The potential of body weight change and glycemic control as markers for early detection of pancreatic cancer in the diabetic population

Pancreatic cancer is a devastating disease with poor prognosis. In fact, it is associated with one of the lowest survival rates of all cancers. Early detection of pancreatic tumors is the key to sustainably reducing pancreatic cancer mortality. Thus, effective screening programs are eagerly awaited enabling disease detection at an early stage when patients are still free from subjective complaints. Patients with a new onset of diabetes mellitus (DM) represent a known risk group for pancreatic cancer. Long-standing DM is also associated with the development of pancreatic cancer, although to a lesser extent. Given the huge number of individuals with these conditions, further risk stratification is needed to enrich the population to be screened for pancreatic cancer.
This thesis aimed to contribute to the establishment of groups within the DM population that are eligible for pancreatic cancer screening. The thesis comprises three studies, two case-control studies and a descriptive study, using data from the United Kingdom-based Clinical Practice Research Datalink GOLD. The primary care database contains anonymized electronic health care records of millions of patients who are registered with some 700 different practices.
Study 3.1 characterized the role of body weight change and blood glucose concentration as markers in the early detection of pancreatic cancer in patients with new-onset DM. Blood glucose levels and weight change before the onset of DM were compared between pancreatic cancer cases and controls. The study provided evidence that weight loss and blood glucose levels in the normal range (i.e. absence of pre-diabetes) before the onset of DM may be predictive of pancreatic cancer-associated DM. In particular modest weight loss before the onset of DM was identified as a potential early marker for pancreatic cancer.
Study 3.2 evaluated the role of glycemic control and body weight change as markers in the early detection of pancreatic cancer in patients with long-standing DM. HbA1c levels, blood glucose levels, and weight change before cancer detection were compared between pancreatic cancer cases and controls. The study showed that poor glycemic control (HbA1c ≥ 8%) may help identifying patients with long-standing DM at risk for pancreatic cancer at an earlier stage. More importantly, in this study, HbA1c values of ≥ 8% were associated with an increasing risk of pancreatic cancer with closer proximity to the cancer diagnosis in the 4 to 5 years before cancer detection, indicating that in particular DM deterioration may serve as an early marker for pancreatic cancer. Furthermore, an increased risk of pancreatic cancer was observed in patients with body weight loss in the past 3 years, with adjusted odds ratios increasing with increasing weight loss.
Study 3.3 assessed glycemic and body weight patterns in patients with pancreatic cancer-associated deterioration of DM. Non-cancer patients with DM progression were used as a comparison group. The study revealed that steep increases in HbA1c levels and loss in body weight occur distinctly more often in association with pancreatic cancer-associated DM deterioration than with typical type 2 DM progression. Also, persistent elevation of HbA1c after DM treatment intensification may be a characteristic feature of pancreatic cancer-associated DM deterioration.
In summary, the large population-based studies conducted in the context of this thesis, provide important data for the establishment of groups within the diabetic population that are eligible for pancreatic cancer screening, thereby contributing to the challenging task of disease detection at an early stage (i.e. when patients are still free from subjective complaints). Some results may be of immediate relevance for physicians. Others may trigger further research.