimulating the release of insulin by the pancreas. These drugs are typically prescribed when the oral antidiabetic drugs can no longer control blood glucose levels. Because of their stimulating effects on the pancreas, it has long been thought that the incretin therapies could promote the occurrence of pancreatic cancer. 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. 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 antidiabetic 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.”
However, investigating whether or not a patient has undiagnosed pancreatic cancer is difficult, and the researchers say that using prescription databases in the way that they have could help to develop methods to identify which patients may have early, nonsymptomatic pancreatic cancer.
“There is currently no good, noninvasive method for detecting pancreatic cancer that is not yet showing any visible signs or symptoms. 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,” concluded Ms. Koechlin. ■
Disclosure: Ms. Koechlin and Dr. Autier reported no potential conflicts of interest.
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