Pancreatic Cancer and New-Onset Diabetes

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New-onset adult diabetes mellitus appears to be both a risk factor for and a sequelae of pancreatic cancer.
New-onset adult diabetes mellitus appears to be both a risk factor for and a sequelae of pancreatic cancer.

Pancreatic cancer is a lethal malignancy and represents the fourth leading cause of cancer-related death in the United States.1 Patients who develop pancreatic cancer can clinically present in various ways. The most common symptoms include weight loss, decreased appetite, fatigue, abdominal pain, jaundice, dark urine, and acholic stools.2 A patient's symptoms are typically related to the location of the malignancy within the pancreas. Up to 70% of malignancies are found within the head of the pancreas and are more likely to present with weight loss, jaundice, acholic stools, and steatorrhea.3 In comparison, up to 25% of malignancies are found in the body or tail of the pancreas and are less likely to present with these “classic” symptoms and more likely to be linked with reports of back pain.

Outside of these traditional presentations, new-onset adult diabetes mellitus (DM2) can represent a subtler manifestation of pancreatic cancer. “New-onset” usually refers to DM2 that has been diagnosed in fewer than 36 months. Hyperglycemia and DM2 can be present in up to 80% of patients with pancreatic cancer.4 Long-standing DM2 (a diagnosis of longer than 36 months) has been recognized as a risk factor for developing pancreatic cancer and confers an approximately 2-fold increased risk based on epidemiological studies.5 Despite this link, the role of DM2 as a potential screening test for pancreatic cancer is under investigation.4-6 The connection between these two factors can be challenging to study, however, because many patients may have had undiagnosed DM2 for years but are characterized as “newly” diagnosed when the presence of the condition is finally recognized. In addition, both DM2 and pancreatic cancer share similar risk factors such as age, family history, and obesity.6 Therefore, many of the studies evaluating diabetes as a marker for pancreatic cancer have produced mixed findings.

A population-based cohort study conducted by Chari and colleagues evaluated over 2000 patients who were aged at least 50 years with newly diagnosed diabetes for the development of pancreatic cancer within 3 years of initial diagnosis.4 Of the 2122 patients with diabetes, 18 (0.85%) were diagnosed with pancreatic cancer within 3 years.  This represented a 3-year incidence of close to 8 times that of the general population. Most of these patients did not have a family history of diabetes and 50% had “cancer-related” symptoms (although these were not defined in the study), and 10 out of 18 patients had their cancer diagnosed less than 6 months after meeting the diagnostic criteria for DM2.

A more recent study conducted by Setiawan and colleagues focused on African American and Latino patients and the link between recent-onset DM2 and pancreatic cancer.5 These patient populations were chosen because both groups have an increased risk of developing DM2, although African Americans have a significantly higher risk of pancreatic cancer compared with Latinos. This prospective, population-based cohort study identified 48,995 African American and Latino patients in California, of which 15,833 (32.3%) developed diabetes. A total of 408 patients developed pancreatic cancer, of which 128 were diagnosed with new-onset diabetes compared with 280 who did not have incident diabetes. Diabetes was associated with pancreatic cancer at ages 65 and 75 (HR = 4.6 and HR = 2.39, respectively). In patients with pancreatic cancer who developed DM2, 52.3% developed the condition during the 36 months preceding a cancer diagnosis.  At age 75, patients with new-onset diabetes (defined as < 3 years) had a 2.3-fold greater association with pancreatic cancer compared with long-standing DM2 (> 3 years). The authors concluded that new-onset diabetes is a manifestation of pancreatic cancer.

Based on anatomy and pathophysiology, it would appear that new-onset DM2 could be unique to patients who develop pancreatic cancer. However, to evaluate whether or not newly diagnosed DM2 was related to malignancies other than pancreatic cancer, Aggarwal and colleagues conducted a retrospective chart review of 500 patients with cancer.6 This cohort included 100 patients each with pancreatic, colorectal, lung, breast, and prostate cancer, and these patients were compared with 100 control patients without cancer. The study found a higher prevalence of DM2 (68%) in patients with pancreatic cancer compared with all other groups: lung cancer (19.6%), breast cancer (19.4%), prostate cancer (14.8%), colorectal cancer (20.7%), and noncancer controls (23.5%). Forty percent of patients with pancreatic cancer developed DM2 within the 36 months preceding the cancer diagnosis, which was significantly higher than the rates seen across other patient groups (ranging from 3.3% to 5.7%, P < .0001).

DM2 appears to be both a risk factor for and a sequelae of pancreatic cancer. Health care practitioners should be cognizant of this when evaluating adult patients with both long-standing and new-onset diabetes. More studies are needed in the future to further clarify how screening tests for pancreatic cancer could be coupled with available tests for DM2.

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30.
  2. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol. 2005 Jun;7(5):189-197.
  3. Modolell I, Guarner L, Malagelada JR. Vagaries of clinical presentation of pancreatic and biliary tract cancer. Ann Oncol. 1999;10(suppl-4):S82-S84.
  4. Chari ST, Leibson CL, Rabe KG, Ransom J, de Andrade M, Petersen GM. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005;129(2):504-511.
  5. Setiawan VW, Stram DO, Porcel J, et al. Pancreatic cancer following incident diabetes in African Americans and Latinos: The Multiethnic Cohort [published online June 18, 2018]. J Natl Cancer Inst. doi: 10.1093/jnci/djy090
  6. Aggarwal G, Kamada P, Chari ST. Prevalence of diabetes mellitus in pancreatic cancer compared to common cancers. Pancreas. 2013;42(2):198-201.

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