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Pancreatic Cancer Sign: Rapid Deterioration of Diabetes Control

At diagnosis and shortly thereafter, if their control deteriorates rapidly it could be a sign of asymptomatic pancreatic cancer.

550,000 diabetes patients participated in a study where they found that patients who received glucagon-like peptide-1 (GLP-1) receptor agonists, or incretin mimetics, were at significantly increased risk of developing pancreatic cancer.

However, the researchers observed that the increased risk diminished rapidly after diagnosis of diabetes. Given that they also found that the risk for pancreatic cancer was markedly increased after starting insulin therapy, they suggested that “reverse causation” may be in play, with asymptomatic pancreatic cancer initially causing diabetes before progressing to a symptomatic stage.

Medical professionals should be aware that their diabetes patients should be aware that the onset of diabetes or rapidly deteriorating diabetes control could be the first sign of hidden pancreatic cancer, and steps should be taken to investigate it. As of today there is currently no good, noninvasive method for detecting asymptomatic pancreatic cancer.

The researchers added that they hope the results will encourage the search for blood markers indicating the presence of pancreatic cancer. Most patients with pancreatic cancer are not diagnosed at a curable stage.

Dr. Auther added that, this study opens up the possibility of combining 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,”

Philippe Autier, MD, led the study to investigate the complex interaction between type 2 diabetes and pancreatic cancer, and to study the safety of GLP-1 receptor agonists in patients with diabetes.

These drugs act as incretin mimetics and reduce diabetic hyperglycemia via modifying the release of insulin by the pancreas. It has been posited that such therapies could promote the development of pancreatic cancer.

For the safety study of GLP-1 receptors, the researchers collated information on all patients with diabetes who had a first prescription of a noninsulin, nonincretin antidiabetic drug (NIAD), such as metformin, or an incretin mimetic from 2008 onward and followed them until the end of 2013 in Belgium and the end of 2012. The Belgian cohort included 368,654 patients, of whom 22,982 were receiving incretin therapy; the Lombardy cohort comprised 190,371 individuals, of whom 10,310 were treated with incretins. The mean age of the patients who received incretin mimetics was between 56 years and 58 years; the mean age for those taking NIADs was between 61 years and 65 years. The vast majority of patients were not receiving insulin therapy.

Multivariate analysis indicated that the risk for pancreatic cancer was significantly increased among patients receiving incretin therapy compared with those given NIADs.

They examined the risk for pancreatic cancer associated with insulin prescription during follow-up, which they regarded as an indication of worsening diabetes. The adjusted hazard ratio for developing pancreatic cancer among patients prescribed insulin vs those not given insulin was 6.61 in the Belgian cohort, 7.46 in the Lombardy cohort, and 6.89 overall.

When the researchers analyzed the relationship between pancreatic cancer and incretin use by duration of exposure, they found, however, that the risk of developing cancer decreased over time, from a peak 2.3-fold increased risk at 3 to 6 months, a 2.0-fold increased risk at 12 months, and a 1.7-fold increased risk after the first year.

These, in turn, may lead to the development of type 2 diabetes, which then rapidly progresses to the point at which insulin therapy is necessary. It is at this stage that the pancreatic cancer often becomes symptomatic and, thus, detectable.

The theory is supported by observations from previous studies, such as a recent meta-analysis of 88 studies that demonstrated a decrease in the risk for pancreatic adenoma carcinoma with increasing duration of diabetes.

So the question becomes should these patients diagnosed with diabetes be screened for pancreatic cancer?

“For now, no such test exists, but we could imagine in the future something like this: If the patient is diagnosed with diabetes and his/her diabetes degrades rapidly, there could be…some tests to identify markers for pancreatic cancer. Then, the pancreatic cancer could be diagnosed at an earlier stage, and with more chance of curing the disease,” Dr. Auther added.

Dr. Auther wondered, given the high hazard ratios, whether it would be beneficial for patients to undergo CT scanning at the time of diagnosis to determine whether they had pancreatic cancer. it is important to “identify a sequence of events that would lead to higher risk and then give CT scans,”  Dr. Auther added: “I don’t think we can prescribe this to all newly diagnosed patients.”

Practice Pearls:

  • It is important to identify a sequence of events that would lead to higher risk and then give CT scans.
  • New tests for pancreatic cancer are under development, including a test based on metabolomics.
  • By the time a person with diabetes is diagnosed with pancreatic cancer, cure rates are very poor.

European CanCer Organization (ECCO) Congress 2017. Abstract 540, presented January 30, 2017.